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Financial burdens reduce QOL for cancer survivors
receiving treatment
Photo by Rhoda Baer
An analysis of nearly 20 million cancer survivors showed that almost 29% had financial burdens as a result of their cancer diagnosis and/or treatment.
In other words, they borrowed money, declared bankruptcy, worried about paying large medical bills, were unable to cover the cost of medical visits, or made other financial sacrifices.
Furthermore, such hardships could have lasting effects on a cancer survivor’s quality of life (QOL).
Hrishikesh Kale and Norman Carroll, PhD, both of Virginia Commonwealth University School of Pharmacy in Richmond, reported these findings in Cancer.
The pair analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors, assessing financial burden and QOL.
Subjects were considered to have financial burden if they reported 1 of the following problems: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.
Nearly 29% of the cancer survivors reported at least 1 financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment.
Of all the cancer survivors in the analysis, 20.9% worried about paying large medical bills, 11.5% were unable to cover the cost of medical care visits, 7.6% reported borrowing money or going into debt, 1.4% declared bankruptcy, and 8.6% reported other financial sacrifices.
Cancer survivors who faced such financial difficulties had lower physical and mental health-related QOL, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence, when compared with cancer survivors who did not face financial problems.
In addition, as the number of financial problems reported by cancer survivors increased, their QOL continued to decrease. And their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.
“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” Dr Carroll said.
“Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.” 
receiving treatment
Photo by Rhoda Baer
An analysis of nearly 20 million cancer survivors showed that almost 29% had financial burdens as a result of their cancer diagnosis and/or treatment.
In other words, they borrowed money, declared bankruptcy, worried about paying large medical bills, were unable to cover the cost of medical visits, or made other financial sacrifices.
Furthermore, such hardships could have lasting effects on a cancer survivor’s quality of life (QOL).
Hrishikesh Kale and Norman Carroll, PhD, both of Virginia Commonwealth University School of Pharmacy in Richmond, reported these findings in Cancer.
The pair analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors, assessing financial burden and QOL.
Subjects were considered to have financial burden if they reported 1 of the following problems: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.
Nearly 29% of the cancer survivors reported at least 1 financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment.
Of all the cancer survivors in the analysis, 20.9% worried about paying large medical bills, 11.5% were unable to cover the cost of medical care visits, 7.6% reported borrowing money or going into debt, 1.4% declared bankruptcy, and 8.6% reported other financial sacrifices.
Cancer survivors who faced such financial difficulties had lower physical and mental health-related QOL, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence, when compared with cancer survivors who did not face financial problems.
In addition, as the number of financial problems reported by cancer survivors increased, their QOL continued to decrease. And their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.
“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” Dr Carroll said.
“Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.”
receiving treatment
Photo by Rhoda Baer
An analysis of nearly 20 million cancer survivors showed that almost 29% had financial burdens as a result of their cancer diagnosis and/or treatment.
In other words, they borrowed money, declared bankruptcy, worried about paying large medical bills, were unable to cover the cost of medical visits, or made other financial sacrifices.
Furthermore, such hardships could have lasting effects on a cancer survivor’s quality of life (QOL).
Hrishikesh Kale and Norman Carroll, PhD, both of Virginia Commonwealth University School of Pharmacy in Richmond, reported these findings in Cancer.
The pair analyzed 2011 Medical Expenditure Panel Survey data on 19.6 million cancer survivors, assessing financial burden and QOL.
Subjects were considered to have financial burden if they reported 1 of the following problems: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices.
Nearly 29% of the cancer survivors reported at least 1 financial problem resulting from cancer diagnosis, treatment, or lasting effects of that treatment.
Of all the cancer survivors in the analysis, 20.9% worried about paying large medical bills, 11.5% were unable to cover the cost of medical care visits, 7.6% reported borrowing money or going into debt, 1.4% declared bankruptcy, and 8.6% reported other financial sacrifices.
Cancer survivors who faced such financial difficulties had lower physical and mental health-related QOL, higher risk for depressed mood and psychological distress, and were more likely to worry about cancer recurrence, when compared with cancer survivors who did not face financial problems.
In addition, as the number of financial problems reported by cancer survivors increased, their QOL continued to decrease. And their risk for depressed mood, psychological distress, and worries about cancer recurrence continued to increase.
“Our results suggest that policies and practices that minimize cancer patients’ out-of-pocket costs can improve survivors’ health-related quality of life and psychological health,” Dr Carroll said.
“Reducing the financial burden of cancer care requires integrated efforts, and the study findings are useful for survivorship care programs, oncologists, payers, pharmaceutical companies, and patients and their family members.”
Team identifies gaps in anticoagulant use
Photo courtesy of NIGMS
Many patients with atrial fibrillation (AF) who are at the highest risk of stroke are not receiving the recommended oral anticoagulant therapy, according to a new study.
Researchers did find that AF patients who had a higher risk of stroke according to CHADS2 score or CHA2DS2-VASc score were more likely to receive an oral anticoagulant.
But the prevalence of oral anticoagulant use did not exceed 50%, even among high-risk patients.
Jonathan C. Hsu, MD, of the University of California, San Diego, and his colleagues reported these findings in JAMA Cardiology.
The researchers said it has not been clear if the prescription of oral anticoagulants increases as the risk of stroke increases in AF patients.
To gain some insight, the team studied 429,417 outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry’s PINNACLE Registry between January 2008 and December 2012.
The researchers calculated the CHADS2 score and the CHA2DS2-VASc score for all patients and examined the association between increased stroke risk score and prescription of an oral anticoagulant.
In the entire cohort, 44.9% of patients were prescribed an oral anticoagulant, 25.9% aspirin only, 5.5% aspirin plus a thienopyridine, and 23.8% no antithrombotic therapy.
The researchers found that each 1-point increase in risk score was associated with increased odds of oral anticoagulant prescription when compared with aspirin-only prescription.
When using CHADS2 score, the adjusted odds ratio was 1.158 (95% CI, 1.144-1.172, P<0.001). When using CHA2DS2-VASc score, the adjusted odds ratio was 1.163 (95% CI, 1.157-1.169, P<0.001).
Still, the researchers said they observed a plateau in oral anticoagulant prescription.
The prevalence of oral anticoagulant prescription did not exceed 50%, even in patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4.
Dr Hsu and his colleagues said these findings draw attention to important gaps in the appropriate treatment of patients with AF at the highest risk of stroke and highlight opportunities to understand the reasons behind these gaps.
