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. 2022 Jan;196(1):169-178.
doi: 10.1111/bjh.17840. Epub 2021 Sep 27.

Donor source and post-transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency

Diana X Nichols-Vinueza  1 , Mark Parta  2 , Nirali N Shah  3 , Jennifer M Cuellar-Rodriguez  4 , Thomas R Bauer Jr  5 , Robert R West  5 , Amy P Hsu  4 , Katherine R Calvo  6 , Seth M Steinberg  7 , Luigi D Notarangelo  4 , Steven M Holland  4 , Dennis D Hickstein  5
Affiliations

Donor source and post-transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency

Diana X Nichols-Vinueza et al. Br J Haematol. 2022 Jan.

Abstract

GATA2 deficiency was described in 2011, and shortly thereafter allogeneic hematopoietic stem cell transplantation (HSCT) was shown to reverse the hematologic disease phenotype. However, there remain major unanswered questions regarding the type of conditioning regimen, type of donors, and graft-versus-host disease (GVHD) prophylaxis. We report 59 patients with GATA2 mutations undergoing HSCT at National Institutes of Health between 2013 and 2020. Primary endpoints were engraftment, reverse of the clinical phenotype, secondary endpoints were overall survival (OS), event-free survival (EFS), and the incidence of acute and chronic GVHD. The OS and EFS at 4 years were 85·1% and 82·1% respectively. Ninety-six percent of surviving patients had reversal of the hematologic disease phenotype by one-year post-transplant. Incidence of grade III-IV aGVHD in matched related donor (MRD) and matched unrelated donor recipients (URD) patients receiving Tacrolimus/Methotrexate for GVHD prophylaxis was 32%. In contrast, in the MRD and URD who received post-transplant cyclophosphamide (PT/Cy), no patient developed grade III-IV aGVHD. Six percent of haploidentical related donor (HRD) recipients developed grade III-IV aGVHD. In summary, a busulfan-based HSCT regimen in GATA2 deficiency reverses the hematologic disease phenotype, and the use of PT/Cy reduced the risk of both aGVHD and cGVHD.

Keywords: GATA2; allogeneic; cyclophosphamide; donor; transplantation.

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Conflict of interest statement

Competing Interest Statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
(A) Overall Survival-OS in MRD/URD (Tacro/MTX), MRD/URD (PT/Cy), HRD (PT/Cy) recipients, as a function of years after transplant. Hazard Ratios (HR): MRD/URD (Tacro/MTX) vs. MRD/URD (PT/Cy): HR= 0.723 (95% CI 0.161–3.251); MRD/URD (Tacro/MTX) vs. HRD (PT/Cy): HR= 0.258 (95% CI 0.029–2.313); MRD/URD (PT/Cy) vs. HRD (PT/Cy): HR= 0.372 (95% CI 0.038–3.596). (B) Event Free Survival-EFS in MRD/URD (Tacro/MTX), MRD/URD (PT/Cy), HRD (PT/Cy) recipients, as a function of years after transplant. Hazard Ratios (HR): MRD/URD (Tacro/MTX) vs. MRD/URD (PT/ Cy): HR= 0.940 (95% CI 0.234–3.785); MRD/URD (Tacro/MTX) vs. HRD (PT/Cy): HR = 0.547 (95% CI 0.100–2.985); MRD/URD (PT/Cy) vs. HRD (PT/Cy):HR= 0.590 (95% CI 0.108–3.233).
Figure 2.
Figure 2.
(A) Cumulative Incidence of aGVHD (grade III-IV) in MRD/URD (Tacro/MTX) recipients, MRD/URD (PT/Cy), HRD (PT/Cy). (B) Cumulative Incidence of moderate/severe cGVHD in MRD/URD (Tacro/MTX), MRD/URD (PT/Cy), HRD (PT/Cy) recipients.
Figure 2.
Figure 2.
(A) Cumulative Incidence of aGVHD (grade III-IV) in MRD/URD (Tacro/MTX) recipients, MRD/URD (PT/Cy), HRD (PT/Cy). (B) Cumulative Incidence of moderate/severe cGVHD in MRD/URD (Tacro/MTX), MRD/URD (PT/Cy), HRD (PT/Cy) recipients.
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