title: Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors.
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.
authors.affiliation: Department for Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Klyuchnikov
authors.affiliation: Department for Hematology and Internal Oncology, Georg August University Göttingen, Göttingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.affiliation: Department for Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany.
authors.forename: Nicolaus M
authors.initials: NM
authors.lastname: Kröger
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Parameswaran N
authors.initials: PN
authors.lastname: Hari
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Ahn
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Carreras
authors.affiliation: Bone and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: Veronika
authors.initials: V
authors.lastname: Bachanova
authors.affiliation: Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: Asad
authors.initials: A
authors.lastname: Bashey
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Jonathon B
authors.initials: JB
authors.lastname: Cohen
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Anita
authors.initials: A
authors.lastname: D'Souza
authors.affiliation: South Texas Veterans Health Care System and University of Texas Science Center San Antonio, San Antonio, San Antonio, Texas.
authors.forename: César O
authors.initials: CO
authors.lastname: Freytes
authors.affiliation: Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Blood and Marrow Transplantation, Division of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Department of Haematology, Prince of Wales Hospital, Randwick NSW, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hertzberg
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Leona A
authors.initials: LA
authors.lastname: Holmberg
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: Divison of Hematology/Oncology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klein
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego, San Diego, California.
authors.forename: Grace H
authors.initials: GH
authors.lastname: Ku
authors.affiliation: Division of Bone Marrow Transplantation, Stanford Hospital and Clinics, Stanford, California.
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Department of Oncology, Baylor University Medical Center, Dallas, Texas.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Miller
authors.affiliation: S.C. Ematologia e Trapianto Midollo Osseo, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Università degli Studi di Milano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mussetti
authors.affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Olsson
authors.affiliation: The International Center for Cell Therapy and Cancer Immunotherapy, Tel Aviv, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.affiliation: Department of Hematology, Medical Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina.
authors.forename: Saad Z
authors.initials: SZ
authors.lastname: Usmani
authors.affiliation: Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: William A
authors.initials: WA
authors.lastname: Wood
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Servei d'Hematologia, Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain; European Group for Blood and Marrow Transplantation.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Sureda
authors.affiliation: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: mhamadani@mcw.edu.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008224:Lymphoma, Follicular / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D060787:Neoplasm Grading; D012008:Recurrence; D000069283:Rituximab / Q000627:therapeutic use*; D016019:Survival Analysis; D017741:Survivors; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019653:Myeloablative Agonists; D000069283:Rituximab
keywords: Autologous hematopoietic cell transplantation; Grade 1 and 2 follicular lymphoma; Long-time survival; Reduced-intensity allogeneic hematopoietic cell transplantation