Leukemia, Myelodysplasia, Transplantation

A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.

“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”

Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.

Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.

[email protected]

SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
 

A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.

“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”

Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.

Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.

[email protected]

SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
 

A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.

“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”

Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.

Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.

[email protected]

SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
 

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm associated with the fusion of the BCR gene located on chromosome 22 and the ABL1 gene on chromosome 9. The fusion results in a reciprocal translocation between chromosomes 9 and 22, leading to the formation of the Philadelphia (Ph) chromosome found in 90%-95% of patients with CML. The incidence of CML is 1.5 per 100,000 people per year, with a male predominance and an average age at diagnosis of 64.¹

About 85%-90% of newly diagnosed patients present in the chronic phase and therefore many of them are asymptomatic at the time of diagnosis. If symptoms are present, they often include fatigue, malaise, unintentional weight loss, early satiety, or left upper quadrant pain. Progression of the disease is associated with worsening symptoms such as unexplained fever, significant weight loss, bone or joint pain, bleeding, thrombosis, and infections suggestive of transformation to the accelerated phase or blast crisis. Physical exam findings most commonly include splenomegaly and occasionally mild hepatomegaly.

Atraumatic splenic rupture is a rare complication of this hematologic malignancy, and there are almost no reported cases of CML as the underlying cause.^2-4 Here we present the case of a man with sudden-onset generalized abdominal pain and leukocytosis. A computed-tomography scan showed splenic rupture, and the patient was taken for emergency splenectomy. The patient was subsequently positive for t(9,22)(q34;q11.2).

Case presentation and summary

A 59-year-old white man with a history of hypertension and kidney stones presented to a community emergency department with a chief complaint of abdominal pain. About 30 minutes before his arrival, the patient had woken up from sleep with generalized, nonradiating, abdominal pain, which he described as “like my previous kidney stones.” He also reported worsening dyspnea, nausea without vomiting, and lightheadedness without loss of consciousness. The remainder of the review of systems was negative. A physical exam revealed that he was in moderate distress with clear lung fields and had tachycardia without murmur, no CVA tenderness, and a diffusely tender abdomen.

Complete blood count with differential showed leukocytosis (109.1 x 10³/uL), normocytic anemia (8.1 g/dL), thrombocytopenia (100,000 cells/uL), neutrophils (71.06 cells/uL), bands (27.13 cells/uL), and monocytes (11.63 cells/uL). A CT scan of the abdomen and pelvis showed a grade 4 splenic laceration with significant free abdominal fluid (Figure 1).

After extubation a more thorough history could be obtained from the patient. He denied any history of weight loss, night sweats, or fatigue. Patient denied any known family history of hematologic malignancies. His peripheral smear showed basophilia and granulocytosis with neutrophils and immature granulocytes (Figure 2). The patient was evaluated by the hematology service and was started on allopurinol and hydroxyurea for presumed hematologic malignancy. He was given the meningococcus and streptococcus pneumoniae vaccine and was discharged home in stable condition on day eleven. Patient was subsequently positive for t(9,22)(q34;q11.2) and was started on imatinib. He has continued to follow in the clinic and is currently in remission.

Discussion

CML has a triphasic clinical course and treatment is based on the specific disease phase. The 3 phases of the disease include the chronic (more indolent) phase, accelerated (more aggressive) phase, and blast crisis. If the disease is left untreated, it will inevitably transition from a chronic to an accelerated phase and finally to blast crisis within a median time of 4 years.

The chronic phase is the most common, representing 85% of diagnoses. Patients can be asymptomatic and many in this phase will be diagnosed by routine lab testing.⁵ According to the World Health Organization, the accelerated phase is defined as CML patients with one of the following: 10%-19% blasts, basophils ≥20%, platelets <100,000/microL or >1,000,000/microL, unresponsive to therapy, splenomegaly unresponsive to therapy, an increasing white cell count unresponsive to therapy, or cytogenetic evolution.⁶ Blast crisis is the most aggressive phase and is usually defined by ≥20% blasts, large foci or clusters of blasts on the bone marrow biopsy, or the presence of extramedullary blastic infiltrates.^7,8

The diagnosis of CML should be suspected in the presence of distinct lab abnormalities in the peripheral blood. These include elevated white blood cell counts with a median count of 100,000 cells/microL, elevated platelet counts, and a mild normocytic normochromic anemia. Platelet counts of 600,000 or greater have been seen in 15%-30% of patients at the time of diagnosis. The white count differential can show a variety of cells but there will be a notably greater percentage of myelocytes than metamyelocytes. Bone marrow biopsy will reveal increased cellularity, normal to slightly elevated percentage of blasts, and reticulin fibrosis. The diagnosis should be confirmed by the presence of the Philadelphia chromosome either by cytogenetics, fluorescence in situ hybridization, or reverse-transcription polymerase chain reaction (RT-PCR). The Philadelphia chromosome is found in 90%-95% of patients with CML. Most of the remaining patients will have other translocations, but a small minority will have no detectable genetic abnormalities and those patients are known as Ph-negative.⁹

Treatment options for CML include potential cure with allogeneic hematopoietic stem-cell transplant (HSCT) or disease control using tyrosine kinase inhibitors (TKIs). TKIs are the initial treatment of choice for newly diagnosed patients and are able to produce long-term remission in most patients. The drugs in this category include imatinib, dasatinib, and nilotinib. They work by inhibiting the Bcr-Abl tyrosine kinase, thereby blocking proliferation and inducing apoptosis in Bcr-Abl-positive cells. The majority of patients with chronic-phase CML will have an excellent response to initial treatment with a TKI. It is critical to follow these patients on a regular basis and monitor their disease status. Although the gold standard for assessing cytogenetic response is cytogenetic analysis of a bone marrow biopsy, more sensitive methods such as quantitative PCR using peripheral blood are now available, thereby minimizing the need for bone marrow biopsy. Patients in the accelerated phase are more difficult to manage because they are resistant to most forms of treatment and have short-lived responses to TKI therapy. These patients should strongly be considered for transplantation. Patients in blast crisis have aggressive disease that is more complex and requires more extensive testing. These patients should ideally be treated at tertiary care centers and treatment often involves chemotherapy in addition to TKI therapy usually followed by HSCT.

Atraumatic splenic rupture (ASR) presents similarly to traumatic splenic rupture with typical symptoms being acute onset of upper abdominal, left chest wall, or left shoulder pain (Kehr’s sign) but without a known history of trauma. Quick recognition and surgical intervention represent the best means of definitive care.¹⁰ Renzulli and colleagues conducted a literature review for all ASR cases from 1980-2008, examining 632 publications representing 845 cases. They examined the cases using logistic regression analysis to better define the clinicopathology behind ASR. The reported causes of ASR are neoplastic processes (30.3%), infectious (27.3%), inflammatory noninfectious (20.0%), drug- and treatment-related (9.2%), mechanical (6.8%), and normal spleen (6.4%). Treatment included total splenectomy in 84.1% of cases, organ-preserving surgery in 1.2%, and conservative measures in 14.7%. They reported an ASR-related mortality of 12.2%, with being older than 40 and neoplastic disorders associated with increased mortality – although male sex and splenomegaly have also been reported.^11-13 Thomas and colleagues have reported on 48 cases of ASR related to hematologic malignancy showing acute myeloid leukemia being the most common cause (21%), followed by acute lymphoblastic leukemia (19%).²

Hematologic malignancies commonly cause splenic engorgement and pain although splenic rupture is an extremely rare event. Recent literature review has shown fewer than a thousand reported cases since 1980.⁴ There far fewer reported cases of ASR being related to CML, with most being reported as a complication.^3,14 Based on our review, we could identify only a handful cases of CML with ASR being the initial symptom. These include a patient with Ph-negative CML and ASR following blast crisis, a patient with Phil-negative BCR-ABL-positive essential thrombocythemia, several cases in which the patient ultimately died, and 1 in which the patient survived into remission.^4,14-16 Our case is different because the patient was ultimately positive for t(9,22)(q34;q11.2) and although he experienced multiple complications, he is currently functioning at his baseline and in remission. We hope this case will remind others that CML should be considered in the differential diagnosis of patients ASR.

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm associated with the fusion of the BCR gene located on chromosome 22 and the ABL1 gene on chromosome 9. The fusion results in a reciprocal translocation between chromosomes 9 and 22, leading to the formation of the Philadelphia (Ph) chromosome found in 90%-95% of patients with CML. The incidence of CML is 1.5 per 100,000 people per year, with a male predominance and an average age at diagnosis of 64.¹

About 85%-90% of newly diagnosed patients present in the chronic phase and therefore many of them are asymptomatic at the time of diagnosis. If symptoms are present, they often include fatigue, malaise, unintentional weight loss, early satiety, or left upper quadrant pain. Progression of the disease is associated with worsening symptoms such as unexplained fever, significant weight loss, bone or joint pain, bleeding, thrombosis, and infections suggestive of transformation to the accelerated phase or blast crisis. Physical exam findings most commonly include splenomegaly and occasionally mild hepatomegaly.

Atraumatic splenic rupture is a rare complication of this hematologic malignancy, and there are almost no reported cases of CML as the underlying cause.^2-4 Here we present the case of a man with sudden-onset generalized abdominal pain and leukocytosis. A computed-tomography scan showed splenic rupture, and the patient was taken for emergency splenectomy. The patient was subsequently positive for t(9,22)(q34;q11.2).

