THE RATE AND KINETICS OF MOLECULAR RESPONSE TO DONOR LEUKOCYTE TRANSFUSIONS IN CHRONIC MYELOID-LEUKEMIA PATIENTS TREATED FOR RELAPSE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

We have assessed the molecular response of 30 consecutive patients wit h chronic myeloid leukaemia (CML) treated for relapse after allogeneic bone marrow transplantation (BMT) by donor leucocyte transfusions (DL T). Response was evaluated by qualitative nested and quantitative comp etitive RT-PCR for BCR-ABL mRNA at various time intervals before and a fter DLT. The probability of attaining molecular remission at 2 years was 61% (95% CI 42-78%). Disease state at the time of DLT was signific antly associated with response: molecular remission was achieved for 9 /10 (90%) patients treated early (cytogenetic or molecular relapse) co mpared to only 8/20 (40%) patients treated late (haematological relaps e; P = 0.009), The Kaplan-Meier estimates of molecular remission at 2 years post DLT for patients treated in early or late relapse were 86.6 % and 47.3% respectively (P = 0.004). The median time interval from DL T to molecular remission was 11.0 months (range 25-32). Molecular remi ssions were durable for most (15/17) patients (median follow-up 21.2 m onths; range 0-55). Two patterns of molecular response were found: a v ery rapid decline after an initial lag phase or a more gradual decline over a period of several months. We conclude that molecular monitorin g is a sensitive indicator of response to DLT; different kinetics of m olecular response may reflect disease heterogeneity or differences in the mode of action of DLT.