Two Consecutive Haploid Hematopoietic Stem Cell Transplantation for a Case of Glanzmann Thrombasthenia
Authors: Yu Xue , Gao Bei-Bei , Hu Jiong , Yan Jinsong , Kang Zhijie 
Published: December 2024

Introduction
Glanzmann Thrombasthenia（GT) is an autosomal recessive hereditary disease with an incidence of about one in a million. Common clinical manifestations include spontaneous bleeding or bleeding tendency, such as petechial spots and petechiae on the skin, nasal bleeding, gum bleeding. Its pathogenesis is a genetic defect in the platelet membrane glycoprotein GPⅡb/Ⅲa (αⅡbβ3), which leads to abnormal expression, maturation and transport of the GPⅡb/Ⅲa complex, ultimately causing platelet dysfunction and poor fibrinogen binding. Common treatments for GT include hemostatic therapy, platelet transfusion, and the use of recombinant activated factor Ⅶa (rFⅦa), while gene therapy is still in the research. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only treatment for curing GT. Less than 100 cases of HSCT for GT have been reported with graft from matched sibling, unrelated donor or umbilical cord blood stem cells. Till now, no haploidentical HSCT has been reported for GT. Here, we report a 7-year-old patient with GT who recovered for nearly 6 years after two consecutive haploidentical allo-HSCT.
Case report
The girl was diagnosed with GT at 3 years old and had been suffering from skin petechiae, intermittent gingival and nasal bleeding for 4 years. She had to receive platelet transfusion every month due to worsening bleeding symptoms in the past six months. The chief criminal is a missense homozygous mutation on exon 23 of the ITGA2B gene on chromosome 17, which was inherited from her parents, who both carry heterozygous mutation at the same locus of ITGA2B respectively. The gene mutation resulted with c.2333A &gt; C, in a mutation of glutamine to proline (p.Q778P).
For no matching sibling donors and unrelated donors, haploidentical allo-HSCT was performed on August 8, 2018. The patient's mother was selected as the donor with HLA 6/10, blood type O+ for O+. The conditioning regimen with Flu-BuCy (fludarabine 120mg/m2, Busulfan 6.4mg/kg, cyclophosphamide 100mg/kg) was used, and to control Graft-Versus-Host Disease (GVHD) with ATG 5mg/kg/day. The graft was bone marrow plus peripheral blood stem cells, including CD34+ cells 5.22×106/kg and mononuclear cells 12.85×108/kg. Neutrophil and platelet recovery on day +12 and day +13 after transplantation respectively. Transplantation chimerism assessment (TCA) was complete donor type (TCA 98.7%) on day +13. Unfortunately, infection of CMV led to rapid decline in leukocytes and platelets on day +16. Then TCA decreased to 70.8% on day +24, to 0.8% on day +32, suggesting first transplant failure.
The possible reasons for transplant failure may be insufficient myeloablative or poor stem cell function of the donor. A sequential haploidentical allo-HSCT was initiated on September 20, 2018, with a replacement donor for the patient's father (HLA 5/10, blood type B+ for O+). The conditioning regimen was applied with modified Flu-BuCy (fludarabine 150mg/m2, Busulfan 9.6mg/kg, cyclophosphamide 100mg/kg) and to control GVHD with ATG 5mg/kg. The graft was bone marrow plus peripheral blood stem cells, including 17.45×106/kg CD34+ cells and 20.87×108/kg mononuclear cells. Neutrophil recovery on day +11 and platelet recovery on day +13 after transplantation, and the bone marrow and peripheral blood TCA was complete donor type (99%).
As of 1st August 2024, the patient was followed up for 6 years approximately after transplant and did not develop any III-IV° GVHD with TCA &gt;99% consistently. The patient's illness has been cured and she have returned to normal life.