AUTHOR=Oved Joseph Hai , Shah Yash B. , Venella Kimberly , Paessler Michele E. , Olson Timothy S. 

TITLE=Non-myeloablative conditioning is sufficient to achieve complete donor myeloid chimerism following matched sibling donor bone marrow transplant for myeloproliferative leukemia virus oncogene (MPL) mutation-driven congenital amegakaryocytic thrombocytopenia: Case report

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.903872

DOI=10.3389/fped.2022.903872

ISSN=2296-2360

ABSTRACT=Background: Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder of platelet production that is most commonly caused by loss of function biallelic mutations in MPL, the gene encoding the thrombopoietin receptor (TPOR). Patients with MPL-mutant CAMT are not only at risk for life-threatening bleeding events, many affected individuals will ultimately develop bone marrow aplasia owing to absence of thrombopoietin/TPOR signaling required for maintenance of hematopoietic stem cells. Curative allogeneic stem cell transplant for patients with CAMT has historically used myeloablative conditioning; however, given the inherent stem cell defect in MPL-mutant CAMT, a less intensive regimen may prove equally effective with reduced morbidity, particularly in patients with evolving aplasia. 
Methods: We report the case of a 2-year-old boy with MPL-mutant CAMT and bone marrow hypocellularity who underwent matched sibling donor bone marrow transplant using a non-myeloablative regimen consisting of fludarabine, cyclophosphamide and ATG. 
Results: The patient achieved rapid trilinear engraftment and resolution of thrombocytopenia. While initial myeloid donor chimerism was mixed (88% donor), due to competitive advantage of donor hematopoietic cells, myeloid chimerism increased to 100% by 4 months post-transplant.  Donor chimerism and blood counts remained stable through 1-year post-transplant. 
Conclusions: This experience suggests that non-myeloablative conditioning is a suitable approach for patients with MPL-mutant CAMT undergoing MSD-BMT and is associated with reduced risks of conditioning related toxicity compared to traditional myeloablative regimens.