AVAHO

Background

Monoclonal B cell lymphocytosis (MBL) is defined as presence of clonal b cell population that is fewer than 5 × 10(9)/L B-cells in peripheral blood and no other signs of a lymphoproliferative disorder. Patients with MBL are usually monitored with periodic history, physical exam and blood counts. Here we presented a case of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in breast in a patient with a history of MBL.

Case Presentation

68-year-old male with history of MBL underwent mammogram for breast mass. It showed suspicious 4.4 x 1.6 cm solid and cystic lesion containing a 1.7 x 0.9 x 1.8 cm solid hypervascular mass. Patient underwent left breast mass excision. Histologic sections focus of ADH involving papilloma with uninvolved margins. Lymphoid infiltrates noted had CLL/SLL immunophenotype and that it consists mostly of small B cells positive for CD5, CD20, CD23, CD43, Bcl-2, LEF1. CT CAP and PET/CT were negative for lymphadenopathy. Bone marrow biopsy showed marrow involvement by mature B-cell lymphoproliferative process, immunophenotypically consistent with CLL/SLL. As intra-ductal papilloma completely excised and hemogram was normal tumor board recommended surveillance only for CLL/SLL.

Discussion

MBL can progress to CLL, but it can rarely be presented as an extra-nodal mass in solid organs. We described a case of MBL that progressed to CLL/ SLL in breast mass in a male patient. This is the first reported case in literature where MBL progressed to CLL/ SLL of breast without lymphadenopathy. Upon literature review 8 case reports were found where CLL/SLL were described in breast tissue. 7 of them were in females and 1 one was in male. Two patients had CLL before breast mass but none of them had a history of MBL. 3 described cases in females had CLL/SLL infiltration of breast along with invasive ductal carcinoma. So, a patient with MBL can progress to involve solid organs despite no absolute lymphocytosis and should be considered in differentials of a new mass. Although more common in females, but it can occur in males as well. It’s important to consider the possibility of both CLL/SLL and breast cancer existing simultaneously.

Background

Monoclonal B cell lymphocytosis (MBL) is defined as presence of clonal b cell population that is fewer than 5 × 10(9)/L B-cells in peripheral blood and no other signs of a lymphoproliferative disorder. Patients with MBL are usually monitored with periodic history, physical exam and blood counts. Here we presented a case of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in breast in a patient with a history of MBL.

Case Presentation

68-year-old male with history of MBL underwent mammogram for breast mass. It showed suspicious 4.4 x 1.6 cm solid and cystic lesion containing a 1.7 x 0.9 x 1.8 cm solid hypervascular mass. Patient underwent left breast mass excision. Histologic sections focus of ADH involving papilloma with uninvolved margins. Lymphoid infiltrates noted had CLL/SLL immunophenotype and that it consists mostly of small B cells positive for CD5, CD20, CD23, CD43, Bcl-2, LEF1. CT CAP and PET/CT were negative for lymphadenopathy. Bone marrow biopsy showed marrow involvement by mature B-cell lymphoproliferative process, immunophenotypically consistent with CLL/SLL. As intra-ductal papilloma completely excised and hemogram was normal tumor board recommended surveillance only for CLL/SLL.

Discussion

MBL can progress to CLL, but it can rarely be presented as an extra-nodal mass in solid organs. We described a case of MBL that progressed to CLL/ SLL in breast mass in a male patient. This is the first reported case in literature where MBL progressed to CLL/ SLL of breast without lymphadenopathy. Upon literature review 8 case reports were found where CLL/SLL were described in breast tissue. 7 of them were in females and 1 one was in male. Two patients had CLL before breast mass but none of them had a history of MBL. 3 described cases in females had CLL/SLL infiltration of breast along with invasive ductal carcinoma. So, a patient with MBL can progress to involve solid organs despite no absolute lymphocytosis and should be considered in differentials of a new mass. Although more common in females, but it can occur in males as well. It’s important to consider the possibility of both CLL/SLL and breast cancer existing simultaneously.

Background

Monoclonal B cell lymphocytosis (MBL) is defined as presence of clonal b cell population that is fewer than 5 × 10(9)/L B-cells in peripheral blood and no other signs of a lymphoproliferative disorder. Patients with MBL are usually monitored with periodic history, physical exam and blood counts. Here we presented a case of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in breast in a patient with a history of MBL.

Case Presentation

68-year-old male with history of MBL underwent mammogram for breast mass. It showed suspicious 4.4 x 1.6 cm solid and cystic lesion containing a 1.7 x 0.9 x 1.8 cm solid hypervascular mass. Patient underwent left breast mass excision. Histologic sections focus of ADH involving papilloma with uninvolved margins. Lymphoid infiltrates noted had CLL/SLL immunophenotype and that it consists mostly of small B cells positive for CD5, CD20, CD23, CD43, Bcl-2, LEF1. CT CAP and PET/CT were negative for lymphadenopathy. Bone marrow biopsy showed marrow involvement by mature B-cell lymphoproliferative process, immunophenotypically consistent with CLL/SLL. As intra-ductal papilloma completely excised and hemogram was normal tumor board recommended surveillance only for CLL/SLL.

