Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease

Abstract

Please cite this article as: D.A. Patel, A.M. Akinsete, J. de la Fuente, A.A. Kassim, Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease: An update, Hematology/Oncology and Stem Cell Therapy (2020), doi: https://doi. AbstractHematopoietic cell transplant (HCT) can cure both children and adults with sickle cell disease. Outcomes have historically been poor for the vast majority of patients who lack a matched sibling donor. However, the development of haploidentical HCT (haplo-HCT) with high doses of posttransplant cyclophosphamide (PTCy) has allowed for curative long-term potential with favorable transplantrelated outcomes, though this has not obviated the potential for graft rejection from human leukocyte antigen mismatch and repeated 2 red blood cell transfusions. Accordingly, multiple strategies have been developed to improve outcomes, the majority of which are based on the Johns Hopkins platform from 2012. Presently, we aim to discuss results from pertinent studies and compare outcomes with the two most recent approaches involving either thiotepa plus 200-cGy total body irradiation or 400-cGy total body irradiation.Direct comparisons are required to determine the optimized curative potential. Transplant-eligible patients must be referred to tertiary medical centers for consideration of haplo-HCT.

Excellent outcome of stem cell transplantation for sickle cell disease

“…Since SCD is a non-malignant hematologic disorder, avoiding GVHD is of utmost importance. Successful GVHD prevention by in vitro or in vivo lymphodepletion has been reported for haploidentical HSCT in SCD [ 17 – 20 ]. GVHD rates were remarkably low in our patients with the complete absence of severe acute and chronic GVHD in all donor groups including 9/10 MUD and MMFD.…”

“…Therefore, HSCT from HLA-haploidentical mismatched family donors (MMFD) is a relevant alternative [ 16 ]. HSCT from MMFD was increasingly successful over the last years due to improved methods of GVHD prevention by in vitro or in vivo lymphodepletion [ 17 – 20 ]. In vivo manipulation of alloreactive T-cells with post transplantation cyclophosphamide (PTCY) is attractive because of low GVHD rates reported in malignant disorders and its minimal economic impact, making it a feasible option also at HSCT centers in low to middle-income countries [ 6 , 16 , 21 ].…”

Global perspectives on cellular therapy for children with sickle cell disease

“…However, stable partial donor engraftment after allogeneic HSCT is sufficient to achieve disease amelioration [68–70]. Therefore, reduced toxicity and nonmyeloablative conditioning regimens for allogeneic HSCT are of high research interest and, if successful, could have broad global applicability [51–54,71 ▪▪ ,72]. Currently applied nonmyeloablative regimens require optimization before use should become widespread and higher risk of graft rejection must be mitigated.…”

Hematopoietic Stem Cell Transplantation in Children With Hemoglobinopathies: Brazilian Society of Bone Marrow Transplantation Consensus

“…The HSCT with haploidentical donors is an important option but with few cases published so far 19,35 . Haploidentical transplants should be performed only in the context of clinical trials at this time 19,36 .…”