Abstract
We assessed the long-term outcome of consecutive patients in the chronic phase of chronic myeloid leukemia (CML) treated with interferon-alpha (INF-α) in Central and Northern Moravia between 1989 and 2006. A retrospective study focused on the response, prognostic factors and side-effects of INF-α. 118 patients (67 males and 51 females, median age 50 years; range 18-71) were analyzed. The median follow-up was 82.6 months (12.4-212.6). Thirty-six patients (30.5%) achieved major cytogenetic response (CyR) in median of 18.3 months (3.7-47.3) and maintained it for a median of 64.0 months (7.0-176.0). Sixty-one patients treated with INF-α for more than 12 months had an overall survival (OS) of 137.0 months (95% CI 117.6-156.4). Eighteen (29.5%) achieved complete CyR (CCyR). 109 patients discontinued the treatment with INF-α because of hematologic or cytogenetic resistance in 53 (48.7%), progression of CML in 31 (28.4%) and intolerance to INF-α in 17 (15.6%) patients. The percentage of peripheral blasts, leukocyte count (>50x10(9)/L), splenomegaly, anemia (Hgb≤110 g/L) and Sokal score had statistical impact on the OS in univariate assessment but only the Sokal score remained significant in multivariate analysis. Additional cytogenetic abnormalities at diagnosis were associated with poor prognosis. In most patients, treatment with INF-α had to be stopped because of a failure to induce response, progression of CML or side-effects but nearly one third of patients treated at least for one year had a long-term benefit from INF-α. The best prognosis was associated with achievement of CCyR and negativity of BCR-ABL in nested RT-PCR.
Highlights
Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm characterized by acquisition of the Philadelphia (Ph) chromosome in stem cells and their progeny[1]
In our long-term retrospective study, we evaluated the outcome of all consecutive CML patients treated in the Northern and Central Moravia regions with INF-α alone or in combination with cytosine arabinoside (Ara-C) or hydroxyurea, with special attention to treatment response, side-effects and assessment of prognostic factors
Diagnosis of CML was based on cytogenetic assessment with confirmation of the Ph chromosome and/or demonstration of the BCR-ABL1 fusion gene using nested Reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH)
Summary
Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm characterized by acquisition of the Philadelphia (Ph) chromosome in stem cells and their progeny[1]. The aberrant chromosome results of a reciprocal translocation between the long arms of chromosomes 9 and 22 t(9;22)(q34;q11), giving rise to the fusion gene BCR-ABL1. This fusion gene encodes for a constitutively active tyrosine kinase which has become the major therapeutic target of CML treatment today[2,3]. Responses achieved after imatinib therapy may not be durable[5] which could be a clinical correlation of CML stem cell resistance to TKIs. CML origin is supposed to arise from the transformed line of CD34+CD38- normal stem cells since these cells themselves and their progeny carry the BCR-ABL1 fusion gene[6]. Hematopoietic stem cells are largely quiescent and express high levels of the multidrug resistance-1 gene[8] that might limit imatinib uptake[9]
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