Transplantation

Bone marrow harvest

Photo by Chad McNeeley

Patients receiving hematopoietic stem cell transplants from unrelated donors have better quality of life if they receive cells derived from bone marrow (BM) rather than peripheral blood (PB), according to a large study.

Recipients of BM transplants reported better psychological well-being, had fewer symptoms of graft-versus-host disease (GVHD), and were more likely to be back at work 5 years after their transplant.

However, there was no significant difference in overall survival, treatment-related death, or relapse between patients who received BM grafts and those who received PB transplants.

Stephanie Lee, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and her colleagues reported these results in JAMA Oncology.

“We’re hoping that, once we provide information about long-term quality of life and recovery, patients and their doctors can take this into account when they’re planning their transplants,” Dr Lee said.

She noted, however, that the results would only be applicable to transplant patients who are similar to those enrolled in this study.

The study included 551 patients, ages 16 to 66, who were receiving transplants from unrelated donors to treat hematologic neoplasms. The patients were randomly assigned to receive PB or BM grafts.

From 6 months to 5 years after transplant, researchers called the patients periodically to assess how they were doing.

At the 5-year mark, 102 BM recipients and 93 PB recipients were still alive and eligible for assessment.

At a median follow-up of 73 months (range, 30-121 months), there was no significant difference in survival rate, relapse incidence, or treatment-related mortality between BM and PB recipients.

The survival rate was 40% for BM recipients and 39% for PB recipients (P=0.84). The relapse rates were 32% and 29%, respectively (P=0.47). And the treatment-related mortality rates were 29% and 32%, respectively (P=0.44).

However, BM recipients were more likely to report better psychological well-being, earning higher Mental Health Inventory Psychological Well-Being scores than PB recipients. The mean scores were 78.9 and 72.2, respectively (P=0.01).

In addition, BM recipients had fewer symptoms of GVHD, earning lower Lee Chronic GVHD symptom scores than PB recipients. The mean scores were 13.1 and 19.3, respectively (P=0.004).

The researchers suspected, but could not confirm, that BM recipients had better psychological well-being because they experienced fewer self-reported symptoms of chronic GVHD.

The researchers also found that BM recipients were more likely than PB recipients to be working full-time or part-time 5 years after transplant. When the team adjusted for work status before transplant, the odds ratio was 1.5 (P=0.002).

“Results of this study set bone marrow as the standard source of stem cells for transplantation from unrelated donors,” said study author Claudio Anasetti, MD, of Moffitt Cancer Center in Tampa, Florida.

“When both your disease and the recommended treatment are life-threatening, I don’t think people are necessarily asking, ‘Which treatment is going to give me better quality of life years from now?’” Dr Lee added.

“Yet, if you’re going to make it through, as many patients do, you want to do it with good quality of life. That’s the whole point of having the transplant. It’s not just to cure your disease but also to try to get back to as normal a lifestyle as you can.”

Bone marrow harvest

Photo by Chad McNeeley

Patients receiving hematopoietic stem cell transplants from unrelated donors have better quality of life if they receive cells derived from bone marrow (BM) rather than peripheral blood (PB), according to a large study.

Recipients of BM transplants reported better psychological well-being, had fewer symptoms of graft-versus-host disease (GVHD), and were more likely to be back at work 5 years after their transplant.

However, there was no significant difference in overall survival, treatment-related death, or relapse between patients who received BM grafts and those who received PB transplants.

Stephanie Lee, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and her colleagues reported these results in JAMA Oncology.

“We’re hoping that, once we provide information about long-term quality of life and recovery, patients and their doctors can take this into account when they’re planning their transplants,” Dr Lee said.

She noted, however, that the results would only be applicable to transplant patients who are similar to those enrolled in this study.

The study included 551 patients, ages 16 to 66, who were receiving transplants from unrelated donors to treat hematologic neoplasms. The patients were randomly assigned to receive PB or BM grafts.

From 6 months to 5 years after transplant, researchers called the patients periodically to assess how they were doing.

At the 5-year mark, 102 BM recipients and 93 PB recipients were still alive and eligible for assessment.

At a median follow-up of 73 months (range, 30-121 months), there was no significant difference in survival rate, relapse incidence, or treatment-related mortality between BM and PB recipients.

The survival rate was 40% for BM recipients and 39% for PB recipients (P=0.84). The relapse rates were 32% and 29%, respectively (P=0.47). And the treatment-related mortality rates were 29% and 32%, respectively (P=0.44).

However, BM recipients were more likely to report better psychological well-being, earning higher Mental Health Inventory Psychological Well-Being scores than PB recipients. The mean scores were 78.9 and 72.2, respectively (P=0.01).

In addition, BM recipients had fewer symptoms of GVHD, earning lower Lee Chronic GVHD symptom scores than PB recipients. The mean scores were 13.1 and 19.3, respectively (P=0.004).

The researchers suspected, but could not confirm, that BM recipients had better psychological well-being because they experienced fewer self-reported symptoms of chronic GVHD.

The researchers also found that BM recipients were more likely than PB recipients to be working full-time or part-time 5 years after transplant. When the team adjusted for work status before transplant, the odds ratio was 1.5 (P=0.002).

“Results of this study set bone marrow as the standard source of stem cells for transplantation from unrelated donors,” said study author Claudio Anasetti, MD, of Moffitt Cancer Center in Tampa, Florida.

“When both your disease and the recommended treatment are life-threatening, I don’t think people are necessarily asking, ‘Which treatment is going to give me better quality of life years from now?’” Dr Lee added.

“Yet, if you’re going to make it through, as many patients do, you want to do it with good quality of life. That’s the whole point of having the transplant. It’s not just to cure your disease but also to try to get back to as normal a lifestyle as you can.”

Bone marrow harvest

Photo by Chad McNeeley

Patients receiving hematopoietic stem cell transplants from unrelated donors have better quality of life if they receive cells derived from bone marrow (BM) rather than peripheral blood (PB), according to a large study.

Recipients of BM transplants reported better psychological well-being, had fewer symptoms of graft-versus-host disease (GVHD), and were more likely to be back at work 5 years after their transplant.

However, there was no significant difference in overall survival, treatment-related death, or relapse between patients who received BM grafts and those who received PB transplants.

Stephanie Lee, MD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and her colleagues reported these results in JAMA Oncology.

“We’re hoping that, once we provide information about long-term quality of life and recovery, patients and their doctors can take this into account when they’re planning their transplants,” Dr Lee said.

She noted, however, that the results would only be applicable to transplant patients who are similar to those enrolled in this study.

The study included 551 patients, ages 16 to 66, who were receiving transplants from unrelated donors to treat hematologic neoplasms. The patients were randomly assigned to receive PB or BM grafts.

From 6 months to 5 years after transplant, researchers called the patients periodically to assess how they were doing.

At the 5-year mark, 102 BM recipients and 93 PB recipients were still alive and eligible for assessment.

At a median follow-up of 73 months (range, 30-121 months), there was no significant difference in survival rate, relapse incidence, or treatment-related mortality between BM and PB recipients.

The survival rate was 40% for BM recipients and 39% for PB recipients (P=0.84). The relapse rates were 32% and 29%, respectively (P=0.47). And the treatment-related mortality rates were 29% and 32%, respectively (P=0.44).

However, BM recipients were more likely to report better psychological well-being, earning higher Mental Health Inventory Psychological Well-Being scores than PB recipients. The mean scores were 78.9 and 72.2, respectively (P=0.01).

In addition, BM recipients had fewer symptoms of GVHD, earning lower Lee Chronic GVHD symptom scores than PB recipients. The mean scores were 13.1 and 19.3, respectively (P=0.004).

The researchers suspected, but could not confirm, that BM recipients had better psychological well-being because they experienced fewer self-reported symptoms of chronic GVHD.

The researchers also found that BM recipients were more likely than PB recipients to be working full-time or part-time 5 years after transplant. When the team adjusted for work status before transplant, the odds ratio was 1.5 (P=0.002).

“Results of this study set bone marrow as the standard source of stem cells for transplantation from unrelated donors,” said study author Claudio Anasetti, MD, of Moffitt Cancer Center in Tampa, Florida.

“When both your disease and the recommended treatment are life-threatening, I don’t think people are necessarily asking, ‘Which treatment is going to give me better quality of life years from now?’” Dr Lee added.

“Yet, if you’re going to make it through, as many patients do, you want to do it with good quality of life. That’s the whole point of having the transplant. It’s not just to cure your disease but also to try to get back to as normal a lifestyle as you can.”

HSCT preparation

Photo by Chad McNeeley

Results of a large, retrospective study suggest that receiving mogamulizumab before allogeneic hematopoietic stem cell transplant (allo-HSCT) can worsen outcomes in patients with adult T-cell leukemia/lymphoma (ATLL).

Patients who received mogamulizumab had a higher risk of grade 3/4 acute graft-versus-host disease (GVHD), a higher incidence of nonrelapse mortality, and worse overall survival than patients who did not take the drug.

Researchers reported these findings in the Journal of Clinical Oncology.

Previous research suggested that pre-HSCT mogamulizumab can produce adverse effects, but these studies had small patient numbers. Researchers have suggested the adverse effects may occur because mogamulizumab depletes regulatory T cells for several months, but there has been no direct evidence supporting this idea.

To investigate the issue, Shigeo Fuji, MD, of National Cancer Center Hospital in Tokyo, Japan, and colleagues assessed the impact of pre-HSCT mogamulizumab in a large group of ATLL patients undergoing allo-HSCT.

The study included 996 patients age 70 and younger. Patients had aggressive ATLL diagnosed between 2000 and 2013. They received intensive chemotherapy as first-line treatment.

Eighty-two of the patients received mogamulizumab before HSCT, with a median of 45 days from the last mogamulizumab treatment to allo-HSCT.

Pre-HSCT mogamulizumab was associated with an increased risk of grade 3/4 acute GVHD, with a relative risk of 1.80 (P<0.01).

Patients who received mogamulizumab were also more likely to be refractory to the systemic corticosteroids given to treat acute GVHD, with a relative risk of 2.09 (P<0.01).

The 1-year cumulative incidence of nonrelapse mortality was significantly higher among patients who received mogamulizumab than among those who did not—43.7% and 25.1%, respectively (P<0.01).

And the probability of 1-year overall survival was significantly lower in patients who received mogamulizumab than in those who did not—32.3% and 49.4%, respectively (P<0.01).

The researchers noted that outcomes were particularly poor when patients received mogamulizumab within less than 50 days of allo-HSCT.

The team said this study appears to confirm that pre-HSCT mogamulizumab significantly worsens clinical outcomes, mainly because of an increased risk of severe/corticosteroid-refractory acute GVHD. And the results support the idea that the drug depletes regulatory T cells.

The researchers concluded that mogamulizumab should be used with caution in ATLL patients who are eligible for allo-HSCT. And the possibility of intensifying GVHD prophylaxis in patients who do receive pre-HSCT mogamulizumab should be explored.

HSCT preparation

Photo by Chad McNeeley

Results of a large, retrospective study suggest that receiving mogamulizumab before allogeneic hematopoietic stem cell transplant (allo-HSCT) can worsen outcomes in patients with adult T-cell leukemia/lymphoma (ATLL).

Patients who received mogamulizumab had a higher risk of grade 3/4 acute graft-versus-host disease (GVHD), a higher incidence of nonrelapse mortality, and worse overall survival than patients who did not take the drug.

Researchers reported these findings in the Journal of Clinical Oncology.

Previous research suggested that pre-HSCT mogamulizumab can produce adverse effects, but these studies had small patient numbers. Researchers have suggested the adverse effects may occur because mogamulizumab depletes regulatory T cells for several months, but there has been no direct evidence supporting this idea.

To investigate the issue, Shigeo Fuji, MD, of National Cancer Center Hospital in Tokyo, Japan, and colleagues assessed the impact of pre-HSCT mogamulizumab in a large group of ATLL patients undergoing allo-HSCT.

The study included 996 patients age 70 and younger. Patients had aggressive ATLL diagnosed between 2000 and 2013. They received intensive chemotherapy as first-line treatment.

Eighty-two of the patients received mogamulizumab before HSCT, with a median of 45 days from the last mogamulizumab treatment to allo-HSCT.

Pre-HSCT mogamulizumab was associated with an increased risk of grade 3/4 acute GVHD, with a relative risk of 1.80 (P<0.01).

Patients who received mogamulizumab were also more likely to be refractory to the systemic corticosteroids given to treat acute GVHD, with a relative risk of 2.09 (P<0.01).

The 1-year cumulative incidence of nonrelapse mortality was significantly higher among patients who received mogamulizumab than among those who did not—43.7% and 25.1%, respectively (P<0.01).

And the probability of 1-year overall survival was significantly lower in patients who received mogamulizumab than in those who did not—32.3% and 49.4%, respectively (P<0.01).

The researchers noted that outcomes were particularly poor when patients received mogamulizumab within less than 50 days of allo-HSCT.

The team said this study appears to confirm that pre-HSCT mogamulizumab significantly worsens clinical outcomes, mainly because of an increased risk of severe/corticosteroid-refractory acute GVHD. And the results support the idea that the drug depletes regulatory T cells.

The researchers concluded that mogamulizumab should be used with caution in ATLL patients who are eligible for allo-HSCT. And the possibility of intensifying GVHD prophylaxis in patients who do receive pre-HSCT mogamulizumab should be explored.

HSCT preparation

Photo by Chad McNeeley

Results of a large, retrospective study suggest that receiving mogamulizumab before allogeneic hematopoietic stem cell transplant (allo-HSCT) can worsen outcomes in patients with adult T-cell leukemia/lymphoma (ATLL).

Patients who received mogamulizumab had a higher risk of grade 3/4 acute graft-versus-host disease (GVHD), a higher incidence of nonrelapse mortality, and worse overall survival than patients who did not take the drug.

Researchers reported these findings in the Journal of Clinical Oncology.

Previous research suggested that pre-HSCT mogamulizumab can produce adverse effects, but these studies had small patient numbers. Researchers have suggested the adverse effects may occur because mogamulizumab depletes regulatory T cells for several months, but there has been no direct evidence supporting this idea.

To investigate the issue, Shigeo Fuji, MD, of National Cancer Center Hospital in Tokyo, Japan, and colleagues assessed the impact of pre-HSCT mogamulizumab in a large group of ATLL patients undergoing allo-HSCT.

