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 Lazarus; Alan 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

doi:10.1016/j.bbmt.2015.07.028

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.

Authors

Evgeny Klyuchnikov¹, Ulrike Bacher², Nicolaus M Kröger¹, Parameswaran N Hari³, Kwang Woo Ahn⁴, Jeanette Carreras³, Veronika Bachanova⁵, Asad Bashey⁶, Jonathon B Cohen⁷, Anita D'Souza³, César O Freytes⁸, Robert Peter Gale⁹, Siddhartha Ganguly¹⁰, Mark S Hertzberg¹¹, Leona A Holmberg¹², Mohamed A Kharfan-Dabaja¹³, Andreas Klein¹⁴, Grace H Ku¹⁵, Ginna G Laport¹⁶, Hillard M Lazarus¹⁷, Alan M Miller¹⁸, Alberto Mussetti¹⁹, Richard F Olsson²⁰, Shimon Slavin²¹, Saad Z Usmani²², Ravi Vij²³, William A Wood²⁴, David G Maloney¹², Anna M Sureda²⁵, Sonali M Smith²⁶, Mehdi Hamadani²⁷

Affiliations

¹ Department for Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany.
² Department for Hematology and Internal Oncology, Georg August University Göttingen, Göttingen, Germany.
³ Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁴ 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.
⁵ Bone and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, Minnesota.
⁶ Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
⁷ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
⁸ South Texas Veterans Health Care System and University of Texas Science Center San Antonio, San Antonio, San Antonio, Texas.
⁹ Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
¹⁰ Blood and Marrow Transplantation, Division of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas.
¹¹ Department of Haematology, Prince of Wales Hospital, Randwick NSW, Australia.
¹² Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
¹³ Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
¹⁴ Divison of Hematology/Oncology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
¹⁵ Division of Blood and Marrow Transplantation, Department of Medicine, University of California, San Diego, San Diego, California.
¹⁶ Division of Bone Marrow Transplantation, Stanford Hospital and Clinics, Stanford, California.
¹⁷ Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
¹⁸ Department of Oncology, Baylor University Medical Center, Dallas, Texas.
¹⁹ S.C. Ematologia e Trapianto Midollo Osseo, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Università degli Studi di Milano, Milan, Italy.
²⁰ Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
²¹ The International Center for Cell Therapy and Cancer Immunotherapy, Tel Aviv, Israel.
²² Department of Hematology, Medical Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina.
²³ Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri.
²⁴ Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
²⁵ Servei d'Hematologia, Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain; European Group for Blood and Marrow Transplantation.
²⁶ Section of Hematology/Oncology, University of Chicago, Chicago, Illinois.
²⁷ Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: [email protected].

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding