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

Evgeny Klyuchnikov, Ulrike Bacher, Nicolaus M. Kröger, Parameswaran N. Hari, Kwang Woo Ahn, Jeanette Carreras, Veronika Bachanova, Asad Bashey, Jonathon B. Cohen, Anita D'Souza, César O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Mark S. Hertzberg, Leona A. Holmberg, Mohamed A. Kharfan-Dabaja, Andreas Klein, Grace H. Ku, Ginna G. Laport, Hillard M. LazarusAlan M. Miller, Alberto Mussetti, Richard F. Olsson, Shimon Slavin, Saad Z. Usmani, Ravi Vij, William A. Wood, David G. Maloney, Anna M. Sureda, Sonali M. Smith, Mehdi Hamadani

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2091-2099
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number12
DOIs
StatePublished - Dec 2015

Bibliographical note

Funding Information:
The CIBMTR is supported by Public Health Service grant /cooperative agreement U24-CA076518 from the National Cancer Institute (NCI) , the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) ; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS) ; 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research ; and grants from * Actinium Pharmaceuticals ; Allos Therapeutics, Inc. ; * Amgen, Inc. ; anonymous donation to the Medical College of Wisconsin; Ariad ; Be the Match Foundation ; * Blue Cross and Blue Shield Association ; * Celgene Corporation ; Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Fresenius-Biotech North America, Inc. ; * Gamida Cell Teva Joint Venture Ltd. ; Genentech, Inc. ;* Gentium SpA ; Genzyme Corporation ; GlaxoSmithKline ; Health Research, Inc. Roswell Park Cancer Institute ; HistoGenetics, Inc. ; Incyte Corporation ; Jeff Gordon Children's Foundation ; Kiadis Pharma ; The Leukemia & Lymphoma Society ; Medac GmbH ; The Medical College of Wisconsin ; Merck & Co, Inc. ; Millennium: The Takeda Oncology Co. ; * Milliman USA, Inc. ; * Miltenyi Biotec, Inc. ; National Marrow Donor Program ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Osiris Therapeutics, Inc. ; Otsuka America Pharmaceutical, Inc. ; Perkin Elmer, Inc. ; * Remedy Informatics ; * Sanofi US ; Seattle Genetics ; Sigma-Tau Pharmaceuticals ; Soligenix, Inc. ; St. Baldrick's Foundation ; StemCyte, A Global Cord Blood Therapeutics Co. ; Stemsoft Software, Inc. ; Swedish Orphan Biovitrum ; * Tarix Pharmaceuticals ; * TerumoBCT ; * Teva Neuroscience, Inc. ; * THERAKOS, Inc. ; University of Minnesota ; University of Utah ; and * Wellpoint, Inc . The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government.

Keywords

  • Autologous hematopoietic cell transplantation
  • Grade 1 and 2 follicular lymphoma
  • Long-time survival
  • Reduced-intensity allogeneic hematopoietic cell transplantation

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