title: Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and Rituximab Is Associated with Improved Outcomes Compared with Fludarabine and Busulfan after Allogeneic Stem Cell Transplantation for B Cell Malignancies.
abstract: Reduced-intensity conditioning (RIC) has been used increasingly for allogeneic hematopoietic cell transplantation to minimize transplant-related mortality while maintaining the graft-versus-tumor effect. In B cell lymphoid malignancies, reduced-intensity regimens containing rituximab, an antiCD20 antibody, have been associated with favorable survival; however, the long-term outcomes of rituximab-containing versus nonrituximab-containing regimens for allogeneic hematopoietic cell transplantation in B cell lymphoid malignancies remain to be determined. We retrospectively analyzed 94 patients who received an allogeneic transplant for a B cell lymphoid malignancy. Of these, 33 received RIC with fludarabine, cyclophosphamide, and rituximab (FCR) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin inhibitor and mini-methotrexate, and 61 received RIC with fludarabine and busulfan (FluBu) and GVHD prophylaxis with a calcineurin inhibitor and mycophenolate mofetil. The 2-year overall survival was superior in patients who received FCR versus FluBu (72.7% versus 54.1%, P = .031), and in multivariable analysis adjusted for Disease Risk Index and donor type, only the conditioning regimen (FluBu versus FCR: HR, 2.06; 95% CI, 1.04 to 4.08; P = .037) and Disease Risk Index (low versus intermediate/high: HR, .38; 95% CI, .17 to .86; P = .02) were independent predictors of overall survival. The 2-year cumulative incidence of chronic GVHD was lower in patients who received FCR versus FluBu (24.2% versus 51.7%, P = .01). There was no difference in rate of relapse/progression or acute GVHD. Our results demonstrate that the use of RIC with FCR and GVHD prophylaxis with a calcineurin inhibitor and mini-methotrexate is associated with decreased chronic GVHD and improved overall survival.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: vanessa.e.kennedy@vanderbilt.edu.
authors.forename: Vanessa E
authors.initials: VE
authors.lastname: Kennedy
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplant, Department of Medicine, Veterans Affairs Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: John P
authors.initials: JP
authors.lastname: Greer
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Adetola A
authors.initials: AA
authors.lastname: Kassim
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Engelhardt
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplant, Department of Medicine, Veterans Affairs Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Goodman
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Salyka
authors.initials: S
authors.lastname: Sengsayadeth
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplant, Department of Medicine, Veterans Affairs Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Wichai
authors.initials: W
authors.lastname: Chinratanalab
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D015448:Leukemia, B-Cell / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008727:Methotrexate
keywords: Chronic graft-versus-host disease; Conditioning regimen; Reduced-intensity conditioning; Rituximab