Case presentation and summary

A 59-year-old white man with a history of hypertension and kidney stones presented to a community emergency department with a chief complaint of abdominal pain. About 30 minutes before his arrival, the patient had woken up from sleep with generalized, nonradiating, abdominal pain, which he described as “like my previous kidney stones.” He also reported worsening dyspnea, nausea without vomiting, and lightheadedness without loss of consciousness. The remainder of the review of systems was negative. A physical exam revealed that he was in moderate distress with clear lung fields and had tachycardia without murmur, no CVA tenderness, and a diffusely tender abdomen.

Complete blood count with differential showed leukocytosis (109.1 x 10³/uL), normocytic anemia (8.1 g/dL), thrombocytopenia (100,000 cells/uL), neutrophils (71.06 cells/uL), bands (27.13 cells/uL), and monocytes (11.63 cells/uL). A CT scan of the abdomen and pelvis showed a grade 4 splenic laceration with significant free abdominal fluid (Figure 1).

After extubation a more thorough history could be obtained from the patient. He denied any history of weight loss, night sweats, or fatigue. Patient denied any known family history of hematologic malignancies. His peripheral smear showed basophilia and granulocytosis with neutrophils and immature granulocytes (Figure 2). The patient was evaluated by the hematology service and was started on allopurinol and hydroxyurea for presumed hematologic malignancy. He was given the meningococcus and streptococcus pneumoniae vaccine and was discharged home in stable condition on day eleven. Patient was subsequently positive for t(9,22)(q34;q11.2) and was started on imatinib. He has continued to follow in the clinic and is currently in remission.

Discussion

CML has a triphasic clinical course and treatment is based on the specific disease phase. The 3 phases of the disease include the chronic (more indolent) phase, accelerated (more aggressive) phase, and blast crisis. If the disease is left untreated, it will inevitably transition from a chronic to an accelerated phase and finally to blast crisis within a median time of 4 years.

The chronic phase is the most common, representing 85% of diagnoses. Patients can be asymptomatic and many in this phase will be diagnosed by routine lab testing.⁵ According to the World Health Organization, the accelerated phase is defined as CML patients with one of the following: 10%-19% blasts, basophils ≥20%, platelets <100,000/microL or >1,000,000/microL, unresponsive to therapy, splenomegaly unresponsive to therapy, an increasing white cell count unresponsive to therapy, or cytogenetic evolution.⁶ Blast crisis is the most aggressive phase and is usually defined by ≥20% blasts, large foci or clusters of blasts on the bone marrow biopsy, or the presence of extramedullary blastic infiltrates.^7,8

The diagnosis of CML should be suspected in the presence of distinct lab abnormalities in the peripheral blood. These include elevated white blood cell counts with a median count of 100,000 cells/microL, elevated platelet counts, and a mild normocytic normochromic anemia. Platelet counts of 600,000 or greater have been seen in 15%-30% of patients at the time of diagnosis. The white count differential can show a variety of cells but there will be a notably greater percentage of myelocytes than metamyelocytes. Bone marrow biopsy will reveal increased cellularity, normal to slightly elevated percentage of blasts, and reticulin fibrosis. The diagnosis should be confirmed by the presence of the Philadelphia chromosome either by cytogenetics, fluorescence in situ hybridization, or reverse-transcription polymerase chain reaction (RT-PCR). The Philadelphia chromosome is found in 90%-95% of patients with CML. Most of the remaining patients will have other translocations, but a small minority will have no detectable genetic abnormalities and those patients are known as Ph-negative.⁹

Treatment options for CML include potential cure with allogeneic hematopoietic stem-cell transplant (HSCT) or disease control using tyrosine kinase inhibitors (TKIs). TKIs are the initial treatment of choice for newly diagnosed patients and are able to produce long-term remission in most patients. The drugs in this category include imatinib, dasatinib, and nilotinib. They work by inhibiting the Bcr-Abl tyrosine kinase, thereby blocking proliferation and inducing apoptosis in Bcr-Abl-positive cells. The majority of patients with chronic-phase CML will have an excellent response to initial treatment with a TKI. It is critical to follow these patients on a regular basis and monitor their disease status. Although the gold standard for assessing cytogenetic response is cytogenetic analysis of a bone marrow biopsy, more sensitive methods such as quantitative PCR using peripheral blood are now available, thereby minimizing the need for bone marrow biopsy. Patients in the accelerated phase are more difficult to manage because they are resistant to most forms of treatment and have short-lived responses to TKI therapy. These patients should strongly be considered for transplantation. Patients in blast crisis have aggressive disease that is more complex and requires more extensive testing. These patients should ideally be treated at tertiary care centers and treatment often involves chemotherapy in addition to TKI therapy usually followed by HSCT.

Atraumatic splenic rupture (ASR) presents similarly to traumatic splenic rupture with typical symptoms being acute onset of upper abdominal, left chest wall, or left shoulder pain (Kehr’s sign) but without a known history of trauma. Quick recognition and surgical intervention represent the best means of definitive care.¹⁰ Renzulli and colleagues conducted a literature review for all ASR cases from 1980-2008, examining 632 publications representing 845 cases. They examined the cases using logistic regression analysis to better define the clinicopathology behind ASR. The reported causes of ASR are neoplastic processes (30.3%), infectious (27.3%), inflammatory noninfectious (20.0%), drug- and treatment-related (9.2%), mechanical (6.8%), and normal spleen (6.4%). Treatment included total splenectomy in 84.1% of cases, organ-preserving surgery in 1.2%, and conservative measures in 14.7%. They reported an ASR-related mortality of 12.2%, with being older than 40 and neoplastic disorders associated with increased mortality – although male sex and splenomegaly have also been reported.^11-13 Thomas and colleagues have reported on 48 cases of ASR related to hematologic malignancy showing acute myeloid leukemia being the most common cause (21%), followed by acute lymphoblastic leukemia (19%).²

Hematologic malignancies commonly cause splenic engorgement and pain although splenic rupture is an extremely rare event. Recent literature review has shown fewer than a thousand reported cases since 1980.⁴ There far fewer reported cases of ASR being related to CML, with most being reported as a complication.^3,14 Based on our review, we could identify only a handful cases of CML with ASR being the initial symptom. These include a patient with Ph-negative CML and ASR following blast crisis, a patient with Phil-negative BCR-ABL-positive essential thrombocythemia, several cases in which the patient ultimately died, and 1 in which the patient survived into remission.^4,14-16 Our case is different because the patient was ultimately positive for t(9,22)(q34;q11.2) and although he experienced multiple complications, he is currently functioning at his baseline and in remission. We hope this case will remind others that CML should be considered in the differential diagnosis of patients ASR.

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm associated with the fusion of the BCR gene located on chromosome 22 and the ABL1 gene on chromosome 9. The fusion results in a reciprocal translocation between chromosomes 9 and 22, leading to the formation of the Philadelphia (Ph) chromosome found in 90%-95% of patients with CML. The incidence of CML is 1.5 per 100,000 people per year, with a male predominance and an average age at diagnosis of 64.¹

About 85%-90% of newly diagnosed patients present in the chronic phase and therefore many of them are asymptomatic at the time of diagnosis. If symptoms are present, they often include fatigue, malaise, unintentional weight loss, early satiety, or left upper quadrant pain. Progression of the disease is associated with worsening symptoms such as unexplained fever, significant weight loss, bone or joint pain, bleeding, thrombosis, and infections suggestive of transformation to the accelerated phase or blast crisis. Physical exam findings most commonly include splenomegaly and occasionally mild hepatomegaly.

Atraumatic splenic rupture is a rare complication of this hematologic malignancy, and there are almost no reported cases of CML as the underlying cause.^2-4 Here we present the case of a man with sudden-onset generalized abdominal pain and leukocytosis. A computed-tomography scan showed splenic rupture, and the patient was taken for emergency splenectomy. The patient was subsequently positive for t(9,22)(q34;q11.2).

Case presentation and summary

A 59-year-old white man with a history of hypertension and kidney stones presented to a community emergency department with a chief complaint of abdominal pain. About 30 minutes before his arrival, the patient had woken up from sleep with generalized, nonradiating, abdominal pain, which he described as “like my previous kidney stones.” He also reported worsening dyspnea, nausea without vomiting, and lightheadedness without loss of consciousness. The remainder of the review of systems was negative. A physical exam revealed that he was in moderate distress with clear lung fields and had tachycardia without murmur, no CVA tenderness, and a diffusely tender abdomen.

Complete blood count with differential showed leukocytosis (109.1 x 10³/uL), normocytic anemia (8.1 g/dL), thrombocytopenia (100,000 cells/uL), neutrophils (71.06 cells/uL), bands (27.13 cells/uL), and monocytes (11.63 cells/uL). A CT scan of the abdomen and pelvis showed a grade 4 splenic laceration with significant free abdominal fluid (Figure 1).

After extubation a more thorough history could be obtained from the patient. He denied any history of weight loss, night sweats, or fatigue. Patient denied any known family history of hematologic malignancies. His peripheral smear showed basophilia and granulocytosis with neutrophils and immature granulocytes (Figure 2). The patient was evaluated by the hematology service and was started on allopurinol and hydroxyurea for presumed hematologic malignancy. He was given the meningococcus and streptococcus pneumoniae vaccine and was discharged home in stable condition on day eleven. Patient was subsequently positive for t(9,22)(q34;q11.2) and was started on imatinib. He has continued to follow in the clinic and is currently in remission.

Discussion

CML has a triphasic clinical course and treatment is based on the specific disease phase. The 3 phases of the disease include the chronic (more indolent) phase, accelerated (more aggressive) phase, and blast crisis. If the disease is left untreated, it will inevitably transition from a chronic to an accelerated phase and finally to blast crisis within a median time of 4 years.

The chronic phase is the most common, representing 85% of diagnoses. Patients can be asymptomatic and many in this phase will be diagnosed by routine lab testing.⁵ According to the World Health Organization, the accelerated phase is defined as CML patients with one of the following: 10%-19% blasts, basophils ≥20%, platelets <100,000/microL or >1,000,000/microL, unresponsive to therapy, splenomegaly unresponsive to therapy, an increasing white cell count unresponsive to therapy, or cytogenetic evolution.⁶ Blast crisis is the most aggressive phase and is usually defined by ≥20% blasts, large foci or clusters of blasts on the bone marrow biopsy, or the presence of extramedullary blastic infiltrates.^7,8

The diagnosis of CML should be suspected in the presence of distinct lab abnormalities in the peripheral blood. These include elevated white blood cell counts with a median count of 100,000 cells/microL, elevated platelet counts, and a mild normocytic normochromic anemia. Platelet counts of 600,000 or greater have been seen in 15%-30% of patients at the time of diagnosis. The white count differential can show a variety of cells but there will be a notably greater percentage of myelocytes than metamyelocytes. Bone marrow biopsy will reveal increased cellularity, normal to slightly elevated percentage of blasts, and reticulin fibrosis. The diagnosis should be confirmed by the presence of the Philadelphia chromosome either by cytogenetics, fluorescence in situ hybridization, or reverse-transcription polymerase chain reaction (RT-PCR). The Philadelphia chromosome is found in 90%-95% of patients with CML. Most of the remaining patients will have other translocations, but a small minority will have no detectable genetic abnormalities and those patients are known as Ph-negative.⁹

Treatment options for CML include potential cure with allogeneic hematopoietic stem-cell transplant (HSCT) or disease control using tyrosine kinase inhibitors (TKIs). TKIs are the initial treatment of choice for newly diagnosed patients and are able to produce long-term remission in most patients. The drugs in this category include imatinib, dasatinib, and nilotinib. They work by inhibiting the Bcr-Abl tyrosine kinase, thereby blocking proliferation and inducing apoptosis in Bcr-Abl-positive cells. The majority of patients with chronic-phase CML will have an excellent response to initial treatment with a TKI. It is critical to follow these patients on a regular basis and monitor their disease status. Although the gold standard for assessing cytogenetic response is cytogenetic analysis of a bone marrow biopsy, more sensitive methods such as quantitative PCR using peripheral blood are now available, thereby minimizing the need for bone marrow biopsy. Patients in the accelerated phase are more difficult to manage because they are resistant to most forms of treatment and have short-lived responses to TKI therapy. These patients should strongly be considered for transplantation. Patients in blast crisis have aggressive disease that is more complex and requires more extensive testing. These patients should ideally be treated at tertiary care centers and treatment often involves chemotherapy in addition to TKI therapy usually followed by HSCT.

Atraumatic splenic rupture (ASR) presents similarly to traumatic splenic rupture with typical symptoms being acute onset of upper abdominal, left chest wall, or left shoulder pain (Kehr’s sign) but without a known history of trauma. Quick recognition and surgical intervention represent the best means of definitive care.¹⁰ Renzulli and colleagues conducted a literature review for all ASR cases from 1980-2008, examining 632 publications representing 845 cases. They examined the cases using logistic regression analysis to better define the clinicopathology behind ASR. The reported causes of ASR are neoplastic processes (30.3%), infectious (27.3%), inflammatory noninfectious (20.0%), drug- and treatment-related (9.2%), mechanical (6.8%), and normal spleen (6.4%). Treatment included total splenectomy in 84.1% of cases, organ-preserving surgery in 1.2%, and conservative measures in 14.7%. They reported an ASR-related mortality of 12.2%, with being older than 40 and neoplastic disorders associated with increased mortality – although male sex and splenomegaly have also been reported.^11-13 Thomas and colleagues have reported on 48 cases of ASR related to hematologic malignancy showing acute myeloid leukemia being the most common cause (21%), followed by acute lymphoblastic leukemia (19%).²

Hematologic malignancies commonly cause splenic engorgement and pain although splenic rupture is an extremely rare event. Recent literature review has shown fewer than a thousand reported cases since 1980.⁴ There far fewer reported cases of ASR being related to CML, with most being reported as a complication.^3,14 Based on our review, we could identify only a handful cases of CML with ASR being the initial symptom. These include a patient with Ph-negative CML and ASR following blast crisis, a patient with Phil-negative BCR-ABL-positive essential thrombocythemia, several cases in which the patient ultimately died, and 1 in which the patient survived into remission.^4,14-16 Our case is different because the patient was ultimately positive for t(9,22)(q34;q11.2) and although he experienced multiple complications, he is currently functioning at his baseline and in remission. We hope this case will remind others that CML should be considered in the differential diagnosis of patients ASR.

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

SALT LAKE CITY – Chimeric antigen receptor (CAR) T-cell therapy may be an effective bridge to hematopoietic cell transplant (HCT) for high-risk B-cell malignancies, according to a systematic analysis of patient data from the National Cancer Institute.

Additionally, patients who have received CAR T-cell therapy are likely to enter HCT with a minimal residual disease (MRD)–negative complete response, which raises the possibility of a significantly less intense conditioning regimen that could omit total body irradiation (TBI), Haneen Shalabi, DO, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

“Patients who underwent HCT post–CAR T therapy did not have increased transplant-related morbidity or mortality,” said Dr. Shalabi, a pediatric oncologist in the hematologic diseases division of the National Cancer Institute’s pediatric oncology branch.

The combined approach also overcomes the frequent relapses seen after CAR T-cell therapy in this population. Of the 45 patients who received CAR T-cell therapy and achieved MRD-negative complete response as measured by flow cytometry, 20 did not go on to receive HCT. Of the 20 who didn’t receive HCT, 16 (80%) relapsed; 19 of the 20 (95%) had received prior HCT, said Dr. Shalabi.

However, of the 25 patients who proceeded on to receive HCT, 15 (60%) were in ongoing remission, with a median duration of 35 months (range, 11-55 months). Six patients (24%) experienced transplant-related mortality; four of these patients had no prior HCT. Ten patients (40%) experienced acute graft-versus-host disease (GVHD); two of these patients experienced grade 4 GVHD, and one experienced grade 3 GVHD.

Of the 25 patients who went on to HCT, 19 were receiving their first transplant, with a median time to transplant after CAR T-cell therapy of 57 days. Five patients (20%) had primary refractory disease. Most patients (n = 18; 72%) had TBI-based conditioning prior to their post–CAR T-cell therapy HCT. The median patient age was 15 (range, 5-30) years.

The systematic review included patients from two phase 1 studies; one was of CD19-28z CAR T-cell therapy for children and young adults with B-cell leukemia or lymphoma, and the other was of CD22-41BB CAR T-cell therapy for children and young adults with recurrent or refractory B-cell malignancies expressing CD22.

To weigh the benefit of the combined CAR T-cell therapy/HCT approach, Dr. Shalabi and her colleagues used a competing risk analysis to determine the risk of relapse post-HCT versus the risk of transplant-related mortality. Among patients undergoing their first HCT, the researchers found a 12-month cumulative incidence of relapse of 5.3% with the combined CAR T-cell therapy/HCT approach (95% confidence interval, 0.3%-22.1%). The 24-month cumulative incidence of relapse was 11.3% (95% CI, 1.7%-31.1%).

[email protected]

SOURCE: Shalabi H et al. 2018 BMT Tandem Meetings, Abstract 6.

SALT LAKE CITY – Chimeric antigen receptor (CAR) T-cell therapy may be an effective bridge to hematopoietic cell transplant (HCT) for high-risk B-cell malignancies, according to a systematic analysis of patient data from the National Cancer Institute.

Additionally, patients who have received CAR T-cell therapy are likely to enter HCT with a minimal residual disease (MRD)–negative complete response, which raises the possibility of a significantly less intense conditioning regimen that could omit total body irradiation (TBI), Haneen Shalabi, DO, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

“Patients who underwent HCT post–CAR T therapy did not have increased transplant-related morbidity or mortality,” said Dr. Shalabi, a pediatric oncologist in the hematologic diseases division of the National Cancer Institute’s pediatric oncology branch.

The combined approach also overcomes the frequent relapses seen after CAR T-cell therapy in this population. Of the 45 patients who received CAR T-cell therapy and achieved MRD-negative complete response as measured by flow cytometry, 20 did not go on to receive HCT. Of the 20 who didn’t receive HCT, 16 (80%) relapsed; 19 of the 20 (95%) had received prior HCT, said Dr. Shalabi.

However, of the 25 patients who proceeded on to receive HCT, 15 (60%) were in ongoing remission, with a median duration of 35 months (range, 11-55 months). Six patients (24%) experienced transplant-related mortality; four of these patients had no prior HCT. Ten patients (40%) experienced acute graft-versus-host disease (GVHD); two of these patients experienced grade 4 GVHD, and one experienced grade 3 GVHD.