Discussion

MBL can progress to CLL, but it can rarely be presented as an extra-nodal mass in solid organs. We described a case of MBL that progressed to CLL/ SLL in breast mass in a male patient. This is the first reported case in literature where MBL progressed to CLL/ SLL of breast without lymphadenopathy. Upon literature review 8 case reports were found where CLL/SLL were described in breast tissue. 7 of them were in females and 1 one was in male. Two patients had CLL before breast mass but none of them had a history of MBL. 3 described cases in females had CLL/SLL infiltration of breast along with invasive ductal carcinoma. So, a patient with MBL can progress to involve solid organs despite no absolute lymphocytosis and should be considered in differentials of a new mass. Although more common in females, but it can occur in males as well. It’s important to consider the possibility of both CLL/SLL and breast cancer existing simultaneously.

A new analysis hints that there may be a benefit from aspirin for hospitalized patients with leukemia. In a preliminary study, researchers found that aspirin users had much lower odds of intracranial bleeding, deep vein thrombosis, in-hospital mortality, and septic stroke.

Aspirin users also spent less time in the hospital and had less costly care. 

No one is suggesting that clinicians give aspirin to hospitalized patients with leukemia when the drug is not otherwise indicated. However, the findings, released at the Society of Hematologic Oncology (SOHO 2024) meeting in Houston, do indicate that more research is warranted, study lead author Jayalekshmi Jayakumar, MD, of the Brooklyn Hospital Center in New York City, said in a presentation.

“We hope our study can act as background for further prospective and experimental studies to explore this association,” she said. “If we can establish causation, then aspirin has a potential to be a thromboprophylactic agent to enhance outcomes and reduce resource utilization among leukemia hospitalizations.”

Dr. Jayakumar noted that previous research has suggested aspirin may help prevent deep vein thrombosis in patients with breast and pancreatic cancer. And in blood cancer, animal research has suggested that aspirin may “promote apoptosis in leukemia cells and decrease the spread of leukemia cells through platelet inhibition,” she said. 

However, “we do not have any prospective or retrospective studies to establish causation or to see if this actually has some value within the clinical practice,” she noted.

Dr. Jayakumar stated that new study aims to detect whether aspirin may be beneficial in leukemia. She and her colleagues retrospectively tracked 1,663,149 US hospitalizations of patients with leukemia from 2016 to 2020 via the National Inpatient Sample. Of those patients, 11.2% used aspirin, although the data didn’t say whether they started it during hospitalization, and dosages were not reported. Aspirin users were older (mean age, 74.53 years vs 64.83 years in nonusers).

After adjustment for confounders, aspirin users had lower odds of several conditions than nonusers:

• Epistaxis (odds ratio [OR], 0.63; 95% CI, 0.55-0.72; P < .001)
• Hemoptysis (OR, 0.71; 95% CI, 0.61-0.82; P < .001)
• Intracranial bleed (OR, 0.74; 95% CI, 0.64-0.85; P < .001)
• Deep vein thrombosis (OR, 0.72; 95% CI, 0.66-0.78; P < .001) 
• In-hospital mortality (OR, 0.54; 95% CI, 0.50-0.58; P < .001)
• Sepsis (OR, 0.71; 95% CI, 0.68-0.75; P < .001)
• Septic shock (OR, 0.55; 95% CI, 0.50-0.60; P < .001)

There was no association reported for gastrointestinal bleeding, a possible side effect of aspirin use, or tumor lysis syndrome. Aspirin users also had a shorter typical stay (−2.8 days) and lower typical hospital charges ($40,719).

“We also found that aspirin users had a slightly reduced risk of minor bleeding and infection compared to non–aspirin users,” Dr. Jayakumar said.

In an interview, Dr. Jayakumar noted that the study is retrospective and declined to speculate on why aspirin may have benefits or why it may have the seemingly contradictory effect of reducing both blood clots and bleeding.

Aspirin is one of the least expensive drugs in existence. 

In an interview, Richard M. Stone, MD, oncologist at Dana-Farber Cancer Institute in Boston, who’s familiar with the study findings but didn’t take part in the research, said the findings are “totally counterintuitive.”

“It doesn’t mean they should be rejected, but they should be highly scrutinized,” he said. 

