Relapse of Lymphoma After Allogeneic Hematopoietic Cell Transplantation: Management Strategies and Outcome

The outcome and management of relapsed lymphoma after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), reduction of immunosuppression (RIS), chemotherapy, radiation, immunotherapy, second HCT, and experimental treatments, but reported data contrasting the response and efficacy of these salvage treatments are limited. We describe the treatments, response, prognosis, and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT. Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0-1898 days); 37 had early (<100 days) post-HCT relapse. Forty-four had non-Hodgkin lymphoma (7 mantle cell, 5 indolent, 15 diffuse large B cell, 4 Burkitt's, and 13 T/Natural Killer cell), and 28 patients had Hodgkin lymphoma. At the time of HCT, 62 patients were in remission (22 in complete [CR] and 40 in partial [PR]), 1 had stable whereas 9 had progressive disease. Seventeen cases received myeloablative and 55 received a reduced-intensity conditioning regimen. At relapse, most patients had generalized lymphadenopathy, extranodal organ involvement, and advanced disease. Five patients received no intervention for the post-HCT relapse. Immunosuppressive treatment was reduced or withdrawn as the first-line therapy in 58 patients (80.5%); 47 were treated using combinations of conventional chemotherapy (n = 22), rituximab (n = 27), interferon (IFN) (n = 1), DLI (n = 7), second HCT (n = 2), local radiation (n = 23), and other therapy (n = 6). Thirty-eight patients had an objective response (CR in 30, PR in 8), and 2 had stable disease (SD). At the post-HCT relapse, favorable prognostic factors for survival after HCT included good ECOG performance status (0-2), normal lactate dehydrogenase (LDH), early stage disease (stage I-III), isolated extranodal organ involvement, and later relapse (>100 days) post-HCT. Three-year survival after HCT was significantly better in late than early relapse (53%; 95% confidence interval [CI] [34%-69%] versus 36%, [20%-52%], P = .02). Of 72 relapsed patients, 29 (40%) survived at a median of 34 (3-148) months posttransplant. The most common cause of death was underlying lymphoma (79%). The overall prognosis of relapsed/progressive lymphoma after allogeneic HCT is disappointing, yet half of patients respond to withdrawal of immunosuppression and additional therapies. Novel treatments can control lymphoma with acceptable morbidity. Particularly for patients with later relapse, ongoing treatment after relapse can yield meaningful benefit and prolonged survival.