Chemo-free transplant can cure SCD, team says

Transplant preparation

Photo by Chad McNeeley

Chemotherapy-free allogeneic transplant can cure sickle cell disease (SCD) in adults, according to researchers.

In a phase 1/2 trial, the treatment normalized hemoglobin concentrations, reduced SCD-related complications, and improved cardiopulmonary function in 12 of 13 patients.

The single graft failure was due to noncompliance with post-transplant treatment.

There were no deaths and no cases of graft-vs-host disease. However, most patients did experience some form of transplant-related toxicity.

These transplants were performed at the University of Illinois Hospital & Health Sciences System in Chicago. But the chemotherapy-free transplant regimen was developed—and initially tested—at the National Institutes of Health in Bethesda, Maryland.

Physicians there have treated 30 patients with the regimen. An account of that work was published in JAMA last year.

The current study has been published in Biology of Blood & Marrow Transplantation.

“Adults with sickle cell disease can be cured without chemotherapy—the main barrier that has stood in the way for them for so long,” said study author Damiano Rondelli, MD, of the University of Illinois Hospital & Health Sciences System.

“Our data provide more support that this therapy is safe and effective and prevents patients from living shortened lives, condemned to pain and progressive complications.”

Treatment and outcome

The study included 13 patients, ages 17 to 40, who were transplanted between November 2011 and June 2014. Prior to transplant, patients received alemtuzumab and total-body irradiation (300 cGy).

They then received peripheral blood stem cells from matched related donors. All donors were a 10/10 human leukocyte antigen match, but 2 donors had different blood types than the recipients. After transplant, the patients received sirolimus.

All 13 patients initially engrafted, but 1 patient experienced secondary graft failure due to noncompliance with sirolimus.

At a median follow-up of 22 months (range, 12-44), all 13 patients are alive, and 12 have maintained a stable mixed donor/recipient chimerism.

At 1 year after transplant, the 12 patients with stable donor chimerism had significant improvements from baseline in hemoglobin, reticulocyte percentage, lactate dehydrogenase concentration, and cardiopulmonary function.

One of these patients required readmission to the hospital for vaso-occlusive crisis. Before transplant, this patient experienced about 12 crises a year.

No other SCD-related complications have occurred. And 4 patients have been able to stop taking sirolimus without transplant rejection or other complications.

Nine of the engrafted patients completed quality of life assessments before transplant and at 1 year after the procedure. They reported improvements in pain, general health, vitality, and social functioning.

“[W]ith this chemotherapy-free transplant, we are curing adults with sickle cell disease, and we see that their quality of life improves vastly within just 1 month of the transplant,” Dr Rondelli said. “They are able to go back to school, go back to work, and can experience life without pain.”

Toxicity

Four patients did not experience any transplant-related toxicity. And there were no cases of acute or chronic graft-vs-host disease.

One patient developed gram-negative rods in her hip prosthesis after transplant, 1 patient experienced delayed hemolytic transfusion reaction after exchange transfusion, 1 patient developed viral pharyngitis, and 1 patient developed Coxsackie B.

One patient developed a urinary tract infection due to extended spectrum beta-lactamase, Clostridium difficile colitis, and Mycoplasma pneumoniae.

Two patients had grade 2 mucositis, one of whom also developed line-associated deep vein thrombosis and cytomegalovirus (CMV) reactivation. Two other patients had CMV reactivation as well, one of whom also had methicillin-resistant Staphylococcus aureus pneumonia.

All 3 patients with CMV reactivation were successfully treated with valgancyclovir and did not develop CMV disease.

Six patients had arthralgias attributed to sirolimus, and 2 of them required dose reductions.

One patient developed chest pain and a decline in carbon monoxide diffusion capacity by 30% that was attributed to sirolimus. The patient was switched to cyclosporine but developed posterior reversible encephalopathy syndrome and was then put on mycophenolate mofetil.

The patient has since maintained stable donor chimerism, and the carbon monoxide diffusing capacity has increased to near-baseline value.

Transplant preparation

Photo by Chad McNeeley

Chemotherapy-free allogeneic transplant can cure sickle cell disease (SCD) in adults, according to researchers.

In a phase 1/2 trial, the treatment normalized hemoglobin concentrations, reduced SCD-related complications, and improved cardiopulmonary function in 12 of 13 patients.

The single graft failure was due to noncompliance with post-transplant treatment.

There were no deaths and no cases of graft-vs-host disease. However, most patients did experience some form of transplant-related toxicity.

These transplants were performed at the University of Illinois Hospital & Health Sciences System in Chicago. But the chemotherapy-free transplant regimen was developed—and initially tested—at the National Institutes of Health in Bethesda, Maryland.

Physicians there have treated 30 patients with the regimen. An account of that work was published in JAMA last year.

The current study has been published in Biology of Blood & Marrow Transplantation.

“Adults with sickle cell disease can be cured without chemotherapy—the main barrier that has stood in the way for them for so long,” said study author Damiano Rondelli, MD, of the University of Illinois Hospital & Health Sciences System.

“Our data provide more support that this therapy is safe and effective and prevents patients from living shortened lives, condemned to pain and progressive complications.”

Treatment and outcome

The study included 13 patients, ages 17 to 40, who were transplanted between November 2011 and June 2014. Prior to transplant, patients received alemtuzumab and total-body irradiation (300 cGy).

They then received peripheral blood stem cells from matched related donors. All donors were a 10/10 human leukocyte antigen match, but 2 donors had different blood types than the recipients. After transplant, the patients received sirolimus.

All 13 patients initially engrafted, but 1 patient experienced secondary graft failure due to noncompliance with sirolimus.

At a median follow-up of 22 months (range, 12-44), all 13 patients are alive, and 12 have maintained a stable mixed donor/recipient chimerism.

At 1 year after transplant, the 12 patients with stable donor chimerism had significant improvements from baseline in hemoglobin, reticulocyte percentage, lactate dehydrogenase concentration, and cardiopulmonary function.

One of these patients required readmission to the hospital for vaso-occlusive crisis. Before transplant, this patient experienced about 12 crises a year.

No other SCD-related complications have occurred. And 4 patients have been able to stop taking sirolimus without transplant rejection or other complications.

Nine of the engrafted patients completed quality of life assessments before transplant and at 1 year after the procedure. They reported improvements in pain, general health, vitality, and social functioning.

“[W]ith this chemotherapy-free transplant, we are curing adults with sickle cell disease, and we see that their quality of life improves vastly within just 1 month of the transplant,” Dr Rondelli said. “They are able to go back to school, go back to work, and can experience life without pain.”

Toxicity

Four patients did not experience any transplant-related toxicity. And there were no cases of acute or chronic graft-vs-host disease.

One patient developed gram-negative rods in her hip prosthesis after transplant, 1 patient experienced delayed hemolytic transfusion reaction after exchange transfusion, 1 patient developed viral pharyngitis, and 1 patient developed Coxsackie B.

One patient developed a urinary tract infection due to extended spectrum beta-lactamase, Clostridium difficile colitis, and Mycoplasma pneumoniae.

Two patients had grade 2 mucositis, one of whom also developed line-associated deep vein thrombosis and cytomegalovirus (CMV) reactivation. Two other patients had CMV reactivation as well, one of whom also had methicillin-resistant Staphylococcus aureus pneumonia.

All 3 patients with CMV reactivation were successfully treated with valgancyclovir and did not develop CMV disease.

Six patients had arthralgias attributed to sirolimus, and 2 of them required dose reductions.

One patient developed chest pain and a decline in carbon monoxide diffusion capacity by 30% that was attributed to sirolimus. The patient was switched to cyclosporine but developed posterior reversible encephalopathy syndrome and was then put on mycophenolate mofetil.

The patient has since maintained stable donor chimerism, and the carbon monoxide diffusing capacity has increased to near-baseline value.

