Chronic myeloid leukaemia: clinico-haematological features and treatment response to hydroxyurea

ABSTRACT

Chronic myeloid leukaemia [CML] is one of the common cancers of adult age and accounts for 20-30% of all leukaemias. Almost 90-95% cases show Philadelphia chromosome which results in fusion of c-able oncogene of chromosome 9 with bcr of chromosome 22. The hybrid protein [p210] thus transcribed from bcr-able fusion product is an abnormal tyrosine kinase responsible for uncontrolled proliferation of myeloid precursors. The disease primarily affects older adults in the 4[th] and 5[th] decades of life and after a chronic phase of variable duration eventually terminates into a blastic phase. Short of bone marrow transplant there is no curative treatment for this disease although recent studies on the use of interferon seem to be promising. Cytotoxic therapy mostly comprising a single drug myeleran or hydroxyurea is aimed at prolonging the chronic phase and ameliorating the symptoms. Of the two, hydroxyurea is far less toxic and has a rapid effect but needs close monitoring and dose adjustments because of its short lived effect. In a prospective study we determined the clinico-haematological features of CML and response to hydroxyurea. This study revealed that CML occurs at a comparatively young age [median age 34 years] in our population. Most of the clinico-haematological features are similar to those described by others. However, the incidence of myelofibrosis is far higher [100%] than reported in other series. Hydroxyurea when used in a dose of 35 mg/kg body weight brings down the total WBC count to maintenance of total WBC count at this level with dose adjustments at 4-weekly intervals was not achieved. The spleen size did not reduce satisfactorily. We conclude that hydroxyurea should be used in the treatment of CML but the induction dose should be increased if WBC count at presentation is > 150x10[9]/L. Follow up and dose adjustments during the maintenance phase should be more frequent [2 weekly] to keep the WBC count below 20x10[9]/L