Nonmyeloablative Matched Sibling Donor Hematopoietic Cell Transplantation in Children and Adolescents with Sickle Cell Disease

Abstract

Sickle cell disease is a potentially debilitating hemoglobinopathy associated with early mortality. The only established curative therapy is hematopoietic cell transplantation (HCT) with a matched sibling donor. The National Institutes of Health nonmyeloablative regimen of alemtuzumab/300 cGy total body irradiation and prolonged sirolimus exposure for graft-versus-host disease (GVHD) prophylaxis was administered to 16 children and adolescents. Infused products were unmanipulated granulocyte colony stimulating factor mobilized peripheral blood stem cells. All patients achieved mixed donor-recipient engraftment with no cases of secondary graft failure to date. Two patients have donor myeloid chimerism in the range of 30% to 40%. No sickling crises post-HCT have been observed. Event-free and overall survival rates are 100% with median follow-up of 19.5 months. No cases of GVHD have been observed. Sirolimus weaning was possible in all but one eligible patient to date. Ongoing followup and a larger prospective clinical trial are required to determine the long-term safety and efficacy of this regimen in children.

Successful treatment with eculizumab for posterior reversible encephalopathy syndrome due to underlying transplant‐associated thrombotic microangiopathy in patients transplanted for sickle cell disease

“…A combination of preexisting endothelial damage secondary to ongoing hemolysis and additional insult to the vascular endothelium during HCT places patients with SCD at greater risk of endothelial injury syndromes such as PRES, VOD, and TA‐TMA . The use of reduced‐intensity conditioning regimens and sirolimus for GVHD prophylaxis in this population has led to a decrease in incidence of VOD and PRES, respectively . While PRES and TA‐TMA share similar risk factors (CNI, steroid exposure, and GVHD), it is unclear if concurrent TA‐TMA was present in prior reports of PRES‐affected SCD transplant recipients .…”

Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA‐matched haematopoietic cell transplant for sickle cell disease

“…As such, differences in conditioning regimens, GVHD prophylaxis, and supportive care could have impacted transfusion outcomes in ways that were not controlled even with multiple variable analysis. Finally, all of the patients transplanted in this study received myeloablative, busulfan‐based conditioning or melphalan‐based reduced‐intensity conditioning; future work should investigate the association of HLA class I alloimmunization and platelet transfusion support after conditioning with alemtuzumab and low‐dose total body irradiation, a regimen that has shown excellent results in SCD (Hsieh et al , ; Saraf et al , ; Guilcher et al , ).…”

Stable renal function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation

“…The existing literature suggests that while existing sickling injury is not reversed, new complications related to SCD are not expected post-HSCT. 25,36,41 Both SCD and HSCT with the use of traditional MAC regimens may cause kidney injury. Although the RIC and NMA approaches to HSCT are considered less toxic, they still involve the use of nephrotoxic medications.…”

“…The NMA regimen and supportive care are illustrated in Figure 1, with more detailed description by Guilcher et al 41 43 Pre-HSCT renal ultrasound reports were also documented for any structural abnormalities.…”