Successful Use of Haploid Hematopoietic Stem Cell Transplantation for Severe Glanzmann's Thrombasthenia

Objective: Glanzmann's thrombasthenia (GT) is a rare autosomal recessive disorder, which characterized by the clinical manifestations from purpura to severe bleeding. It was caused by mutations of the ITGA2B or ITGB3 gene on chromosome 17, which lead to deficits or reduced expression of the platelet membrane glycoprotein GPIIb/IIIa. We report 5 pediatric patients with severe Glanzmann's thrombasthenia who underwent allogeneic hematopoietic stem cell transplant, to observe the outcomes of allo-HSCT in children with severe Glanzmann's thrombasthenia.

Methods: We retrospectively summarized the clinical and genetic profiles of five patients with Glanzmann's thrombasthenia who underwent allo-HSCT from June 2021 to July 2023. All patients were reduced intensity conditioning (Bufulsan 3.2-6.4mg/kg, CTX 120mg/kg, FLU 180mg/m², ATG 10mg/kg). After conditioning chemotherapy, all the patients received stem cells collected via bone marrow harvest and/or peripheral blood apheresis (PBSC) with CD34 dose of 2.89-7.2×10⁶/kg and received graft vs. host disease (GvHD) prophylaxis with cyclosporine (CSA) and methotrexate (MTX).

Results: There were five children were involved in this observation, one patient suffered from recurrent epistaxis bleeding which was life-threatening; the second suffered from gastrointestinal bleeding and could only accept liquid diet to 10-years-old; other patients also suffered from epistaxis bleeding, gum bleeding or gastrointestinal bleeding. For all the patients, regular red cell transfusions were required, platelet transfusions and recombinant factor VIIa were also used in severe and life-threatening bleeding events. Two of the five developed antiplatelet antibodies before HSCT. All the patients were successfully treated with allo-HSCT. One case received non-relative matched donor of 10/10 HLA, one case with sibling matched donor, and 3 cases with haploid transplantation of HLA 5-6/10 matched. The mean time to neutrophil engraftment was 11 days (11-12 days), and the mean time to platelet engraftment was 16 days (15-18 days). One case had CMV reactivation, one case had HHV-6b infection, one case had grade II acute GVHD of the skin which was controlled rapidly. There was no evidence of chronic GVHD for all the patients. The platelet disorder was corrected to a normal level after allo-HSCT, with no significant complication related to the transplantation. Comparing with HLA matched donor, either from sibling or non-related, the patients receiving haploid transplantation with 5-6/10 HLA matched got similar outcome.

Conclusions: We proposed haploid transplantation treated with the reduced intensity conditioning regimens produced similar outcomes as HLA matched did which could be recommended as an alternative donor for severe Glanzmann's thrombasthenia.