Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

Biol Blood Marrow Transplant. 2015 Dec;21(12):2091-2099. doi: 10.1016/j.bbmt.2015.07.028. Epub 2015 Aug 4.

Abstract

This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P < .0001); relapse/progression: 54% versus 20% (P < .0001); progression-free survival (PFS): 41% versus 58% (P < .001), and overall survival (OS): 74% versus 66% (P = .05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P < .0001) and worse PFS (RR, 2.9; P < .0001) beyond 11 months after HCT. In the first 24 months after HCT, auto-HCT was associated with improved OS (RR, .41; P < .0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P = .006). A landmark analysis of patients alive and progression-free at 2 years after HCT confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P < .0001) and inferior PFS (RR, 3.2; P < .0001) and OS (RR, 2.1; P = .04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity-conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors.

Keywords: Autologous hematopoietic cell transplantation; Grade 1 and 2 follicular lymphoma; Long-time survival; Reduced-intensity allogeneic hematopoietic cell transplantation.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Longitudinal Studies
  • Lymphoma, Follicular / immunology
  • Lymphoma, Follicular / mortality
  • Lymphoma, Follicular / pathology
  • Lymphoma, Follicular / therapy*
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use*
  • Neoplasm Grading
  • Recurrence
  • Rituximab / therapeutic use*
  • Survival Analysis
  • Survivors
  • Transplantation Conditioning / methods*
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Myeloablative Agonists
  • Rituximab