Chronic phase chronic myeloid leukemia: response of imatinib mesylate and significance of Sokal score, age and disease duration in predicting the hematological and cytogenetic response.

OBJECTIVE: To evaluate the response of imatinib mesylate in chronic phase of chronic myeloid leukemia and to observe the significance of Sokal score and various factors which predict the response. METHODS : This was a descriptive, prospective study conducted from May 2001 to September 2006. One hundred and thirty six patients with diagnosis of chronic myeloid leukemia in chronic phase were analyzed. Hematologic and cytogenetic responses were assessed according to defined criteria. RESULTS: The median age at time of diagnosis was 33 years (range, 12-65 years). Among them 86 were males, 50 were females. At the end of study response was analyzed overall and according to Sokal score. At median follow-up of 18 months, 122 patients were evaluable for cytogenetic response. Complete hematologic response was seen 86% while complete and major cytogenetic response was observed in 34.4% and 49.2% cases respectively. Analysis of variables like younger age, disease duration at time of starting imatinib failed to show any significant influence on response to imatinib mesylate, however, response was found to be higher in patients who had low Sokal score at the time of presentation. CONCLUSION: Imatinib mesylate has substantial activity in chronic phase of CML. Low Sokal score at time of presentation predict the higher hematologic as well as cytogenetic response in patients with chronic phase.

Hematological and molecular response evaluation of CML patients on imatinib.

BACKGROUND: The BCR-ABL tyrosine kinase is a well-validated therapeutic target in Chronic Myeloid Leukemia (CML). Imatinib mesylate (formerly STI-571), a tyrosine kinase inhibitor is highly effective at the hematological, cytogenetic and molecular level in CML. AIMS: To evaluate hematological and molecular response in CML patients on Imatinib and also the side effects of the therapy if any. METHODS AND MATERIALS: Sixteen patients were diagnosed as having chronic phase CML at Kasturba Medical College Hospital, Attavar, Mangalore during the period of two years from January 2004 to January 2006 and were given Imatinib at 400 mg/day orally. They were followed closely over a period of 1 year using the following parameters: (1) monthly clinical examination, (2) monthly peripheral blood smear examination, (3) real time reverse transcriptase quantitative polymerase chain reaction (RT Q-PCR) for BCR-ABL at the end of every 6 months. The findings were evaluated after one year for hematological and molecular response achieved. RESULTS: Fifteen (93.75%) patients achieved complete hematological response within three months of therapy. Six (37.5%) patients achieved complete molecular response(CMR) within six months of therapy as measured by real time RT Q-PCR. None of the patients who did not achieve CMR within first six months of therapy achieved it after one year of therapy. No patient lost the initial response. The median BCR--ABL/ABL value at the end of the six months was 11% and at the end of the one year was 3.38%. CONCLUSION: Imatinib mesylate is highly effective in the treatment of chronic phase CML and so should be considered as the drug of first choice in CML. Molecular response evaluation after six months can predict the subsequent molecular response and can also be usedas a surrogate monitor of the marrow cytogenetic response to imatinib therapy in CML.

Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia

Chronic myeloid leukemia (CML) originates from the hematopoietic stem cell and is characterized by the reciprocal translocation t(9;22)(q34;q11), which results in the BCR-ABL fusion gene on chromosome 22q-, also known as the Philadelphia chromosome. This chimeric gene codes for a cytoplasmic protein with constitutive tyrosine-kinase activity, responsible for cellular transformation and leukemogenesis in CML. The aim of this observational cohort study was to discriminate and quantify BCR-ABL transcripts in the peripheral blood of patients with CML who were treated with imatinib mesylate (Glivec, Novartis). Twenty-two patients were followed for six months during treatment. Quantitative real time polymerase chain reaction was performed before treatment and after 3 and 6 months from treatment initiation. As compared with the third month, there was a significant decrease in BCR-ABL expression in the sixth month of treatment (P = 0.0002). At the sixth month, there was a significant difference in the levels of the two major transcripts of BCR-ABL, B2A2 and B3A2 (P = 0.0347), indicating that B2A2 may be more sensitive to imatinib. The results of our study indicate that imatinib is able to modify the natural history of CML, and raise the hypothesis that patients who express the B2A2 transcript may have a better prognosis.