Presented to the AACT 2015 Conference

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure SCD but myeloablative conditioning regimens are associated with substantial morbidity and mortality. The experience of HSCT in adult patients is therefore very limited and only recently a non-myeloablative regimen with alemtuzumab and low-dose total body irradiation (TBI) conditioning regimen was successfully utilized at the National Institute of Health in a small cohort of HLA and ABO matched related transplants. This approach was never replicated elsewhere and our center tested the same strategy in 13 adult patients with HLA matched related donors even if ABO mismatched. We utilized the NIH conditioning with alemtuzumab/total body irradiation (TBI) 300 cGy and sirolimus as post-transplant immunosuppression in 13 high risk SCD adult patients transplanted between November 2011 and June 2014. Patients received MRD G-CSF mobilized peripheral blood stem cells that in 2 cases were ABO incompatible. Quality-of-Life (QoL) measurments were performed at different time-points after HSCT.

All patients initially engrafted. Over 12 months, a mix donor/recipient chimerism was maintained stable in 11 patients (85%), slowly reduced in 1 patient, while another patient who was not compliant experienced a secondary graft failure. With a median follow-up of 15 months (range: 11-37 months) there was no mortality, no acute or chronic GVHD and no grade 3-4 extramedullary toxicity. At 1 year post-transplant, 12 patients with any persistent level of donor cell chimerism normalized the hemoglobin concentration regardless of ABO matching; improved cardio-pulmonary paramenters and QoL paramenters such as bodily pain, general health, and vitality. In two patients sirolimus was stopped without rejection or SCD complications.

These results validate for the first time the successful use of a chemotherapy-free regimen in MRD HSCT for high risk SCD, here also in ABO mismatched cases, and demonstrate an improvement in QoL without risk of GVHD or mortality.