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Outcome of allogeneic peripheral blood stem cell transplantation by donor graft CD3+/Tregs ratio: a single-center experience.
Biol Blood Marrow Transplant. 2013 Mar; 19(3):495-9.BB

Abstract

The therapeutic efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) for hematological malignancies relies largely on the graft-versus-leukemia (GVL) effects exerted by the donor CD3 cells, but there is a risk of onset of uncontrolled graft-versus-host disease (GVHD). Regulatory T cells (Tregs) (CD4+CD25(high) Foxp3+) are believed to maintain tolerance and to inhibit acute GVHD (aGVHD) after allogeneic PBSCT. Nevertheless, when looking at post-allotransplantation patient outcomes, although the impact of aGVHD on survival is amply documented, so far there is no evidence that the donor graft CD3/Tregs ratio may affect overall survival (OS), nonrelapse mortality (NRM), disease-free survival (DFS), and relapse rates. Our aim was to study the possible impact of the gCD3/Tregs ratio on survival after myeloablative allogeneic PBSCT. We analyzed 74 consecutive patients diagnosed with acute myeloid leukemia (n = 62), acute lymphoblastic leukemia (n = 10), and chronic myeloid leukemia (n = 2) who underwent transplantation with unmanipulated PBSCs from a human leukocyte antigen-identical related donor (n = 48) or a human leukocyte antigen-identical unrelated donor (n = 26). Patients were subdivided into a high gCD3/Tregs ratio (≥36) group (HR group, n = 30) and a low gCD3/Tregs ratio (<36) group (LR group, n = 44). The OS, DFS, NRM, and relapse rates at 3 years were 53%, 51%, 29%, and 34%, respectively. Comparing the LR and HR groups, a statistically significant difference was demonstrated for the 3-year OS, DFS, and NRM rates (65% vs 31%, P = .0001; 67 versus 26%, P = .0001; 5% versus 71%, P < .0001, respectively) but not for relapse (30% vs 25%, P = ns). By multivariate analysis, LR significantly predicted better OS (P = .019), DFS (P = .003), and NRM (P = .05), whereas there was no statistically significant association between LR and relapse (P = .155). Overall, our data may suggest that LR preserves GVL effects but is also protective against aGVHD in allotransplantation patients.

Authors+Show Affiliations

Hematology Section, Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11,Bari, Italy. mario.delia@tiscali.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23200706

Citation

Delia, Mario, et al. "Outcome of Allogeneic Peripheral Blood Stem Cell Transplantation By Donor Graft CD3+/Tregs Ratio: a Single-center Experience." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 19, no. 3, 2013, pp. 495-9.
Delia M, Pastore D, Mestice A, et al. Outcome of allogeneic peripheral blood stem cell transplantation by donor graft CD3+/Tregs ratio: a single-center experience. Biol Blood Marrow Transplant. 2013;19(3):495-9.
Delia, M., Pastore, D., Mestice, A., Carluccio, P., Perrone, T., Gaudio, F., Ricco, A., Sgherza, N., Albano, F., & Specchia, G. (2013). Outcome of allogeneic peripheral blood stem cell transplantation by donor graft CD3+/Tregs ratio: a single-center experience. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 19(3), 495-9. https://doi.org/10.1016/j.bbmt.2012.11.015
Delia M, et al. Outcome of Allogeneic Peripheral Blood Stem Cell Transplantation By Donor Graft CD3+/Tregs Ratio: a Single-center Experience. Biol Blood Marrow Transplant. 2013;19(3):495-9. PubMed PMID: 23200706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Outcome of allogeneic peripheral blood stem cell transplantation by donor graft CD3+/Tregs ratio: a single-center experience. AU - Delia,Mario, AU - Pastore,Domenico, AU - Mestice,Anna, AU - Carluccio,Paola, AU - Perrone,Tommasina, AU - Gaudio,Francesco, AU - Ricco,Alessandra, AU - Sgherza,Nicola, AU - Albano,Francesco, AU - Specchia,Giorgina, Y1 - 2012/11/27/ PY - 2012/08/28/received PY - 2012/11/12/accepted PY - 2012/12/4/entrez PY - 2012/12/4/pubmed PY - 2013/7/31/medline SP - 495 EP - 9 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 19 IS - 3 N2 - The therapeutic efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) for hematological malignancies relies largely on the graft-versus-leukemia (GVL) effects exerted by the donor CD3 cells, but there is a risk of onset of uncontrolled graft-versus-host disease (GVHD). Regulatory T cells (Tregs) (CD4+CD25(high) Foxp3+) are believed to maintain tolerance and to inhibit acute GVHD (aGVHD) after allogeneic PBSCT. Nevertheless, when looking at post-allotransplantation patient outcomes, although the impact of aGVHD on survival is amply documented, so far there is no evidence that the donor graft CD3/Tregs ratio may affect overall survival (OS), nonrelapse mortality (NRM), disease-free survival (DFS), and relapse rates. Our aim was to study the possible impact of the gCD3/Tregs ratio on survival after myeloablative allogeneic PBSCT. We analyzed 74 consecutive patients diagnosed with acute myeloid leukemia (n = 62), acute lymphoblastic leukemia (n = 10), and chronic myeloid leukemia (n = 2) who underwent transplantation with unmanipulated PBSCs from a human leukocyte antigen-identical related donor (n = 48) or a human leukocyte antigen-identical unrelated donor (n = 26). Patients were subdivided into a high gCD3/Tregs ratio (≥36) group (HR group, n = 30) and a low gCD3/Tregs ratio (<36) group (LR group, n = 44). The OS, DFS, NRM, and relapse rates at 3 years were 53%, 51%, 29%, and 34%, respectively. Comparing the LR and HR groups, a statistically significant difference was demonstrated for the 3-year OS, DFS, and NRM rates (65% vs 31%, P = .0001; 67 versus 26%, P = .0001; 5% versus 71%, P < .0001, respectively) but not for relapse (30% vs 25%, P = ns). By multivariate analysis, LR significantly predicted better OS (P = .019), DFS (P = .003), and NRM (P = .05), whereas there was no statistically significant association between LR and relapse (P = .155). Overall, our data may suggest that LR preserves GVL effects but is also protective against aGVHD in allotransplantation patients. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/23200706/Outcome_of_allogeneic_peripheral_blood_stem_cell_transplantation_by_donor_graft_CD3+/Tregs_ratio:_a_single_center_experience_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(12)00523-X DB - PRIME DP - Unbound Medicine ER -