title: Nonmyeloablative allogeneic hematopoietic stem cell transplant for the treatment of patients with hematologic malignancies using busulfan, fludarabine, and total body irradiation conditioning is effective in an elderly and infirm population.
abstract: The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m(2) IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. Electronic address: jbrammer1982@gmail.com.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Brammer
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stentz
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.affiliation: Division of Bone Marrow Transplantation, Moores Cancer Center, University of California San Diego, La Jolla, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Curtin
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Brandon
authors.initials: B
authors.lastname: Hayes-Lattin
authors.affiliation: Division of Hematology/Bone Marrow Transplantation, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovacsovics
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, Arizona.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Meyers
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Eneida
authors.initials: E
authors.lastname: Nemecek
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Nan
authors.initials: N
authors.lastname: Subbiah
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Rachel
authors.initials: R
authors.lastname: Frires
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Gundula
authors.initials: G
authors.lastname: Palmbach
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Galit Perets
authors.initials: GP
authors.lastname: Avraham
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Susan
authors.initials: S
authors.lastname: Slater
authors.affiliation: Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D016330:Frail Elderly; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014740:Vidarabine; D002066:Busulfan; D009173:Mycophenolic Acid; C024352:fludarabine
keywords: Comorbidity index; Elderly; Leukemia; Lymphoma; Nonmyeloablative; Stem cell transplantation