0000000000276063
AUTHOR
Diamante Turri
BCR-ABL Derived Peptide Vaccine in Chronic Myeloid Leukemia Patients with Molecular Minimal Residual Disease During Imatinib: Interim Analysis of a Phase 2 Multicenter GIMEMA CML Working Party Trial.
Abstract Abstract 648 Introduction: Imatinib (IM) 400mg daily is the standard treatment for chronic myeloid leukemia (CML) patients and a complete cytogenetic response (CCyR) is achieved in the majority of patients within one year of treatment. In addition, a considerable number of patients reach a major molecular response (i.e BCR-ABL/ABL ratio <0.1%) but BCR-ABL transcript is still measurable in most of treated patients revealing the persistence of a minimal residual disease (MRD). In a previous small pilot study, vaccinations with p210 b3a2-derived fusion peptides in IM treated CML patients appeared to induce both a peptide specific immune response and a reduction of residual disease …
Differences among young adults, adults and elderly chronic myeloid leukemia patients
Abstract BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old)…
Gene Expression Profile of Chronic Myeloid Leukemia Innately Resistant to Imatinib
Background. Most chronic myeloid leukemia patients who receive imatinib as first line-terapy will obtain, after 12 months treatment, complete cytogenetic and molecular response . However several cases will not achieve molecular response, but their innate mechanism(s) of resistance remain poorly understood. We tried to explore the molecular events involved in innate resistance in CML. Study design. Five patients who were molecular “non responder” and seven “major” responder were investigated by using the expression profile of a set of 380 genes. Multiple testing procedure (MTP), Significance Analysis of Microarrays (SAM), Empirical Bayes Analysis of Microarrays (EBAM), False Discovery Rate (…
High BCR-ABL/GUSIS Levels At Diagnosis Are Associated With Unfavorable Responses To Imatinib
Abstract The approval of three tyrosine kinase inhibitors (TKIs) for the first line treatment of Chronic Myeloid Leukemia (CML) has generated an urgent need for molecular parameters predictive of unfavorable therapeutic outcomes. Recent evidence suggests that failure to achieve early molecular responses (i.e. BCR-ABL/ABLIS levels <10% after 3 months or <1% after 6 months of TKI treatment) results in inferior rates of both overall and progression-free survival. With the current study, we wanted to establish if high BCR-ABL transcripts at diagnosis would be associated with unfavorable responses to Imatinib Mesylate (IM). Thus, we correlated quantitative determinations of BCR-ABL levels …
High BCR-ABL Levels At Diagnosis Are Associated with Unfavorable Responses to Imatinib Mesylate.
Abstract Abstract 2790 The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of Chronic Myeloid Leukemia (CML) has generated a need for early molecular parameters associated with inadequate responses to Imatinib Mesylate (IM). Recent evidence suggests that CML patients presenting BCR-ABL/ABLIS levels >10% after 3 months of IM or >1% after 6 months of treatment have inferior outcomes in terms of both overall survival (OS) and progression-free survival. We wanted to establish if high BCR-ABL transcripts at diagnosis would also be associated with unfavorable responses to IM. To this end, we correlated quantitative determinations of BCR-ABL measu…
Outcome of patients with CML treated with dasatinib or nilotinib after failure of second prior TKIs.
Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients …