Allogeneic Hematopoietic Stem-Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study includes 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD/URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for two days, fludarabine for 5 days, 2-3 days of busulfan depending upon cytogenetics, and 200 cGy total body irradiation (TBI). MRD/URD recipients received tacrolimus/short course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PT/Cy) followed by tacrolimus and mycophenolate mofetil. At median follow-up of 24 months (range, 9-50), 19/22 patients are alive with reversal of the disease phenotype and correction of the MDS, including eradication of cytogenetic abnormalities. Three patients died: one from refractory acute myelogenous leukemia (AML), one from GVHD, and one from sepsis. There was a 26% incidence of grade III-IV acute GVHD in the MRD/URD groups, and no grade III-IV aGVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD/URD cohort, whereas only 28% of HRD recipients developed cGVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PT/Cy to the MRD/URD cohorts to reduce GVHD. Copyright © 2018. Published by Elsevier Inc.

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