CML Heads Up !


	CML Heads Up !


	From (EHA)European Hematology Conference Abstracts, June 2003, Lyon, France abstract nr.: 0596 CML PATIENTS WITH COMPLETE KARYOTYPIC RESPONSE TO STI571 (GLIVEC) THERAPY SHOW RAPID REDUCTION OF BCR-ABL TRANSCRIPTS Author: G. Martinelli, Inst. of Hematology and Medical Oncology,Bologna, Italy Co-author(s): B. Giannini, Inst. of Hematology and Medical Oncology, Bologna, Italy G. Rosti, Inst. of Hematology and Medical Oncology, Bologna, Italy M. Amabile, Inst. of Hematology and Medical Oncology, Bologna, Italy S. Bassi, Inst. of Hematology and Medical Oncology, Bologna, ItalyE. Trabacchi, Inst. of Hematology and Medical Oncology, Bologna, Italy N. Testoni, Inst. of Hematology and Medical Oncology, Bologna, Italy F. Pane, Federico II University, Naples, Italy G. Saglio, University of Turin, Turin, Italy D. Alberti, Novartis Pharma, Origgio - Varese, Italy M. Baccarani, Inst. of Hematology and Medical Oncology, Bologna, Italy B. Izzo, Federico II University, Naples, Italy E. Gottardi, University of Turin, Turin, Italy E. Giugliano, University of Turin, Turin, Italy M. Intrieri, Federico II University, Naples, Italy Introduction: Chronic Myelogenous Leukemia (CML) is characterized by a bcr-abl gene that encodes a fusion protein with deregulated tyrosine kinase activity inducing tyrosine phosphorylation and alteration of several signaling pathways that deregulate cellular growth and prevent apoptosis. STI571 (Glivec- Imatinib mesylate), a BCR-ABL tyrosine kinase inhibitor, inhibits the growth, induces apoptosis, and is a promising drug entered into clinical trials as a candidate treatment of BCR-ABL positive CML. The Italian Cooperative Study Group on CML (ICGS on CML) has activated a phase II multicenter study (CML/002/STI571) to evaluate efficacy and safety of Glivec in patients with Ph+ chronic myeloid leukemia, in chronic phase failing IFNalpha for resistance or intolerance. The endpoints of this study were: cytogenetic response, molecular response, time to progression, and overall survival. Search the Mariners FAQ and Glossary Database Join the Discussion Forum CML Ahoy ! Join our on-line community

Conclusion:

The amount of the BCR/ABL transcript before treatment does not predict the (cytogenetic) response to treatment, at least in this population of late chronic phase patients. This could not apply to previously untreated, early chronic phase patients;

A significant and substantial decrease of the transcript was shown during the first half year. During the subsequent 6 months no further decrease was detectable. To understand if molecular response will level off or will improve with time, more samples and a longer treatment time are required;

Assessing the frequency of complete molecular response requires:

more time and more data are early chronic phase patients,

a definition of "complete" moleculare response, which is still lacking;

4) At any time point in the great majority of cases the BCR/ABL transcript level was significantly lower in peripheral blood vs bone marrow samples. To assess the kinetics of the response, peripheral blood cells are valuable, but to assess the degree of the response, bone marrow samples are likely to provide a more precise estimate.

Anjana's Commentary

Major points here:

1. The study is on late chronic phase patients. The level of BCR-ABL transcripts before therapy did not pinpoint CCR patients.

2. Those that attained CCR showed a rapid reduction in BCR-ABL transcripts in the first 6 months of therapy and nothing afterwards.

3. A larger patient cohort and those in early chronic phase must be looked at to find answers for molecular remission and what is complete molecular remission.

4. BCR-ABL transcripts in the blood were lower than in the marrow and the authors suggest a marrow PCR may be more indicative of response to treatment

As to the question whether molecular responses level off with time or get better, I am happy to report that one of my friends is showing 0.04% in his qPCR from Hammersmith Hospital, after 3 years on Gleevec. It is at this value Prof Goldman in his article says that there is less likelihood of relapse. I have been following his PCR values, there have been spikes along the way but a gradual drop in the past few months.

See CML Bouys on PCR

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