Of the 25 patients who went on to HCT, 19 were receiving their first transplant, with a median time to transplant after CAR T-cell therapy of 57 days. Five patients (20%) had primary refractory disease. Most patients (n = 18; 72%) had TBI-based conditioning prior to their post–CAR T-cell therapy HCT. The median patient age was 15 (range, 5-30) years.

The systematic review included patients from two phase 1 studies; one was of CD19-28z CAR T-cell therapy for children and young adults with B-cell leukemia or lymphoma, and the other was of CD22-41BB CAR T-cell therapy for children and young adults with recurrent or refractory B-cell malignancies expressing CD22.

To weigh the benefit of the combined CAR T-cell therapy/HCT approach, Dr. Shalabi and her colleagues used a competing risk analysis to determine the risk of relapse post-HCT versus the risk of transplant-related mortality. Among patients undergoing their first HCT, the researchers found a 12-month cumulative incidence of relapse of 5.3% with the combined CAR T-cell therapy/HCT approach (95% confidence interval, 0.3%-22.1%). The 24-month cumulative incidence of relapse was 11.3% (95% CI, 1.7%-31.1%).

[email protected]

SOURCE: Shalabi H et al. 2018 BMT Tandem Meetings, Abstract 6.

SALT LAKE CITY – Chimeric antigen receptor (CAR) T-cell therapy may be an effective bridge to hematopoietic cell transplant (HCT) for high-risk B-cell malignancies, according to a systematic analysis of patient data from the National Cancer Institute.

Additionally, patients who have received CAR T-cell therapy are likely to enter HCT with a minimal residual disease (MRD)–negative complete response, which raises the possibility of a significantly less intense conditioning regimen that could omit total body irradiation (TBI), Haneen Shalabi, DO, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

“Patients who underwent HCT post–CAR T therapy did not have increased transplant-related morbidity or mortality,” said Dr. Shalabi, a pediatric oncologist in the hematologic diseases division of the National Cancer Institute’s pediatric oncology branch.

The combined approach also overcomes the frequent relapses seen after CAR T-cell therapy in this population. Of the 45 patients who received CAR T-cell therapy and achieved MRD-negative complete response as measured by flow cytometry, 20 did not go on to receive HCT. Of the 20 who didn’t receive HCT, 16 (80%) relapsed; 19 of the 20 (95%) had received prior HCT, said Dr. Shalabi.

However, of the 25 patients who proceeded on to receive HCT, 15 (60%) were in ongoing remission, with a median duration of 35 months (range, 11-55 months). Six patients (24%) experienced transplant-related mortality; four of these patients had no prior HCT. Ten patients (40%) experienced acute graft-versus-host disease (GVHD); two of these patients experienced grade 4 GVHD, and one experienced grade 3 GVHD.

Of the 25 patients who went on to HCT, 19 were receiving their first transplant, with a median time to transplant after CAR T-cell therapy of 57 days. Five patients (20%) had primary refractory disease. Most patients (n = 18; 72%) had TBI-based conditioning prior to their post–CAR T-cell therapy HCT. The median patient age was 15 (range, 5-30) years.

The systematic review included patients from two phase 1 studies; one was of CD19-28z CAR T-cell therapy for children and young adults with B-cell leukemia or lymphoma, and the other was of CD22-41BB CAR T-cell therapy for children and young adults with recurrent or refractory B-cell malignancies expressing CD22.

To weigh the benefit of the combined CAR T-cell therapy/HCT approach, Dr. Shalabi and her colleagues used a competing risk analysis to determine the risk of relapse post-HCT versus the risk of transplant-related mortality. Among patients undergoing their first HCT, the researchers found a 12-month cumulative incidence of relapse of 5.3% with the combined CAR T-cell therapy/HCT approach (95% confidence interval, 0.3%-22.1%). The 24-month cumulative incidence of relapse was 11.3% (95% CI, 1.7%-31.1%).

[email protected]

SOURCE: Shalabi H et al. 2018 BMT Tandem Meetings, Abstract 6.

Leukemia incidence varies considerably by geography and subtype, according to an analysis of World Health Organization cancer databases.

Incidence also is generally higher in males, with a global male to female ratio of 1.4. For men, the highest regional leukemia rate – estimated at 11.3 per 100,000 population for 2012 – was found in Australia and New Zealand, with northern America (the United States and Canada) next at 10.5 per 100,000. Australia/New Zealand and northern America had the highest rate for women at 7.2 per 100,000, followed by western Europe and northern Europe at 6.0 per 100,000, reported Adalberto Miranda-Filho, PhD, of the WHO’s International Agency for Research on Cancer in Lyon, France, and his associates.

The lowest regional rates for women were found in western Africa (1.2 per 100,000), middle Africa (1.8), and Micronesia/Polynesia (2.1). For men, leukemia incidence was lowest in western Africa (1.4 per 100,000), middle Africa (2.6), and south-central Asia (3.4), according to data from the WHO’s GLOBOCAN database. The report was published in The Lancet Haematology.

Estimates for leukemia subtypes in 2003-2007 – calculated for 54 countries, not regions – also showed a great deal of variation. For acute lymphoblastic leukemia, Ecuador had the highest rates for both males (2.8 per 100,000) and females (3.3), with high rates seen in Costa Rica, Columbia, and Cyprus. Rates in the United States were near the top: 2.1 for males and 1.6 for females. Rates were lowest for men in Jamaica (0.4) and Serbia (0.6) and for women in India (0.5) and Serbia and Cuba (0.6), Dr. Miranda-Filho and his associates said.

Incidence rates for acute myeloid leukemia were highest in Australia for men (2.8 per 100,000) and Austria for women (2.2), with the United States near the top for both men (2.6) and women (1.9). The lowest rates occurred in Cuba and Egypt for men (0.9 per 100,000) and Cuba for women (0.4), data from the WHO’s Cancer Incidence in Five Continents Volume X show.

Chronic lymphocytic leukemia incidence was highest for men in Canada (4.5 per 100,000), Ireland and Lithuania (4.4), and Slovakia (4.3). The incidence was highest for women in Lithuania (2.5), Canada (2.3), and Slovakia and Denmark (2.1). Incidence in the United States was 3.5 for men and 1.8 for women. At the other end of the scale, the lowest rates for both men and women were in Japan and Malaysia (0.1), the investigators’ analysis showed.

Chronic myeloid leukemia rates were the lowest of the subtypes, and Tunisia was the lowest for men at 0.4 per 100,000 and tied for lowest with Serbia, Slovenia, and Puerto Rico for women at 0.3. Incidence was highest for men in Australia at 1.8 per 100,000 and highest for women in Uruguay at 1.1. Rates in the United States were 1.3 for men and 0.8 for women, Dr. Miranda-Filho and his associates said.

“The higher incidence of acute lymphoblastic leukaemia in parts of South America, as well as of chronic lymphocytic leukaemia in populations across North America and Oceania, alongside a lower incidence in Asia, might be important markers for further epidemiological study, and a means to better understand the underlying factors to support future cancer prevention strategies,” the investigators wrote.

[email protected]

SOURCE: Miranda-Filho A et al. Lancet Haematol. 2018;5:e14-24.

Leukemia incidence varies considerably by geography and subtype, according to an analysis of World Health Organization cancer databases.

Incidence also is generally higher in males, with a global male to female ratio of 1.4. For men, the highest regional leukemia rate – estimated at 11.3 per 100,000 population for 2012 – was found in Australia and New Zealand, with northern America (the United States and Canada) next at 10.5 per 100,000. Australia/New Zealand and northern America had the highest rate for women at 7.2 per 100,000, followed by western Europe and northern Europe at 6.0 per 100,000, reported Adalberto Miranda-Filho, PhD, of the WHO’s International Agency for Research on Cancer in Lyon, France, and his associates.

The lowest regional rates for women were found in western Africa (1.2 per 100,000), middle Africa (1.8), and Micronesia/Polynesia (2.1). For men, leukemia incidence was lowest in western Africa (1.4 per 100,000), middle Africa (2.6), and south-central Asia (3.4), according to data from the WHO’s GLOBOCAN database. The report was published in The Lancet Haematology.

Estimates for leukemia subtypes in 2003-2007 – calculated for 54 countries, not regions – also showed a great deal of variation. For acute lymphoblastic leukemia, Ecuador had the highest rates for both males (2.8 per 100,000) and females (3.3), with high rates seen in Costa Rica, Columbia, and Cyprus. Rates in the United States were near the top: 2.1 for males and 1.6 for females. Rates were lowest for men in Jamaica (0.4) and Serbia (0.6) and for women in India (0.5) and Serbia and Cuba (0.6), Dr. Miranda-Filho and his associates said.

Incidence rates for acute myeloid leukemia were highest in Australia for men (2.8 per 100,000) and Austria for women (2.2), with the United States near the top for both men (2.6) and women (1.9). The lowest rates occurred in Cuba and Egypt for men (0.9 per 100,000) and Cuba for women (0.4), data from the WHO’s Cancer Incidence in Five Continents Volume X show.