Dr. Stone added that bleeding is a major risk in leukemia due to low platelet counts, although platelet transplants can be helpful, and patients rarely die of bleeding. Thrombosis is also a problem in leukemia, he said, and it’s being increasingly recognized as a risk in acute myeloid leukemia.

No funding was reported. Dr. Jayakumar and Dr. Stone had no disclosures.
 

A version of this article appeared on Medscape.com.

A new analysis hints that there may be a benefit from aspirin for hospitalized patients with leukemia. In a preliminary study, researchers found that aspirin users had much lower odds of intracranial bleeding, deep vein thrombosis, in-hospital mortality, and septic stroke.

Aspirin users also spent less time in the hospital and had less costly care. 

No one is suggesting that clinicians give aspirin to hospitalized patients with leukemia when the drug is not otherwise indicated. However, the findings, released at the Society of Hematologic Oncology (SOHO 2024) meeting in Houston, do indicate that more research is warranted, study lead author Jayalekshmi Jayakumar, MD, of the Brooklyn Hospital Center in New York City, said in a presentation.

“We hope our study can act as background for further prospective and experimental studies to explore this association,” she said. “If we can establish causation, then aspirin has a potential to be a thromboprophylactic agent to enhance outcomes and reduce resource utilization among leukemia hospitalizations.”

Dr. Jayakumar noted that previous research has suggested aspirin may help prevent deep vein thrombosis in patients with breast and pancreatic cancer. And in blood cancer, animal research has suggested that aspirin may “promote apoptosis in leukemia cells and decrease the spread of leukemia cells through platelet inhibition,” she said. 

However, “we do not have any prospective or retrospective studies to establish causation or to see if this actually has some value within the clinical practice,” she noted.

Dr. Jayakumar stated that new study aims to detect whether aspirin may be beneficial in leukemia. She and her colleagues retrospectively tracked 1,663,149 US hospitalizations of patients with leukemia from 2016 to 2020 via the National Inpatient Sample. Of those patients, 11.2% used aspirin, although the data didn’t say whether they started it during hospitalization, and dosages were not reported. Aspirin users were older (mean age, 74.53 years vs 64.83 years in nonusers).

After adjustment for confounders, aspirin users had lower odds of several conditions than nonusers:

• Epistaxis (odds ratio [OR], 0.63; 95% CI, 0.55-0.72; P < .001)
• Hemoptysis (OR, 0.71; 95% CI, 0.61-0.82; P < .001)
• Intracranial bleed (OR, 0.74; 95% CI, 0.64-0.85; P < .001)
• Deep vein thrombosis (OR, 0.72; 95% CI, 0.66-0.78; P < .001) 
• In-hospital mortality (OR, 0.54; 95% CI, 0.50-0.58; P < .001)
• Sepsis (OR, 0.71; 95% CI, 0.68-0.75; P < .001)
• Septic shock (OR, 0.55; 95% CI, 0.50-0.60; P < .001)

There was no association reported for gastrointestinal bleeding, a possible side effect of aspirin use, or tumor lysis syndrome. Aspirin users also had a shorter typical stay (−2.8 days) and lower typical hospital charges ($40,719).

“We also found that aspirin users had a slightly reduced risk of minor bleeding and infection compared to non–aspirin users,” Dr. Jayakumar said.

In an interview, Dr. Jayakumar noted that the study is retrospective and declined to speculate on why aspirin may have benefits or why it may have the seemingly contradictory effect of reducing both blood clots and bleeding.

Aspirin is one of the least expensive drugs in existence. 

In an interview, Richard M. Stone, MD, oncologist at Dana-Farber Cancer Institute in Boston, who’s familiar with the study findings but didn’t take part in the research, said the findings are “totally counterintuitive.”

“It doesn’t mean they should be rejected, but they should be highly scrutinized,” he said. 

Dr. Stone added that bleeding is a major risk in leukemia due to low platelet counts, although platelet transplants can be helpful, and patients rarely die of bleeding. Thrombosis is also a problem in leukemia, he said, and it’s being increasingly recognized as a risk in acute myeloid leukemia.

No funding was reported. Dr. Jayakumar and Dr. Stone had no disclosures.
 

A version of this article appeared on Medscape.com.

A new analysis hints that there may be a benefit from aspirin for hospitalized patients with leukemia. In a preliminary study, researchers found that aspirin users had much lower odds of intracranial bleeding, deep vein thrombosis, in-hospital mortality, and septic stroke.

Aspirin users also spent less time in the hospital and had less costly care. 

No one is suggesting that clinicians give aspirin to hospitalized patients with leukemia when the drug is not otherwise indicated. However, the findings, released at the Society of Hematologic Oncology (SOHO 2024) meeting in Houston, do indicate that more research is warranted, study lead author Jayalekshmi Jayakumar, MD, of the Brooklyn Hospital Center in New York City, said in a presentation.

“We hope our study can act as background for further prospective and experimental studies to explore this association,” she said. “If we can establish causation, then aspirin has a potential to be a thromboprophylactic agent to enhance outcomes and reduce resource utilization among leukemia hospitalizations.”

Dr. Jayakumar noted that previous research has suggested aspirin may help prevent deep vein thrombosis in patients with breast and pancreatic cancer. And in blood cancer, animal research has suggested that aspirin may “promote apoptosis in leukemia cells and decrease the spread of leukemia cells through platelet inhibition,” she said. 

However, “we do not have any prospective or retrospective studies to establish causation or to see if this actually has some value within the clinical practice,” she noted.

Dr. Jayakumar stated that new study aims to detect whether aspirin may be beneficial in leukemia. She and her colleagues retrospectively tracked 1,663,149 US hospitalizations of patients with leukemia from 2016 to 2020 via the National Inpatient Sample. Of those patients, 11.2% used aspirin, although the data didn’t say whether they started it during hospitalization, and dosages were not reported. Aspirin users were older (mean age, 74.53 years vs 64.83 years in nonusers).

After adjustment for confounders, aspirin users had lower odds of several conditions than nonusers:

• Epistaxis (odds ratio [OR], 0.63; 95% CI, 0.55-0.72; P < .001)
• Hemoptysis (OR, 0.71; 95% CI, 0.61-0.82; P < .001)
• Intracranial bleed (OR, 0.74; 95% CI, 0.64-0.85; P < .001)
• Deep vein thrombosis (OR, 0.72; 95% CI, 0.66-0.78; P < .001) 
• In-hospital mortality (OR, 0.54; 95% CI, 0.50-0.58; P < .001)
• Sepsis (OR, 0.71; 95% CI, 0.68-0.75; P < .001)
• Septic shock (OR, 0.55; 95% CI, 0.50-0.60; P < .001)

There was no association reported for gastrointestinal bleeding, a possible side effect of aspirin use, or tumor lysis syndrome. Aspirin users also had a shorter typical stay (−2.8 days) and lower typical hospital charges ($40,719).

“We also found that aspirin users had a slightly reduced risk of minor bleeding and infection compared to non–aspirin users,” Dr. Jayakumar said.

In an interview, Dr. Jayakumar noted that the study is retrospective and declined to speculate on why aspirin may have benefits or why it may have the seemingly contradictory effect of reducing both blood clots and bleeding.

Aspirin is one of the least expensive drugs in existence. 

In an interview, Richard M. Stone, MD, oncologist at Dana-Farber Cancer Institute in Boston, who’s familiar with the study findings but didn’t take part in the research, said the findings are “totally counterintuitive.”

“It doesn’t mean they should be rejected, but they should be highly scrutinized,” he said. 

Dr. Stone added that bleeding is a major risk in leukemia due to low platelet counts, although platelet transplants can be helpful, and patients rarely die of bleeding. Thrombosis is also a problem in leukemia, he said, and it’s being increasingly recognized as a risk in acute myeloid leukemia.

No funding was reported. Dr. Jayakumar and Dr. Stone had no disclosures.
 

A version of this article appeared on Medscape.com.

Introduction

Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).

Case Presentation

A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.

Discussion

Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.

Introduction

Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).

Case Presentation

A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.

Discussion

Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.

Introduction

Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).

Case Presentation

A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.

Discussion

Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.

Background

Agent Orange (AO) exposure may be linked to development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.

Methods

All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR (CPRS) and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).

Results

129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.

Conclusions

This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML.

Background

Agent Orange (AO) exposure may be linked to development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.

Methods

All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR (CPRS) and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).

Results

129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.

Conclusions

This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML.

Background

Agent Orange (AO) exposure may be linked to development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.

Methods

All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR (CPRS) and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).

Results

129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.

Conclusions

This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML.

Introduction

Autoimmune hemolytic anemia (AIHA) can rarely be seen as an extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD), mostly ulcerative colitis (UC). This case report describes the clinical significance of recognizing AIHA in the context of UC.

Case Presentation

A 32-year-old male presented with profound fatigue, pallor, and dyspnea on exertion for one month. He also recalled intermittent bloody diarrhea for two years for which he never sought medical attention. Physical examination was unremarkable except for mid-abdominal tenderness. Labs revealed microcytosis, hemoglobin of 3.8 g/dL, total bilirubin 2.9 mg/ dL, indirect bilirubin of 2.0 mg/dL, LDH 132 U/L alk-p 459 U/L AST 98 U/L ALT 22 U/L. Direct Coombs test was positive suggesting warm AIHA with pan-agglutinin positive on the eluate test. Further testing revealed negative hepatitis and HIV panels and positive fecal calprotectin. CT abdomen and pelvis showed ascites, right pleural effusion and hepatosplenomegaly. Colonoscopy confirmed the diagnosis of ulcerative colitis, with extensive involvement of the colon. Mesalamine was initiated. Hematology was consulted for AIHA, who started the patient on methylprednisone leading to resolution of hemolytic anemia and improvement in gastrointestinal symptoms.