The study included 996 patients age 70 and younger. Patients had aggressive ATLL diagnosed between 2000 and 2013. They received intensive chemotherapy as first-line treatment.

Eighty-two of the patients received mogamulizumab before HSCT, with a median of 45 days from the last mogamulizumab treatment to allo-HSCT.

Pre-HSCT mogamulizumab was associated with an increased risk of grade 3/4 acute GVHD, with a relative risk of 1.80 (P<0.01).

Patients who received mogamulizumab were also more likely to be refractory to the systemic corticosteroids given to treat acute GVHD, with a relative risk of 2.09 (P<0.01).

The 1-year cumulative incidence of nonrelapse mortality was significantly higher among patients who received mogamulizumab than among those who did not—43.7% and 25.1%, respectively (P<0.01).

And the probability of 1-year overall survival was significantly lower in patients who received mogamulizumab than in those who did not—32.3% and 49.4%, respectively (P<0.01).

The researchers noted that outcomes were particularly poor when patients received mogamulizumab within less than 50 days of allo-HSCT.

The team said this study appears to confirm that pre-HSCT mogamulizumab significantly worsens clinical outcomes, mainly because of an increased risk of severe/corticosteroid-refractory acute GVHD. And the results support the idea that the drug depletes regulatory T cells.

The researchers concluded that mogamulizumab should be used with caution in ATLL patients who are eligible for allo-HSCT. And the possibility of intensifying GVHD prophylaxis in patients who do receive pre-HSCT mogamulizumab should be explored.

Lab mouse

Photo by Aaron Logan

A treatment strategy that increases the production of regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) in mice, according to research published in The Journal of Experimental Medicine.

One way to prevent GVHD after allogeneic hematopoietic stem cell transplant (allo-HSCT) is to co-transplant large numbers of Tregs, which can suppress the donor cells’ effects on healthy tissue without affecting their ability to kill tumor cells.

This approach is challenging, however, because the Tregs must first be isolated from the donor’s peripheral blood or bone marrow and then cultivated in the lab to produce sufficient numbers for transplant.

Andreas Beilhack, MD, of University Hospital Würzburg in Germany, and his colleagues have found a way to overcome this obstacle, at least in mice.

The team developed a protein agonist called STAR2, which selectively activates TNFR2. The researchers noted that TNF and its receptors, TNFR1 and TNFR2, have been shown to play a crucial role in both GVHD and the graft-versus-leukemia effect.

With their experiments, Dr Beilhack and his colleagues showed that STAR2 binds to TNFR2, activating a signaling pathway that increases the number of natural Tregs in vitro and in vivo.

The team also tested STAR2 in mice with lymphoma. Pretreating the mice with STAR2 protected them from developing GVHD after allo-HSCT. And the donor-derived cells retained their ability to kill lymphoma cells.

In addition, the researchers found that a slightly modified version of STAR2 has a similar effect on human Tregs, which suggests this approach could also prevent GVHD in humans undergoing allo-HSCT.

“Furthermore, this strategy may be beneficial for other pathological settings in which elevated numbers of regulatory T cells are desirable, such as autoimmune diseases and solid organ transplantation,” Dr Beilhack said.

Lab mouse

Photo by Aaron Logan

A treatment strategy that increases the production of regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) in mice, according to research published in The Journal of Experimental Medicine.

One way to prevent GVHD after allogeneic hematopoietic stem cell transplant (allo-HSCT) is to co-transplant large numbers of Tregs, which can suppress the donor cells’ effects on healthy tissue without affecting their ability to kill tumor cells.

This approach is challenging, however, because the Tregs must first be isolated from the donor’s peripheral blood or bone marrow and then cultivated in the lab to produce sufficient numbers for transplant.

Andreas Beilhack, MD, of University Hospital Würzburg in Germany, and his colleagues have found a way to overcome this obstacle, at least in mice.

The team developed a protein agonist called STAR2, which selectively activates TNFR2. The researchers noted that TNF and its receptors, TNFR1 and TNFR2, have been shown to play a crucial role in both GVHD and the graft-versus-leukemia effect.

With their experiments, Dr Beilhack and his colleagues showed that STAR2 binds to TNFR2, activating a signaling pathway that increases the number of natural Tregs in vitro and in vivo.

The team also tested STAR2 in mice with lymphoma. Pretreating the mice with STAR2 protected them from developing GVHD after allo-HSCT. And the donor-derived cells retained their ability to kill lymphoma cells.

In addition, the researchers found that a slightly modified version of STAR2 has a similar effect on human Tregs, which suggests this approach could also prevent GVHD in humans undergoing allo-HSCT.

“Furthermore, this strategy may be beneficial for other pathological settings in which elevated numbers of regulatory T cells are desirable, such as autoimmune diseases and solid organ transplantation,” Dr Beilhack said.

Lab mouse

Photo by Aaron Logan

A treatment strategy that increases the production of regulatory T cells (Tregs) can prevent graft-versus-host disease (GVHD) in mice, according to research published in The Journal of Experimental Medicine.

One way to prevent GVHD after allogeneic hematopoietic stem cell transplant (allo-HSCT) is to co-transplant large numbers of Tregs, which can suppress the donor cells’ effects on healthy tissue without affecting their ability to kill tumor cells.

This approach is challenging, however, because the Tregs must first be isolated from the donor’s peripheral blood or bone marrow and then cultivated in the lab to produce sufficient numbers for transplant.

Andreas Beilhack, MD, of University Hospital Würzburg in Germany, and his colleagues have found a way to overcome this obstacle, at least in mice.

The team developed a protein agonist called STAR2, which selectively activates TNFR2. The researchers noted that TNF and its receptors, TNFR1 and TNFR2, have been shown to play a crucial role in both GVHD and the graft-versus-leukemia effect.

With their experiments, Dr Beilhack and his colleagues showed that STAR2 binds to TNFR2, activating a signaling pathway that increases the number of natural Tregs in vitro and in vivo.

The team also tested STAR2 in mice with lymphoma. Pretreating the mice with STAR2 protected them from developing GVHD after allo-HSCT. And the donor-derived cells retained their ability to kill lymphoma cells.

In addition, the researchers found that a slightly modified version of STAR2 has a similar effect on human Tregs, which suggests this approach could also prevent GVHD in humans undergoing allo-HSCT.

“Furthermore, this strategy may be beneficial for other pathological settings in which elevated numbers of regulatory T cells are desirable, such as autoimmune diseases and solid organ transplantation,” Dr Beilhack said.

HSCT preparation

Photo by Chad McNeeley

The protein angiogenin (ANG) plays a significant role in the regulation of hematopoiesis, according to a group of researchers.

The team discovered that ANG suppresses the proliferation of hematopoietic stem and progenitor cells (HSPCs) while promoting the proliferation of myeloid progenitor cells.

They also showed that treatment with recombinant ANG protein improved survival in irradiated mice and enhanced the regenerative capabilities of HSPCs.

The researchers believe these findings have significant implications for hematopoietic stem cell transplant (HSCT) and bone marrow injury.

The team reported the findings in Cell.

“We knew that ANG was involved in promoting cell growth, so it was not unexpected to find that ANG stimulates proliferation of myeloid progenitor cells,” said study author Guo-fu Hu, PhD, of Tufts Medical Center in Boston, Massachusetts.

“But it was surprising to find that ANG also suppresses growth of stem cells and that it accomplishes these divergent promotion or suppression functions through RNA processing events specific to individual cell types.”

The researchers discovered that, in HSPCs, ANG induces processing of tiRNA, which suppresses global protein synthesis. And in myeloid progenitor cells, ANG induces processing of rRNA, which enhances protein synthesis.

The team also tested ANG’s ability to prevent and mitigate radiation-induced bone marrow failure. They found that treating mice with recombinant ANG protein, either before or after lethal irradiation, increased survival, improved bone marrow cellularity, and enhanced peripheral blood content.

Finally, the researchers assessed the effects of ANG in the context of HSCT in mice. They found that treating mouse long-term HSCs with ANG ex vivo resulted in a “dramatic” increase in multi-lineage reconstitution over 24 weeks after HSCT.

Upon secondary transplant, enhanced regeneration occurred over 16 weeks, and mice had elevated peripheral blood counts at 1 year post-HSCT, without any signs of leukemia.

The researchers observed similar results in experiments with human cells. They transplanted CD34+ cord blood cells—cultured in the presence or absence of ANG—into mice. Treatment with ANG resulted in enhanced multi-lineage regeneration and enhanced reconstitution upon secondary transplant.

“Proper blood cell production is dependent on functioning hematopoietic stem and progenitor cells that are destroyed during conditioning procedures for transplantation or following bone marrow injury,” said study author Kevin A. Goncalves, of Tufts Medical Center.

“Our study demonstrates that ANG regulates critical functions of both clinically relevant cell types.”

HSCT preparation

Photo by Chad McNeeley

The protein angiogenin (ANG) plays a significant role in the regulation of hematopoiesis, according to a group of researchers.

The team discovered that ANG suppresses the proliferation of hematopoietic stem and progenitor cells (HSPCs) while promoting the proliferation of myeloid progenitor cells.

They also showed that treatment with recombinant ANG protein improved survival in irradiated mice and enhanced the regenerative capabilities of HSPCs.

The researchers believe these findings have significant implications for hematopoietic stem cell transplant (HSCT) and bone marrow injury.

The team reported the findings in Cell.

“We knew that ANG was involved in promoting cell growth, so it was not unexpected to find that ANG stimulates proliferation of myeloid progenitor cells,” said study author Guo-fu Hu, PhD, of Tufts Medical Center in Boston, Massachusetts.

“But it was surprising to find that ANG also suppresses growth of stem cells and that it accomplishes these divergent promotion or suppression functions through RNA processing events specific to individual cell types.”

The researchers discovered that, in HSPCs, ANG induces processing of tiRNA, which suppresses global protein synthesis. And in myeloid progenitor cells, ANG induces processing of rRNA, which enhances protein synthesis.

The team also tested ANG’s ability to prevent and mitigate radiation-induced bone marrow failure. They found that treating mice with recombinant ANG protein, either before or after lethal irradiation, increased survival, improved bone marrow cellularity, and enhanced peripheral blood content.

Finally, the researchers assessed the effects of ANG in the context of HSCT in mice. They found that treating mouse long-term HSCs with ANG ex vivo resulted in a “dramatic” increase in multi-lineage reconstitution over 24 weeks after HSCT.

Upon secondary transplant, enhanced regeneration occurred over 16 weeks, and mice had elevated peripheral blood counts at 1 year post-HSCT, without any signs of leukemia.

The researchers observed similar results in experiments with human cells. They transplanted CD34+ cord blood cells—cultured in the presence or absence of ANG—into mice. Treatment with ANG resulted in enhanced multi-lineage regeneration and enhanced reconstitution upon secondary transplant.

“Proper blood cell production is dependent on functioning hematopoietic stem and progenitor cells that are destroyed during conditioning procedures for transplantation or following bone marrow injury,” said study author Kevin A. Goncalves, of Tufts Medical Center.

“Our study demonstrates that ANG regulates critical functions of both clinically relevant cell types.”

HSCT preparation

Photo by Chad McNeeley

The protein angiogenin (ANG) plays a significant role in the regulation of hematopoiesis, according to a group of researchers.

The team discovered that ANG suppresses the proliferation of hematopoietic stem and progenitor cells (HSPCs) while promoting the proliferation of myeloid progenitor cells.

They also showed that treatment with recombinant ANG protein improved survival in irradiated mice and enhanced the regenerative capabilities of HSPCs.

The researchers believe these findings have significant implications for hematopoietic stem cell transplant (HSCT) and bone marrow injury.

The team reported the findings in Cell.

“We knew that ANG was involved in promoting cell growth, so it was not unexpected to find that ANG stimulates proliferation of myeloid progenitor cells,” said study author Guo-fu Hu, PhD, of Tufts Medical Center in Boston, Massachusetts.

“But it was surprising to find that ANG also suppresses growth of stem cells and that it accomplishes these divergent promotion or suppression functions through RNA processing events specific to individual cell types.”

The researchers discovered that, in HSPCs, ANG induces processing of tiRNA, which suppresses global protein synthesis. And in myeloid progenitor cells, ANG induces processing of rRNA, which enhances protein synthesis.

The team also tested ANG’s ability to prevent and mitigate radiation-induced bone marrow failure. They found that treating mice with recombinant ANG protein, either before or after lethal irradiation, increased survival, improved bone marrow cellularity, and enhanced peripheral blood content.

Finally, the researchers assessed the effects of ANG in the context of HSCT in mice. They found that treating mouse long-term HSCs with ANG ex vivo resulted in a “dramatic” increase in multi-lineage reconstitution over 24 weeks after HSCT.

Upon secondary transplant, enhanced regeneration occurred over 16 weeks, and mice had elevated peripheral blood counts at 1 year post-HSCT, without any signs of leukemia.

The researchers observed similar results in experiments with human cells. They transplanted CD34+ cord blood cells—cultured in the presence or absence of ANG—into mice. Treatment with ANG resulted in enhanced multi-lineage regeneration and enhanced reconstitution upon secondary transplant.

“Proper blood cell production is dependent on functioning hematopoietic stem and progenitor cells that are destroyed during conditioning procedures for transplantation or following bone marrow injury,” said study author Kevin A. Goncalves, of Tufts Medical Center.

“Our study demonstrates that ANG regulates critical functions of both clinically relevant cell types.”

Lab mice

Photo by Aaron Logan

Research in mice suggests it’s feasible to use an immunotherapy conditioning regimen rather than radiation or chemotherapy prior to hematopoietic stem cell transplant (HSCT).

Investigators found that combining an antibody against the HSC receptor c-Kit with a CD47-blocking therapy could eliminate host HSCs and allow for successful engraftment of donor HSCs in immunocompetent recipient mice.

Adding T-cell-depleting antibodies to the mix allowed for robust HSC engraftment in a clinically relevant model of allogeneic HSCT.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues conducted this research and reported the results in Science Translational Medicine.

The researchers first found that ACK2, an antibody against c-Kit, successfully depleted HSCs in immune-deficient mice.

“However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said study author Akanksha Chhabra, PhD, of Stanford University School of Medicine.

So the researchers sought to enhance the effectiveness of ACK2 by combining it with antibodies or biologic agents that block CD47. They found that blocking CD47—particularly with an antagonist known as CV1mb—liberated macrophages to engulf target cells.

In this way, the immune system effectively depleted host HSCs in the immunocompetent mice, clearing the way for donor HSCs to take up residence in the bone marrow.

Finally, the researchers set out to determine whether conditioning with an anti-c-Kit antibody and CD47-blocking therapy could be extended to a clinically relevant model of allogeneic HSCT, in which the donor and recipient are matched through human leukocyte antigen alleles but mismatched at minor histocompatibility complex (mHC) antigens.

So the team conditioned mice with either ACK2 and CV1mb or ACK2 and the anti-CD47 antibody MIAP410. And they achieved immune ablation with T-cell-depleting antibodies—GK1.5 (anti-CD4) and YTS169.4 (anti-CD8). The mice then received mHC-mismatched HSCs.

The researchers found that either conditioning regimen, when combined with a T-cell-depleting regimen, resulted in substantial granulocyte, B-cell, T-cell, and NK-cell chimerism, as well as HSC engraftment in the bone marrow.

The success of these techniques in mice raises the researchers’ hopes that similar techniques will succeed in humans.

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20% to effectively 0,” said study author Judith Shizuru, MD, PhD, of Stanford University School of Medicine.

“If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” Dr Weissman said.

Lab mice

Photo by Aaron Logan

Research in mice suggests it’s feasible to use an immunotherapy conditioning regimen rather than radiation or chemotherapy prior to hematopoietic stem cell transplant (HSCT).

Investigators found that combining an antibody against the HSC receptor c-Kit with a CD47-blocking therapy could eliminate host HSCs and allow for successful engraftment of donor HSCs in immunocompetent recipient mice.

Adding T-cell-depleting antibodies to the mix allowed for robust HSC engraftment in a clinically relevant model of allogeneic HSCT.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues conducted this research and reported the results in Science Translational Medicine.

The researchers first found that ACK2, an antibody against c-Kit, successfully depleted HSCs in immune-deficient mice.

“However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said study author Akanksha Chhabra, PhD, of Stanford University School of Medicine.

So the researchers sought to enhance the effectiveness of ACK2 by combining it with antibodies or biologic agents that block CD47. They found that blocking CD47—particularly with an antagonist known as CV1mb—liberated macrophages to engulf target cells.

In this way, the immune system effectively depleted host HSCs in the immunocompetent mice, clearing the way for donor HSCs to take up residence in the bone marrow.

Finally, the researchers set out to determine whether conditioning with an anti-c-Kit antibody and CD47-blocking therapy could be extended to a clinically relevant model of allogeneic HSCT, in which the donor and recipient are matched through human leukocyte antigen alleles but mismatched at minor histocompatibility complex (mHC) antigens.

So the team conditioned mice with either ACK2 and CV1mb or ACK2 and the anti-CD47 antibody MIAP410. And they achieved immune ablation with T-cell-depleting antibodies—GK1.5 (anti-CD4) and YTS169.4 (anti-CD8). The mice then received mHC-mismatched HSCs.

The researchers found that either conditioning regimen, when combined with a T-cell-depleting regimen, resulted in substantial granulocyte, B-cell, T-cell, and NK-cell chimerism, as well as HSC engraftment in the bone marrow.

The success of these techniques in mice raises the researchers’ hopes that similar techniques will succeed in humans.

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20% to effectively 0,” said study author Judith Shizuru, MD, PhD, of Stanford University School of Medicine.

“If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” Dr Weissman said.

Lab mice

Photo by Aaron Logan

Research in mice suggests it’s feasible to use an immunotherapy conditioning regimen rather than radiation or chemotherapy prior to hematopoietic stem cell transplant (HSCT).

Investigators found that combining an antibody against the HSC receptor c-Kit with a CD47-blocking therapy could eliminate host HSCs and allow for successful engraftment of donor HSCs in immunocompetent recipient mice.

Adding T-cell-depleting antibodies to the mix allowed for robust HSC engraftment in a clinically relevant model of allogeneic HSCT.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues conducted this research and reported the results in Science Translational Medicine.

The researchers first found that ACK2, an antibody against c-Kit, successfully depleted HSCs in immune-deficient mice.

“However, this antibody alone would not be effective in immune-competent recipients, who represent a majority of potential bone marrow transplant recipients,” said study author Akanksha Chhabra, PhD, of Stanford University School of Medicine.

So the researchers sought to enhance the effectiveness of ACK2 by combining it with antibodies or biologic agents that block CD47. They found that blocking CD47—particularly with an antagonist known as CV1mb—liberated macrophages to engulf target cells.

In this way, the immune system effectively depleted host HSCs in the immunocompetent mice, clearing the way for donor HSCs to take up residence in the bone marrow.

Finally, the researchers set out to determine whether conditioning with an anti-c-Kit antibody and CD47-blocking therapy could be extended to a clinically relevant model of allogeneic HSCT, in which the donor and recipient are matched through human leukocyte antigen alleles but mismatched at minor histocompatibility complex (mHC) antigens.

So the team conditioned mice with either ACK2 and CV1mb or ACK2 and the anti-CD47 antibody MIAP410. And they achieved immune ablation with T-cell-depleting antibodies—GK1.5 (anti-CD4) and YTS169.4 (anti-CD8). The mice then received mHC-mismatched HSCs.

The researchers found that either conditioning regimen, when combined with a T-cell-depleting regimen, resulted in substantial granulocyte, B-cell, T-cell, and NK-cell chimerism, as well as HSC engraftment in the bone marrow.

The success of these techniques in mice raises the researchers’ hopes that similar techniques will succeed in humans.

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20% to effectively 0,” said study author Judith Shizuru, MD, PhD, of Stanford University School of Medicine.

“If and when this is accomplished, it will be a whole new era in disease treatment and regenerative medicine,” Dr Weissman said.

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

T cells

Image by NIAID

Researchers have reported “favorable” long-term results from a pair of phase 1 trials in which they used the non-viral Sleeping Beauty (SB) transposon/transposase system to create CD19-specific chimeric antigen receptor (CAR) T cells.

These CAR T cells appeared to be safe, and results suggested they can provide additional control of leukemia and lymphoma when given after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

In addition, the researchers said use of the SB transposon/transposase platform could reduce the costs and complexity associated with recombinant viral vector-based immunotherapy.

The team described their results with the SB system in The Journal of Clinical Investigation. Results from these trials were previously reported at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The trials were sponsored by MD Anderson Cancer Center in collaboration with the National Cancer Institute, National Center for Research Resources, Intrexon Corporation, and Ziopharm Oncology.

The trials included 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell non-Hodgkin lymphoma (NHL, n=9).

The patients received SB-modified T cells after autologous (n=7) or allogeneic (n=19) HSCT.

The researchers said SB-mediated gene transfer and stimulation resulted in large ex vivo expansion of T cells while retaining CAR expression and without integration hotspots.

Autologous and allogeneic T cells survived after infusion an average of 201 days and 51 days, respectively.

Safety

The researchers said there were no unexpected acute infusion or delayed toxicities. Mild elevations in cytokines were observed but not cytokine storm.

