title: Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.
abstract: To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.
authors.affiliation: Hematology, Centre Hospitalier Lyon Sud, Pierre Bénite, France. mauricette.michallet@chu-lyon.fr
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Mohamad
authors.initials: M
authors.lastname: Sobh
authors.forename: Jacques-O
authors.initials: JO
authors.lastname: Bay
authors.forename: Stéphane
authors.initials: S
authors.lastname: Morisset
authors.forename: Hélène
authors.initials: H
authors.lastname: Labussière-Wallet
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizi
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Jean
authors.initials: J
authors.lastname: El-Cheikh
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D000069283:Rituximab; D016879:Salvage Therapy; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000379:methods
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine