Is Conventional Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) an Optimal Long-Term Strategy for Non Hodgkin Lymphomas: A Retrospective Study from 1987 to 2004.

Conventional chemotherapy in NHL does not substantially modify the natural course of disease especially for indolent lymphomas. A major advantage of allogeneic HSCT is the immunological recognition of lymphoma cells by the allogeneic donors cells and the low relapse risk in long-term survivors is highly suggestive of a graft-versus-lymphoma effect. However the still high mortality rate of this procedure mainly due to GVHD limits its indications. To determine the place of allogeneic HSCT in the NHL therapeutic strategies, we performed a retrospective study from 1987 to 2004. Twenty-six patients [17 males, 9 females, median age of 37 years (18–61)] underwent allogeneic HSCT: 18 conventional bone marrow transplantations and 8 allogeneic HSCT after reduced intensity conditioning (RICT) from HLA identical sibling donors. The diagnosis pre transplant were: 11 high grade lymphomas (9 phenotype B and 2 T), 8 patients with a transformation of an indolent form (2 CLL, 2 follicular and 3 marginal zone lymphomas, 1 mycosis fungoides) [73% aggressive forms of NHL] and 7 indolent forms (3 lymphocytic lymphomas, 3 follicular lymphomas and 1 mantle cell). All patients have received at least 3 courses of chemotherapy (3–7). Eighty-eight percent had a stage IV at diagnosis, 7% a stage III and 7% a stage II. At transplant, 10 (38.5%) were in complete remission, 2 in partial response, 9 in stable disease and 5 (19%) in relapse or progressive disease. Twenty-two patients received bone marrow as HSC source and 4 PBSC. Total body irradiation was used as part of the conditioning regimen in 78% of patients. With a median follow-up of 85 months (41–225) from diagnosis and 66 months (9–185) from transplantation, 13 (50%) are alive without evidence of lymphoma at last follow-up and 13 died [9 (35%) from transplant-related causes (1 acute GVHD grade IV, 3 pneumonitis, 1 septicemia, 1 veino-occlusive disease, 1 leucoencephalitis and 2 others causes) and 4 (15%) from relapse. Eight (30%) did not develop any acute GVHD, 9 a grade I, 4 a grade II, 3 a grade III and 2 a grade IV. Nineteen patients did not develop chronic GVHD, 6 a limited form and only one an extensive form. Overall survival at 5 years was 61.5% [95%CI (48%–83%)] from diagnosis and 57% [95% CI (40%–80%)] from transplantation. Transplant-related mortality was estimated at 35%. Multivariate analysis did not show any significant influence on overall survival (OS) of age, disease status, type of transplantation (conventional vs RICT), HSC source, TBI, acute or chronic GVHD but this lack of significance is probably in relation with the small number of patients. The long-term follow-up in this study demonstrated the effectiveness of allogeneic HSCT in achieving long-term disease control even in heavily pretreated aggressive NHL patients.