The Reconstitution of T-cells after Allogeneic Hematopoietic Stem Cell Transplant in a Pediatric Patient with Congenital Amegakaryocytic Thrombocytopenia (CAMT)

Abstract

Background: Congenital amegakaryocytic thrombocytopenia (CAMT) is a bone marrow failure syndrome with autosomal recessive inheritance characterized by the lack of megakaryocytes and thrombo-cytopenia. The cause of the disease is a mutation in the c-Mpl gene, which encodes the thrombopoietin (TPO) receptor. The main treatment for this genetic disorder is an allogeneic hematopoietic stem cell trans-plant (allo-HSCT). However, transplant-related mortality, development of acute and chronic graft-versus-host disease (GvHD), and susceptibility to opportunistic infections are major barriers to transplantation. Delay in the reconstitution of T cells and imbalance in the regeneration of distinct functional CD4 and CD8 T-cell subsets mainly affect post-transplant complications. We report a case of CAMT, who developed acute GvHD but had no signs and symptoms of chronic GvHD following allo-HSCT. Case Presentation: At the age of four, she presented with petechiae and purpura. In laboratory investiga-tions, pancytopenia without organomegaly, and cellularity less than 5% in bone marrow biopsy, were ob-served. A primary diagnosis of idiopathic aplastic anemia was made, and she was treated with prednisolone, cyclosporine, and anti-thymocyte globulin (ATG), which did not respond. Genetic analysis revealed the mutation c.1481T>G (p. L494W) in exon 10 of the c-Mpl gene, and the diagnosis of CAMT was confirmed. The patient underwent allo-HSCT from a healthy sibling donor. Alloimmunization reactions and immune disorders were present due to long-term treatment with immunosuppressive medications and repeated blood and platelet transfusions. Hence, the regeneration of T-lymphocytes after allo-HSCT was evaluated. Conclusion: Successful treatment of acute GvHD prevented advancing the condition to chronic GvHD, and this was accompanied by delayed T-cell reconstitution through an increase in Treg:Tcons ratio.