Serial measurement of BCR-ABL transcripts in the peripheral blood after allogeneic stem cell transplant for chronic myeloid leukemia: an attempt to define patients who may not require further therapy

We identified 243 patients with Ph-positive CML who had BCR-ABL transcripts monitored by quantitative RT-PCR after allogeneic stem cell transplant for a median of 84.3 months. Individual patients were regarded as having achieved molecular relapse (MR) if the BCR-ABL/ABL ratio exceeded 0.02% on three occasions or reached 0.05% on two occasions. Patients were allocated to one of four categories: (1) 36 patients were 'persistently negative' or had a single low level positive result, (2) 51 patients, 'fluctuating positive, low level', had more than one positive result but never more than two consecutive positive results; (3) 27 patients, 'persistently positive, low level', had persisting low levels of BCR-ABL transcripts but never more than three consecutive positive results, and (4) 129 patients relapsed. In 107 of these relapse was based initially only on molecular criteria; in 72 (67.3%) patients the leukemia progressed to cytogenetic or hematologic relapse either prior to or during treatment with donor lymphocyte infusions. We conclude that the pattern of BCR-ABL transcript levels after allograft is variable; only a minority of patients with fluctuating or persistent low levels of BCR-ABL transcript satisfied our definitions of MR whereas the majority of patients who did so were likely to progress further

Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)

This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in BCR-ABL transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) ≤ 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (P < .001). This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at www.clinicaltrials.gov as NCT00006343