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Fludarabine/Busulfan versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma.
Biol Blood Marrow Transplant. 2016 10; 22(10):1808-1815.BB

Abstract

There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

Authors+Show Affiliations

Division of Hematology, The Ottawa Hospital, Ottawa, Ontario, Canada.Department of Hematology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.Hematology Department, University Hospital, Instituto Biosanitario de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.Department of Hematology/Oncology, Hospital Clinico Universitario, Valencia, Valencia, Spain.Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Jose Carreras Leukemia Research Institute, Barcelona, Spain.Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.Hematology Department, University Hospital, Instituto Biosanitario de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.Department of Hematology/Oncology, Hospital Clinico Universitario, Valencia, Valencia, Spain.Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Jose Carreras Leukemia Research Institute, Barcelona, Spain.Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.Hematology Department, University Hospital, Instituto Biosanitario de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.Department of Hematology/Oncology, Hospital Clinico Universitario, Valencia, Valencia, Spain.Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.Department of Hematology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. Electronic address: josea.perez.simon.sspa@juntadeandalucia.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27470290

Citation

Kekre, Natasha, et al. "Fludarabine/Busulfan Versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 22, no. 10, 2016, pp. 1808-1815.
Kekre N, Marquez-Malaver FJ, Cabrero M, et al. Fludarabine/Busulfan versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma. Biol Blood Marrow Transplant. 2016;22(10):1808-1815.
Kekre, N., Marquez-Malaver, F. J., Cabrero, M., Piñana, J., Esquirol, A., Soiffer, R. J., Caballero, D., Terol, M. J., Martino, R., Antin, J. H., Lopez-Corral, L., Solano, C., Armand, P., & Pérez-Simon, J. A. (2016). Fludarabine/Busulfan versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 22(10), 1808-1815. https://doi.org/10.1016/j.bbmt.2016.07.006
Kekre N, et al. Fludarabine/Busulfan Versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma. Biol Blood Marrow Transplant. 2016;22(10):1808-1815. PubMed PMID: 27470290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fludarabine/Busulfan versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma. AU - Kekre,Natasha, AU - Marquez-Malaver,Francisco J, AU - Cabrero,Monica, AU - Piñana,Jl, AU - Esquirol,Albert, AU - Soiffer,Robert J, AU - Caballero,Dolores, AU - Terol,M J, AU - Martino,Rodrigo, AU - Antin,Joseph H, AU - Lopez-Corral,L, AU - Solano,Carlos, AU - Armand,Philippe, AU - Pérez-Simon,Jose A, Y1 - 2016/07/25/ PY - 2016/03/29/received PY - 2016/07/15/accepted PY - 2016/7/30/entrez PY - 2016/7/30/pubmed PY - 2018/1/27/medline KW - Allogeneic KW - Busulfan KW - Fludarabine KW - Lymphoma KW - Melphalan KW - Reduced-intensity conditioning KW - Stem cell transplantation SP - 1808 EP - 1815 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 22 IS - 10 N2 - There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/27470290/Fludarabine/Busulfan_versus_Fludarabine/Melphalan_Conditioning_in_Patients_Undergoing_Reduced_Intensity_Conditioning_Hematopoietic_Stem_Cell_Transplantation_for_Lymphoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(16)30222-1 DB - PRIME DP - Unbound Medicine ER -