Shifting paradigms from myeloablation to immune modulation: pre-transplant immune-suppression and post-transplant cyclophosphamide in human leucocyte antigen identical related donor hematopoietic stem cell transplantation for sickle cell disease

Abstract

Excellent outcomes of HLA identical related donor hematopoietic stem cell transplant (HSCT) in patients with sickle cell disease (SCD) have put it as a standard of care in symptomatic patients especially after a failed hydroxyurea therapy, however a large part of this data comes from resourcerich settings. These encouraging outcomes are in-turn due to patients being considered for HSCT in relatively well-preserved condition, safer transplant conditioning, better GvHD prophylaxis strategies and improved overall supportive care. Large-scale real-world data from resource-constraint settings is however missing. We retrospectively analysed baseline characteristics and longitudinal data of 85 paediatric and young adults who underwent matched sibling donor (MSD) HSCT for SCD over a decade. Patients received conditioning as per APOLLO PROTOCOL from May 2019. Median age was 8 years (range 10 months – 32 years). Median time to neutrophil and platelet engraftment was 13 days (range, 10-19) and 14 days (range, 6-48). None experienced primary graft failure and one had secondary graft failure. Acute GvHD was seen in 5 patients (4- acute skin GvHD, grade I/II; 1- gut GvHD, grade IV). At a median follow up of 1191 days (range, 23–4226), Kaplan Meier estimated EFS and OS is 94.11% and 96.47% respectively. OS in APOLLO protocol cohort was 100% and 91.4% using conventional (BU-CY or TTF based conditioning). Age > 10 years turned out to be the only significant risk factor affecting outcome (100% vs 89.28%, P=0.007). This emphasizes the need of early intervention < 10 years of age for best clinical outcomes.