Back to Search
Start Over
Addition of 10-Day Decitabine to Fludarabine/Total Body Irradiation Conditioning is Feasible and Induces Tumor-Associated Antigen-Specific T Cell Responses.
- Source :
-
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2016 Jun; Vol. 22 (6), pp. 1000-1008. Date of Electronic Publication: 2016 Feb 06. - Publication Year :
- 2016
-
Abstract
- Allogeneic hematopoietic cell transplantation (HCT) offers the possibility of curative therapy for patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myelogenous leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics and in patients who cannot tolerate consolidation chemotherapy (eg, due to previous toxicity). We assessed the toxicity and efficacy of 10-day decitabine (Dec), fludarabine (Flu), and 2 Gy total body irradiation (TBI) as a new conditioning regimen for allogeneic HCT in patients with MDS, CMML, or AML. Thirty patients were enrolled, including 11 with MDS, 2 with CMML, and 17 with AML. Patients received 20 mg/m(2)/day Dec on days -11 to -2, 30 mg/m(2)/day Flu on days -4 to -2, and 2 Gy TBI on day -1, followed by infusion of a donor stem cell graft on day 0. Postgrafting immunosuppression consisted of cyclosporin A and mycophenolate mofetil. At a median follow-up of 443 days, the overall survival was 53%, relapse incidence was 27%, and nonrelapse mortality was 27%. The incidence of severe acute (grade III/IV) graft-versus-host disease (GVHD) was 27%, and that of (predominantly mild) chronic GVHD was 60%. Immunomonitoring studies revealed that specific CD8(+) T cell responses against epigenetically silenced tumor-associated antigens (TAAs), including cancer-testis antigens (MAGE-A1/A2/A3 and PRAME) and RHAMM, occurred more frequently in patients who had received Dec/Flu/TBI conditioning (8 of 11 patients) compared with a control group of patients who had received only Flu/TBI conditioning (2 of 9 patients). In summary, Dec/Flu/TBI conditioning proved feasible and effective and enhanced the induction of TAA-reactive CD8(+) T cell responses in vivo, which may contribute to disease control post-transplantation.<br /> (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Antigens, Neoplasm immunology
Antimetabolites, Antineoplastic administration & dosage
Azacitidine administration & dosage
Azacitidine pharmacology
CD8-Positive T-Lymphocytes drug effects
Decitabine
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation adverse effects
Hematopoietic Stem Cell Transplantation methods
Hematopoietic Stem Cell Transplantation mortality
Humans
Leukemia, Myeloid, Acute mortality
Leukemia, Myelomonocytic, Chronic mortality
Male
Middle Aged
Myelodysplastic Syndromes mortality
Survival Analysis
Transplantation Conditioning adverse effects
Transplantation, Homologous
Vidarabine administration & dosage
Vidarabine analogs & derivatives
Whole-Body Irradiation
Azacitidine analogs & derivatives
CD8-Positive T-Lymphocytes immunology
Leukemia, Myeloid, Acute therapy
Leukemia, Myelomonocytic, Chronic therapy
Myelodysplastic Syndromes therapy
Transplantation Conditioning methods
Subjects
Details
- Language :
- English
- ISSN :
- 1523-6536
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 26860635
- Full Text :
- https://doi.org/10.1016/j.bbmt.2016.02.003