Double‐unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA‐identical sibling bone marrow transplantation

Abstract

UCBT recipients with TM are at high risk of EF related to low number of stem cells and prior alloimmunization after multiple blood transfusions. Here, we evaluated the safety and efficacy of double-unit UCBT using TT-containing conditioning regimens in TM. Retrospective analysis of children who underwent double-unit UCBT for TM in the Prince of Wales Hospital between August 2007 and January 2017, and outcome of double-unit UCBT for TM was compared with outcome of HLA-matched sibling BMT. Ten patients, median age 4.2 years, received double-unit UCBT. All patients except one engrafted at a median of 19 days. None of the patients with successful engraftment had grade III or IV aGVHD. Among nine patients with successful engraftment, six of nine patients evaluable after day 100 developed cGVHD.All patients with cGVHD were well controlled after treatment with steroids and/ or supportive care and maintained good quality of life. In comparison with patients receiving BMT, those given UCBT had slower platelet recovery, and more cGVHD.With a median follow-up of 272 months after BMT and 84 months after UCBT, the 8-year OS after BMT and UCBT was 92% and 90% (P = .84), whereas 8-year DFS after BMT and UCBT was 87% and 80% (P = .54). UCB could be an acceptable source of stem cells for transplantation of TM patients when HLA-matched family bone marrow donors are NA.

Curative therapy for hemoglobinopathies: an International Society for Cell & Gene Therapy Stem Cell Engineering Committee review comparing outcomes, accessibility and cost of ex vivo stem cell gene therapy versus allogeneic hematopoietic stem cell transplantation

“…When higher cell doses were used in TDT, the 5-year OS and EFS were 88.3% and 73.9%, respectively [66]. Strategies to improve outcomes in unrelated CB HSCT include the use of multiple CB units [67,68]; combining CB with Tcell-depleted, HLA-haploidentical CD34+ HSCs [69]; and ex vivo expansion of umbilical CB-derived stem and progenitor cells [70,71].…”

Improving outcomes and quality of life for patients with transfusion-dependent β-thalassemia: recommendations for best clinical practice and the use of novel treatment strategies

“…It is estimated that > 70% of patients do not have a suitable sibling HLA-matched donor, although non-sibling-related donors may also be available, particularly in populations where large families and consanguineous marriages are common [54,57,58]. Some evidence suggests that good outcomes can be achieved with unrelated donors, provided that donor and recipient are closely HLA-matched; in some cases, outcomes with unrelated donors were comparable to those achieved using matched sibling donors [8,57,[59][60][61][62]. Other alternative HSCT strategies, such as HLA-antigen-mismatch donors [58], pretransplant immunosuppression [61], or double-unit unrelated cord blood transplantation [62], may further broaden the safety and/or applicability of HSCT.…”

“…Some evidence suggests that good outcomes can be achieved with unrelated donors, provided that donor and recipient are closely HLA-matched; in some cases, outcomes with unrelated donors were comparable to those achieved using matched sibling donors [8,57,[59][60][61][62]. Other alternative HSCT strategies, such as HLA-antigen-mismatch donors [58], pretransplant immunosuppression [61], or double-unit unrelated cord blood transplantation [62], may further broaden the safety and/or applicability of HSCT. In addition, advances in preimplantation genetic diagnosis have enabled the selection of an HLA-matched embryo to produce a sibling donor, although the ethics of producing 'savior siblings' have been questioned [63,64].…”