title: Comparison of reduced-intensity and conventional myeloablative regimens for allogeneic transplantation in non-Hodgkin's lymphoma.
abstract: Reduced-intensity regimens (RIRs) are being used with increasing frequency in patients with non-Hodgkin's lymphoma (NHL) undergoing allogeneic transplantation. The impact of dose reduction on relapse and survival has not been extensively studied. We performed a retrospective analysis of 88 patients conditioned with conventional myeloablative regimens (CMRs) (n = 48) and an RIR (n = 40) of fludarabine 125 mg/m(2) and melphalan 140 mg/m(2). Compared with the patients receiving CMR, those receiving RIR were older, had more often failed autologous transplantation, and had more frequently received peripheral blood and unrelated donor transplants. Graft-versus-host disease prophylaxis was provided with cyclosporine + methotrexate +/- prednisone for the CMR and with cyclosporine + mycophenolate +/- methotrexate for the RIR. The relapse rate was significantly lower in the patients receiving CMR than in those receiving RIR (13% vs 28%; P = .05). The 1-year transplantation-related mortality rate was 33% for CMR and 28% for RIR (P = .40). Kaplan-Meier 2-year overall survival and progression-free survival were 52% and 46% for CMR versus 53% and 40% for RIR (P = not significant). Using cumulative incidence functions based on competing risks, univariate analysis, and treatment-related prognostic factors, we found that higher treatment intensity (P = .03; relative risk [RR] = 35%) and absence of previous autologous transplantation (P = .0007; RR = 20%) were associated with a lower relapse rate. Using a Cox univariate proportional hazards model, we found that chemosensitive disease at transplantation (P = .05; RR = 57%) and absence of previous autologous transplantation (P = .002; RR = 37%) were associated with improved survival. Our observation of similar survival in the patients receiving CMR and those receiving RIR confirms that RIRs are feasible alternatives for high-risk patients with NHL; however, the data suggest that reduced treatment intensity and previous autologous transplantation are associated with increased relapse.
authors.affiliation: Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, California 91001, USA. robertorodgriguez@coh.org
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Auayporn
authors.initials: A
authors.lastname: Nademanee
authors.forename: Nora
authors.initials: N
authors.lastname: Ruel
authors.forename: Eileen
authors.initials: E
authors.lastname: Smith
authors.forename: Amrita
authors.initials: A
authors.lastname: Krishnan
authors.forename: Leslie
authors.initials: L
authors.lastname: Popplewell
authors.forename: Jasmine
authors.initials: J
authors.lastname: Zain
authors.forename: Kathy
authors.initials: K
authors.lastname: Patane
authors.forename: Neil
authors.initials: N
authors.lastname: Kogut
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Nakamura
authors.forename: Clarence
authors.initials: C
authors.lastname: Sarkodee-Adoo
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D002423:Cause of Death; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology / Q000401:mortality; D006801:Humans; D007239:Infections / Q000209:etiology / Q000401:mortality; D053208:Kaplan-Meier Estimate; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000401:mortality; D008224:Lymphoma, Follicular / Q000401:mortality / Q000601:surgery; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000601:surgery; D020522:Lymphoma, Mantle-Cell / Q000401:mortality / Q000601:surgery; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000601:surgery*; D016399:Lymphoma, T-Cell / Q000401:mortality / Q000601:surgery; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000706:statistics & numerical data*; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality; D016016:Proportional Hazards Models; D012086:Reoperation / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000706:statistics & numerical data; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan