Management of Postransplant Relapse and Persistent Disease in Lymphoid Malignancies: Exploring the Graft versus Lymphoma Effect

Allogenic hematopoietic Stem Cell Transplantation (AlloSCT) is potentially a curative option for relapse or refractory lympho proliferative disorders, based in part on the Graft Versus Lymphoma Effect (GVLE). However, the role of GVLE enhancement and the means of implementing it effectively in relapse or persistent disease after AlloSCT remain unclear. We report the evaluation of 26 patients with post-AlloSCT relapse or persistent disease in a series of 112 AlloSCTs. In 19/26 (73%) patients, GVLE was enhanced by tapering immunosuppressive treatment (IST) and/or Donor Lymphocyte Infusion (DLI), achieving a response in 13 (68%), 11 of which were Complete Remissions (CRs). With respect to histology’s, an immune-mediated response was observed in 6/6 patients with NHL, 5/7 with CLL and 2/6 with HL. Graft Versus Host Disease (GVHD) appeared in 16/19 (84%); only one death was ascribed to GVHD. The remaining 7/26patients, in whom GVLE enhancement was not possible due to GVHD, received conventional chemotherapy with or without radiotherapy; two patients achieved CR and one achieved Partial Remission (PR). Four-Year Progression-Free Survival (PFS) and Overall Survival (OS) after treatment of relapse/refractory patients were 40% and 45%,respectively (median follow-up, 56 months; range 11-138 months). Disease response to immune manipulation proves the existence of GVLE, which appears in all histological subtypes, although less frequently in HL. GVLE enhancement enables us to ensure maintained responses, with PFS and OS similar to those in non-relapsing patients. Therefore, the immune approach should always be considered as a treatment for relapse/refractory patients.