Chronic lymphocytic leukemia incidence was highest for men in Canada (4.5 per 100,000), Ireland and Lithuania (4.4), and Slovakia (4.3). The incidence was highest for women in Lithuania (2.5), Canada (2.3), and Slovakia and Denmark (2.1). Incidence in the United States was 3.5 for men and 1.8 for women. At the other end of the scale, the lowest rates for both men and women were in Japan and Malaysia (0.1), the investigators’ analysis showed.

Chronic myeloid leukemia rates were the lowest of the subtypes, and Tunisia was the lowest for men at 0.4 per 100,000 and tied for lowest with Serbia, Slovenia, and Puerto Rico for women at 0.3. Incidence was highest for men in Australia at 1.8 per 100,000 and highest for women in Uruguay at 1.1. Rates in the United States were 1.3 for men and 0.8 for women, Dr. Miranda-Filho and his associates said.

“The higher incidence of acute lymphoblastic leukaemia in parts of South America, as well as of chronic lymphocytic leukaemia in populations across North America and Oceania, alongside a lower incidence in Asia, might be important markers for further epidemiological study, and a means to better understand the underlying factors to support future cancer prevention strategies,” the investigators wrote.

[email protected]

SOURCE: Miranda-Filho A et al. Lancet Haematol. 2018;5:e14-24.

Leukemia incidence varies considerably by geography and subtype, according to an analysis of World Health Organization cancer databases.

Incidence also is generally higher in males, with a global male to female ratio of 1.4. For men, the highest regional leukemia rate – estimated at 11.3 per 100,000 population for 2012 – was found in Australia and New Zealand, with northern America (the United States and Canada) next at 10.5 per 100,000. Australia/New Zealand and northern America had the highest rate for women at 7.2 per 100,000, followed by western Europe and northern Europe at 6.0 per 100,000, reported Adalberto Miranda-Filho, PhD, of the WHO’s International Agency for Research on Cancer in Lyon, France, and his associates.

The lowest regional rates for women were found in western Africa (1.2 per 100,000), middle Africa (1.8), and Micronesia/Polynesia (2.1). For men, leukemia incidence was lowest in western Africa (1.4 per 100,000), middle Africa (2.6), and south-central Asia (3.4), according to data from the WHO’s GLOBOCAN database. The report was published in The Lancet Haematology.

Estimates for leukemia subtypes in 2003-2007 – calculated for 54 countries, not regions – also showed a great deal of variation. For acute lymphoblastic leukemia, Ecuador had the highest rates for both males (2.8 per 100,000) and females (3.3), with high rates seen in Costa Rica, Columbia, and Cyprus. Rates in the United States were near the top: 2.1 for males and 1.6 for females. Rates were lowest for men in Jamaica (0.4) and Serbia (0.6) and for women in India (0.5) and Serbia and Cuba (0.6), Dr. Miranda-Filho and his associates said.

Incidence rates for acute myeloid leukemia were highest in Australia for men (2.8 per 100,000) and Austria for women (2.2), with the United States near the top for both men (2.6) and women (1.9). The lowest rates occurred in Cuba and Egypt for men (0.9 per 100,000) and Cuba for women (0.4), data from the WHO’s Cancer Incidence in Five Continents Volume X show.

Chronic lymphocytic leukemia incidence was highest for men in Canada (4.5 per 100,000), Ireland and Lithuania (4.4), and Slovakia (4.3). The incidence was highest for women in Lithuania (2.5), Canada (2.3), and Slovakia and Denmark (2.1). Incidence in the United States was 3.5 for men and 1.8 for women. At the other end of the scale, the lowest rates for both men and women were in Japan and Malaysia (0.1), the investigators’ analysis showed.

Chronic myeloid leukemia rates were the lowest of the subtypes, and Tunisia was the lowest for men at 0.4 per 100,000 and tied for lowest with Serbia, Slovenia, and Puerto Rico for women at 0.3. Incidence was highest for men in Australia at 1.8 per 100,000 and highest for women in Uruguay at 1.1. Rates in the United States were 1.3 for men and 0.8 for women, Dr. Miranda-Filho and his associates said.

“The higher incidence of acute lymphoblastic leukaemia in parts of South America, as well as of chronic lymphocytic leukaemia in populations across North America and Oceania, alongside a lower incidence in Asia, might be important markers for further epidemiological study, and a means to better understand the underlying factors to support future cancer prevention strategies,” the investigators wrote.

[email protected]

SOURCE: Miranda-Filho A et al. Lancet Haematol. 2018;5:e14-24.

Photo by Rhoda Baer

Researchers have developed a new method to measure social networks of adolescent and young adult (AYA) cancer survivors.

This method indicated that AYA cancer survivors often have stronger social networks than their non-cancer peers.

However, the strength of the social network varied by diagnosis, with the lymphoma and leukemia survivors having the greatest support.

These findings were published in Cancer.

“Cancer survivors need healthy social connections, and, to the best of our knowledge, this is the first published study to quantify social networks of adolescent and young adult cancer survivors compared to their peers,” said study author I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“The study introduces a method we developed and validated for evaluating social networks of these cancer survivors.”

The method, called the functional social network index (FSNI), measures marital status, contact frequency with friends and relatives, and available resources for health support/advice, which includes emotional support, tangible support, physical activity advice, and weight management advice.

The researchers compared the FSNI to a pair of traditional social network indices—density and betweenness centrality.

Density represents the ratio of the existing relationships/connections within a network to all possible relationships/connections. And betweenness centrality represents the ratio of the existing shortest paths between 2 friends/relatives of the study participants to the shortest possible paths between 2 friends/relatives.

Subjects

The researchers used the 3 social network indices to analyze 102 AYA cancer survivors, ages 18 to 30, and 102 young adults with no cancer history who were matched to the survivors by age, sex, and race.

Subjects were recruited from a commercial national Internet survey panel. They reported detailed social connection information with up to 25 friends and relatives.

The cancer survivors were between 15 and 30 years old when their cancer was diagnosed, and all had completed treatment at least 5 years prior.

Results

Neither the density index nor the betweenness centrality index demonstrated significant differences between cancer survivors and controls (all P values were less than 0.05).

However, according to the FSNI, cancer survivors had more available resources for emotional support (beta [b]=3.02; P=0.003), tangible support (b=4.17; P<0.001), physical activity advice (b=3.94; P<0.001), and weight management advice (b=4.10; P<0.001).

“This makes sense,” Dr Huang said. “Because of their cancer, survivors often have strong networks of physicians, friends, and relatives to provide advice and support.”

However, the FSNI showed the strength of cancer survivors’ support network varied by diagnosis.

Lymphoma survivors ranked highest on the FSNI (b=2.765; P=0.02), followed by survivors of leukemia (b=2.542; P=0.03) and solid tumors (b=2.178; P=0.047), with central nervous system malignancies as the reference.

The researchers also found a higher FSNI was associated with better coping skills, including using emotional support (b=0.08; P=0.04), using instrumental support (b=0.12; P<0.001), venting of emotions (b=0.10; P=0.004), positive reframing (b=0.12; P=0.003), planning for the future (b=0.08; P=0.03), participating in religious activities (b=0.16; P<0.001), and less denial (b=0.10; P=0.01) and destructive behavior (b=0.08; P=0.04).

The researchers said long-term follow-up is needed to understand how social networks and social support may change over time.

“Adolescents and young adult cancer survivors are in a transitory stage of independence from parents,” Dr Huang said. “While this study suggests that survivors often report strong social connections, our previous studies have reported that childhood cancer survivors are more likely than their peers to struggle mentally and physically and report issues like distress and loneliness.”

Dr Huang and his colleagues are working to streamline the FSNI to make it easier for healthcare providers to assess support available to cancer survivors of any age.

Meanwhile, researchers are working to better understand how social connections affect health outcomes in order to design interventions to foster those connections.

“A lack of social connections with friends and relatives is associated with poor quality of life, risky health behaviors, chronic health conditions, and premature death,” Dr Huang said. “Once we identify the mechanism between social connections and health outcomes, we can start designing interventions to use social networks to improve health outcomes of cancer survivors.”

Photo by Rhoda Baer

Researchers have developed a new method to measure social networks of adolescent and young adult (AYA) cancer survivors.

This method indicated that AYA cancer survivors often have stronger social networks than their non-cancer peers.

However, the strength of the social network varied by diagnosis, with the lymphoma and leukemia survivors having the greatest support.

These findings were published in Cancer.

“Cancer survivors need healthy social connections, and, to the best of our knowledge, this is the first published study to quantify social networks of adolescent and young adult cancer survivors compared to their peers,” said study author I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“The study introduces a method we developed and validated for evaluating social networks of these cancer survivors.”

The method, called the functional social network index (FSNI), measures marital status, contact frequency with friends and relatives, and available resources for health support/advice, which includes emotional support, tangible support, physical activity advice, and weight management advice.

The researchers compared the FSNI to a pair of traditional social network indices—density and betweenness centrality.

Density represents the ratio of the existing relationships/connections within a network to all possible relationships/connections. And betweenness centrality represents the ratio of the existing shortest paths between 2 friends/relatives of the study participants to the shortest possible paths between 2 friends/relatives.

Subjects

The researchers used the 3 social network indices to analyze 102 AYA cancer survivors, ages 18 to 30, and 102 young adults with no cancer history who were matched to the survivors by age, sex, and race.

Subjects were recruited from a commercial national Internet survey panel. They reported detailed social connection information with up to 25 friends and relatives.

