Clinical value of assessing the response to imatinib monitored by interphase FISH and RQ-PCR for BCR-ABL in peripheral blood for long-term survival of chronic phase CML patients: results of the Niigata CML-multi-institutional co-operative clinical study

Abstract

This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.46 years. At 5 years, the overall survival (OS) rate and progression-free survival (PFS) rate were 94.4 and 92.0%, respectively. The estimated rate of the CCyRe and MMR were 81.7 and 67.1%, respectively. 106 patients achieving the CCyRe had significantly better OS and PFS than 27 patients without achieving the CCyRe. Patients with MMR had significantly better survival free from death, progression, imatinib withdrawal and a loss of the CCyRe, than patients whose response level remained in the CCyRe without achieving MMR until 18 months. Our observation suggests that the response level of the CCyRe on PB serve as a prognostic indicator, and achieving MMR provides stable long-term survival.

Leucemia mieloide crônica

“…Regarding the outcomes event-free survival, including transformation to accelerated phase and blast crisis; death from any cause; loss of adherence to treatment; or loss of cytogenetic response, there are more patients who attain molecular response than those who do not. Patients with major molecular response have better survival than patients with complete cytogenetic response who do not achieve major molecular response 53…”

Chronic myeloid leukemia treatment guidelines: Brazilian Association of Hematology, Hemotherapy and Cell Therapy. Brazilian Medical Association Guidelines Project - 2012

“…The association with PCR allows the molecular response to be monitored. In a study published by Reinhold et al, the estimated cytogenetic and molecular responses at 5 years were 81.7% and 67.1%, respectively (54) (B). However, the comparison between the results of FISH using peripheral blood leukocytes and the cytogenetics of the bone marrow may not establish an appropriate correlation in the measurement of CML activity during imatinib treatment (91) (B).…”

“…In respect to event-free survival, including transformation to accelerated and blast crisis phases, death from any cause, loss of adherence to treatment or loss of cytogenetic response, patients who attain molecular response have a higher response compared to those who do not. Patients with major molecular response have better survival than patients with complete cytogenetic response, who do not achieve major molecular response (54) (B).…”

Practical Monitoring of Chronic Myelogenous Leukemia: When to Change Treatment

“…Monitoring cytogenetic response through fluorescence in situ hybridization (FISH) analysis of blood cells is still debated. Few studies have compared conventional cytogenetics and FISH analysis on marrow and/or blood cells, 24,25 and cytogenetic analysis is still needed to detect additional chromosome abnormalities (ACA) in the Ph-positive clone or other chromosome abnormalities (OCA) in the Ph-negative population. Therefore, FISH currently must be considered complementary and not an alternative to conventional cytogenetic analysis.…”