Discussion

IBD typically manifests as colitis, and the incidence of EIM as an initial symptom is observed in less than 10% cases. However, over the course of their lifetime, approximately 25% of patients will experience EIM, underscoring their relevance to clinical outcomes. Anemia is very common in IBD patients, mostly iron deficiency anemia (IDA) or anemia of chronic disease (ACD). However, AIHA can represent a rare but significant EIM of ulcerative colitis (UC), often posing diagnostic challenges. The underlying pathophysiological mechanisms linking UC and AIHA remain incompletely understood, necessitating a multidisciplinary approach to management. Treatment strategies focus on controlling both the hemolysis and the underlying IBD, emphasizing the importance of tailored interventions.

Conclusion

This case underscores the clinical significance of AIHA as an EIM of ulcerative colitis (UC), particularly when presenting as the primary symptom. Timely recognition is paramount to optimizing patient outcomes and preventing disease progression. Further research is warranted to elucidate the underlying mechanisms and therapeutic strategies for AIHA in the context of UC.

Introduction

Autoimmune hemolytic anemia (AIHA) can rarely be seen as an extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD), mostly ulcerative colitis (UC). This case report describes the clinical significance of recognizing AIHA in the context of UC.

Case Presentation

A 32-year-old male presented with profound fatigue, pallor, and dyspnea on exertion for one month. He also recalled intermittent bloody diarrhea for two years for which he never sought medical attention. Physical examination was unremarkable except for mid-abdominal tenderness. Labs revealed microcytosis, hemoglobin of 3.8 g/dL, total bilirubin 2.9 mg/ dL, indirect bilirubin of 2.0 mg/dL, LDH 132 U/L alk-p 459 U/L AST 98 U/L ALT 22 U/L. Direct Coombs test was positive suggesting warm AIHA with pan-agglutinin positive on the eluate test. Further testing revealed negative hepatitis and HIV panels and positive fecal calprotectin. CT abdomen and pelvis showed ascites, right pleural effusion and hepatosplenomegaly. Colonoscopy confirmed the diagnosis of ulcerative colitis, with extensive involvement of the colon. Mesalamine was initiated. Hematology was consulted for AIHA, who started the patient on methylprednisone leading to resolution of hemolytic anemia and improvement in gastrointestinal symptoms.

Discussion

IBD typically manifests as colitis, and the incidence of EIM as an initial symptom is observed in less than 10% cases. However, over the course of their lifetime, approximately 25% of patients will experience EIM, underscoring their relevance to clinical outcomes. Anemia is very common in IBD patients, mostly iron deficiency anemia (IDA) or anemia of chronic disease (ACD). However, AIHA can represent a rare but significant EIM of ulcerative colitis (UC), often posing diagnostic challenges. The underlying pathophysiological mechanisms linking UC and AIHA remain incompletely understood, necessitating a multidisciplinary approach to management. Treatment strategies focus on controlling both the hemolysis and the underlying IBD, emphasizing the importance of tailored interventions.

Conclusion

This case underscores the clinical significance of AIHA as an EIM of ulcerative colitis (UC), particularly when presenting as the primary symptom. Timely recognition is paramount to optimizing patient outcomes and preventing disease progression. Further research is warranted to elucidate the underlying mechanisms and therapeutic strategies for AIHA in the context of UC.

Introduction

Autoimmune hemolytic anemia (AIHA) can rarely be seen as an extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD), mostly ulcerative colitis (UC). This case report describes the clinical significance of recognizing AIHA in the context of UC.

Case Presentation

A 32-year-old male presented with profound fatigue, pallor, and dyspnea on exertion for one month. He also recalled intermittent bloody diarrhea for two years for which he never sought medical attention. Physical examination was unremarkable except for mid-abdominal tenderness. Labs revealed microcytosis, hemoglobin of 3.8 g/dL, total bilirubin 2.9 mg/ dL, indirect bilirubin of 2.0 mg/dL, LDH 132 U/L alk-p 459 U/L AST 98 U/L ALT 22 U/L. Direct Coombs test was positive suggesting warm AIHA with pan-agglutinin positive on the eluate test. Further testing revealed negative hepatitis and HIV panels and positive fecal calprotectin. CT abdomen and pelvis showed ascites, right pleural effusion and hepatosplenomegaly. Colonoscopy confirmed the diagnosis of ulcerative colitis, with extensive involvement of the colon. Mesalamine was initiated. Hematology was consulted for AIHA, who started the patient on methylprednisone leading to resolution of hemolytic anemia and improvement in gastrointestinal symptoms.