The cancer survivors were between 15 and 30 years old when their cancer was diagnosed, and all had completed treatment at least 5 years prior.

Results

Neither the density index nor the betweenness centrality index demonstrated significant differences between cancer survivors and controls (all P values were less than 0.05).

However, according to the FSNI, cancer survivors had more available resources for emotional support (beta [b]=3.02; P=0.003), tangible support (b=4.17; P<0.001), physical activity advice (b=3.94; P<0.001), and weight management advice (b=4.10; P<0.001).

“This makes sense,” Dr Huang said. “Because of their cancer, survivors often have strong networks of physicians, friends, and relatives to provide advice and support.”

However, the FSNI showed the strength of cancer survivors’ support network varied by diagnosis.

Lymphoma survivors ranked highest on the FSNI (b=2.765; P=0.02), followed by survivors of leukemia (b=2.542; P=0.03) and solid tumors (b=2.178; P=0.047), with central nervous system malignancies as the reference.

The researchers also found a higher FSNI was associated with better coping skills, including using emotional support (b=0.08; P=0.04), using instrumental support (b=0.12; P<0.001), venting of emotions (b=0.10; P=0.004), positive reframing (b=0.12; P=0.003), planning for the future (b=0.08; P=0.03), participating in religious activities (b=0.16; P<0.001), and less denial (b=0.10; P=0.01) and destructive behavior (b=0.08; P=0.04).

The researchers said long-term follow-up is needed to understand how social networks and social support may change over time.

“Adolescents and young adult cancer survivors are in a transitory stage of independence from parents,” Dr Huang said. “While this study suggests that survivors often report strong social connections, our previous studies have reported that childhood cancer survivors are more likely than their peers to struggle mentally and physically and report issues like distress and loneliness.”

Dr Huang and his colleagues are working to streamline the FSNI to make it easier for healthcare providers to assess support available to cancer survivors of any age.

Meanwhile, researchers are working to better understand how social connections affect health outcomes in order to design interventions to foster those connections.

“A lack of social connections with friends and relatives is associated with poor quality of life, risky health behaviors, chronic health conditions, and premature death,” Dr Huang said. “Once we identify the mechanism between social connections and health outcomes, we can start designing interventions to use social networks to improve health outcomes of cancer survivors.”

Photo by Rhoda Baer

Researchers have developed a new method to measure social networks of adolescent and young adult (AYA) cancer survivors.

This method indicated that AYA cancer survivors often have stronger social networks than their non-cancer peers.

However, the strength of the social network varied by diagnosis, with the lymphoma and leukemia survivors having the greatest support.

These findings were published in Cancer.

“Cancer survivors need healthy social connections, and, to the best of our knowledge, this is the first published study to quantify social networks of adolescent and young adult cancer survivors compared to their peers,” said study author I-Chan Huang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“The study introduces a method we developed and validated for evaluating social networks of these cancer survivors.”

The method, called the functional social network index (FSNI), measures marital status, contact frequency with friends and relatives, and available resources for health support/advice, which includes emotional support, tangible support, physical activity advice, and weight management advice.

The researchers compared the FSNI to a pair of traditional social network indices—density and betweenness centrality.

Density represents the ratio of the existing relationships/connections within a network to all possible relationships/connections. And betweenness centrality represents the ratio of the existing shortest paths between 2 friends/relatives of the study participants to the shortest possible paths between 2 friends/relatives.

Subjects

The researchers used the 3 social network indices to analyze 102 AYA cancer survivors, ages 18 to 30, and 102 young adults with no cancer history who were matched to the survivors by age, sex, and race.

Subjects were recruited from a commercial national Internet survey panel. They reported detailed social connection information with up to 25 friends and relatives.

The cancer survivors were between 15 and 30 years old when their cancer was diagnosed, and all had completed treatment at least 5 years prior.

Results

Neither the density index nor the betweenness centrality index demonstrated significant differences between cancer survivors and controls (all P values were less than 0.05).

However, according to the FSNI, cancer survivors had more available resources for emotional support (beta [b]=3.02; P=0.003), tangible support (b=4.17; P<0.001), physical activity advice (b=3.94; P<0.001), and weight management advice (b=4.10; P<0.001).

“This makes sense,” Dr Huang said. “Because of their cancer, survivors often have strong networks of physicians, friends, and relatives to provide advice and support.”

However, the FSNI showed the strength of cancer survivors’ support network varied by diagnosis.

Lymphoma survivors ranked highest on the FSNI (b=2.765; P=0.02), followed by survivors of leukemia (b=2.542; P=0.03) and solid tumors (b=2.178; P=0.047), with central nervous system malignancies as the reference.

The researchers also found a higher FSNI was associated with better coping skills, including using emotional support (b=0.08; P=0.04), using instrumental support (b=0.12; P<0.001), venting of emotions (b=0.10; P=0.004), positive reframing (b=0.12; P=0.003), planning for the future (b=0.08; P=0.03), participating in religious activities (b=0.16; P<0.001), and less denial (b=0.10; P=0.01) and destructive behavior (b=0.08; P=0.04).

The researchers said long-term follow-up is needed to understand how social networks and social support may change over time.

“Adolescents and young adult cancer survivors are in a transitory stage of independence from parents,” Dr Huang said. “While this study suggests that survivors often report strong social connections, our previous studies have reported that childhood cancer survivors are more likely than their peers to struggle mentally and physically and report issues like distress and loneliness.”

Dr Huang and his colleagues are working to streamline the FSNI to make it easier for healthcare providers to assess support available to cancer survivors of any age.

Meanwhile, researchers are working to better understand how social connections affect health outcomes in order to design interventions to foster those connections.

“A lack of social connections with friends and relatives is associated with poor quality of life, risky health behaviors, chronic health conditions, and premature death,” Dr Huang said. “Once we identify the mechanism between social connections and health outcomes, we can start designing interventions to use social networks to improve health outcomes of cancer survivors.”

Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR⁴ and MR^4.5, according to the researchers.

In an open-label phase 2 study, the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR^4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine.

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

[email protected]

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094.

Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR⁴ and MR^4.5, according to the researchers.

In an open-label phase 2 study, the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR^4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine.

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

[email protected]

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094.

Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR⁴ and MR^4.5, according to the researchers.

In an open-label phase 2 study, the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR^4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine.

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

[email protected]

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094.

Photo by Bill Branson

Childhood cancer survivors (CCSs) have an increased risk of premature cardiovascular disease in adulthood, according to a new study.

Researchers found a nearly 2-fold increased risk of cardiovascular diseases in CCSs compared to the general population.

Cardiovascular disease was identified in 4.5% of CCSs and occurred in most before they reached the age of 40, nearly 8 years earlier than in the general population.

“Our results show that these survivors of childhood cancer have a substantially elevated burden of prematurely occurring traditional cardiovascular risk factors and cardiovascular diseases,” said study author Joerg Faber, MD, PhD, of the Johannes Gutenberg University Mainz in Germany.

Dr Faber and his colleagues reported these results in the European Heart Journal.

The researchers evaluated 951 adult CCSs (ages 23 to 48), referred to as the CVSS cohort (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer Study).

The patients had been diagnosed with cancer between 1980 and 1990. The most common diagnoses were leukemia (43.5%), central nervous system tumors (12.8%), and lymphoma (9.9%).

For this study, the patients underwent standardized clinical and laboratory cardiovascular screening. The mean time from cancer diagnosis to cardiovascular screening was 28.4 years (range, 23–36).

The researchers compared the incidence of cardiovascular risk factors and cardiovascular disease in the CVSS cohort and subjects from the Gutenberg Health Study (GHS), a population-based study including more than 15,000 subjects.

Risk factors

The CVSS cohort had a greater risk of 2 cardiovascular risk factors—arterial hypertension and dyslipidemia—than the GHS cohort. In the CVSS cohort, the incidence of dyslipidemia was 28.3%, and the incidence of hypertension was 23.0%.

CVSS subjects had an age-adjusted 38% increase in risk for hypertension (relative risk [RR]=1.38) and a 26% increase in risk for dyslipidemia (RR=1.26).

Hypertension occurred about 6 years earlier in CVSS subjects than GHS subjects (rate advancement period estimator [RAP]=5.75). And dyslipidemia occurred about 8 years earlier in the CVSS cohort (RAP=8.16).

“[T]he premature onset of high blood pressure and blood lipid disorders may play an important role in the development of severe cardiovascular conditions, such as heart disease and stroke, in the long-term,” said study author Philipp S. Wild, MD, of the German Center for Cardiovascular Research (DZHK) in Mainz, Germany.

“We also found that a remarkable number [of CVSS subjects] attended their clinical examination for this study with previously unidentified cardiovascular risk factors and cardiovascular disease. For example, only 62 out of 269 were aware of having dyslipidemia. Consequently, 207, approximately 80%, were only diagnosed at that point.”

Disease

In the CVSS cohort, 4.5% of patients had at least 1 type of cardiovascular disease. This included venous thromboembolism (2.0%), congestive heart failure (1.2%), stroke (0.5%), peripheral artery disease (0.5%), atrial fibrillation (0.4%), and coronary heart disease (0.3%).

CVSS subjects had nearly twice the risk of cardiovascular disease as GHS subjects. The age-adjusted RR was 1.89. And CVSS subjects developed cardiovascular disease roughly 8 years earlier than GHS subjects (RAP=7.9).

