Non-myeloablative human leukocyte antigen-matched related donor transplantation in sickle cell disease: outcomes from three independent centres

Abstract

Non-myeloablative haematopoietic progenitor cell transplantation (HPCT) from matched related donors (MRD) has been increasingly utilized in sickle cell disease (SCD). A total of 122 patients received 300 cGy of total body irradiation (TBI), alemtuzumab, unmanipulated filgrastim-mobilized peripheral blood HPC and sirolimus. The median follow-up was four years; median age at HPCT was 29 years. Median neutrophil and platelet engraftment occurred on day 22 and 19 respectively; 41 patients required no platelet transfusions. Overall and sickle-free survival at one and five years were 93% and 85% respectively. Age, sex, pre-HPCT sickle complications, ferritin and infused HPC numbers were similar between graft failure and engrafted patients. Mean donor myeloid chimaerism at one and five years post HPCT were 84% and 88%, and CD3 was 48% and 53% respectively. Two patients developed grade 1 and 2 skin graft-versus-host disease (GVHD) with no chronic GVHD. Median days of recipients taking immunosuppression were 489; 83% of engrafted patients have discontinued immunosuppression. Haemoglobin, haemolytic parameters and hepatic iron levels improved post HPCT. Pulmonary function testing, hepatic histology and neurovascular imaging remained stable, suggesting cessation of further sickle-related injury. Fourteen patients had children. In this largest group of adult SCD patients, this regimen was highly efficacious, well-tolerated despite compromised organ functions pre HPCT, and without clinically significant GVHD.