Photo courtesy of NIGMS
Many patients with atrial fibrillation (AF) who are at the highest risk of stroke are not receiving the recommended oral anticoagulant therapy, according to a new study.
Researchers did find that AF patients who had a higher risk of stroke according to CHADS2 score or CHA2DS2-VASc score were more likely to receive an oral anticoagulant.
But the prevalence of oral anticoagulant use did not exceed 50%, even among high-risk patients.
Jonathan C. Hsu, MD, of the University of California, San Diego, and his colleagues reported these findings in JAMA Cardiology.
The researchers said it has not been clear if the prescription of oral anticoagulants increases as the risk of stroke increases in AF patients.
To gain some insight, the team studied 429,417 outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry’s PINNACLE Registry between January 2008 and December 2012.
The researchers calculated the CHADS2 score and the CHA2DS2-VASc score for all patients and examined the association between increased stroke risk score and prescription of an oral anticoagulant.
In the entire cohort, 44.9% of patients were prescribed an oral anticoagulant, 25.9% aspirin only, 5.5% aspirin plus a thienopyridine, and 23.8% no antithrombotic therapy.
The researchers found that each 1-point increase in risk score was associated with increased odds of oral anticoagulant prescription when compared with aspirin-only prescription.
When using CHADS2 score, the adjusted odds ratio was 1.158 (95% CI, 1.144-1.172, P<0.001). When using CHA2DS2-VASc score, the adjusted odds ratio was 1.163 (95% CI, 1.157-1.169, P<0.001).
Still, the researchers said they observed a plateau in oral anticoagulant prescription.
The prevalence of oral anticoagulant prescription did not exceed 50%, even in patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4.
Dr Hsu and his colleagues said these findings draw attention to important gaps in the appropriate treatment of patients with AF at the highest risk of stroke and highlight opportunities to understand the reasons behind these gaps.
Photo courtesy of NIGMS
Many patients with atrial fibrillation (AF) who are at the highest risk of stroke are not receiving the recommended oral anticoagulant therapy, according to a new study.
Researchers did find that AF patients who had a higher risk of stroke according to CHADS2 score or CHA2DS2-VASc score were more likely to receive an oral anticoagulant.
But the prevalence of oral anticoagulant use did not exceed 50%, even among high-risk patients.
Jonathan C. Hsu, MD, of the University of California, San Diego, and his colleagues reported these findings in JAMA Cardiology.
The researchers said it has not been clear if the prescription of oral anticoagulants increases as the risk of stroke increases in AF patients.
To gain some insight, the team studied 429,417 outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry’s PINNACLE Registry between January 2008 and December 2012.
The researchers calculated the CHADS2 score and the CHA2DS2-VASc score for all patients and examined the association between increased stroke risk score and prescription of an oral anticoagulant.
In the entire cohort, 44.9% of patients were prescribed an oral anticoagulant, 25.9% aspirin only, 5.5% aspirin plus a thienopyridine, and 23.8% no antithrombotic therapy.
The researchers found that each 1-point increase in risk score was associated with increased odds of oral anticoagulant prescription when compared with aspirin-only prescription.
When using CHADS2 score, the adjusted odds ratio was 1.158 (95% CI, 1.144-1.172, P<0.001). When using CHA2DS2-VASc score, the adjusted odds ratio was 1.163 (95% CI, 1.157-1.169, P<0.001).
Still, the researchers said they observed a plateau in oral anticoagulant prescription.
The prevalence of oral anticoagulant prescription did not exceed 50%, even in patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4.
Dr Hsu and his colleagues said these findings draw attention to important gaps in the appropriate treatment of patients with AF at the highest risk of stroke and highlight opportunities to understand the reasons behind these gaps.
FDA approves drug for 2 indications in MM
Photo courtesy of
Spectrum Pharmaceuticals
The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.
The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.
Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).
This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
The full prescribing information for Evomela is available at www.evomela.com.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.
Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.
Phase 2 study
Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.
Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.
Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.
The patients received Evomela at 200 mg/m2, given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).
All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.
Photo courtesy of
Spectrum Pharmaceuticals
The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.
The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.
Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).
This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
The full prescribing information for Evomela is available at www.evomela.com.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.
Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.
Phase 2 study
Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.
Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.
Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.
The patients received Evomela at 200 mg/m2, given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).
All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.
Photo courtesy of
Spectrum Pharmaceuticals
The US Food and Drug Administration (FDA) has approved a new formulation of melphalan for injection (Evomela) for 2 indications.
The drug is now approved for use as a high-dose conditioning treatment prior to autologous hematopoietic stem cell transplant (HSCT) in patients with multiple myeloma (MM) and for the palliative treatment of patients with MM for whom oral therapy is not appropriate.
Evomela is the first product to be FDA-approved for the high-dose conditioning indication in MM. The FDA previously granted the drug orphan designation for this indication.
About Evomela
Evomela is a Captisol-enabled, propylene glycol-free melphalan formulation. This formulation eliminates the need to use a propylene glycol-containing custom diluent, which is required with other intravenous melphalan formulations and has been reported to cause renal and cardiac side effects.
Captisol is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
The use of Captisol technology to reformulate melphalan is reported to improve the drug’s stability, extending its use time. The technology allows the admixture solution to be stable for 4 hours at room temperature, in addition to the 1 hour following reconstitution, and for 24 hours at refrigerated temperature (5°C).
This is anticipated to simplify preparation and administration logistics and allow for slower infusion rates and longer administration durations for pre-transplant chemotherapy.
The full prescribing information for Evomela is available at www.evomela.com.
Spectrum Pharmaceuticals gained global development and commercialization rights to Evomela from Ligand Pharmaceuticals Incorporated in March 2013.
Spectrum assumed responsibility for completing the pivotal phase 2 trial of Evomela and was responsible for filing the new drug application. Spectrum filed the application in December 2014, and the FDA accepted it the following March.
Phase 2 study
Evomela was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a phase 2 study.
Initial results from this trial (phase 2a) were published in Bone Marrow Transplantation in June 2014. Phase 2b results were published in Biology of Blood and Marrow Transplantation in September 2015.
Phase 2b included 61 patients. Fifty-six had newly diagnosed MM, and 5 had relapsed MM following prior HSCT.
The patients received Evomela at 200 mg/m2, given as 2 doses on day -3 and day -2 prior to autologous HSCT (day 0).
All 61 patients achieved myeloablation at a median of 5 days post-HSCT. And all patients had successful neutrophil and platelet engraftment at a median of 12 days and 13 days post-HSCT, respectively.
Efficacy was assessed by clinical response at day 100. According to investigator assessment, the overall response rate was 95%, and the complete response (CR) rate was 31%.
According to independent pathology review, the overall response rate was 100%, and the CR rate was 21%. The lower rate of confirmed CRs in the independent review was due to missing data.
Treatment-related mortality was 0%, and non-hematologic adverse events were mostly grade 1 and 2 in severity. The incidence of grade 3 mucositis and grade 3 stomatitis were 10% and 5%, respectively, with no grade 4 mucositis or stomatitis reported.
Twenty percent of patients experienced treatment-emergent serious adverse events, most of which were grade 3 and consisted of events commonly reported in patients undergoing myeloablative chemotherapy. No new safety signals were identified.
Combo appears superior to G-CSF for mobilizing HSCs
in the bone marrow
A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.
The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.
In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.
And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.
“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.
“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”
Combination vs monotherapy
Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.
However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.
The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.
To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.
The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.
In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).
The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.
Comparisons with G-CSF
Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.
BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.
And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.
But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.
The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.
Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.
To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.
They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.
However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.
The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.
in the bone marrow
A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.
The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.
In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.
And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.
“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.
“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”
Combination vs monotherapy
Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.
However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.
The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.
To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.
The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.
In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).
The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.
Comparisons with G-CSF
Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.
BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.
And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.
But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.
The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.
Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.
To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.
They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.
However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.
The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.
in the bone marrow
A 2-drug combination can be more effective than granulocyte colony-stimulating factor (G-CSF) for mobilizing hematopoietic stem cells (HSCs), according to preclinical research published in Nature Communications.
The combination consists of the dual α9β1/α4β1 antagonist BOP and the CXCR4 antagonist AMD3100, also known as plerixafor.
In experiments with mice, researchers found that treatment with BOP and AMD3100 directly impacts HSCs so they can be seen in the blood stream within an hour.
And when these HSCs are transplanted into recipient mice, they can replenish the entire hematopoietic system.
“Current treatment requires [a transplant donor] to have growth factor injections for several days leading up to the [harvesting] procedure,” said study author Susie Nilsson, PhD, of Monash University in Clayton, Victoria, Australia.
“Using the [2-drug combination] eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour.”
Combination vs monotherapy
Dr Nilsson and her colleagues found that, when given alone, AMD3100 and BOP produced similar increases in white blood cell (WBC) counts and the proportion of progenitors (LSK cells) in the peripheral blood (PB) of mice.
However, BOP produced a significantly greater increase in the proportion of HSCs (LSKSLAM cells) in the PB. The researchers said this suggests that AMD3100 predominantly mobilizes progenitors, and BOP predominantly mobilizes HSCs.
The team also found that, in combination, BOP and AMD3100 mobilized WBCs, progenitors, and HSCs more effectively than either agent alone.
To determine if these drugs could mobilize HSCs and progenitors with long-term multi-lineage engraftment potential, the researchers performed limiting dilution transplant analysis using BOP, AMD3100, or both drugs.
The team observed superior survival in mice that received 30 ml of PB mobilized using the combination, when compared to either drug alone.
In addition, PB mobilized with the combination resulted in a greater repopulation frequency (1 HSC in 23 ml PB) than PB mobilized with BOP (1 HSC in 327 ml) or AMD3100 (1 HSC in 351 ml).
The researchers said this was a more than 10-fold improvement with the combination, as compared to monotherapy.
Comparisons with G-CSF
Treating mice with a single dose of BOP following 4 days of G-CSF treatment resulted in significant synergistic increases in HSCs (LSKSLAM cells) and progenitors (LSK cells), when compared to G-CSF alone.
BOP and AMD3100 in combination produced equivalent numbers of HSCs and progenitors as G-CSF alone.
And the combination of G-CSF and AMD3100 mobilized significantly more HSCs and progenitors than G-CSF alone.
But the greatest number of HSCs and progenitors were mobilized with the combination of G-CSF, AMD3100, and BOP. This combination produced a significant increase in cells when compared with G-CSF alone or the combination of AMD3100 and BOP.
The researchers also compared the hematopoietic potential of PB mobilized with multiple doses of G-CSF to PB mobilized with a single dose of BOP and AMD3100 in combination.
Although equivalent numbers of HSCs were mobilized, BOP and AMD3100 significantly enhanced short-term and long-term multi-lineage engraftment, when compared to G-CSF.
To determine whether the HSC mobilization observed in these experiments is equivalent in humans, the researchers tested the mobilizing agents in humanized NSG mice.
They found that a single dose of BOP or AMD3100 alone, or multiple doses of G-CSF for 4 days, did not significantly increase human WBCs or human CD34+ stem and progenitor cells.
However, a single dose of BOP and AMD3100 in combination produced a significant increase in both WBCs and stem and progenitor cells.
The researchers said the next step is a phase 1 trial assessing the combination of BOP with G-CSF before they can test the combination of BOP and AMD3100 in humans.
Starting all CML patients on imatinib could cut costs, team says
Photo courtesy of the CDC
New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.
Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.
In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.
“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.
“This amounts to a huge cost savings for them and their insurers.”
Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.
The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.
The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).
The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.
However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.
So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.
“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”
“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”
Photo courtesy of the CDC
New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.
Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.
In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.
“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.
“This amounts to a huge cost savings for them and their insurers.”
Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.
The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.
The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).
The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.
However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.
So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.
“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”
“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”
Photo courtesy of the CDC
New research suggests that starting all patients with chronic myeloid leukemia (CML) on the generic form of Gleevec, imatinib, could result in substantial savings for patients and insurance companies in the US.
Researchers found that starting treatment with generic imatinib and then switching patients to the second-generation tyrosine kinase inhibitors (TKIs) dasatinib (Sprycel) and nilotinib (Tasigna) if necessary would be more cost-effective than the current standard of care, which allows physicians to start patients on any of the aforementioned TKIs.
In fact, the data suggest that starting all CML patients on generic imatinib could reduce the cost of treatment per patient over 5 years by nearly $90,000.
“If we start all patients on the generic form of Gleevec, and it works, then they are on a generic for the rest of their lives,” said study author William V. Padula, PhD, of Johns Hopkins University in Baltimore, Maryland.
“This amounts to a huge cost savings for them and their insurers.”
Dr Padula and his colleagues described these potential savings in the Journal of the National Cancer Institute.
The researchers compared the cost-effectiveness of the different TKIs by analyzing Truven Health Analytics MarketScan data from newly diagnosed CML patients between January 1, 2011, and December 31, 2012.
The team constructed Markov models to compare the 5-year cost-effectiveness of imatinib-first vs physician’s choice. The main outcome of the models was cost per quality-adjusted life-year (QALY).
The researchers interpreted outcomes based on a willingness-to-pay threshold of $100,000/QALY. They found that both imatinib-first and physician’s choice met that threshold.
However, imatinib-first cost less over 5 years and conferred only slightly fewer QALYs than physician’s choice—$277,401 and 3.87 QALYs for imatinib-first and $365,744 and 3.97 QALYs for physician’s choice.
So that’s a 0.10 decrement in QALYs and a savings of $88,343 over 5 years with imatinib-first. The imatinib-first incremental cost-effectiveness ratio was about $883,730/QALY.
“There is minimal risk to starting all patients on imatinib first,” Dr Padula said. “If the patient can’t tolerate the medication or it seems to be ineffective in that patient, then we can switch the patient to a more expensive drug.”
“Insurance companies have the ability to dictate which drugs physicians prescribe first, and they regularly do. Doing so here would mean very little risk to health and a lot of cost savings.”
Doc laments increasing use of P values
Photo by Rhoda Baer
A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.
“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.
He and his colleagues reviewed the use of P values and recounted their findings in JAMA.
The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.
The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.
They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.
The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.
In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.
Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.
“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”
“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”
For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.
He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.
They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.
Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.
In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.
In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.
“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”
Photo by Rhoda Baer
A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.
“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.
He and his colleagues reviewed the use of P values and recounted their findings in JAMA.
The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.
The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.
They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.
The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.
In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.
Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.
“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”
“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”
For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.
He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.
They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.
Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.
In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.
In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.
“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”
Photo by Rhoda Baer
A review of the biomedical literature indicates an increase in the use of P values in recent years, but researchers say this technique can provide misleading results.
“It’s usually a suboptimal technique, and then it’s used in a biased way, so it can become very misleading,” said John Ioannidis, MD, of Stanford University in California.
He and his colleagues reviewed the use of P values and recounted their findings in JAMA.
The team used automated text-mining analysis to extract data on P values reported in 12,821,790 MEDLINE abstracts and 843,884 abstracts and full-text articles in PubMed Central from 1990 to 2015.
The researchers also assessed the reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed.
They manually evaluated a random sample of 1000 MEDLINE abstracts for reporting of P values and other types of statistical information. And of those abstracts reporting empirical data, 100 articles were assessed in their entirety.
The data showed that reporting of P values more than doubled from 1990 to 2014—increasing from 7.3% to 15.6%.
In abstracts from core medical journals, 33% reported P values in 2014. And in the subset of randomized, controlled clinical trials, nearly 55% reported P values in 2014.
Dr Ioannidis noted that some researchers mistakenly think a P value is an estimate of how likely it is that a result is true.
“The P value does not tell you whether something is true,” he explained. “If you get a P value of 0.01, it doesn’t mean you have a 1% chance of something not being true.”
“A P value of 0.01 could mean the result is 20% likely to be true, 80% likely to be true, or 0.1% likely to be true—all with the same P value. The P value alone doesn’t tell you how true your result is.”
For an actual estimate of how likely a result is to be true or false, Dr Ioannidis said, researchers should instead use false-discovery rates or Bayes factor calculations.
He and his colleagues assessed the use of false-discovery rates, Bayes factor calculations, effect sizes, and confidence intervals in the 796 papers in their review that contained empirical data.
They found that 111 of these papers reported effect sizes, and 18 reported confidence intervals. None of the papers reported Bayes factors or false-discovery rates.
Fewer than 2% of the abstracts the team reviewed reported both an effect size and a confidence interval.
In a manual review of 99 randomly selected full-text articles, the researchers found that 55 articles reported at least 1 P value. But only 4 articles reported confidence intervals for all effect sizes, none used Bayesian methods, and 1 used false-discovery rates.
In light of these findings, Dr Ioannidis advocates more stringent approaches to analyzing data.
“The way to move forward is that P values need to be used more selectively,” he said. “When used, they need to be complemented by effect sizes and uncertainty [confidence intervals]. And it would often be a good idea to use a Bayesian approach or a false-discovery rate to answer the question, ‘How likely is this result to be true?’”
Protein plays key role in B-ALL subtype
An RNA binding protein promotes the development of MLL-rearranged B-cell acute lymphoblastic leukemia (B-ALL), according to research published in The Journal of Clinical Investigation.
Researchers found an overabundance of the protein, IGF2BP3, in MLL-rearranged B-ALL.
They also identified genes that are directly regulated by IFG2BP3, and many of them turned out to be oncogenes that have already been implicated in cancers.
The overall effect of IFG2BP3 in MLL-rearranged B-ALL is to promote the proliferation of B cells by shifting the expression of a large number of genes, explained study author Jeremy Sanford, PhD, of the University of California Santa Cruz.
“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” he noted. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated, for the first time, that aberrant expression of this protein is sufficient to induce pathology.”
This research began in the lab of Dinesh Rao, PhD, an assistant professor at the University of California Los Angeles who was studying MLL-rearranged B-ALL.
After researchers in Dr Rao’s lab identified IGF2BP3 as one of the top dysregulated genes in this malignancy, they began working with Dr Sanford’s lab to figure out which genes were being directly regulated by IGF2BP3.
Dr Sanford’s lab was among the few using individual nucleotide resolution crosslinking immunoprecipitation (iCLIP), a technique that can capture RNA molecules bound to a particular protein.
iCLIP enabled the researchers to identify IGF2BP3 binding sites in several hundred RNA transcripts in 2 B-ALL cell lines.
The work also revealed that IGF2BP3 enhanced the expression of MYC and other oncogenes in hematopoietic stem cells.
In experiments with mice, the researchers found that overexpression of IGF2BP3 in the bone marrow leads to proliferation of hematopoietic stem cells and B-cell progenitors, reproducing some features of MLL-rearranged B-ALL.
“Understanding its mechanism of action is important for thinking about therapeutics that might interfere with the action of this protein in disease,” Dr Sanford said.
“One possibility is an RNA-based therapeutic that could sequester the protein and keep it from binding to RNA transcripts. That would be a way to influence the expression of many genes involved in the proliferation of cancer cells.”
An RNA binding protein promotes the development of MLL-rearranged B-cell acute lymphoblastic leukemia (B-ALL), according to research published in The Journal of Clinical Investigation.
Researchers found an overabundance of the protein, IGF2BP3, in MLL-rearranged B-ALL.
They also identified genes that are directly regulated by IFG2BP3, and many of them turned out to be oncogenes that have already been implicated in cancers.
The overall effect of IFG2BP3 in MLL-rearranged B-ALL is to promote the proliferation of B cells by shifting the expression of a large number of genes, explained study author Jeremy Sanford, PhD, of the University of California Santa Cruz.
“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” he noted. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated, for the first time, that aberrant expression of this protein is sufficient to induce pathology.”
This research began in the lab of Dinesh Rao, PhD, an assistant professor at the University of California Los Angeles who was studying MLL-rearranged B-ALL.
After researchers in Dr Rao’s lab identified IGF2BP3 as one of the top dysregulated genes in this malignancy, they began working with Dr Sanford’s lab to figure out which genes were being directly regulated by IGF2BP3.
Dr Sanford’s lab was among the few using individual nucleotide resolution crosslinking immunoprecipitation (iCLIP), a technique that can capture RNA molecules bound to a particular protein.
iCLIP enabled the researchers to identify IGF2BP3 binding sites in several hundred RNA transcripts in 2 B-ALL cell lines.
The work also revealed that IGF2BP3 enhanced the expression of MYC and other oncogenes in hematopoietic stem cells.
In experiments with mice, the researchers found that overexpression of IGF2BP3 in the bone marrow leads to proliferation of hematopoietic stem cells and B-cell progenitors, reproducing some features of MLL-rearranged B-ALL.
“Understanding its mechanism of action is important for thinking about therapeutics that might interfere with the action of this protein in disease,” Dr Sanford said.
“One possibility is an RNA-based therapeutic that could sequester the protein and keep it from binding to RNA transcripts. That would be a way to influence the expression of many genes involved in the proliferation of cancer cells.”
An RNA binding protein promotes the development of MLL-rearranged B-cell acute lymphoblastic leukemia (B-ALL), according to research published in The Journal of Clinical Investigation.
Researchers found an overabundance of the protein, IGF2BP3, in MLL-rearranged B-ALL.
They also identified genes that are directly regulated by IFG2BP3, and many of them turned out to be oncogenes that have already been implicated in cancers.
The overall effect of IFG2BP3 in MLL-rearranged B-ALL is to promote the proliferation of B cells by shifting the expression of a large number of genes, explained study author Jeremy Sanford, PhD, of the University of California Santa Cruz.
“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” he noted. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated, for the first time, that aberrant expression of this protein is sufficient to induce pathology.”
This research began in the lab of Dinesh Rao, PhD, an assistant professor at the University of California Los Angeles who was studying MLL-rearranged B-ALL.
After researchers in Dr Rao’s lab identified IGF2BP3 as one of the top dysregulated genes in this malignancy, they began working with Dr Sanford’s lab to figure out which genes were being directly regulated by IGF2BP3.
Dr Sanford’s lab was among the few using individual nucleotide resolution crosslinking immunoprecipitation (iCLIP), a technique that can capture RNA molecules bound to a particular protein.
iCLIP enabled the researchers to identify IGF2BP3 binding sites in several hundred RNA transcripts in 2 B-ALL cell lines.
The work also revealed that IGF2BP3 enhanced the expression of MYC and other oncogenes in hematopoietic stem cells.
In experiments with mice, the researchers found that overexpression of IGF2BP3 in the bone marrow leads to proliferation of hematopoietic stem cells and B-cell progenitors, reproducing some features of MLL-rearranged B-ALL.
“Understanding its mechanism of action is important for thinking about therapeutics that might interfere with the action of this protein in disease,” Dr Sanford said.
“One possibility is an RNA-based therapeutic that could sequester the protein and keep it from binding to RNA transcripts. That would be a way to influence the expression of many genes involved in the proliferation of cancer cells.”
Idelalisib trials stopped due to AEs
Photo courtesy of
Gilead Sciences
The US Food and Drug Administration (FDA) has reported that Gilead Sciences, Inc., is stopping 6 clinical trials of idelalisib (Zydelig) due to adverse events (AEs) observed in patients receiving idelalisib in combination with other drugs.
The AEs, which include deaths, were mostly related to infections.
The trials include patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas.
The FDA said it is reviewing the findings of these trials and will communicate new information as necessary.
A few days ago, the European Medicines Agency (EMA) announced its decision to review the safety of idelalisib due to the aforementioned AEs. The EMA said it is reviewing data from 3 idelalisib trials.
While this review is underway, the EMA advised that patients starting or already on treatment with idelalisib be carefully monitored for signs of infection. If the drug is well tolerated, treatment should not be stopped.
The FDA has not made any recommendations about treatment with idelalisib.
About idelalisib
Idelalisib is currently approved by the FDA for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.
Idelalisib also has accelerated approval from the FDA to treat patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies and patients with relapsed small lymphocytic lymphoma who have received at least 2 prior systemic therapies.
In the European Union, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients deemed unsuitable for chemo-immunotherapy.
Idelalisib is also approved in the European Union as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.
Photo courtesy of
Gilead Sciences
The US Food and Drug Administration (FDA) has reported that Gilead Sciences, Inc., is stopping 6 clinical trials of idelalisib (Zydelig) due to adverse events (AEs) observed in patients receiving idelalisib in combination with other drugs.
The AEs, which include deaths, were mostly related to infections.
The trials include patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas.
The FDA said it is reviewing the findings of these trials and will communicate new information as necessary.
A few days ago, the European Medicines Agency (EMA) announced its decision to review the safety of idelalisib due to the aforementioned AEs. The EMA said it is reviewing data from 3 idelalisib trials.
While this review is underway, the EMA advised that patients starting or already on treatment with idelalisib be carefully monitored for signs of infection. If the drug is well tolerated, treatment should not be stopped.
The FDA has not made any recommendations about treatment with idelalisib.
About idelalisib
Idelalisib is currently approved by the FDA for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.
Idelalisib also has accelerated approval from the FDA to treat patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies and patients with relapsed small lymphocytic lymphoma who have received at least 2 prior systemic therapies.
In the European Union, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients deemed unsuitable for chemo-immunotherapy.
Idelalisib is also approved in the European Union as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.
Photo courtesy of
Gilead Sciences
The US Food and Drug Administration (FDA) has reported that Gilead Sciences, Inc., is stopping 6 clinical trials of idelalisib (Zydelig) due to adverse events (AEs) observed in patients receiving idelalisib in combination with other drugs.
The AEs, which include deaths, were mostly related to infections.
The trials include patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, and indolent non-Hodgkin lymphomas.
The FDA said it is reviewing the findings of these trials and will communicate new information as necessary.
A few days ago, the European Medicines Agency (EMA) announced its decision to review the safety of idelalisib due to the aforementioned AEs. The EMA said it is reviewing data from 3 idelalisib trials.
