Ex Vivo CD34+-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response.

Abstract

Ex vivo CD34+-selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+-selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34+-selected TCD allograft as a calcineurin inhibitor-free intervention for the prevention of GVHD in patients with acute leukemia and MDS.

• Authors: Pere Barba, Patrick Hilden, Sean M Devlin, Molly Maloy, Djamilia Dierov, Jimmy Nieves, Matthew D Garrett, Julie Sogani, Christina Cho, Juliet N Barker, Nancy A Kernan, Hugo Castro-Malaspina, Ann A Jakubowski, Guenther Koehne, Esperanza B Papadopoulos, Susan Prockop, Craig Sauter, Roni Tamari, Marcel R M van den Brink, Scott T Avecilla, Richard Meagher, Richard J O'Reilly, Jenna D Goldberg, James W Young, Sergio Giralt, Miguel-Angel Perales, Doris M Ponce
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 23 Issue 3 Pg. 452-458 (Mar 2017) ISSN: 1523-6536 [Electronic] United States
• PMID: 28017734 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD34

Topics

• Acute Disease
• Adult
• Aged
• Antigens, CD34
• Female
• Graft vs Host Disease (etiology, pathology, prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods, mortality)
• Humans
• Incidence
• Leukemia (therapy)
• Lymphocyte Depletion (methods)
• Male
• Middle Aged
• Myelodysplastic Syndromes (therapy)
• Peripheral Blood Stem Cell Transplantation (adverse effects, methods, mortality)
• Survival Analysis
• Transplantation, Homologous
• Treatment Outcome
• Young Adult