HLA Identical (Related/Unrelated) Donor Hematopoietic Stem Cell Transplant for Hemoglobinopathies using Pre-transplant Immune Suppression and Post-transplant Cyclophosphamide: Does it Help Consolidate Our Gains?

Abstract

Abstract Awaiting gene therapy, hematopoietic stem cell transplant (HSCT) is only curative treatment for Transfusion Dependent Thalassemia (TDT)/Sickle Cell Disease (SCD). Although conventional myeloablative conditioning (MAB) with calcineurin inhibitor (CNI) based graft-versus-host-disease (GvHD) prophylaxis in HLA identical donors (related/unrelated) (MSD/MRD/MUD) have shown good outcomes but are associated with increased regimen related toxicity (RRT), acute and chronic GvHD especially with use of peripheral blood stem cells (PBSC). We hereby report our experience of using (APOLLO protocol) for HLA identical donor HSCT for TDT/SCD. Thirty-two consecutive patients (TDT-16/SCD-16) were enrolled. Fourteen underwent MUD-HSCT whereas 18 received MSD/MRD. GvHD prophylaxis was with post-transplant cyclophosphamide (PTCY), sirolimus, and mycophenolate mofetil. All tolerated pre-transplant immune-suppression (PTIS) well and proceeded to HSCT. No significant RRT was seen in any of our patients. One patient developed acute grade II/IV GvHD (skin/liver) whereas none of the evaluable patients had chGvHD. Out of 32 evaluable patients at a median follow-up of 249.5 days (range 18–1074), 31 are alive and disease free, making an overall survival (OS) and disease-free survival (DFS) of 96.88 %. APOLLO protocol including PTIS, augmented John Hopkins conditioning and PTCY can safely be extended to HLA identical donors with minimal RRT, acute or chronic GvHD.