Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency

• Mutations in the GATA2 gene result cause immune deficiency as well as bone marrow dysplasia and hematologic malignancy.
• We report outcomes on a cohort of 14 patients who were treated with hematopoietic stem cell transplantation using a nonmyeloablative conditioning regimen.
• Matched related donor and unrelated donor groups had the best survival with 3 of 4 patients in each group alive at 2 years.
• The ideal timing of transplantation and conditioning regimen have yet to be determined. Given the high incidence of relapse and rejection, a myeloablative regimen may be optimal.

We treated 14 patients with GATA2 deficiency using a nonmyeloablative allogeneic hematopoietic stem cell transplantation regimen. Four patients received peripheral blood stem cells from matched related donors (MRD), 4 patients received peripheral blood stem cells from matched unrelated donors (URD), 4 patients received hematopoietic stem cells from umbilical cord blood donors (UCB), and 2 patients received bone marrow cells from haploidentical related donors. MRD and URD recipients received conditioning with 3 days of fludarabine and 200 cGy total body irradiation (TBI). Haploidentical related donor recipients and UCB recipients received cyclophosphamide and 2 additional days of fludarabine along with 200 cGY TBI. MRD, URD, and UCB recipients received tacrolimus and sirolimus for post-transplantation immunosuppression, whereas haploidentical recipients received high-dose cyclophosphamide followed by tacrolimus and mycophenolate mofetil. Eight patients are alive with reconstitution of the severely deficient monocyte, B cell, and natural killer cell populations and reversal of the clinical phenotype at a median follow-up of 3.5 years. Two patients (1 URD recipient and 1 UCB recipient) rejected the donor graft and 1 MRD recipient relapsed with myelodysplastic syndrome after transplantation. We are currently using a high-dose conditioning regimen with busulfan and fludarabine in patients with GATA2 deficiency to achieve more consistent engraftment and eradication of the malignant myeloid clones.