Outcomes in Hematopoietic Stem Cell Transplantation for Congenital Amegakaryocytic Thrombocytopenia.

Abstract Background: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, inherited bone marrow failure syndrome. Hematopoietic stem cell transplant (HSCT) is considered a curative treatment option, but existing descriptions of patient and transplant characteristics and outcomes after related and unrelated donor HSCT are sparse. Objectives: We describe outcomes after HSCT for congenital amegakaryocytic thrombocytopenia (CAMT; n=86) from 2000 to 2018. Study Design: We conducted an analysis of data collected by the Center for International Blood and Marrow Transplant Research on patients with CAMT receiving therapeutic allogeneic HSCT. Results: The predominant donor type was HLA-matched or mismatched unrelated donors (n=58, 67%). The remaining included HLA-matched sibling (n=23, 27%) and HLA-mismatched relative (n=5, 6%). The predominant graft types were bone marrow (n=53, 62%) and cord blood (n=25, 29%). The median age at transplantation was 3 years with 82 of 86 patients being transplanted aged ≤10 years. The 5-year graft failure-free and overall survival were 83% (95% CI 74-90) and 86% (95% CI 78-93), respectively. An examination for risk factors confirmed mortality was higher after HLA-mismatched relative and mismatched unrelated donor HSCT compared to HLA-matched sibling and matched unrelated donor HSCT (hazard ratio 3.52, p=0.04; 75% versus 93%). The 1-year incidence of graft failure was 19% after HLA-mismatched HSCT (n=32) compared to 7% after HLA-matched HSCT (n=54, p=0.15). Day-100 grade II-IV acute graft-versus-host disease was 13%, 26% and 30% after HLA-matched sibling, HLA-matched and mismatched unrelated donor HSCT. The 5-year incidence of chronic graft-versus-host disease was 33% with 24 of 28 patients having received grafts from HLA-matched (n=13) and mismatched unrelated (n=11) donors. Conclusion: While HLA-matched donors are preferred, HLA-mismatched donors also extend survival for CAMT.