While this review is underway, the EMA advised that patients starting or already on treatment with idelalisib be carefully monitored for signs of infection. If the drug is well tolerated, treatment should not be stopped.
The FDA has not made any recommendations about treatment with idelalisib.
About idelalisib
Idelalisib is currently approved by the FDA for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone.
Idelalisib also has accelerated approval from the FDA to treat patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies and patients with relapsed small lymphocytic lymphoma who have received at least 2 prior systemic therapies.
In the European Union, idelalisib is approved for use in combination with rituximab to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients deemed unsuitable for chemo-immunotherapy.
Idelalisib is also approved in the European Union as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.
Drug granted orphan designation for DLBCL
The US Food and Drug Administration (FDA) has granted orphan designation to the oncology drug candidate PNT2258 for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs intended to treat conditions affecting fewer than 200,000 patients in the US.
The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.
About PNT2258
PNT2258 is designed to target cancers that overexpress BCL2, and BCL2 overexpression is thought to be a key driver of DLBCL.
PNT2258 consists of a single-stranded, 24-base DNAi oligonucleotide known as PNT100 that is encapsulated in lipid nanoparticles (LNPs).
The DNAi technology platform is based on a discovery that single-stranded DNA oligonucleotides can interact with genomic DNA to interfere with oncogenes. PNT100 DNAi is designed to target a genetic regulatory region associated with BCL2.
The LNPs are designed to provide enhanced serum stability and optimized pharmacokinetic properties to facilitate broad systemic distribution after intravenous infusion. Within the acidic environment found in tumors, the LNPs become positively charged and therefore more amenable to cellular uptake and cytoplasmic release of their payloads.
Trials of PNT2258
PNT2258 is being developed by ProNAi Therapeutics, Inc. The company has completed 2 trials of PNT2258 to date—a phase 1 trial of patients with solid tumors and a phase 2 trial of patients with non-Hodgkin lymphoma.
The phase 1 trial enrolled 22 patients with relapsed or refractory solid tumor malignancies. Results were published in Cancer Chemotherapy and Pharmacology in February 2014.
PNT2258 was deemed well-tolerated in this trial. There was no evidence of a systemic immune response to the LNPs or PNT100. There were no significant changes in immune-stimulatory cytokines or clinical signs of anaphylaxis following PNT2258 administration.
The phase 2 trial enrolled 13 patients with relapsed or refractory non-Hodgkin lymphoma. Results were presented at ASH 2014 (abstract 1716).
Six patients responded to PNT2258—4 with complete responses and 2 with partial responses. Five patients had stable disease, and 2 progressed. All 4 of the DLBCL patients in this trial responded—3 with complete responses and 1 with a partial response.
Adverse events reported in this trial include nausea (n=11), pain (n=9), chills (n=7), diarrhea (n=7), vomiting (n=7), fatigue (n=6), fever (n=6), headache (n=6), dyspnea (n=5), generalized aching (n=4), anorexia (n=4), back pain (n=4), sensory neuropathy (n=4), hypophosphatemia (n=4), anemia (n=3), hypokalemia (n=3), hyperuricemia (n=2), neutropenia (n=2), thrombocytopenia (n=4), and elevated AST/ALT (n=1).
ProNAi Therapeutics is now enrolling patients in “Wolverine,” a phase 2 trial evaluating PNT2258 in patients with relapsed or refractory DLBCL, and in “Brighton,” a phase 2 trial evaluating PNT2258 for the treatment of Richter’s transformation.
The US Food and Drug Administration (FDA) has granted orphan designation to the oncology drug candidate PNT2258 for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs intended to treat conditions affecting fewer than 200,000 patients in the US.
The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.
About PNT2258
PNT2258 is designed to target cancers that overexpress BCL2, and BCL2 overexpression is thought to be a key driver of DLBCL.
PNT2258 consists of a single-stranded, 24-base DNAi oligonucleotide known as PNT100 that is encapsulated in lipid nanoparticles (LNPs).
The DNAi technology platform is based on a discovery that single-stranded DNA oligonucleotides can interact with genomic DNA to interfere with oncogenes. PNT100 DNAi is designed to target a genetic regulatory region associated with BCL2.
The LNPs are designed to provide enhanced serum stability and optimized pharmacokinetic properties to facilitate broad systemic distribution after intravenous infusion. Within the acidic environment found in tumors, the LNPs become positively charged and therefore more amenable to cellular uptake and cytoplasmic release of their payloads.
Trials of PNT2258
PNT2258 is being developed by ProNAi Therapeutics, Inc. The company has completed 2 trials of PNT2258 to date—a phase 1 trial of patients with solid tumors and a phase 2 trial of patients with non-Hodgkin lymphoma.
The phase 1 trial enrolled 22 patients with relapsed or refractory solid tumor malignancies. Results were published in Cancer Chemotherapy and Pharmacology in February 2014.
PNT2258 was deemed well-tolerated in this trial. There was no evidence of a systemic immune response to the LNPs or PNT100. There were no significant changes in immune-stimulatory cytokines or clinical signs of anaphylaxis following PNT2258 administration.
The phase 2 trial enrolled 13 patients with relapsed or refractory non-Hodgkin lymphoma. Results were presented at ASH 2014 (abstract 1716).
Six patients responded to PNT2258—4 with complete responses and 2 with partial responses. Five patients had stable disease, and 2 progressed. All 4 of the DLBCL patients in this trial responded—3 with complete responses and 1 with a partial response.
Adverse events reported in this trial include nausea (n=11), pain (n=9), chills (n=7), diarrhea (n=7), vomiting (n=7), fatigue (n=6), fever (n=6), headache (n=6), dyspnea (n=5), generalized aching (n=4), anorexia (n=4), back pain (n=4), sensory neuropathy (n=4), hypophosphatemia (n=4), anemia (n=3), hypokalemia (n=3), hyperuricemia (n=2), neutropenia (n=2), thrombocytopenia (n=4), and elevated AST/ALT (n=1).
ProNAi Therapeutics is now enrolling patients in “Wolverine,” a phase 2 trial evaluating PNT2258 in patients with relapsed or refractory DLBCL, and in “Brighton,” a phase 2 trial evaluating PNT2258 for the treatment of Richter’s transformation.
The US Food and Drug Administration (FDA) has granted orphan designation to the oncology drug candidate PNT2258 for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs intended to treat conditions affecting fewer than 200,000 patients in the US.
The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.
