Successful allogenic bone marrow transplant post reduced-intensity conditioning chemotherapy in an adult patient with severe phenotype Glanzmann thrombasthenia: A case report

Abstract

Background: In patients with severe Glanzmann thrombasthenia (GT), a genetic platelet surface receptor disorder of glycoprotein IIb/IIIa (integrin αIIbβ3) that results in prolonged and chronic bleeding, hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. Unfortunately, approximately 30% of all patients undergoing HSCT die from this toxic procedure, owing to the associated risk of infection or chronic graft-versus-host disease, with adults at a higher risk.Case presentation: Herein, we describe the case of a 21-year-old woman from Saudi Arabia who had symptomatic GT for the past 15 years and underwent HSCT following a modified reduced-intensity conditioning (RIC) protocol. This is the fifth reported case of the use of HSCT for treating an adult patient with GT in which RIC HSCT has resulted in long term sustained chimerism with minimal toxicity. The patient was genetically confirmed to have GT since childhood. Owing to recurrent severe bleeding events, the patient had received multiple blood and platelet transfusions and hormonal therapy affecting her quality of life. In September 2019, the patient underwent allogeneic stem cell transplantation from her HLA-matched healthy brother, who was genetically negative for GT. A reduced-intensity conditioning chemotherapy regimen of anti-thymocyte globulin, fludarabine/busulfan (9.6 mg/kg), and a dose of 2.96 × 106 CD34+ cells were administered. The patient experienced moderate mucositis with associated oral mucosal bleeding during HSCT, which was managed. Low cytomegalovirus viremia occurred 25 days after transplant and resolved with treatment. Neutrophil engraftment occurred on day +23, and platelet engraftment on day +27. A platelet aggregation test repeated after 1 year and 10 months was negative. At 24 months following HSCT, the patient was well and graft versus host disease-free, had no bleeding tendency, and discontinued all immunosuppressant therapy.Conclusion: HSCT in adults with severe phenotype GT is possible if indicated, but careful consideration of different aspects of care should be considered and strictly followed for a successful outcome. Future research through more case reports or series utilizing similar reduced intensity conditioning HSCT is needed to fill the knowledge gap given the rarity of indication and the new protocol.