Abstract
Mixed chimerism (MC) occurs frequently after allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) and may be associated with rejection. We report the outcome of MC in 132 TM patients conditioned with Busulphan/Cyclophosphamide, who had successful engraftment and had ⩾1 year follow-up. Chimerism was first assessed at day +28, then every 3-9 months or more frequently if there was MC. If rejection was suspected, immunosuppression was stopped and donor-lymphocyte infusion (DLI) was given if there was no response. Among 132 patients, aged 7 years (range: 2-24), 46/132 (34.8%) had MC in the first year, 32/46 (69.6%) at day +28 and another 14 (30%) between day +28 and 1 year post HSCT. MC was quantified at level 1 (residual host chimerism (RHC) <10%) in 20 (43.5%), level II (RHC 10-25%) in 14 (30.4%) and level III (RHC >25%) in 12 (26.1%). On tapering immunosuppression, 15 (32.6%) developed acute GvHD and 8 (17.4%) had chronic GvHD with reversal to complete chimerism (CC). DLI was administered to 5/46 (10.9%), 1 evolved to CC but 4 rejected the graft. At median follow-up of 60 months (range: 16-172), 20/46 (43.5%) had CC, 18/46 (39.1%) had persistent MC with hemoglobin of 11.5 g/dL (range: 8.4-13.6), whereas 8 (17.4%) rejected the graft. Close monitoring and early intervention is needed with increasing recipient chimerism. Novel strategies are required for preventing graft rejection.
Highlights
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only available curative treatment for β-thalassemia major (TM).[1,2] Graft rejection is a major complication of HSCT for TM and has been reported to occur in 5–30%.3 Different approaches have been taken to reduce graft rejection by either intensifying myeloablative conditioning or by enhancing immunosuppression.[2]
We evaluated the course of mixed chimerism (MC) in TM patients who underwent HSCT using Busulphan/Cyclophosphamide (Bu/Cy)based conditioning, to determine the clinical course, final outcome and possible predictors of such outcomes of MC
None of the remaining 86 patients with complete chimerism (CC) had a drop in blood counts to suggest the possibility of MC at any point beyond 1 year post HSCT
Summary
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only available curative treatment for β-thalassemia major (TM).[1,2] Graft rejection is a major complication of HSCT for TM and has been reported to occur in 5–30%.3 Different approaches have been taken to reduce graft rejection by either intensifying myeloablative conditioning or by enhancing immunosuppression.[2]. Different approaches have been taken to reduce graft rejection by either intensifying myeloablative conditioning or by enhancing immunosuppression.[2] Residual host cells (RHCs) can persist without graft rejection in a stable state referred to as mixed chimerism (MC), observed in 30–40% of patients after HSCT for hemoglobinopathies.[1,3] Intriguingly, many of these patients demonstrate stable and durable co-existence of donor and host cells associated with transfusion independence and the lack of continued clinical manifestations of their disease.[1,2,3,4,5,6,7,8]. Myeloid engraftment (neutrophil recovery) was defined as an ANC ⩾ 500 × 109/L for 3 consecutive days after nadir and platelet engraftment as a platelet count of 420 000 × 109/L independent of platelet transfusions for at least 7 consecutive days.[5]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call