About PNT2258
PNT2258 is designed to target cancers that overexpress BCL2, and BCL2 overexpression is thought to be a key driver of DLBCL.
PNT2258 consists of a single-stranded, 24-base DNAi oligonucleotide known as PNT100 that is encapsulated in lipid nanoparticles (LNPs).
The DNAi technology platform is based on a discovery that single-stranded DNA oligonucleotides can interact with genomic DNA to interfere with oncogenes. PNT100 DNAi is designed to target a genetic regulatory region associated with BCL2.
The LNPs are designed to provide enhanced serum stability and optimized pharmacokinetic properties to facilitate broad systemic distribution after intravenous infusion. Within the acidic environment found in tumors, the LNPs become positively charged and therefore more amenable to cellular uptake and cytoplasmic release of their payloads.
Trials of PNT2258
PNT2258 is being developed by ProNAi Therapeutics, Inc. The company has completed 2 trials of PNT2258 to date—a phase 1 trial of patients with solid tumors and a phase 2 trial of patients with non-Hodgkin lymphoma.
The phase 1 trial enrolled 22 patients with relapsed or refractory solid tumor malignancies. Results were published in Cancer Chemotherapy and Pharmacology in February 2014.
PNT2258 was deemed well-tolerated in this trial. There was no evidence of a systemic immune response to the LNPs or PNT100. There were no significant changes in immune-stimulatory cytokines or clinical signs of anaphylaxis following PNT2258 administration.
The phase 2 trial enrolled 13 patients with relapsed or refractory non-Hodgkin lymphoma. Results were presented at ASH 2014 (abstract 1716).
Six patients responded to PNT2258—4 with complete responses and 2 with partial responses. Five patients had stable disease, and 2 progressed. All 4 of the DLBCL patients in this trial responded—3 with complete responses and 1 with a partial response.
Adverse events reported in this trial include nausea (n=11), pain (n=9), chills (n=7), diarrhea (n=7), vomiting (n=7), fatigue (n=6), fever (n=6), headache (n=6), dyspnea (n=5), generalized aching (n=4), anorexia (n=4), back pain (n=4), sensory neuropathy (n=4), hypophosphatemia (n=4), anemia (n=3), hypokalemia (n=3), hyperuricemia (n=2), neutropenia (n=2), thrombocytopenia (n=4), and elevated AST/ALT (n=1).
ProNAi Therapeutics is now enrolling patients in “Wolverine,” a phase 2 trial evaluating PNT2258 in patients with relapsed or refractory DLBCL, and in “Brighton,” a phase 2 trial evaluating PNT2258 for the treatment of Richter’s transformation.
Intervention helps parents cope with kids’ HSCT
Photo by Chad McNeeley
A new social-cognitive intervention can reduce stress in parents of children undergoing hematopoietic stem cell transplant (HSCT), according to research published in the Journal of Consulting and Clinical Psychology.
In the short-term, the parent social-cognitive intervention program (P-SCIP) appeared more effective than the current best-practice psychosocial care (BPC) for reducing anxiety, depression, and traumatic distress.
However, there was not much difference between P-SCIP and BPC when it came to long-term results.
Certain subgroups of parents seemed to derive more benefit from P-SCIP than other parents.
“[P]revious research from our team and others has shown that between 20% and 66% of caregivers have elevated depression and/or anxiety prior to their child’s transplant procedure,” said study author Sharon Manne, PhD, of the Rutgers Cancer Institute of New Jersey in New Brunswick.
“It was our aim in this study to develop and test an individual intervention program that targets cognitive and social processing strategies associated with caregiver adjustment and compare that to available best-practice psychosocial care.”
Interventions
This study included 218 biological or foster parents of HSCT recipients under age 19. The parents were assigned to receive P-SCIP or BPC.
P-SCIP required parents to view an interactive CD-ROM for five 60-minute sessions over a 2- to 3-week period following the child’s transplant.
The CD-ROM addressed parents’ worries about their child, coping with solvable concerns related to HSCT, coping with unchangeable problems related to HSCT, and communication and the importance of expressing feelings and needs.
Parents receiving BPC viewed a 1-hour video guide to pediatric HSCT and received a pamphlet covering common caregiver issues. The parents were also given the option of having someone watch their child for up to 5 hours and the use of walkie-talkies so the parents could communicate with their child when they were not in the room.
All participants were asked to complete an in-person survey within a month’s time of their child receiving the transplant and to complete follow-up surveys by phone or mail at 1 month, 6 months, and 1 year post-HSCT.
One hundred and ten parents were randomized to P-SCIP and 108 to BPC. Sixty-six parents completed P-SCIP through the last follow-up, as did 72 parents assigned to BPC.
Results
The researchers found that P-SCIP could reduce anxiety, depression, and—to a marginal degree—traumatic distress more than BPC.
However, the beneficial effects of P-SCIP relative to BPC were only seen at the first follow-up. The overall psychological benefits of P-SCIP were no longer evident at the 6-month or 1-year follow ups.
Still, anxiety, depression, and traumatic distress declined among all the parents over the 1-year follow-up period, which is consistent with other research on caregiver distress after pediatric HSCT.
“Our study suggests that our intervention had an impact when primary caregivers were experiencing high levels of trauma and stress—during the time of the actual transplant and hospitalization—and that the intervention was more beneficial for specific subgroups of caregivers,” Dr Manne said.
P-SCIP had a stronger effect than BPC among parents who began the study reporting higher depression and anxiety and among parents whose children developed graft-versus-host disease.
Similarly, P-SCIP had long-term effects on traumatic distress among parents who reported higher anxiety pre-HSCT and among parents whose children had graft-versus-host disease at HSCT discharge.
“Our findings suggest that screening caregivers for elevations in anxiety and targeting interventions specifically to them may prove beneficial,” Dr Manne said.
She added that a next step for this research might be to examine possible differences between mothers and fathers in the caregiver role, as most of the primary caregivers in this study were mothers.
Additionally, if this intervention is carried into the clinical setting, methods of improving intervention attendance might be considered. Utilizing phone or web-based contact that would allow the parent to remain in the room with the child during hospitalization might help the caregivers more easily access the intervention.
Photo by Chad McNeeley
A new social-cognitive intervention can reduce stress in parents of children undergoing hematopoietic stem cell transplant (HSCT), according to research published in the Journal of Consulting and Clinical Psychology.
In the short-term, the parent social-cognitive intervention program (P-SCIP) appeared more effective than the current best-practice psychosocial care (BPC) for reducing anxiety, depression, and traumatic distress.
However, there was not much difference between P-SCIP and BPC when it came to long-term results.