In the CVSS cohort, the probability of developing cardiovascular disease was estimated as 2.9% at age 30 and 9.6% at age 45.

The researchers said these findings show that CCSs have a greater risk of cardiovascular disease that continues to increase with age. This, in turn, means CCSs may be more likely to die earlier. However, this might be preventable, according to Dr Wild.

“Early systematic screening, particularly focusing on blood pressure and lipid measurements, might be suggested in all childhood cancer survivors irrespective of the type of cancer or treatment they had had,” Dr Wild said. “This might help to prevent long-term cardiovascular diseases by intervening early—for instance, by modifying lifestyles and having treatment for high blood pressure.”

“Usually, survivors are followed for only 5 to 10 years after completion of therapy, and this is focused on the risk of the cancer returning and the acute adverse effects of their treatment, rather than on other conditions,” added Dr Faber.

“Current guidelines recommend cardiovascular assessments only for subgroups known to be at risk, such as for patients who were treated with anthracycline therapy and/or radiation therapy. However, further investigations are needed to answer questions about the best follow-up care.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) have an increased risk of premature cardiovascular disease in adulthood, according to a new study.

Researchers found a nearly 2-fold increased risk of cardiovascular diseases in CCSs compared to the general population.

Cardiovascular disease was identified in 4.5% of CCSs and occurred in most before they reached the age of 40, nearly 8 years earlier than in the general population.

“Our results show that these survivors of childhood cancer have a substantially elevated burden of prematurely occurring traditional cardiovascular risk factors and cardiovascular diseases,” said study author Joerg Faber, MD, PhD, of the Johannes Gutenberg University Mainz in Germany.

Dr Faber and his colleagues reported these results in the European Heart Journal.

The researchers evaluated 951 adult CCSs (ages 23 to 48), referred to as the CVSS cohort (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer Study).

The patients had been diagnosed with cancer between 1980 and 1990. The most common diagnoses were leukemia (43.5%), central nervous system tumors (12.8%), and lymphoma (9.9%).

For this study, the patients underwent standardized clinical and laboratory cardiovascular screening. The mean time from cancer diagnosis to cardiovascular screening was 28.4 years (range, 23–36).

The researchers compared the incidence of cardiovascular risk factors and cardiovascular disease in the CVSS cohort and subjects from the Gutenberg Health Study (GHS), a population-based study including more than 15,000 subjects.

Risk factors

The CVSS cohort had a greater risk of 2 cardiovascular risk factors—arterial hypertension and dyslipidemia—than the GHS cohort. In the CVSS cohort, the incidence of dyslipidemia was 28.3%, and the incidence of hypertension was 23.0%.

CVSS subjects had an age-adjusted 38% increase in risk for hypertension (relative risk [RR]=1.38) and a 26% increase in risk for dyslipidemia (RR=1.26).

Hypertension occurred about 6 years earlier in CVSS subjects than GHS subjects (rate advancement period estimator [RAP]=5.75). And dyslipidemia occurred about 8 years earlier in the CVSS cohort (RAP=8.16).

“[T]he premature onset of high blood pressure and blood lipid disorders may play an important role in the development of severe cardiovascular conditions, such as heart disease and stroke, in the long-term,” said study author Philipp S. Wild, MD, of the German Center for Cardiovascular Research (DZHK) in Mainz, Germany.

“We also found that a remarkable number [of CVSS subjects] attended their clinical examination for this study with previously unidentified cardiovascular risk factors and cardiovascular disease. For example, only 62 out of 269 were aware of having dyslipidemia. Consequently, 207, approximately 80%, were only diagnosed at that point.”

Disease

In the CVSS cohort, 4.5% of patients had at least 1 type of cardiovascular disease. This included venous thromboembolism (2.0%), congestive heart failure (1.2%), stroke (0.5%), peripheral artery disease (0.5%), atrial fibrillation (0.4%), and coronary heart disease (0.3%).

CVSS subjects had nearly twice the risk of cardiovascular disease as GHS subjects. The age-adjusted RR was 1.89. And CVSS subjects developed cardiovascular disease roughly 8 years earlier than GHS subjects (RAP=7.9).

In the CVSS cohort, the probability of developing cardiovascular disease was estimated as 2.9% at age 30 and 9.6% at age 45.

The researchers said these findings show that CCSs have a greater risk of cardiovascular disease that continues to increase with age. This, in turn, means CCSs may be more likely to die earlier. However, this might be preventable, according to Dr Wild.

“Early systematic screening, particularly focusing on blood pressure and lipid measurements, might be suggested in all childhood cancer survivors irrespective of the type of cancer or treatment they had had,” Dr Wild said. “This might help to prevent long-term cardiovascular diseases by intervening early—for instance, by modifying lifestyles and having treatment for high blood pressure.”

“Usually, survivors are followed for only 5 to 10 years after completion of therapy, and this is focused on the risk of the cancer returning and the acute adverse effects of their treatment, rather than on other conditions,” added Dr Faber.

“Current guidelines recommend cardiovascular assessments only for subgroups known to be at risk, such as for patients who were treated with anthracycline therapy and/or radiation therapy. However, further investigations are needed to answer questions about the best follow-up care.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) have an increased risk of premature cardiovascular disease in adulthood, according to a new study.

Researchers found a nearly 2-fold increased risk of cardiovascular diseases in CCSs compared to the general population.

Cardiovascular disease was identified in 4.5% of CCSs and occurred in most before they reached the age of 40, nearly 8 years earlier than in the general population.

“Our results show that these survivors of childhood cancer have a substantially elevated burden of prematurely occurring traditional cardiovascular risk factors and cardiovascular diseases,” said study author Joerg Faber, MD, PhD, of the Johannes Gutenberg University Mainz in Germany.

Dr Faber and his colleagues reported these results in the European Heart Journal.

The researchers evaluated 951 adult CCSs (ages 23 to 48), referred to as the CVSS cohort (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer Study).

The patients had been diagnosed with cancer between 1980 and 1990. The most common diagnoses were leukemia (43.5%), central nervous system tumors (12.8%), and lymphoma (9.9%).

For this study, the patients underwent standardized clinical and laboratory cardiovascular screening. The mean time from cancer diagnosis to cardiovascular screening was 28.4 years (range, 23–36).

The researchers compared the incidence of cardiovascular risk factors and cardiovascular disease in the CVSS cohort and subjects from the Gutenberg Health Study (GHS), a population-based study including more than 15,000 subjects.

Risk factors

The CVSS cohort had a greater risk of 2 cardiovascular risk factors—arterial hypertension and dyslipidemia—than the GHS cohort. In the CVSS cohort, the incidence of dyslipidemia was 28.3%, and the incidence of hypertension was 23.0%.

CVSS subjects had an age-adjusted 38% increase in risk for hypertension (relative risk [RR]=1.38) and a 26% increase in risk for dyslipidemia (RR=1.26).

Hypertension occurred about 6 years earlier in CVSS subjects than GHS subjects (rate advancement period estimator [RAP]=5.75). And dyslipidemia occurred about 8 years earlier in the CVSS cohort (RAP=8.16).

“[T]he premature onset of high blood pressure and blood lipid disorders may play an important role in the development of severe cardiovascular conditions, such as heart disease and stroke, in the long-term,” said study author Philipp S. Wild, MD, of the German Center for Cardiovascular Research (DZHK) in Mainz, Germany.

“We also found that a remarkable number [of CVSS subjects] attended their clinical examination for this study with previously unidentified cardiovascular risk factors and cardiovascular disease. For example, only 62 out of 269 were aware of having dyslipidemia. Consequently, 207, approximately 80%, were only diagnosed at that point.”

Disease

In the CVSS cohort, 4.5% of patients had at least 1 type of cardiovascular disease. This included venous thromboembolism (2.0%), congestive heart failure (1.2%), stroke (0.5%), peripheral artery disease (0.5%), atrial fibrillation (0.4%), and coronary heart disease (0.3%).

CVSS subjects had nearly twice the risk of cardiovascular disease as GHS subjects. The age-adjusted RR was 1.89. And CVSS subjects developed cardiovascular disease roughly 8 years earlier than GHS subjects (RAP=7.9).

In the CVSS cohort, the probability of developing cardiovascular disease was estimated as 2.9% at age 30 and 9.6% at age 45.

The researchers said these findings show that CCSs have a greater risk of cardiovascular disease that continues to increase with age. This, in turn, means CCSs may be more likely to die earlier. However, this might be preventable, according to Dr Wild.

“Early systematic screening, particularly focusing on blood pressure and lipid measurements, might be suggested in all childhood cancer survivors irrespective of the type of cancer or treatment they had had,” Dr Wild said. “This might help to prevent long-term cardiovascular diseases by intervening early—for instance, by modifying lifestyles and having treatment for high blood pressure.”

“Usually, survivors are followed for only 5 to 10 years after completion of therapy, and this is focused on the risk of the cancer returning and the acute adverse effects of their treatment, rather than on other conditions,” added Dr Faber.

“Current guidelines recommend cardiovascular assessments only for subgroups known to be at risk, such as for patients who were treated with anthracycline therapy and/or radiation therapy. However, further investigations are needed to answer questions about the best follow-up care.”

Henrique Orlandi Mourao

Researchers say they have discovered a way to target the transcription factor MEF2C in acute myeloid leukemia (AML).

