HAEMATOLOGICAL COMPLICATIONS OF IMATINIB MESYLATE IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA

Abstract

Background: Imatinib mesylate, a competitive inhibitor of tyrosine kinase is considered the
treatment of choice for patients at all stages of chronic myeloid leukaemia (CML). In the
majority of patients, the drug is well tolerated. However, a significant number of haematological
complications including anaemia, thrombocytopenia, neutropenia, Pancytopenia and
autoimmune haemolytic anaemia have been reported.
Materials and Patients: This study prospectively investigated the spectrum and severity of
haematologic anomalies associated with the use of imatinib in a population of Nigerian CML
patients. Consenting Philadelphia chromosome and/or BCR-ABL1 positive CML patients seen at
the Department of Haematology and Blood Transfusion (OAUTHC), Ile-Ife, in chronic and
accelerated phases and managed with imatinib were recruited. They were commenced on 400
600 mg of imatinib. Full blood count was obtained before, and then at three and six months after
commencing imatinib, using an auto-analyser (Sysmex PocH-100i) to assess the effect of the
drug on haemoglobin concentration, platelet count and absolute neutrophil count (ANC). Twelve
patients who developed transfusion-dependent, imatinib-related anaemia had bone marrow
aspiration.
Results: Fifty percent of the patients had anaemia at 3 months and 26% at 6 months, 20% of the
patients had neutropenia at 3 months and 59% at 6 months, while 7% and 15% had
thrombocytopenia at 3 and 6 months respectively. Grade 3/4 cytopenia was found in 21 patients,
ten patients at 3 months and 11 patients at 6 months. Bicytopenia was found in 12 patients,
patients each at 3 and 6 months with combination of anaemia and neutropenia being the most
common bicytopenia. Pancytopenia was found in three (4%) patients. Although there was no
statistically significant difference between the pre-imatinib haemoglobin concentration and at 3
months, haemoglobin concentration at 6 months was higher than that of pre-imatinib
haemoglobin concentration (p < 0.001). The mean platelet counts at 0 and 3months were 428.77
± 276.85 x 109/l and 269.40 ± 159.60 x109/l respectively, (p < 0.001) while the mean for 0 and 6
month were 428.77 ± 276.85 x 109/l and 214.0 ± 141.4 x 109/l respectively,(p < 0.001). The
mean absolute neutrophil count at 0 and 3 month was 62,769 ± 83,229/μl and 10,984 ± 17,229/μl
respectively, (p < 0.001). The mean value at 6 months was 4,076 ± 10,631/μl. Analysis of bone
marrow cytology in six of the patients revealed micronormoblastic erythropoiesis and other
features in keeping with iron deficiency anaemia. The marrow trephine showed hypocellular
marrow replaced by extensive sheets of mature adipocytes.
Conclusion: This study has shown that imatinib even though well tolerated in the majority of
patients with chronic myeloid leukaemia, presents with various forms of cytopenias and in some
instances severe enough to cause transfusion dependence.

HAEMATOLOGICAL COMPLICATIONS OF IMATINIB MESYLATE IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA