title: BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD.
abstract: Myelosuppression, graft-versus-host disease (GVHD), and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. In this phase 1/2 study, we tested the safety and efficacy of escalating doses of bendamustine (70, 90, 110, and 130 mg/m2 per day for 3 days), coupled with our historical fixed doses of fludarabine and rituximab (BFR), as a nonmyeloablative allogeneic conditioning regimen for patients with relapsed lymphoma (n = 41) and chronic lymphocytic leukemia (CLL) (n = 15). Ten patients entered the phase 1 study; none experienced a dose-limiting toxicity. Forty-six additional patients were then treated in the phase 2 study at the maximum dose of 130 mg/m2 per day for 3 days. The proportions of transplants from matched siblings or unrelated donors were 54% and 46%. Remarkably, 55% of patients did not experience severe neutropenia. Forty-nine patients (88%) did not require platelet transfusion. The incidence of acute grade II-IV GVHD was 11%. The 2-year rate of extensive chronic GVHD was 26%. After a median follow-up duration of 26 months (range, 6-50 months), the 2-year overall and progression-free survival rates were 90% and 75%. In conclusion, our new BFR regimen is safe and effective for relapsed CLL and lymphoma patients.
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Issa F
authors.initials: IF
authors.lastname: Khouri
authors.affiliation: Biostatistics.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Martin
authors.initials: M
authors.lastname: Korbling
authors.affiliation: Lymphoma & Myeloma, and.
authors.forename: Francesco
authors.initials: F
authors.lastname: Turturro
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Sairah
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Amin
authors.initials: A
authors.lastname: Alousi
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Anderlini
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ciurea
authors.affiliation: Leukemia, and.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Uday R
authors.initials: UR
authors.lastname: Popat
authors.affiliation: Departments of Stem Cell Transplantation and Cellular Therapy.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Biostatistics.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Bassett
authors.affiliation: Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Alison
authors.initials: A
authors.lastname: Gulbis
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000069461:Bendamustine Hydrochloride; D003131:Combined Modality Therapy / Q000379:methods; D004338:Drug Combinations; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology*; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage*; D012008:Recurrence; D000069283:Rituximab; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D004338:Drug Combinations; D009588:Nitrogen Mustard Compounds; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C024352:fludarabine