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

Biol Blood Marrow Transplant. 2016 Oct;22(10):1801-1807. doi: 10.1016/j.bbmt.2016.06.029. Epub 2016 Jul 1.

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.

Keywords: Chronic graft-versus-host disease; Conditioning regimen; Reduced-intensity conditioning; Rituximab.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / therapeutic use
  • Calcineurin Inhibitors / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Leukemia, B-Cell / complications
  • Leukemia, B-Cell / mortality
  • Leukemia, B-Cell / therapy*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Rituximab / therapeutic use
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use

Substances

  • Calcineurin Inhibitors
  • Rituximab
  • Cyclophosphamide
  • Vidarabine
  • Busulfan
  • fludarabine
  • Methotrexate