Transplant preparation

Photo by Chad McNeeley

Chemotherapy-free allogeneic transplant can cure sickle cell disease (SCD) in adults, according to researchers.

In a phase 1/2 trial, the treatment normalized hemoglobin concentrations, reduced SCD-related complications, and improved cardiopulmonary function in 12 of 13 patients.

The single graft failure was due to noncompliance with post-transplant treatment.

There were no deaths and no cases of graft-vs-host disease. However, most patients did experience some form of transplant-related toxicity.

These transplants were performed at the University of Illinois Hospital & Health Sciences System in Chicago. But the chemotherapy-free transplant regimen was developed—and initially tested—at the National Institutes of Health in Bethesda, Maryland.

Physicians there have treated 30 patients with the regimen. An account of that work was published in JAMA last year.

The current study has been published in Biology of Blood & Marrow Transplantation.

“Adults with sickle cell disease can be cured without chemotherapy—the main barrier that has stood in the way for them for so long,” said study author Damiano Rondelli, MD, of the University of Illinois Hospital & Health Sciences System.

“Our data provide more support that this therapy is safe and effective and prevents patients from living shortened lives, condemned to pain and progressive complications.”

Treatment and outcome

The study included 13 patients, ages 17 to 40, who were transplanted between November 2011 and June 2014. Prior to transplant, patients received alemtuzumab and total-body irradiation (300 cGy).

They then received peripheral blood stem cells from matched related donors. All donors were a 10/10 human leukocyte antigen match, but 2 donors had different blood types than the recipients. After transplant, the patients received sirolimus.

All 13 patients initially engrafted, but 1 patient experienced secondary graft failure due to noncompliance with sirolimus.

At a median follow-up of 22 months (range, 12-44), all 13 patients are alive, and 12 have maintained a stable mixed donor/recipient chimerism.

At 1 year after transplant, the 12 patients with stable donor chimerism had significant improvements from baseline in hemoglobin, reticulocyte percentage, lactate dehydrogenase concentration, and cardiopulmonary function.

One of these patients required readmission to the hospital for vaso-occlusive crisis. Before transplant, this patient experienced about 12 crises a year.

No other SCD-related complications have occurred. And 4 patients have been able to stop taking sirolimus without transplant rejection or other complications.

Nine of the engrafted patients completed quality of life assessments before transplant and at 1 year after the procedure. They reported improvements in pain, general health, vitality, and social functioning.

“[W]ith this chemotherapy-free transplant, we are curing adults with sickle cell disease, and we see that their quality of life improves vastly within just 1 month of the transplant,” Dr Rondelli said. “They are able to go back to school, go back to work, and can experience life without pain.”

Toxicity

Four patients did not experience any transplant-related toxicity. And there were no cases of acute or chronic graft-vs-host disease.

One patient developed gram-negative rods in her hip prosthesis after transplant, 1 patient experienced delayed hemolytic transfusion reaction after exchange transfusion, 1 patient developed viral pharyngitis, and 1 patient developed Coxsackie B.

One patient developed a urinary tract infection due to extended spectrum beta-lactamase, Clostridium difficile colitis, and Mycoplasma pneumoniae.

Two patients had grade 2 mucositis, one of whom also developed line-associated deep vein thrombosis and cytomegalovirus (CMV) reactivation. Two other patients had CMV reactivation as well, one of whom also had methicillin-resistant Staphylococcus aureus pneumonia.

All 3 patients with CMV reactivation were successfully treated with valgancyclovir and did not develop CMV disease.

Six patients had arthralgias attributed to sirolimus, and 2 of them required dose reductions.

One patient developed chest pain and a decline in carbon monoxide diffusion capacity by 30% that was attributed to sirolimus. The patient was switched to cyclosporine but developed posterior reversible encephalopathy syndrome and was then put on mycophenolate mofetil.

The patient has since maintained stable donor chimerism, and the carbon monoxide diffusing capacity has increased to near-baseline value.