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Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party.
J Hematol Oncol. 2017 01 24; 10(1):31.JH

Abstract

BACKGROUND

The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored.

METHODS

We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.

RESULTS

Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10-5). Recipient age above 50 years was the only other factor associated with worse survivals.

CONCLUSIONS

These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.

Authors+Show Affiliations

Service d'Hématologie et de Médecine interne, Hôpital Brabois, CHRU Nancy, Nancy, France. mt_rubio@hotmail.com. IMoPA, CNRS UMR 7365, Nancy, France. mt_rubio@hotmail.com. Université de Lorraine, Nancy, France. mt_rubio@hotmail.com.Service d'Hématologie et de Médecine interne, Hôpital Brabois, CHRU Nancy, Nancy, France. m.daveni-piney@chru-nancy.fr. IMoPA, CNRS UMR 7365, Nancy, France. m.daveni-piney@chru-nancy.fr. Université de Lorraine, Nancy, France. m.daveni-piney@chru-nancy.fr.ALWP Office, Hôpital Saint Antoine, Paris, France. Service d'Hématologie et de Thérapie Cellulaire, Hôpital Saint Antoine, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France.Service Hématologie Greffe de Moëlle, Centre Pierre et Marie Curie, Alger, Algeria.Servicio de Hematologia, Hospital Universitario La Fe, Valencia, Spain.Programme de Transplantation and Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France.Hematology Division, BMT Unit, Hematology Reserach Laboratory, Training and Medical, Baskent University Hospital, Adana, Turkey.Hopital Jean Minjoz, Service d`Hématologie, Besancon, France.Servicio de Hematología-Hemoterapia, Hospital U. Marqués de Valdecilla, Santander, Spain.Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Ospedale Civile, Pescara, Italy.Azienda Ospedaliera, Centro Unico Regionale Trapianti, Reggio, Calabria, Italy.Hôpital HURIEZ UAM allo-CSH, CHRU, Lille, France.Hematology and BMT Department, Beilinson Hospital, Petach-Tikva, Israel.Sección de Transplante de Medula Osea, Hospital Gregorio Marañón, Madrid, Spain.ALWP Office, Hôpital Saint Antoine, Paris, France. Service d'Hématologie et de Thérapie Cellulaire, Hôpital Saint Antoine, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France.ALWP Office, Hôpital Saint Antoine, Paris, France. Vanderbilt University Medical Center, Nashville, TN, USA.ALWP Office, Hôpital Saint Antoine, Paris, France. Université Pierre et Marie Curie, Paris, France. Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

28118857

Citation

Rubio, Marie Thérèse, et al. "Impact of in Vivo T Cell Depletion in HLA-identical Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission Conditioned With a Fludarabine Iv-busulfan Myeloablative Regimen: a Report From the EBMT Acute Leukemia Working Party." Journal of Hematology & Oncology, vol. 10, no. 1, 2017, p. 31.
Rubio MT, D'Aveni-Piney M, Labopin M, et al. Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party. J Hematol Oncol. 2017;10(1):31.
Rubio, M. T., D'Aveni-Piney, M., Labopin, M., Hamladji, R. M., Sanz, M. A., Blaise, D., Ozdogu, H., Daguindeau, E., Richard, C., Santarone, S., Irrera, G., Yakoub-Agha, I., Yeshurun, M., Diez-Martin, J. L., Mohty, M., Savani, B. N., & Nagler, A. (2017). Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party. Journal of Hematology & Oncology, 10(1), 31. https://doi.org/10.1186/s13045-016-0389-4
Rubio MT, et al. Impact of in Vivo T Cell Depletion in HLA-identical Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission Conditioned With a Fludarabine Iv-busulfan Myeloablative Regimen: a Report From the EBMT Acute Leukemia Working Party. J Hematol Oncol. 2017 01 24;10(1):31. PubMed PMID: 28118857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party. AU - Rubio,Marie Thérèse, AU - D'Aveni-Piney,Maud, AU - Labopin,Myriam, AU - Hamladji,Rose-Marie, AU - Sanz,Miguel A, AU - Blaise,Didier, AU - Ozdogu,Hakan, AU - Daguindeau,Etienne, AU - Richard,Carlos, AU - Santarone,Stella, AU - Irrera,Giuseppe, AU - Yakoub-Agha,Ibrahim, AU - Yeshurun,Moshe, AU - Diez-Martin,Jose L, AU - Mohty,Mohamad, AU - Savani,Bipin N, AU - Nagler,Arnon, Y1 - 2017/01/24/ PY - 2016/10/04/received PY - 2016/12/31/accepted PY - 2017/1/26/entrez PY - 2017/1/26/pubmed PY - 2017/11/29/medline KW - Acute myeloid leukemia KW - Allogeneic stem cell transplantation KW - GRFS KW - Graft-versus-host disease KW - HLA-matched related donor KW - In vivo T cell depletion KW - Relapse incidence SP - 31 EP - 31 JF - Journal of hematology & oncology JO - J Hematol Oncol VL - 10 IS - 1 N2 - BACKGROUND: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. METHODS: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10-5). Recipient age above 50 years was the only other factor associated with worse survivals. CONCLUSIONS: These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk. SN - 1756-8722 UR - https://www.unboundmedicine.com/medline/citation/28118857/Impact_of_in_vivo_T_cell_depletion_in_HLA_identical_allogeneic_stem_cell_transplantation_for_acute_myeloid_leukemia_in_first_complete_remission_conditioned_with_a_fludarabine_iv_busulfan_myeloablative_regimen:_a_report_from_the_EBMT_Acute_Leukemia_Working_Party_ L2 - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-016-0389-4 DB - PRIME DP - Unbound Medicine ER -