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Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT.
Haematologica. 2016 06; 101(6):773-80.H

Abstract

The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs myeloablative conditioning regimens after mismatched unrelated donor transplantation. Furthermore, the data support the superiority of reduced-intensity conditioning regimens in older adults receiving transplants from mismatched unrelated donors.

Authors+Show Affiliations

Vanderbilt University Medical Center, Nashville, TN, USA Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France bipin.savani@vanderbilt.edu.Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, France Department of Haematology, Saint Antoine Hospital, Paris, France INSERM UMR 938, Paris, France Université Pierre et Marie Curie, Paris, France.University Hospital Eppendorf, Department of Stem cell Transplantation, Hamburg, Germany.University of Freiburg, Department of Medicine -Hematology, Oncology, Germany.Universitaetsklinikum Dresden, MedizinischeKlinik und Poliklinik I, Germany.University Hospital Leipzig, Div. Hematology, Oncology and Hemostasiology, Germany.Helios-Klinikum Berlin-Buch, Dept. Hematology Berlin, Germany.Klinik fuer Innere Medzin III - Universitätsklinikum Ulm, Germany.Asklepios Klinik St. Georg - Department of Haematology, Hamburg, Germany.Hopital St. Louis - Dept.of Hematology, Paris, France.Karolinska University Hospital, Department of Hematology, Stockholm, Sweden.Center for Clinical Hematology, Queen Elizabeth Hospital, Birmingham, UK.Department of Medicine, Division of Hematology, University of Liège, Belgium.Department of Hematology, Ospedale San Raffaele, Università degli Studi, Milan, Italy.Faculté de Médicine Saint-Antoine, Paris, France.Dept. of Hematology, Hospital Clinic, Barcelona, Spain.Klinikum Augsburg, Dept. of Hematology and Oncology, University of Munich, Augsburg, Germany.Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.Acute Leukemia Working Party, EBMT Paris study office / CEREST-TC, 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, EBMT Paris study office / CEREST-TC, France Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

26969081

Citation

Savani, Bipin N., et al. "Expanding Transplant Options to Patients Over 50 Years. Improved Outcome After Reduced Intensity Conditioning Mismatched-unrelated Donor Transplantation for Patients With Acute Myeloid Leukemia: a Report From the Acute Leukemia Working Party of the EBMT." Haematologica, vol. 101, no. 6, 2016, pp. 773-80.
Savani BN, Labopin M, Kröger N, et al. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT. Haematologica. 2016;101(6):773-80.
Savani, B. N., Labopin, M., Kröger, N., Finke, J., Ehninger, G., Niederwieser, D., Schwerdtfeger, R., Bunjes, D., Glass, B., Socié, G., Ljungman, P., Craddock, C., Baron, F., Ciceri, F., Gorin, N. C., Esteve, J., Schmid, C., Giebel, S., Mohty, M., & Nagler, A. (2016). Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT. Haematologica, 101(6), 773-80. https://doi.org/10.3324/haematol.2015.138180
Savani BN, et al. Expanding Transplant Options to Patients Over 50 Years. Improved Outcome After Reduced Intensity Conditioning Mismatched-unrelated Donor Transplantation for Patients With Acute Myeloid Leukemia: a Report From the Acute Leukemia Working Party of the EBMT. Haematologica. 2016;101(6):773-80. PubMed PMID: 26969081.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT. AU - Savani,Bipin N, AU - Labopin,Myriam, AU - Kröger,Nicolaus, AU - Finke,Jürgen, AU - Ehninger,Gerhard, AU - Niederwieser,Dietger, AU - Schwerdtfeger,Rainer, AU - Bunjes,Donald, AU - Glass,Bertram, AU - Socié,Gerard, AU - Ljungman,Per, AU - Craddock,Charles, AU - Baron,Frédéric, AU - Ciceri,Fabio, AU - Gorin,Norbert Claude, AU - Esteve,Jordi, AU - Schmid,Christoph, AU - Giebel,Sebastian, AU - Mohty,Mohamad, AU - Nagler,Arnon, Y1 - 2016/03/11/ PY - 2015/10/20/received PY - 2016/03/02/accepted PY - 2016/3/13/entrez PY - 2016/3/13/pubmed PY - 2017/7/8/medline SP - 773 EP - 80 JF - Haematologica JO - Haematologica VL - 101 IS - 6 N2 - The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs myeloablative conditioning regimens after mismatched unrelated donor transplantation. Furthermore, the data support the superiority of reduced-intensity conditioning regimens in older adults receiving transplants from mismatched unrelated donors. SN - 1592-8721 UR - https://www.unboundmedicine.com/medline/citation/26969081/Expanding_transplant_options_to_patients_over_50_years__Improved_outcome_after_reduced_intensity_conditioning_mismatched_unrelated_donor_transplantation_for_patients_with_acute_myeloid_leukemia:_a_report_from_the_Acute_Leukemia_Working_Party_of_the_EBMT_ DB - PRIME DP - Unbound Medicine ER -