Three allogeneic HSCT recipients developed graft-vs-host disease (GVHD). One patient developed grade 1 acute skin GVHD that resolved with topical steroids, and 1 developed chronic skin GVHD that responded to systemic steroids.

The third patient, who had a history of drug-induced liver toxicity, developed recurrent liver toxicity with a component of liver GVHD 1 month after T-cell infusion. This patient died of liver failure.

There were 5 other deaths, all of them due to disease relapse.

Efficacy: Autologous HSCT

Seven patients with advanced NHL were treated with autologous HSCT, followed by the administration of patient-derived CAR T cells.

Six of the 7 patients were in complete remission (CR) at a median follow-up of 25.5 months (range, 6.4 to 32.7 months).

The 30-month progression-free survival (PFS) rate was 83%, and the overall survival (OS) rate was 100%.

Efficacy: Allogeneic HSCT

Nineteen patients (ALL n=17, NHL n=2) received donor-derived CAR T cells after allogeneic HSCT. The patients had advanced disease at the time of HSCT, and CAR T cells were administered without additional lymphodepletion.

Eleven of 19 patients were still in CR at a median follow-up of 7.5 months (range, 2.7 to 17.9 months). The 1-year PFS rate was 53%, and the OS rate was 63%.

The researchers also looked at the subset of allogeneic HSCT recipients who received haplo-identical CAR T cells. These 8 patients had a 1-year PFS rate of 75% and an OS rate of 100%.

“By following these patients over an extended duration, as we do in these studies, we can better understand the added benefit of CAR-T over HSCT alone,” said Francois Lebel, MD, of Ziopharm Oncology.

“Although the primary objective of these trials was not to establish efficacy, the recipients’ outcomes are encouraging, with apparent doubling of survivals compared to historical controls. We are encouraged by these clinical data and look forward to results from our phase 1 study infusing our next-generation CD19-specific CAR T cells in patients with advanced lymphoid malignancies.”

T cells

Image by NIAID

Researchers have reported “favorable” long-term results from a pair of phase 1 trials in which they used the non-viral Sleeping Beauty (SB) transposon/transposase system to create CD19-specific chimeric antigen receptor (CAR) T cells.

These CAR T cells appeared to be safe, and results suggested they can provide additional control of leukemia and lymphoma when given after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

In addition, the researchers said use of the SB transposon/transposase platform could reduce the costs and complexity associated with recombinant viral vector-based immunotherapy.

The team described their results with the SB system in The Journal of Clinical Investigation. Results from these trials were previously reported at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The trials were sponsored by MD Anderson Cancer Center in collaboration with the National Cancer Institute, National Center for Research Resources, Intrexon Corporation, and Ziopharm Oncology.

The trials included 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell non-Hodgkin lymphoma (NHL, n=9).

The patients received SB-modified T cells after autologous (n=7) or allogeneic (n=19) HSCT.

The researchers said SB-mediated gene transfer and stimulation resulted in large ex vivo expansion of T cells while retaining CAR expression and without integration hotspots.

Autologous and allogeneic T cells survived after infusion an average of 201 days and 51 days, respectively.

Safety

The researchers said there were no unexpected acute infusion or delayed toxicities. Mild elevations in cytokines were observed but not cytokine storm.

Three allogeneic HSCT recipients developed graft-vs-host disease (GVHD). One patient developed grade 1 acute skin GVHD that resolved with topical steroids, and 1 developed chronic skin GVHD that responded to systemic steroids.

The third patient, who had a history of drug-induced liver toxicity, developed recurrent liver toxicity with a component of liver GVHD 1 month after T-cell infusion. This patient died of liver failure.

There were 5 other deaths, all of them due to disease relapse.

Efficacy: Autologous HSCT

Seven patients with advanced NHL were treated with autologous HSCT, followed by the administration of patient-derived CAR T cells.

Six of the 7 patients were in complete remission (CR) at a median follow-up of 25.5 months (range, 6.4 to 32.7 months).

The 30-month progression-free survival (PFS) rate was 83%, and the overall survival (OS) rate was 100%.

Efficacy: Allogeneic HSCT

Nineteen patients (ALL n=17, NHL n=2) received donor-derived CAR T cells after allogeneic HSCT. The patients had advanced disease at the time of HSCT, and CAR T cells were administered without additional lymphodepletion.

Eleven of 19 patients were still in CR at a median follow-up of 7.5 months (range, 2.7 to 17.9 months). The 1-year PFS rate was 53%, and the OS rate was 63%.

The researchers also looked at the subset of allogeneic HSCT recipients who received haplo-identical CAR T cells. These 8 patients had a 1-year PFS rate of 75% and an OS rate of 100%.

“By following these patients over an extended duration, as we do in these studies, we can better understand the added benefit of CAR-T over HSCT alone,” said Francois Lebel, MD, of Ziopharm Oncology.

“Although the primary objective of these trials was not to establish efficacy, the recipients’ outcomes are encouraging, with apparent doubling of survivals compared to historical controls. We are encouraged by these clinical data and look forward to results from our phase 1 study infusing our next-generation CD19-specific CAR T cells in patients with advanced lymphoid malignancies.”

T cells

Image by NIAID

Researchers have reported “favorable” long-term results from a pair of phase 1 trials in which they used the non-viral Sleeping Beauty (SB) transposon/transposase system to create CD19-specific chimeric antigen receptor (CAR) T cells.

These CAR T cells appeared to be safe, and results suggested they can provide additional control of leukemia and lymphoma when given after autologous or allogeneic hematopoietic stem cell transplant (HSCT).

In addition, the researchers said use of the SB transposon/transposase platform could reduce the costs and complexity associated with recombinant viral vector-based immunotherapy.

The team described their results with the SB system in The Journal of Clinical Investigation. Results from these trials were previously reported at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The trials were sponsored by MD Anderson Cancer Center in collaboration with the National Cancer Institute, National Center for Research Resources, Intrexon Corporation, and Ziopharm Oncology.

The trials included 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell non-Hodgkin lymphoma (NHL, n=9).

The patients received SB-modified T cells after autologous (n=7) or allogeneic (n=19) HSCT.

The researchers said SB-mediated gene transfer and stimulation resulted in large ex vivo expansion of T cells while retaining CAR expression and without integration hotspots.

Autologous and allogeneic T cells survived after infusion an average of 201 days and 51 days, respectively.

Safety

The researchers said there were no unexpected acute infusion or delayed toxicities. Mild elevations in cytokines were observed but not cytokine storm.

Three allogeneic HSCT recipients developed graft-vs-host disease (GVHD). One patient developed grade 1 acute skin GVHD that resolved with topical steroids, and 1 developed chronic skin GVHD that responded to systemic steroids.

The third patient, who had a history of drug-induced liver toxicity, developed recurrent liver toxicity with a component of liver GVHD 1 month after T-cell infusion. This patient died of liver failure.

There were 5 other deaths, all of them due to disease relapse.

Efficacy: Autologous HSCT

Seven patients with advanced NHL were treated with autologous HSCT, followed by the administration of patient-derived CAR T cells.

Six of the 7 patients were in complete remission (CR) at a median follow-up of 25.5 months (range, 6.4 to 32.7 months).

The 30-month progression-free survival (PFS) rate was 83%, and the overall survival (OS) rate was 100%.

