Donor Lymphocyte Transfusion (DLT) in the Treatment of Relapsed CML after Allogeneic PBSCT - A Retrospective Analysis of 346 Patients by the EBMT Chronic Leukemia Working Party.

DLT has become the gold standard for the treatment of reccurrent CML after allogeneic stem cell transplantation. However, so far, published data are based on DLT following bone marrow transplantation (BMT). During recent years, mobilized peripheral blood stem cell transplantation (PBSCT) have been increasingly performed. To evaluate the efficacy of DLT following PBSCT, we retrospectively analysed the results of 86 patients treated with DLT for CML relapse after PBSCT from HLA-identical family donors. Results were compared to 260 patients receiving DLT for relapse after related BMT. Reduced intensity transplants were excluded.

BMT and PBSCT groups were balanced in terms of patient age (median: 40 vs 42 y), conditioning, stage at transplant (84% vs 76% in first chronic phase (CP) p=.2), and stage at relapse (molecular/cytogenetic: 59% both, CP: 28% vs 20%, advanced: 13% vs 21%, p=.2). However, BMT patients had been transplanted in earlier years (median: 1994 vs.1998, p<.001), had a longer remission after transplantation (median: 677 vs. 275 d, p<.001), and had experienced more aGvHD after transplantation (58% vs. 34%, p<.001). Complete molecular or cytogentic remission was achieved in 71% of the patients, with a trend towards better response in BMT recipients (p=.06). Overall (OS) and event free survival (EFS) at five years from DLT are shown in table 1. Outcome was significantly superior in BMT recipients, in particular if DLT was given for hematological, rather than cytogenetic or molecular relapse. In a cox regression model, four factors were associated with better OS/EFS: Transplantation in CP1 (p<.001/.002), early stage at relapse (molecular/cytogenetic vs. hematological, p<.00/<.001), a longer remission after transplantation (p=.005/.028), and BM vs. PBSC for transplantation (p= .003/.004). In contrast, age of patient and donor, acute or chronic GvHD after transplantation, the use of chemotherapy or imatinib before DLT, and the initial number of transfused CD3+ cells were not significant.

The results of this retrospective study suggest a reduced efficacy of DLT in CML relapse following related allogeneic PBSCT as compared to BMT. This effect seems to be independent from established risk factors as disease stage and remission duration. However, since several adverse factors are not equally distributed among the two groups, a bias might be induced, although no statistically significant imbalance could be detected. Therefore, the observation needs to be confirmed in a larger cohort or a prospective study.