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

Abstract

Summary: 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.