Discussion

IBD typically manifests as colitis, and the incidence of EIM as an initial symptom is observed in less than 10% cases. However, over the course of their lifetime, approximately 25% of patients will experience EIM, underscoring their relevance to clinical outcomes. Anemia is very common in IBD patients, mostly iron deficiency anemia (IDA) or anemia of chronic disease (ACD). However, AIHA can represent a rare but significant EIM of ulcerative colitis (UC), often posing diagnostic challenges. The underlying pathophysiological mechanisms linking UC and AIHA remain incompletely understood, necessitating a multidisciplinary approach to management. Treatment strategies focus on controlling both the hemolysis and the underlying IBD, emphasizing the importance of tailored interventions.

Conclusion

This case underscores the clinical significance of AIHA as an EIM of ulcerative colitis (UC), particularly when presenting as the primary symptom. Timely recognition is paramount to optimizing patient outcomes and preventing disease progression. Further research is warranted to elucidate the underlying mechanisms and therapeutic strategies for AIHA in the context of UC.

Background

In 3/2021, chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of multiple myeloma in adult patients with refractory disease. Currently, only the Veterans Affair (VA) center at the Tennessee Valley Healthcare System (TVHS) offers this treatment. Herein, we report a significant healthcare milestone in 2024 when the first patient received CAR T-cell therapy for multiple myeloma in the VA system. Additionally, the rate of hypogammaglobulinemia is the highest for CAR T-cell therapy using idecabtagene vicleucel compared to therapies using other antineoplastic agents (Wat et al, 2021). The complications of hypogammaglobulinemia can be mitigated by intravenous immunoglobulin (IVIG) treatment.

Case Presentation

A 75-year-old male veteran was diagnosed with IgA Kappa multiple myeloma and received induction therapy with bortezomib, lenalidomide, and dexamethasone in 2014. The patient underwent autologous stem cell transplant (SCT) in the same year. His disease recurred in 3/2019, and the patient was started on daratumumab and pomalidomide. He received another autologous SCT in 2/2021, to which he was refractory. The veteran then received treatment with daratumumab and ixazomib, followed by carfilzomib and cyclophosphamide. Starting in 9/2022, the patient also required regular IVIG treatment for hypogammaglobulinemia. He eventually received CAR T-cell therapy with idecabtagene vicleucel at THVS on 4/18/2024. The patient tolerated the treatment well and is undergoing routine disease monitoring. Following CAR T-cell therapy, his hypogammaglobulinemia persists with immunoglobulins level less than 500 mg/dL, and the veteran is still receiving supportive care IVIG.

Discussion

A population estimate of 1.3 million veterans are uninsured and can only access healthcare through the VA (Nelson et al, 2007). This case highlights the first patient to receive CAR T-cell therapy for multiple myeloma in the VA system, indicating that veterans now have access to this life-saving treatment. The rate of hypogammaglobulinemia following CAR T-cell therapy for multiple myeloma is as high as 41%, with an associated infection risk of 70%. Following CAR T-cell therapy with idecabtagene vicleucel, around 61% of patients will require IVIG treatment (Wat el al, 2021). Our case adds to this growing literature on the prevalence of IVIG treatment following CAR T-cell therapy in this patient population.

Background

In 3/2021, chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of multiple myeloma in adult patients with refractory disease. Currently, only the Veterans Affair (VA) center at the Tennessee Valley Healthcare System (TVHS) offers this treatment. Herein, we report a significant healthcare milestone in 2024 when the first patient received CAR T-cell therapy for multiple myeloma in the VA system. Additionally, the rate of hypogammaglobulinemia is the highest for CAR T-cell therapy using idecabtagene vicleucel compared to therapies using other antineoplastic agents (Wat et al, 2021). The complications of hypogammaglobulinemia can be mitigated by intravenous immunoglobulin (IVIG) treatment.

Case Presentation

A 75-year-old male veteran was diagnosed with IgA Kappa multiple myeloma and received induction therapy with bortezomib, lenalidomide, and dexamethasone in 2014. The patient underwent autologous stem cell transplant (SCT) in the same year. His disease recurred in 3/2019, and the patient was started on daratumumab and pomalidomide. He received another autologous SCT in 2/2021, to which he was refractory. The veteran then received treatment with daratumumab and ixazomib, followed by carfilzomib and cyclophosphamide. Starting in 9/2022, the patient also required regular IVIG treatment for hypogammaglobulinemia. He eventually received CAR T-cell therapy with idecabtagene vicleucel at THVS on 4/18/2024. The patient tolerated the treatment well and is undergoing routine disease monitoring. Following CAR T-cell therapy, his hypogammaglobulinemia persists with immunoglobulins level less than 500 mg/dL, and the veteran is still receiving supportive care IVIG.