Efficacy: Allogeneic HSCT

Nineteen patients (ALL n=17, NHL n=2) received donor-derived CAR T cells after allogeneic HSCT. The patients had advanced disease at the time of HSCT, and CAR T cells were administered without additional lymphodepletion.

Eleven of 19 patients were still in CR at a median follow-up of 7.5 months (range, 2.7 to 17.9 months). The 1-year PFS rate was 53%, and the OS rate was 63%.

The researchers also looked at the subset of allogeneic HSCT recipients who received haplo-identical CAR T cells. These 8 patients had a 1-year PFS rate of 75% and an OS rate of 100%.

“By following these patients over an extended duration, as we do in these studies, we can better understand the added benefit of CAR-T over HSCT alone,” said Francois Lebel, MD, of Ziopharm Oncology.

“Although the primary objective of these trials was not to establish efficacy, the recipients’ outcomes are encouraging, with apparent doubling of survivals compared to historical controls. We are encouraged by these clinical data and look forward to results from our phase 1 study infusing our next-generation CD19-specific CAR T cells in patients with advanced lymphoid malignancies.”

Colony of iPSCs

Image from Salk Institute

New research suggests the type of founder cell used to generate induced pluripotent stem cells (iPSCs) does not affect the iPSCs’ ability to differentiate into hematopoietic cells.

Instead, researchers found the expression of certain genes and DNA methylations were better indicators of the efficiency at which a cell line could be differentiated into the hematopoietic lineage.

The team reported these findings in Cell Stem Cell.

The researchers assessed the hematopoietic differentiation capacities of 35 iPSC lines derived from 4 types of somatic tissues—human dermal fibroblasts, hematopoietic cells such as cord blood and peripheral blood, dental pulp cells, and keratinocytes—from 15 donors.

The team also assessed 4 embryonic stem cell lines in early phase and late phase.

The researchers found that hematopoietic commitment capacity was associated with expression of IGF2 in undifferentiated iPSCs, but not with type of founder cell.

Higher expression of IFG2 was indicative of iPSCs initiating their conversion into hematopoietic cells. Even though IFG2 itself is not directly related to hematopoiesis, its uptake corresponded to an increase in the expression of genes that are.

Although IFG2 marked the beginnings of differentiation to hematopoietic lineage, the completion of differentiation was marked by the methylation profiles of the iPSC DNA.

“DNA methylation has an effect on a cell staying pluripotent or differentiating,” explained study author Yoshinori Yoshida, MD, PhD, of the Center for iPS Cell Research and Application at Kyoto University in Japan.

The completion of differentiation correlated with less aberrant methylation during the reprogramming process.

Hematopoietic founder cells showed a much lower propensity for aberrant methylation than did other founder cells, which could explain why, in the past, scientists attributed the founder cell to the effectiveness of differentiating iPSCs to the hematopoietic lineage.

Dr Yoshida and his colleagues said this research revealed molecular factors that can be used to evaluate the differentiation potential of different cell lines, which should expedite the progress of iPSCs to clinical use.

Colony of iPSCs

Image from Salk Institute

New research suggests the type of founder cell used to generate induced pluripotent stem cells (iPSCs) does not affect the iPSCs’ ability to differentiate into hematopoietic cells.

Instead, researchers found the expression of certain genes and DNA methylations were better indicators of the efficiency at which a cell line could be differentiated into the hematopoietic lineage.

The team reported these findings in Cell Stem Cell.

The researchers assessed the hematopoietic differentiation capacities of 35 iPSC lines derived from 4 types of somatic tissues—human dermal fibroblasts, hematopoietic cells such as cord blood and peripheral blood, dental pulp cells, and keratinocytes—from 15 donors.

The team also assessed 4 embryonic stem cell lines in early phase and late phase.

The researchers found that hematopoietic commitment capacity was associated with expression of IGF2 in undifferentiated iPSCs, but not with type of founder cell.

Higher expression of IFG2 was indicative of iPSCs initiating their conversion into hematopoietic cells. Even though IFG2 itself is not directly related to hematopoiesis, its uptake corresponded to an increase in the expression of genes that are.

Although IFG2 marked the beginnings of differentiation to hematopoietic lineage, the completion of differentiation was marked by the methylation profiles of the iPSC DNA.

“DNA methylation has an effect on a cell staying pluripotent or differentiating,” explained study author Yoshinori Yoshida, MD, PhD, of the Center for iPS Cell Research and Application at Kyoto University in Japan.

The completion of differentiation correlated with less aberrant methylation during the reprogramming process.

Hematopoietic founder cells showed a much lower propensity for aberrant methylation than did other founder cells, which could explain why, in the past, scientists attributed the founder cell to the effectiveness of differentiating iPSCs to the hematopoietic lineage.

Dr Yoshida and his colleagues said this research revealed molecular factors that can be used to evaluate the differentiation potential of different cell lines, which should expedite the progress of iPSCs to clinical use.

Colony of iPSCs

Image from Salk Institute

New research suggests the type of founder cell used to generate induced pluripotent stem cells (iPSCs) does not affect the iPSCs’ ability to differentiate into hematopoietic cells.

Instead, researchers found the expression of certain genes and DNA methylations were better indicators of the efficiency at which a cell line could be differentiated into the hematopoietic lineage.

The team reported these findings in Cell Stem Cell.

The researchers assessed the hematopoietic differentiation capacities of 35 iPSC lines derived from 4 types of somatic tissues—human dermal fibroblasts, hematopoietic cells such as cord blood and peripheral blood, dental pulp cells, and keratinocytes—from 15 donors.

The team also assessed 4 embryonic stem cell lines in early phase and late phase.

The researchers found that hematopoietic commitment capacity was associated with expression of IGF2 in undifferentiated iPSCs, but not with type of founder cell.

Higher expression of IFG2 was indicative of iPSCs initiating their conversion into hematopoietic cells. Even though IFG2 itself is not directly related to hematopoiesis, its uptake corresponded to an increase in the expression of genes that are.

Although IFG2 marked the beginnings of differentiation to hematopoietic lineage, the completion of differentiation was marked by the methylation profiles of the iPSC DNA.

“DNA methylation has an effect on a cell staying pluripotent or differentiating,” explained study author Yoshinori Yoshida, MD, PhD, of the Center for iPS Cell Research and Application at Kyoto University in Japan.

The completion of differentiation correlated with less aberrant methylation during the reprogramming process.

Hematopoietic founder cells showed a much lower propensity for aberrant methylation than did other founder cells, which could explain why, in the past, scientists attributed the founder cell to the effectiveness of differentiating iPSCs to the hematopoietic lineage.

Dr Yoshida and his colleagues said this research revealed molecular factors that can be used to evaluate the differentiation potential of different cell lines, which should expedite the progress of iPSCs to clinical use.

Cord blood donation

Photo courtesy of NHS

A single-center study suggests that long-term outcomes may be better among patients who receive a double cord blood transplant (CBT) than those who receive a peripheral blood stem cell transplant from a matched, unrelated donor (MUD).

At 3-years post-transplant, the incidence of chronic graft-versus-host disease (cGVHD) was significantly lower among the CBT recipients studied.

In addition, patients who received CBTs were less likely to be re-hospitalized and more likely to discontinue immunosuppressive therapy.