Certain subgroups of parents seemed to derive more benefit from P-SCIP than other parents.
“[P]revious research from our team and others has shown that between 20% and 66% of caregivers have elevated depression and/or anxiety prior to their child’s transplant procedure,” said study author Sharon Manne, PhD, of the Rutgers Cancer Institute of New Jersey in New Brunswick.
“It was our aim in this study to develop and test an individual intervention program that targets cognitive and social processing strategies associated with caregiver adjustment and compare that to available best-practice psychosocial care.”
Interventions
This study included 218 biological or foster parents of HSCT recipients under age 19. The parents were assigned to receive P-SCIP or BPC.
P-SCIP required parents to view an interactive CD-ROM for five 60-minute sessions over a 2- to 3-week period following the child’s transplant.
The CD-ROM addressed parents’ worries about their child, coping with solvable concerns related to HSCT, coping with unchangeable problems related to HSCT, and communication and the importance of expressing feelings and needs.
Parents receiving BPC viewed a 1-hour video guide to pediatric HSCT and received a pamphlet covering common caregiver issues. The parents were also given the option of having someone watch their child for up to 5 hours and the use of walkie-talkies so the parents could communicate with their child when they were not in the room.
All participants were asked to complete an in-person survey within a month’s time of their child receiving the transplant and to complete follow-up surveys by phone or mail at 1 month, 6 months, and 1 year post-HSCT.
One hundred and ten parents were randomized to P-SCIP and 108 to BPC. Sixty-six parents completed P-SCIP through the last follow-up, as did 72 parents assigned to BPC.
Results
The researchers found that P-SCIP could reduce anxiety, depression, and—to a marginal degree—traumatic distress more than BPC.
However, the beneficial effects of P-SCIP relative to BPC were only seen at the first follow-up. The overall psychological benefits of P-SCIP were no longer evident at the 6-month or 1-year follow ups.
Still, anxiety, depression, and traumatic distress declined among all the parents over the 1-year follow-up period, which is consistent with other research on caregiver distress after pediatric HSCT.
“Our study suggests that our intervention had an impact when primary caregivers were experiencing high levels of trauma and stress—during the time of the actual transplant and hospitalization—and that the intervention was more beneficial for specific subgroups of caregivers,” Dr Manne said.
P-SCIP had a stronger effect than BPC among parents who began the study reporting higher depression and anxiety and among parents whose children developed graft-versus-host disease.
Similarly, P-SCIP had long-term effects on traumatic distress among parents who reported higher anxiety pre-HSCT and among parents whose children had graft-versus-host disease at HSCT discharge.
“Our findings suggest that screening caregivers for elevations in anxiety and targeting interventions specifically to them may prove beneficial,” Dr Manne said.
She added that a next step for this research might be to examine possible differences between mothers and fathers in the caregiver role, as most of the primary caregivers in this study were mothers.
Additionally, if this intervention is carried into the clinical setting, methods of improving intervention attendance might be considered. Utilizing phone or web-based contact that would allow the parent to remain in the room with the child during hospitalization might help the caregivers more easily access the intervention.
Photo by Chad McNeeley
A new social-cognitive intervention can reduce stress in parents of children undergoing hematopoietic stem cell transplant (HSCT), according to research published in the Journal of Consulting and Clinical Psychology.
In the short-term, the parent social-cognitive intervention program (P-SCIP) appeared more effective than the current best-practice psychosocial care (BPC) for reducing anxiety, depression, and traumatic distress.
However, there was not much difference between P-SCIP and BPC when it came to long-term results.
Certain subgroups of parents seemed to derive more benefit from P-SCIP than other parents.
“[P]revious research from our team and others has shown that between 20% and 66% of caregivers have elevated depression and/or anxiety prior to their child’s transplant procedure,” said study author Sharon Manne, PhD, of the Rutgers Cancer Institute of New Jersey in New Brunswick.
“It was our aim in this study to develop and test an individual intervention program that targets cognitive and social processing strategies associated with caregiver adjustment and compare that to available best-practice psychosocial care.”
Interventions
This study included 218 biological or foster parents of HSCT recipients under age 19. The parents were assigned to receive P-SCIP or BPC.
P-SCIP required parents to view an interactive CD-ROM for five 60-minute sessions over a 2- to 3-week period following the child’s transplant.
The CD-ROM addressed parents’ worries about their child, coping with solvable concerns related to HSCT, coping with unchangeable problems related to HSCT, and communication and the importance of expressing feelings and needs.
Parents receiving BPC viewed a 1-hour video guide to pediatric HSCT and received a pamphlet covering common caregiver issues. The parents were also given the option of having someone watch their child for up to 5 hours and the use of walkie-talkies so the parents could communicate with their child when they were not in the room.
All participants were asked to complete an in-person survey within a month’s time of their child receiving the transplant and to complete follow-up surveys by phone or mail at 1 month, 6 months, and 1 year post-HSCT.
One hundred and ten parents were randomized to P-SCIP and 108 to BPC. Sixty-six parents completed P-SCIP through the last follow-up, as did 72 parents assigned to BPC.
Results
The researchers found that P-SCIP could reduce anxiety, depression, and—to a marginal degree—traumatic distress more than BPC.
However, the beneficial effects of P-SCIP relative to BPC were only seen at the first follow-up. The overall psychological benefits of P-SCIP were no longer evident at the 6-month or 1-year follow ups.
Still, anxiety, depression, and traumatic distress declined among all the parents over the 1-year follow-up period, which is consistent with other research on caregiver distress after pediatric HSCT.
“Our study suggests that our intervention had an impact when primary caregivers were experiencing high levels of trauma and stress—during the time of the actual transplant and hospitalization—and that the intervention was more beneficial for specific subgroups of caregivers,” Dr Manne said.
P-SCIP had a stronger effect than BPC among parents who began the study reporting higher depression and anxiety and among parents whose children developed graft-versus-host disease.
Similarly, P-SCIP had long-term effects on traumatic distress among parents who reported higher anxiety pre-HSCT and among parents whose children had graft-versus-host disease at HSCT discharge.
“Our findings suggest that screening caregivers for elevations in anxiety and targeting interventions specifically to them may prove beneficial,” Dr Manne said.
She added that a next step for this research might be to examine possible differences between mothers and fathers in the caregiver role, as most of the primary caregivers in this study were mothers.
Additionally, if this intervention is carried into the clinical setting, methods of improving intervention attendance might be considered. Utilizing phone or web-based contact that would allow the parent to remain in the room with the child during hospitalization might help the caregivers more easily access the intervention.