Discussion

A population estimate of 1.3 million veterans are uninsured and can only access healthcare through the VA (Nelson et al, 2007). This case highlights the first patient to receive CAR T-cell therapy for multiple myeloma in the VA system, indicating that veterans now have access to this life-saving treatment. The rate of hypogammaglobulinemia following CAR T-cell therapy for multiple myeloma is as high as 41%, with an associated infection risk of 70%. Following CAR T-cell therapy with idecabtagene vicleucel, around 61% of patients will require IVIG treatment (Wat el al, 2021). Our case adds to this growing literature on the prevalence of IVIG treatment following CAR T-cell therapy in this patient population.

Background

In 3/2021, chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of multiple myeloma in adult patients with refractory disease. Currently, only the Veterans Affair (VA) center at the Tennessee Valley Healthcare System (TVHS) offers this treatment. Herein, we report a significant healthcare milestone in 2024 when the first patient received CAR T-cell therapy for multiple myeloma in the VA system. Additionally, the rate of hypogammaglobulinemia is the highest for CAR T-cell therapy using idecabtagene vicleucel compared to therapies using other antineoplastic agents (Wat et al, 2021). The complications of hypogammaglobulinemia can be mitigated by intravenous immunoglobulin (IVIG) treatment.

Case Presentation

A 75-year-old male veteran was diagnosed with IgA Kappa multiple myeloma and received induction therapy with bortezomib, lenalidomide, and dexamethasone in 2014. The patient underwent autologous stem cell transplant (SCT) in the same year. His disease recurred in 3/2019, and the patient was started on daratumumab and pomalidomide. He received another autologous SCT in 2/2021, to which he was refractory. The veteran then received treatment with daratumumab and ixazomib, followed by carfilzomib and cyclophosphamide. Starting in 9/2022, the patient also required regular IVIG treatment for hypogammaglobulinemia. He eventually received CAR T-cell therapy with idecabtagene vicleucel at THVS on 4/18/2024. The patient tolerated the treatment well and is undergoing routine disease monitoring. Following CAR T-cell therapy, his hypogammaglobulinemia persists with immunoglobulins level less than 500 mg/dL, and the veteran is still receiving supportive care IVIG.

Discussion

A population estimate of 1.3 million veterans are uninsured and can only access healthcare through the VA (Nelson et al, 2007). This case highlights the first patient to receive CAR T-cell therapy for multiple myeloma in the VA system, indicating that veterans now have access to this life-saving treatment. The rate of hypogammaglobulinemia following CAR T-cell therapy for multiple myeloma is as high as 41%, with an associated infection risk of 70%. Following CAR T-cell therapy with idecabtagene vicleucel, around 61% of patients will require IVIG treatment (Wat el al, 2021). Our case adds to this growing literature on the prevalence of IVIG treatment following CAR T-cell therapy in this patient population.

Background

In 2024, the first two veterans, both from the Michael E. DeBakey Veteran Affairs (VA) Medical Center, received chimeric antigen receptors (CAR) T-cell therapy for refractory multiple myeloma through the Tennessee Valley Healthcare System (TVHS). Currently, TVHS is the only VA where this treatment is available. One of these patients also had penta-refractory multiple myeloma (P-RMM), which is associated with significantly worse progression-free survival and overall survival (OS) (Gill et al, 2021). P-RMM is defined as resistance to at least two immunomodulatory drugs, two different proteasome inhibitors, and one CD38 monoclonal antibody.

Case Presentation

A 71-year-old female veteran was diagnosed with high-risk multiple myeloma and received induction therapy with carfilzomib, lenalidomide, and dexamethasone in 2017. She underwent autologous stem cell transplant (SCT) in 4/2018. The veteran subsequently received maintenance therapy with lenalidomide, bortezomib, and dexamethasone. Her disease recurred in 1/2022. The patient then received two more lines of treatments with daratumumab and pomalidomide followed by selinexor. She had another autologous SCT in 5/2023, to which she was refractory. Her fifth line therapy included addition of bortezomib to her selinexor regimen. She eventually underwent CAR T-cell therapy at THVS on 5/1/2024 with good tolerance of therapy. At her follow-up visit, the patient had significant response to CAR T-cell treatment, based on her symptoms and improvement in free light chains and serum protein electrophoresis.

Discussion

CAR T-cell therapy is one of the newest and most cutting-edge therapies for patients with refractory multiple myeloma. Access to this therapy has been limited throughout the country. However, as shown by our case, this life-saving treatment is now available to patients within the VA. According to a retrospective study on P-RMM patients, the OS in patients who received B-cell maturation antigen (BCMA) targeted therapy was significantly higher than in those who did not (17 vs. 6 months, p < 0.0001). Among the BCMA-targeted therapies, CAR T-cell therapy is associated with the highest OS (29 months) compared to antibody-drug conjugates and bispecific T-cell engagers (Atrash et al, 2023). Thus, accessibility to CAR T-cell therapy was essential in our patient with P-RMM in ensuring her best survival outcomes.

Background

In 2024, the first two veterans, both from the Michael E. DeBakey Veteran Affairs (VA) Medical Center, received chimeric antigen receptors (CAR) T-cell therapy for refractory multiple myeloma through the Tennessee Valley Healthcare System (TVHS). Currently, TVHS is the only VA where this treatment is available. One of these patients also had penta-refractory multiple myeloma (P-RMM), which is associated with significantly worse progression-free survival and overall survival (OS) (Gill et al, 2021). P-RMM is defined as resistance to at least two immunomodulatory drugs, two different proteasome inhibitors, and one CD38 monoclonal antibody.

Case Presentation

A 71-year-old female veteran was diagnosed with high-risk multiple myeloma and received induction therapy with carfilzomib, lenalidomide, and dexamethasone in 2017. She underwent autologous stem cell transplant (SCT) in 4/2018. The veteran subsequently received maintenance therapy with lenalidomide, bortezomib, and dexamethasone. Her disease recurred in 1/2022. The patient then received two more lines of treatments with daratumumab and pomalidomide followed by selinexor. She had another autologous SCT in 5/2023, to which she was refractory. Her fifth line therapy included addition of bortezomib to her selinexor regimen. She eventually underwent CAR T-cell therapy at THVS on 5/1/2024 with good tolerance of therapy. At her follow-up visit, the patient had significant response to CAR T-cell treatment, based on her symptoms and improvement in free light chains and serum protein electrophoresis.

Discussion

CAR T-cell therapy is one of the newest and most cutting-edge therapies for patients with refractory multiple myeloma. Access to this therapy has been limited throughout the country. However, as shown by our case, this life-saving treatment is now available to patients within the VA. According to a retrospective study on P-RMM patients, the OS in patients who received B-cell maturation antigen (BCMA) targeted therapy was significantly higher than in those who did not (17 vs. 6 months, p < 0.0001). Among the BCMA-targeted therapies, CAR T-cell therapy is associated with the highest OS (29 months) compared to antibody-drug conjugates and bispecific T-cell engagers (Atrash et al, 2023). Thus, accessibility to CAR T-cell therapy was essential in our patient with P-RMM in ensuring her best survival outcomes.

Background

In 2024, the first two veterans, both from the Michael E. DeBakey Veteran Affairs (VA) Medical Center, received chimeric antigen receptors (CAR) T-cell therapy for refractory multiple myeloma through the Tennessee Valley Healthcare System (TVHS). Currently, TVHS is the only VA where this treatment is available. One of these patients also had penta-refractory multiple myeloma (P-RMM), which is associated with significantly worse progression-free survival and overall survival (OS) (Gill et al, 2021). P-RMM is defined as resistance to at least two immunomodulatory drugs, two different proteasome inhibitors, and one CD38 monoclonal antibody.

Case Presentation

A 71-year-old female veteran was diagnosed with high-risk multiple myeloma and received induction therapy with carfilzomib, lenalidomide, and dexamethasone in 2017. She underwent autologous stem cell transplant (SCT) in 4/2018. The veteran subsequently received maintenance therapy with lenalidomide, bortezomib, and dexamethasone. Her disease recurred in 1/2022. The patient then received two more lines of treatments with daratumumab and pomalidomide followed by selinexor. She had another autologous SCT in 5/2023, to which she was refractory. Her fifth line therapy included addition of bortezomib to her selinexor regimen. She eventually underwent CAR T-cell therapy at THVS on 5/1/2024 with good tolerance of therapy. At her follow-up visit, the patient had significant response to CAR T-cell treatment, based on her symptoms and improvement in free light chains and serum protein electrophoresis.

Discussion

CAR T-cell therapy is one of the newest and most cutting-edge therapies for patients with refractory multiple myeloma. Access to this therapy has been limited throughout the country. However, as shown by our case, this life-saving treatment is now available to patients within the VA. According to a retrospective study on P-RMM patients, the OS in patients who received B-cell maturation antigen (BCMA) targeted therapy was significantly higher than in those who did not (17 vs. 6 months, p < 0.0001). Among the BCMA-targeted therapies, CAR T-cell therapy is associated with the highest OS (29 months) compared to antibody-drug conjugates and bispecific T-cell engagers (Atrash et al, 2023). Thus, accessibility to CAR T-cell therapy was essential in our patient with P-RMM in ensuring her best survival outcomes.