The team found they could stop the growth of MEF2C-driven AML cells by blocking either LKB1 or the salt-inducible kinases SIK3 and SIK2.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described this research in Molecular Cell.

The current discoveries are the result of a broad search for potential therapeutic strategies against AML that began several years ago in Dr Vakoc’s lab.

In 2013, his team devised a system based on CRISPR gene editing tools. They used this system to screen large numbers of genes, seeking to discover their impact on cancer cell survival.

Now, the system has revealed that LKB1 and SIK are critical for the survival of certain AML cells. These enzymes had not previously been linked to AML, but the researchers learned that LKB1 and SIK help control MEF2C.

The team observed overlapping LKB1, SIK, and MEF2C dependencies in AML cell lines, particularly MLL fusion lines (MOLM-13, MV4-11, NOMO-1, and THP-1). And the researchers found the transcriptional output of MEF2C could be suppressed by inhibition of LKB1 or SIK.

“At the end of project, we realized we’d actually discovered a way to control a transcription factor,” Dr Vakoc said.

He and his colleagues found that SIK3 inactivation had the strongest effect on MEF2C. Two hours of exposure to the SIK inhibitor HG-9-91-01 (100 nM) was enough to suppress the MEF2C signature.

The researchers also noted that the effect of SIK3 targeting on transcription was attenuated if it was performed in cells deficient in HDAC4. This and related findings suggested that LKB1-SIK3 signaling supports the transcriptional output of MEF2C through inhibition of HDAC4.

Dr Vakoc and his colleagues said the “potency and selectivity of AML growth arrest” they observed after targeting LKB1 or SIK2 and SIK3 resembles the effects of targeting other validated kinase oncogenes in AML, such as FLT3.

The team also said the sensitivity of AML cell lines to HG-9-91-01 “compares favorably” to the sensitivity of cancer cell lines to kinase inhibitors already approved for oncology indications. However, “additional optimization” of HG-9-91-01 is needed.

Henrique Orlandi Mourao

Researchers say they have discovered a way to target the transcription factor MEF2C in acute myeloid leukemia (AML).

The team found they could stop the growth of MEF2C-driven AML cells by blocking either LKB1 or the salt-inducible kinases SIK3 and SIK2.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described this research in Molecular Cell.

The current discoveries are the result of a broad search for potential therapeutic strategies against AML that began several years ago in Dr Vakoc’s lab.

In 2013, his team devised a system based on CRISPR gene editing tools. They used this system to screen large numbers of genes, seeking to discover their impact on cancer cell survival.

Now, the system has revealed that LKB1 and SIK are critical for the survival of certain AML cells. These enzymes had not previously been linked to AML, but the researchers learned that LKB1 and SIK help control MEF2C.

The team observed overlapping LKB1, SIK, and MEF2C dependencies in AML cell lines, particularly MLL fusion lines (MOLM-13, MV4-11, NOMO-1, and THP-1). And the researchers found the transcriptional output of MEF2C could be suppressed by inhibition of LKB1 or SIK.

“At the end of project, we realized we’d actually discovered a way to control a transcription factor,” Dr Vakoc said.

He and his colleagues found that SIK3 inactivation had the strongest effect on MEF2C. Two hours of exposure to the SIK inhibitor HG-9-91-01 (100 nM) was enough to suppress the MEF2C signature.

The researchers also noted that the effect of SIK3 targeting on transcription was attenuated if it was performed in cells deficient in HDAC4. This and related findings suggested that LKB1-SIK3 signaling supports the transcriptional output of MEF2C through inhibition of HDAC4.

Dr Vakoc and his colleagues said the “potency and selectivity of AML growth arrest” they observed after targeting LKB1 or SIK2 and SIK3 resembles the effects of targeting other validated kinase oncogenes in AML, such as FLT3.

The team also said the sensitivity of AML cell lines to HG-9-91-01 “compares favorably” to the sensitivity of cancer cell lines to kinase inhibitors already approved for oncology indications. However, “additional optimization” of HG-9-91-01 is needed.

Henrique Orlandi Mourao

Researchers say they have discovered a way to target the transcription factor MEF2C in acute myeloid leukemia (AML).

The team found they could stop the growth of MEF2C-driven AML cells by blocking either LKB1 or the salt-inducible kinases SIK3 and SIK2.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described this research in Molecular Cell.

The current discoveries are the result of a broad search for potential therapeutic strategies against AML that began several years ago in Dr Vakoc’s lab.

In 2013, his team devised a system based on CRISPR gene editing tools. They used this system to screen large numbers of genes, seeking to discover their impact on cancer cell survival.

Now, the system has revealed that LKB1 and SIK are critical for the survival of certain AML cells. These enzymes had not previously been linked to AML, but the researchers learned that LKB1 and SIK help control MEF2C.

The team observed overlapping LKB1, SIK, and MEF2C dependencies in AML cell lines, particularly MLL fusion lines (MOLM-13, MV4-11, NOMO-1, and THP-1). And the researchers found the transcriptional output of MEF2C could be suppressed by inhibition of LKB1 or SIK.

“At the end of project, we realized we’d actually discovered a way to control a transcription factor,” Dr Vakoc said.

He and his colleagues found that SIK3 inactivation had the strongest effect on MEF2C. Two hours of exposure to the SIK inhibitor HG-9-91-01 (100 nM) was enough to suppress the MEF2C signature.

The researchers also noted that the effect of SIK3 targeting on transcription was attenuated if it was performed in cells deficient in HDAC4. This and related findings suggested that LKB1-SIK3 signaling supports the transcriptional output of MEF2C through inhibition of HDAC4.

Dr Vakoc and his colleagues said the “potency and selectivity of AML growth arrest” they observed after targeting LKB1 or SIK2 and SIK3 resembles the effects of targeting other validated kinase oncogenes in AML, such as FLT3.

The team also said the sensitivity of AML cell lines to HG-9-91-01 “compares favorably” to the sensitivity of cancer cell lines to kinase inhibitors already approved for oncology indications. However, “additional optimization” of HG-9-91-01 is needed.

ATLANTA – Mitoxantrone, etoposide, and cytarabine (MEC) in combination with the second-generation proteasome inhibitor ixazomib was well tolerated and effective in a phase 1 expansion study of patients with relapsed or refractory acute myeloid leukemia.

The overall response rate in 30 patients enrolled in the study and treated with the novel combination was 53%; 11 patients had a complete response (CR), and 5 had a complete response with incomplete blood count recovery (CRi). The median overall survival was 4.9 months, Anjali S. Advani, MD, reported at the annual meeting of the American Society of Hematology.

Thirteen patients proceeded to allogeneic hematopoietic cell transplant (AHCT), and one received a donor lymphocyte infusion. Seven of these 14 patients are alive with a median follow-up of 14.5 months, said Dr. Advani of Taussig Cancer Institute, Cleveland Clinic.

The patients, who had a median age of 58 years (range of 18-70 years), were eligible for the study if they had relapsed/refractory acute myeloid leukemia (AML), adequate organ function, and cardiac ejection fraction of at least 45%. The median time from initial diagnosis to enrollment was 7.6 months.

[email protected]

ATLANTA – Mitoxantrone, etoposide, and cytarabine (MEC) in combination with the second-generation proteasome inhibitor ixazomib was well tolerated and effective in a phase 1 expansion study of patients with relapsed or refractory acute myeloid leukemia.

The overall response rate in 30 patients enrolled in the study and treated with the novel combination was 53%; 11 patients had a complete response (CR), and 5 had a complete response with incomplete blood count recovery (CRi). The median overall survival was 4.9 months, Anjali S. Advani, MD, reported at the annual meeting of the American Society of Hematology.

Thirteen patients proceeded to allogeneic hematopoietic cell transplant (AHCT), and one received a donor lymphocyte infusion. Seven of these 14 patients are alive with a median follow-up of 14.5 months, said Dr. Advani of Taussig Cancer Institute, Cleveland Clinic.

The patients, who had a median age of 58 years (range of 18-70 years), were eligible for the study if they had relapsed/refractory acute myeloid leukemia (AML), adequate organ function, and cardiac ejection fraction of at least 45%. The median time from initial diagnosis to enrollment was 7.6 months.

[email protected]

ATLANTA – Mitoxantrone, etoposide, and cytarabine (MEC) in combination with the second-generation proteasome inhibitor ixazomib was well tolerated and effective in a phase 1 expansion study of patients with relapsed or refractory acute myeloid leukemia.

The overall response rate in 30 patients enrolled in the study and treated with the novel combination was 53%; 11 patients had a complete response (CR), and 5 had a complete response with incomplete blood count recovery (CRi). The median overall survival was 4.9 months, Anjali S. Advani, MD, reported at the annual meeting of the American Society of Hematology.

Thirteen patients proceeded to allogeneic hematopoietic cell transplant (AHCT), and one received a donor lymphocyte infusion. Seven of these 14 patients are alive with a median follow-up of 14.5 months, said Dr. Advani of Taussig Cancer Institute, Cleveland Clinic.

The patients, who had a median age of 58 years (range of 18-70 years), were eligible for the study if they had relapsed/refractory acute myeloid leukemia (AML), adequate organ function, and cardiac ejection fraction of at least 45%. The median time from initial diagnosis to enrollment was 7.6 months.

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