Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience).

Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.

[The JAK2 mutation in myeloproliferative disorders: A predictive factor of thrombosis]. / La mutation JAK2 dans les syndromes myéloprolifératifs BCR-ABL négatifs: facteur prédictif de thrombose.

BACKGROUND: BCR-ABL negative myeloproliferative neoplasms (MPN) include polycythemia Vera (PV), essential thrombocythemia (ET) and primitive myelofibrosis (PMF). the JAK2 V617F mutation has been introduced since 2008 as a major diagnostic criterion on the one hand and on the other hand, it would be linked to increased risk of thrombotic complications. AIM: This study aimed to evaluate the association of JAK2 mutation and thrombotic events in MPN. METHODS: A retrospective study concerning 45 BCR-ABL negative MPN patients (mean age=53 old years, sex ratio=0.8) was conducted. RESULTS: They were classified as PV (22 patients), ET (17 patients), PMF (3 patients) and atypical MPN (3 patients). The JAK2 mutation was found in 64.4% of patients: 72.7% of PV patients, 47% of ET patients and 66.7% of PMF patients. Thrombotic events were recorded in 11 patients (24.4%). Cerebral arteries and portal vein were the most frequent localizations. The JAK2 mutation was an independent risk factor of thrombotic events. CONCLUSION: Consequently, it seems that screening for JAK2 mutation in BCR-ABL negative MPN could play a role in identifying patients at high risk of vascular complications.

[Adult lymphocytosis etiology by flow cytometry]. / Classification par cryométrie en flux de 104 cas d'hyperlymphocytose de l'adulte.

BACKGROUND: Positive and differential diagnosis of chronic lymphocytic leukemia (CLL) is based on immunophenotyping analysis. CLL is searched whenever a persistent lymphocytosis is found. AIM: To evaluate the performance of flow cytometry in etiologic diagnosis of lymphocytosis. Could it allow us to distinguish CLL from other causes of lymphocytosis? METHODS: Blood samples from 104 adult patients having a rate of lymphocytes> 5000 élé/mm3 persisting more than three months were analyzed using a large panel of monoclonal antibodies in three colors and Cell Quest software. results: Lymphoproliferative B disorder was retained in 83 cases, including 50 cases of typical CLL with Matutes score≥ 4 and 12 cases of atypical CLL with Matutes score = 3 . Diagnosis of hairy cell leukemia and follicular lymphoma were guided by the respective specific antigen expression CD103 and CD10. Large granular T lymphoma (LGL-T) was the most common etiology of lymphoid T proliferation. Unusual cases of Natural Killer (NK) and NK/T proliferations were found. CONCLUSION: The Flow cytometry is a powerful tool to establish lymphocytosis etiological diagnosis; it avoids invasive investigations in a large number of cases.