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

• Published in: Biology of blood and marrow transplantation 2015-12, Vol.21 (12), p.2091-2099
• Main Authors: Klyuchnikov, Evgeny, Bacher, Ulrike, Kröger, Nicolaus M, Hari, Parameswaran N, Ahn, Kwang Woo, Carreras, Jeanette, Bachanova, Veronika, Bashey, Asad, Cohen, Jonathon B, D'Souza, Anita, Freytes, César O, Gale, Robert Peter, Ganguly, Siddhartha, Hertzberg, Mark S, Holmberg, Leona A, Kharfan-Dabaja, Mohamed A, Klein, Andreas, Ku, Grace H, Laport, Ginna G, Lazarus, Hillard M, Miller, Alan M, Mussetti, Alberto, Olsson, Richard F, Slavin, Shimon, Usmani, Saad Z, Vij, Ravi, Wood, William A, Maloney, David G, Sureda, Anna M, Smith, Sonali M, Hamadani, Mehdi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - therapeutic use; Autologous hematopoietic cell transplantation; Disease Progression; Drug Resistance, Neoplasm; Female; Grade 1 and 2 follicular lymphoma; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation - methods; Humans; Long-time survival; Longitudinal Studies; Lymphoma, Follicular - immunology; Lymphoma, Follicular - mortality; Lymphoma, Follicular - pathology; Lymphoma, Follicular - therapy; Male; Medicin och hälsovetenskap; Middle Aged; Myeloablative Agonists - therapeutic use; Neoplasm Grading; Recurrence; Reduced-intensity allogeneic hematopoietic cell transplantation; Rituximab - therapeutic use; Survival Analysis; Survivors; Transplantation Conditioning - methods; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome
• ISSN: 1083-8791; 1523-6536; 1523-6536
• DOI: 10.1016/j.bbmt.2015.07.028

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.