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Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen.
Biol Blood Marrow Transplant. 2018 06; 24(6):1250-1259.BB

Abstract

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 included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD.

Authors+Show Affiliations

Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, Maryland. Electronic address: mark.parta@nih.gov.Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland.Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland.Department of Internal Medicine, George Washington University Medical Center, Washington, DC.Department of Laboratory Medicine, NIH Clinical Center, Bethesda, Maryland.Department of Pharmacy, NIH Clinical Center, Bethesda, Maryland.Office of the Clinical Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland.Office of the Clinical Director, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Mexico City, Mexico.Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

29412158

Citation

Parta, Mark, et al. "Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 24, no. 6, 2018, pp. 1250-1259.
Parta M, Shah NN, Baird K, et al. Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen. Biol Blood Marrow Transplant. 2018;24(6):1250-1259.
Parta, M., Shah, N. N., Baird, K., Rafei, H., Calvo, K. R., Hughes, T., Cole, K., Kenyon, M., Schuver, B. B., Cuellar-Rodriguez, J., Zerbe, C. S., Holland, S. M., & Hickstein, D. D. (2018). Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 24(6), 1250-1259. https://doi.org/10.1016/j.bbmt.2018.01.030
Parta M, et al. Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen. Biol Blood Marrow Transplant. 2018;24(6):1250-1259. PubMed PMID: 29412158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogeneic Hematopoietic Stem Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen. AU - Parta,Mark, AU - Shah,Nirali N, AU - Baird,Kristin, AU - Rafei,Hind, AU - Calvo,Katherine R, AU - Hughes,Thomas, AU - Cole,Kristen, AU - Kenyon,Meg, AU - Schuver,Bazetta Blacklock, AU - Cuellar-Rodriguez,Jennifer, AU - Zerbe,Christa S, AU - Holland,Steven M, AU - Hickstein,Dennis D, Y1 - 2018/02/03/ PY - 2017/11/25/received PY - 2018/01/29/accepted PY - 2018/2/8/pubmed PY - 2019/4/2/medline PY - 2018/2/8/entrez KW - GATA2 KW - GVHD KW - Graft-versus host disease KW - HSCT KW - Hematopoietic stem cell transplant KW - MDS KW - Myelodysplastic syndrome SP - 1250 EP - 1259 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 24 IS - 6 N2 - 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 included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/29412158/Allogeneic_Hematopoietic_Stem_Cell_Transplantation_for_GATA2_Deficiency_Using_a_Busulfan_Based_Regimen_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(18)30047-8 DB - PRIME DP - Unbound Medicine ER -