Impact of Chimerism and Other Transplant Variables on Allogeneic Transplant Outcome after Reduced Intensity Conditioning (RIC) Regimens.

Abstract

RIC regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated in patients with hematologic malignancies who were not candidates for conventional transplantation because of age or medical co-morbidities. In this kind of transplantation, the analysis of chimerism kinetics remains fundamental. The main aims of this study were to evaluate and compare the impact of pre- and post-transplant variables and chimerism on transplantation outcome. Chimerism status was evaluated in total blood (TB) and in purified CD3+ cells using quantitative PCR (STR/SNP) for all. We analysed donor type and kinetics chimerism of 52 patients (32 M - 20 F) who had undergone allogeneic HSCT after RIC for hematological malignancies. Median age was 40 years (range 25–67 years). Diagnosis were multiple myeloma: 16, acute myeloid leukemia: 13, myelodysplasia: 6, chronic lymphocytic leukemia: 5, Non Hodgkin's lymphoma: 5, acute lymphoblastic leukemia: 1, chronic myeloid leukemia: 2 and primitive myelofibrosis: 4. Conditioning regimens were Fludarabine + Busulfan in 33 patients, Fludarabine + 2 Gys total body irradiation 15, Cyclophasphamide 3 (2 alone/one with Busulfan) and one other chemotherapy. Stem cell source was PB in all except one who received cord blood. Fourty-eight were identical sibling and 4 unrelated donor transplantations. At transplant, 17 patients were in CR, 21 PR and 14 in evolutive diseases. All patients except one engrafted. Twenty-five developed aGVHD ≥ Grade II (16 Grade III-IV). At the last follow-up 22 patients died (9 disease progression and 13 of transplant related mortality, 30 were alive (18 developed chronic graft vs Host disease (cGVHD) 12 extensive/6 limited cGHVD). Among 52 patients, only 49 had a long-term chimerism documentation of CD3 subpopulation (43 TB and CD3+ cells): 15 (14 TB) were full donor chimerism (FDC) throughout the follow-up, and 34 remained mixed chimerism (MC). Among these 34 (29 TB) MC patients at the latest follow-up, 7 (5 TB) remained in MC, 2 (5 TB) converted to recipient profile and 25 (19 TB) converted to donor profile. Univariate analysis demonstrated the close correlation between chimerism status evaluated on PB CD3+ cells only at any time post-transplant and the onset of aGVHD (p = 0.0391) but not cGVHD. Multivariate analysis according to linear regression method did not find any impact of the following variables on chimerism kinetics after RIC transplant: disease status before transplant, age, sex, type of RIC regimen, number of days of ATG, aGVHD (p ≥ 0.11). In conclusion, this study underlines the tight correlation that exists between chimerism status and kinetics on CD3+ PB subpopulations after RIC transplant and acute GVHD development that impacts on transplant outcome.