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Clinical Trial
. 2014 Dec;20(12):1940-8.
doi: 10.1016/j.bbmt.2014.08.004. Epub 2014 Aug 9.

Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2 deficiency

Jennifer Grossman  1 , Jennifer Cuellar-Rodriguez  2 , Juan Gea-Banacloche  3 , Christa Zerbe  2 , Katherine Calvo  4 , Thomas Hughes  5 , Fran Hakim  3 , Kristen Cole  3 , Mark Parta  6 , Alexandra Freeman  2 , Steven M Holland  2 , Dennis D Hickstein  7
Affiliations
Clinical Trial

Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2 deficiency

Jennifer Grossman et al. Biol Blood Marrow Transplant. 2014 Dec.

Abstract

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.

Keywords: Familial acute myelogenous leukemia; GATA2; Hematopoietic stem cell transplantation; Myelodysplastic syndrome.

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Conflict of interest statement

Conflict of Interest: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Typical evolution of pathologic changes in the bone marrow in GATA2 deficiency. Bone marrow findings for patient 7. (A), (C) and (E) show bone marrow biopsy results 2 years prior to transplant, 2 months prior to transplant and 6 months post transplant respectively. (B), (D) and (F) show bone marrow aspirates from the same time points. This demonstrates the progression of the bone marrow from hypocellular to hypercellular and finally to normal trilineage hematopoiesis.
Figure 2
Figure 2
Chimerism after hematopoietic stem cell transplant. Percentage of peripheral blood donor chimerism from myeloid, CD3+, CD14+, NK cell fractions and bone marrow.
Figure 3
Figure 3
Reconstitution of CD19+ B-cells, NK cells, and monocytes 6 months post-transplant in a GATA2 deficient patient.
Figure 4
Figure 4
Kaplan-Meier curves showing overall survival according to type of donor.
See this image and copyright information in PMC

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