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The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years-a report from the EBMT acute leukemia working party.
J Hematol Oncol. 2016 08 03; 9(1):65.JH

Abstract

BACKGROUND

Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited.

METHODS

We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.

RESULTS

HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II-IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD.

CONCLUSIONS

Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.

Authors+Show Affiliations

Department of Hematology, Hôpital Brabois, CHRU Nancy, Vandœuvre-lès-Nancy, France. mt_rubio@hotmail.com. CNRS UMR 7365, IMoPA, Nancy, France. mt_rubio@hotmail.com. Université de Lorraine, Nancy, France. mt_rubio@hotmail.com. Acute Leukemia Working Party of EBMT, Paris, France. mt_rubio@hotmail.com.Acute Leukemia Working Party of EBMT, Paris, France. Bipin.Savani@Vanderbilt.Edu. Vanderbilt University Medical Center, Nashville, TN, USA. Bipin.Savani@Vanderbilt.Edu.Acute Leukemia Working Party of EBMT, Paris, France. EBMT Paris study office/CEREST-TC, Paris, France. Department of Haematology, Saint Antoine Hospital, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France.Acute Leukemia Working Party of EBMT, Paris, France. EBMT Paris study office/CEREST-TC, Paris, France. Department of Haematology, Saint Antoine Hospital, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France.Division Hematology, Oncology and Hemostasiology, University Hospital Leipzig, Leipzig, Germany.Department of Haematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.Deutsche KlinikfürDiagnostik, KMT Zentrum, Wiesbaden, Germany.Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany.Department of Medicine, Hematology, Oncology, University of Freiburg, Freiburg, Germany.MedizinischeKlinik m. S. Hämatologie/Onkologie, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany.Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK.Department of Stem cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.Department of Medicine, University of Cologne, Cologne, Germany.Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic.Acute Leukemia Working Party of EBMT, Paris, France. EBMT Paris study office/CEREST-TC, Paris, France. Department of Haematology, Saint Antoine Hospital, Paris, France. INSERM UMR 938, Paris, France. Université Pierre et Marie Curie, Paris, France.Acute Leukemia Working Party of EBMT, Paris, France. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

27488518

Citation

Rubio, Marie T., et al. "The Impact of HLA-matching On Reduced Intensity Conditioning Regimen Unrelated Donor Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Patients Above 50 Years-a Report From the EBMT Acute Leukemia Working Party." Journal of Hematology & Oncology, vol. 9, no. 1, 2016, p. 65.
Rubio MT, Savani BN, Labopin M, et al. The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years-a report from the EBMT acute leukemia working party. J Hematol Oncol. 2016;9(1):65.
Rubio, M. T., Savani, B. N., Labopin, M., Polge, E., Niederwieser, D., Ganser, A., Schwerdtfeger, R., Ehninger, G., Finke, J., Renate, A., Craddock, C., Kröger, N., Hallek, M., Jindra, P., Mohty, M., & Nagler, A. (2016). The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years-a report from the EBMT acute leukemia working party. Journal of Hematology & Oncology, 9(1), 65. https://doi.org/10.1186/s13045-016-0295-9
Rubio MT, et al. The Impact of HLA-matching On Reduced Intensity Conditioning Regimen Unrelated Donor Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Patients Above 50 Years-a Report From the EBMT Acute Leukemia Working Party. J Hematol Oncol. 2016 08 3;9(1):65. PubMed PMID: 27488518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years-a report from the EBMT acute leukemia working party. AU - Rubio,Marie T, AU - Savani,Bipin N, AU - Labopin,Myriam, AU - Polge,Emmanuelle, AU - Niederwieser,Dietger, AU - Ganser,Arnold, AU - Schwerdtfeger,Rainer, AU - Ehninger,Gerhard, AU - Finke,Jürgen, AU - Renate,Arnold, AU - Craddock,Charles, AU - Kröger,Nicolaus, AU - Hallek,Michael, AU - Jindra,Pavel, AU - Mohty,Mohamad, AU - Nagler,Arnon, Y1 - 2016/08/03/ PY - 2016/06/06/received PY - 2016/07/27/accepted PY - 2016/8/5/entrez PY - 2016/8/5/pubmed PY - 2017/12/2/medline KW - Acute leukemia KW - Allogeneic stem cell transplantation KW - Anti-leukemic effect KW - HLA matching KW - Older patients KW - Toxicity KW - Unrelated donor SP - 65 EP - 65 JF - Journal of hematology & oncology JO - J Hematol Oncol VL - 9 IS - 1 N2 - BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. METHODS: We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II-IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. CONCLUSIONS: Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies. SN - 1756-8722 UR - https://www.unboundmedicine.com/medline/citation/27488518/The_impact_of_HLA_matching_on_reduced_intensity_conditioning_regimen_unrelated_donor_allogeneic_stem_cell_transplantation_for_acute_myeloid_leukemia_in_patients_above_50_years_a_report_from_the_EBMT_acute_leukemia_working_party_ L2 - https://jhoonline.biomedcentral.com/articles/10.1186/s13045-016-0295-9 DB - PRIME DP - Unbound Medicine ER -