Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, the product of Philadelphia chromosome. Imatinib mesylate (IM) is a selective inhibitor of this kinase.
The objective of this study was to determine the hematological and non-hematological complications of IM in patient with CML in Armenian population.
The object of the study were patients of the Hematology Center of the Ministry of Health of the Republic of Armenia, registered from 2000 to 2017. During this period 377 patients with a diagnosis of Ph+ CML were observed. Total of 326 (86%) patients treated with IM were involved in research (45.4% male and 54.6% female, who were at the age of 7-81 years). The 282 patients (86.5%) were in chronic phase, 44 patients (13.5%) - in phase of acceleration and blast crisis. The doses of IM were 400 mg daily for the chronic phase and 600-800 mg daily for the accelerated and blast phase of disease. The patients were thoroughly monitored for both hematological and non-hematological complications, in some cases temporary dose adjustment was necessary.
213 patients experienced various side effects which, in decreasing order of frequency were: peripheral edema, bone pains, joint pains, allergic reactions, muscle cramps, nausea, vomiting, hepatic enzyme elevation, gastric pain and headaches as non-hematologic complications (table 1) and leucopenia, thrombocytopenia and anemia as hematological complications (table 2).Three patients developed grade IV complications in form of toxic hepatitis, anasarca and allergic reaction, which required treatment discontinuation.
Cytopenias developed in cases of 48 patients, and CHR/complete hematological response/ within the first 4 months from the start of therapy was observed in 65.3% of their cases. At the same time, in the group of patients who did not have these complications, CHR was achieved in 84% of cases (p = 0.0207).
It is noteworthy that in case of patients with cytopenias, CCR/complete cytogenetic response/ was achieved in 15.3% of cases, whereas in case of patients without these complications- in 32.4% of cases (p = 0.0754). Thus, hematological complications in the form of cytopenias, which require a temporary cessation of treatment, reduce the likelihood of CHR and CCR.
Such statistics show that hematological complications, quite possibly, were originally due to patients belonging to a higher prognostic group. And the group of patients, who in the first 4 months did not reach the CHR, requires a broader cytogenetic examination according to the karyotype and, if necessary, sequencing.
Imatinib mesylate is a well-tolerated drug with some adverse events that rarely require treatment discontinuation.