Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD). We utilized the chemotherapy-free, alemtuzumab/total body irradiation 300 cGy regimen with sirolimus as post-transplantation immunosuppression in 13 high-risk SCD adult patients between November 2011 and June 2014. Patients received matched related donor (MRD) granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, including 2 cases that were ABO incompatible. Quality-of-life (QoL) measurements were performed at different time points after HSCT. All 13 patients initially engrafted. A stable mixed donor/recipient chimerism was maintained in 12 patients (92%), whereas 1 patient not compliant with sirolimus experienced secondary graft failure. With a median follow-up of 22 months (range, 12 to 44 months) there was no mortality, no acute or chronic graft-versus-host disease (GVHD), and no grades 3 or 4 extramedullary toxicities. At 1 year after transplantation, patients with stable donor chimerism have normalized hemoglobin concentrations and improved cardiopulmonary and QoL parameters including bodily pain, general health, and vitality. In 4 patients, sirolimus was stopped without rejection or SCD-related complications. These results underscore the successful use of a chemotherapy-free regimen in MRD HSCT for high-risk adult SCD patients and demonstrates a high cure rate, absence of GVHD or mortality, and improvement in QoL including the applicability of this regimen in ABO mismatched cases (NCT number 01499888).

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

“…25 Efforts to decrease the early and late complications of transplantation attributed to conditioning regimens have led to RIC regimens. Flu, treosulfan, melphalan, and low-dose TBI 24,[34][35][36] have all been shown to decrease toxicity from the regimen per se, but the risk for rejection is higher. 16 Others have used regimens with minimal toxicity, but that has required prolonged immune suppression to sustain engraftment.…”

Provision of long-term monitoring and late effects services following adult allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based programmes

“…management of infectious 81 complications 4,5 and graft versus host disease [GVHD]), 6 as well as widening of indications to include 82 non-malignant disorders (e.g. haemoglobinopathies) 7 and availability of alternative HSCT donor 83 sources 8 have led to increasing numbers of long-term survivors (i.e. alive two years post-allogeneic 84 HSCT).…”

To condition or not to condition—That is the question: The evolution of nonmyeloablative conditions for transplantation

“…This antibody specifically depletes human lymphocytes and has been successfully used to treat GvHD and chronic lymphocytic leukemia (58). In a recent trial, Dr. Rondelli at the University of Illinois at Chicago coordinated over the course of 3 years the transplantation of 13 adult patients with sickle cell disease with stem cells mobilized in the peripheral blood with granulocyte-colony stimulating factor from matched-related donors who in two cases were ABO incompatible (59). The patients were non-conditioned but received alemtuzumab plus low dose total body irradiation to reduce their immune cells.…”

“…They also received sirolimus as immunosuppression post-transfusion. One year post-transfusion, all 12 of the patients who remained sirolimus compliant expressed stable mixed-donor chimerism and were cured with normal hemoglobin levels, improved cardiopulmonary and quality of life parameters (59). …”

“…For obvious reasons, the number of patients that may benefit from these programs is limited. By contrast, mini-transplants, such as those finally established by Dr. Rondelli (59) are technically simple (they involve a transfusion) and both the harvesting of the graft, by mobilization of a suited relative, and its administration may be performed in day hospital in non-specialized centers. Therefore, this strategy finally opens the way for treatment of large numbers of hemoglobinopathy patients in the country where they live.…”