Evaluation of the Imatinib Treatment of Patients with Chronic Myeloid Leukemia (CML). a Retrospective Study from Algerian Working Group on CML (GAT-LMC)

Introduction: The advent of anti-tyrosine kinase has revolutionized the treatment of chronic myeloid leukemia. Indeed, from 2000, the IMATINIB has become internationally the gold standard of treatment for CML chronic phase, while the allogeneic bone marrow transplant was previously, the 1st intention choice, when an HLA-matched donor is available. The aim of this study is to evaluate the efficiency and the toxicity of a treatment with Imatinib(copy), drug used in Algeria to treat patients with a CML chronic phase. The main objective is to evaluate the overall survival and the progression-free survival to these patients.

Materials and methods: This is a longitudinal study, National, multicenter, retrospective, which included Algerian patients with chronic phase CML and treated with Imatinib between January 2007 and December 2013. A technical form was established and distributed to different hematology services nationwide, to collect and analysis the following data: Patient's general characteristics, disease circumstances of discovery, clinical and para-clinical examinations at diagnosis (blood count, blood smear, bone marrow aspiration, karyotype, molecular biology, Sokal prognostic classification score and Eutos score). The treatment: Imatinib 400 mg / d, a therapeutic assessment is made according to the ELN recommendations adapted to our conditions and capabilities in Algeria: The complete hematologic response (CHR) at 03 months and molecular response and / or cytogenetic and / or Fish at 03, 06.12, 18.24 months and more according to capabilities. At 03mois and / or 6 months we search a bcr / abl rate <10%. At 12 months we research a major molecular response (MMR), defined by a bcr / abl ratio lower than 0, 1% according to the ELN. A ratio between 0.1 to 1% is considered a good response according to GAT-LMC (the CML study Algerian group) so the Imatinib treatment is continued. The median follow-up of patients in December 2014 is 48 months (12-84 months). Overall survival and progression-free survival are determined by using the Kaplan-Meier method. The descriptive analysis of the quantitative variables by calculating averages, medians and the qualitative variables, by using percentages and 95% confidence interval. The Chi2 test is used to compare between two variables.

Results: From 1024 collated sheets, 1007 are assessable; the median age of patients was 45.7 years (06-87 years), it's about 516 men and 491 women with a sex ratio M / F 1.05. The Diagnosis of CML is done by cytogenetic examination in 337 patients (33%), by Fish 214 patients (21%) and by molecular biology in 401 patients (39%). The prognostic classification (PC), according to the Sokal score, found a low risk in 18.7%, 55.5% as intermediate and a high risk in 25.8%. The Eutos score is less than 87 in 97% and more than 87 in 03%. A CHR at 03mois was found in 907 patients (90.1%). There is no correlation between the RHC at 03 months and the SOKAL PC (p = 0.23), by cons we found a significant correlation with the Eutos score (p <10-3). Molecular assessment at 03 and 06 months is performed in 222 patients and a bcr / abl ratio <10% was found in 66.5%. A molecular evaluation at 12 months showed an MMR in 55.4%. Cytogenetic evaluation (FISH) has found a 28.6% CCyR at 3 months, 45% at 6 months, 64.2% at 12 months (IRIS = 68%), 75.7% at 18 months (IRIS = 76.2%) and 85% at 24 months. Overall survival was 84% at 08 years and it is significantly correlated to Sokal score (p <10-6). A failure to TRT was found in 11.5% of the cases and a 10, 1% relapse rate, related to non-adherence to TRT in 50% of the cases and a lack of monitoring by a regular molecular control in the other half of the cases. Event-free survival at 08 years was 76%. A good clinical and biological tolerance is noted in 90% of the cases. Only 8% of patients were switched to a 2nd generation TKIs because of intolerance. A non-adherence to TRT was found in 14.4%.

Conclusion: Imatinib, used in Algeria, is a very interesting molecule both efficiency side and tolerance level. However, we must ensure a molecular monitoring for a patients optimal follow up, and an adequate patient education for a better adherence.