However, there was no significant difference in relapse, transplant-related mortality, or overall survival between CBT recipients and patients who received MUD transplants.

These results were published in Bone Marrow Transplantation.

“Historically, doctors have reserved cord blood for patients without a match,” said study author Jonathan Gutman, MD, of the University of Colorado Denver in Aurora, Colorado.

“A lot of centers reserved cord blood transplants for their worst cases, and so it got an early reputation for being less successful. It also costs a bit more; it takes cord blood cells a little longer to get going, and so patients need to be supported a little longer. However, when you look past the first 100 days—a point at which many centers stop collecting data—there is clear evidence that cord blood outperforms cells from matched, unrelated donors.”

To uncover such evidence, Dr Gutman and his colleagues analyzed adult patients with hematologic malignancies who underwent transplants at the University of Colorado Denver from 2009 to 2014. The team compared 51 consecutive patients receiving double CBT with 57 consecutive patients receiving MUD transplants.

At 3 years post-transplant, the overall rates of cGVHD were 68% following MUD and 32% following CBT (P=0.0017). The rates of severe cGVHD were 44% and 8%, respectively (P=0.0006).

CBT recipients had been off immunosuppression since a median of 268 days from transplant, while patients who received MUD transplants had not ceased immunosuppression to a degree that allowed researchers to determine the median (P<0.0001).

Late hospitalization was significantly reduced among CBT recipients, and there was a trend toward fewer late infections for these patients.

Excluding patients who died during the follow-up period, the relative risk of late infection episode on a per-infection level was 0.77 (P=0.10), and the relative risk of late hospitalization was 0.74 (P<0.001).

The 3-year relapse, transplant-related mortality, and overall survival rates were similar following CBT and MUD transplant.

The cumulative incidence of relapse was 22% for CBT and 24% for MUD (P=0.86). Transplant-related mortality was 25% for CBT and 24% for MUD (P=0.73). And overall survival was 54% for CBT and 52% for MUD (P=0.68).

Dr Gutman said that, due to these results, the University of Colorado Denver has chosen to use cord blood as the first choice for transplant cases where a matched, related donor is unavailable.

Cord blood donation

Photo courtesy of NHS

A single-center study suggests that long-term outcomes may be better among patients who receive a double cord blood transplant (CBT) than those who receive a peripheral blood stem cell transplant from a matched, unrelated donor (MUD).

At 3-years post-transplant, the incidence of chronic graft-versus-host disease (cGVHD) was significantly lower among the CBT recipients studied.

In addition, patients who received CBTs were less likely to be re-hospitalized and more likely to discontinue immunosuppressive therapy.

However, there was no significant difference in relapse, transplant-related mortality, or overall survival between CBT recipients and patients who received MUD transplants.

These results were published in Bone Marrow Transplantation.

“Historically, doctors have reserved cord blood for patients without a match,” said study author Jonathan Gutman, MD, of the University of Colorado Denver in Aurora, Colorado.

“A lot of centers reserved cord blood transplants for their worst cases, and so it got an early reputation for being less successful. It also costs a bit more; it takes cord blood cells a little longer to get going, and so patients need to be supported a little longer. However, when you look past the first 100 days—a point at which many centers stop collecting data—there is clear evidence that cord blood outperforms cells from matched, unrelated donors.”

To uncover such evidence, Dr Gutman and his colleagues analyzed adult patients with hematologic malignancies who underwent transplants at the University of Colorado Denver from 2009 to 2014. The team compared 51 consecutive patients receiving double CBT with 57 consecutive patients receiving MUD transplants.

At 3 years post-transplant, the overall rates of cGVHD were 68% following MUD and 32% following CBT (P=0.0017). The rates of severe cGVHD were 44% and 8%, respectively (P=0.0006).

CBT recipients had been off immunosuppression since a median of 268 days from transplant, while patients who received MUD transplants had not ceased immunosuppression to a degree that allowed researchers to determine the median (P<0.0001).

Late hospitalization was significantly reduced among CBT recipients, and there was a trend toward fewer late infections for these patients.

Excluding patients who died during the follow-up period, the relative risk of late infection episode on a per-infection level was 0.77 (P=0.10), and the relative risk of late hospitalization was 0.74 (P<0.001).

The 3-year relapse, transplant-related mortality, and overall survival rates were similar following CBT and MUD transplant.

The cumulative incidence of relapse was 22% for CBT and 24% for MUD (P=0.86). Transplant-related mortality was 25% for CBT and 24% for MUD (P=0.73). And overall survival was 54% for CBT and 52% for MUD (P=0.68).

Dr Gutman said that, due to these results, the University of Colorado Denver has chosen to use cord blood as the first choice for transplant cases where a matched, related donor is unavailable.

Cord blood donation

Photo courtesy of NHS

A single-center study suggests that long-term outcomes may be better among patients who receive a double cord blood transplant (CBT) than those who receive a peripheral blood stem cell transplant from a matched, unrelated donor (MUD).

At 3-years post-transplant, the incidence of chronic graft-versus-host disease (cGVHD) was significantly lower among the CBT recipients studied.

In addition, patients who received CBTs were less likely to be re-hospitalized and more likely to discontinue immunosuppressive therapy.

However, there was no significant difference in relapse, transplant-related mortality, or overall survival between CBT recipients and patients who received MUD transplants.

These results were published in Bone Marrow Transplantation.

“Historically, doctors have reserved cord blood for patients without a match,” said study author Jonathan Gutman, MD, of the University of Colorado Denver in Aurora, Colorado.

“A lot of centers reserved cord blood transplants for their worst cases, and so it got an early reputation for being less successful. It also costs a bit more; it takes cord blood cells a little longer to get going, and so patients need to be supported a little longer. However, when you look past the first 100 days—a point at which many centers stop collecting data—there is clear evidence that cord blood outperforms cells from matched, unrelated donors.”

To uncover such evidence, Dr Gutman and his colleagues analyzed adult patients with hematologic malignancies who underwent transplants at the University of Colorado Denver from 2009 to 2014. The team compared 51 consecutive patients receiving double CBT with 57 consecutive patients receiving MUD transplants.

At 3 years post-transplant, the overall rates of cGVHD were 68% following MUD and 32% following CBT (P=0.0017). The rates of severe cGVHD were 44% and 8%, respectively (P=0.0006).

CBT recipients had been off immunosuppression since a median of 268 days from transplant, while patients who received MUD transplants had not ceased immunosuppression to a degree that allowed researchers to determine the median (P<0.0001).

Late hospitalization was significantly reduced among CBT recipients, and there was a trend toward fewer late infections for these patients.

Excluding patients who died during the follow-up period, the relative risk of late infection episode on a per-infection level was 0.77 (P=0.10), and the relative risk of late hospitalization was 0.74 (P<0.001).

The 3-year relapse, transplant-related mortality, and overall survival rates were similar following CBT and MUD transplant.

The cumulative incidence of relapse was 22% for CBT and 24% for MUD (P=0.86). Transplant-related mortality was 25% for CBT and 24% for MUD (P=0.73). And overall survival was 54% for CBT and 52% for MUD (P=0.68).

Dr Gutman said that, due to these results, the University of Colorado Denver has chosen to use cord blood as the first choice for transplant cases where a matched, related donor is unavailable.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”