title: Fludarabine/Busulfan versus Fludarabine/Melphalan Conditioning in Patients Undergoing Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation for Lymphoma.
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.affiliation: Division of Hematology, The Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kekre
authors.affiliation: Department of Hematology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Marquez-Malaver
authors.affiliation: Hematology Department, University Hospital, Instituto Biosanitario de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Cabrero
authors.affiliation: Department of Hematology/Oncology, Hospital Clinico Universitario, Valencia, Valencia, Spain.
authors.forename: Jl
authors.initials: J
authors.lastname: Piñana
authors.affiliation: Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Jose Carreras Leukemia Research Institute, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Esquirol
authors.affiliation: Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Hematology Department, University Hospital, Instituto Biosanitario de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.affiliation: Department of Hematology/Oncology, Hospital Clinico Universitario, Valencia, Valencia, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Terol
authors.affiliation: Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Jose Carreras Leukemia Research Institute, Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.affiliation: Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Hematology Department, University Hospital, Instituto Biosanitario de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Lopez-Corral
authors.affiliation: Department of Hematology/Oncology, Hospital Clinico Universitario, Valencia, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.affiliation: Division of Hematologic Malignancies, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.affiliation: 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.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pérez-Simon
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan
keywords: Allogeneic; Busulfan; Fludarabine; Lymphoma; Melphalan; Reduced-intensity conditioning; Stem cell transplantation