Hematologic Response and Frequency of Side Effects in Chronic Myeloid Leukemia Patients Treated with Imatinib (GLIVEC): A South-East Asian Experience

OBJECTIVE:

Chronic Myeloid Leukemia (CML), is a clonal disorder of the hematopoietic stem cells associated with an oncogenic reciprocal translocation t(9;22)(q34;q11), resulting in the Philadelphia chromosome. Estimated to account for 15% of all leukemia's in the developed world, although global prevalence is not known. Imatinib or Glivec (STI-571), the targeting agent for ATP binding sites of tyrosine kinase enzyme is used commonly as a first line treatment modality for CML. This is one of the first studies from Southeast Asia to report the hematological response and side effects of Imatinib in CML patients.

MATERIALS AND METHODS:

This cross sectional study was conducted at Out Patient Departments of Civil Hospital Karachi and Doctor Plaza Clinic in Karachi, Pakistan. Sampling technique used was convenient sampling. The duration of the study was from August 1st, 2015 until August 31st, 2016. By using Open Epi, an open source calculator (version 3), the minimum sample size was calculated to be 14 (with Confidence Interval 95%). Patients of both genders, age 18 or above fulfilling the inclusion criteria were included in this study after verbal or written consent. Newly diagnosed CML patients with Positive bcr-abl gene hybrid evident by either Fluorescence in Situ Hybridization or Polymerase Chain Reaction, with no prior therapy (hydroxyurea, interferon or other tyrosine kinase inhibitors) were recruited. Data from patients who were able to follow up to 6 months were included in the final analysis. Patients with elevated serum creatinine, uric acid, abnormal LFT and positive past medical histories for coronary heart disease or pregnant women were excluded. A total of 80 patients were approached from Out Patient Departments. Out of 80, 11 were excluded on the basis of inclusion/exclusion criteria and remaining 69 newly diagnosed and untreated patients were started on a 400-mg dose of Imatinib once in a day. Those were then followed closely to measure the duration till complete hematologic response was achieved, confirmed by physical examination and complete blood count. Subjects with no or suboptimal response to the drug after three months of starting treatment with 400mg of Imatinib had their doses titrated. . Patients were asked about signs and symptoms of the disease at the initial visit. In regular follow-ups, patient-reported signs and symptoms were noted and drug toxicities were observed through clinical examinations and various lab tests.

RESULTS:

Commonest clinical presentation of patients with CML was found to be splenomegaly (72.5%), followed by fatigue (53.7%), hepatomegaly (33.33%), bleeding dysfunction (14.5%), fever (24.6%) and others (5%). A complete hematological response was achieved by 92.5 % of the individuals within three months of starting treatment with a 400mg dosage of Imatinib once in a day (Range from 1 week to 12 weeks); while 7.2% of the patients only achieved complete hematological response at 6 months of therapy. Commonest side effect observed was weight gain (42%), followed by skin toxicities (36.2%), gastrointestinal symptoms (33.33%), deranged Complete Blood Count (anemia, neutropenia, thrombocytopenia and leukopenia) (14%) and abnormal Liver function Tests (3%).

CONCLUSION:

In a South East Asian population, our study clearly demonstrates that Imatinib is effective in the treatment of CML. Side effect profile are comparable to that experienced by patients in other geographic areas. We found increased incidence of weight gain, skin toxicities and GI symptoms compared to historical data, likely attributable to other environmental factors, were however manageable and reversible. These results show that Imatinib (Glivec) is quite effective and tolerable amongst patients with CML in South East Asia, long term data will be needed to better define its safety profile.