Allogeneic Haematopoietic Stem Cell Transplantation for Beta Thalassaemia Major in Pakistan: Outcome of 186 Cases

Abstract

To analyse outcome of allogeneic haematopoietic stem cell transplantation (HSCT) in patients of beta thalassaemia major treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. The study included 186 consecutive beta thalassaemia patients undergoing HSCT from HLA matched related donors from October 2001 to December 2014. A comparison of conditioning regimens was made between long protocol (HU30mg/kg/day Azathioprine 3mg/kg/day, FLU 150, Bu14, Cy160) and Bu14/Cy200 both with or without Thiotepa, using overall and disease free survival (OS and DFS) as primary endpoints with rejection, acute and chronic GVHD as secondary end points. The study included 124 male and 62 female patients. Median age was 50 months (range 20 months to 13 years). Mean serum ferritin level before transplant was 1912 μg/L (range 426 to 5000). Patients were stratified as class I (n=49), II (n=62), and III (n=75) respectively as per Pesaro risk classification. Ninety three patients received conditioning with long protocol and same number of patients received Bu14/Cy200 conditioning regimen. Thiotepa was given to 38 patients (33 on long protocol and 5 on Bu14/Cy200). At a median follow up of 1683 days OS and DFS were 80.6 % and 69.4% respectively. In patients receiving long protocol OS, DFS and rejections were 85%, 72% and 15% respectively, whereas, in Bu14/Cy200 group OS, DFS and rejections were 76%, 66.7% and 11.8% respectively. Patients receiving Thiotepa during conditioning had lesser rejections (1/38) compared to those receiving conditioning without thiotepa (24/124) p=0.03. Eighty-five (45.7%) patients developed acute GVHD and 7 (3.8%) cases had chronic GVHD. Long conditioning protocol was found to be associated with better survival in beta thalassaemia patients undergoing allogeneic HSCT. Addition of thiotepa to conditioning regimen significantly reduced incidence of graft rejection.