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Imatinib is a relatively specific inhibitor of the BCR/ABL tyrosine kinase, effective in chronic myeloid leukemia (CML). The aim of our study was to analyse the frequency and type of hematological and non-hematological adverse events in our series of late and early chronic phase patients with CML treated with imatinib and correlate the grade of hematological toxicity with the response obtained. Hematological events were seen in 59 out of 150 (39%) late chronic phase (CP) patients: of these, 24% experienced toxicity Grade 3-4. Of the 100 early CP patients, 26 (26%) had hematological adverse event: 7% experienced toxicity Grade 3-4 (p=0.0001). We found that only in early CP patients, the occurrence of hematological side effects of any grade within 6 months of therapy had a negative influence on cytogenetic response. We compared the incidence of non-hematological adverse events occurring in late and in early CP patients and found that in these latter, some side effects were more frequent, such as weight gain, periorbital edema, muscle cramps, skin rashes, diarrhea, weeping. On the contrary, we found that bone pain and hemorrhagic events were more common in late CP patients. Grade 3-4 adverse events were recorded at rates below 4% and decreased over time: in late CP patients hemorrhages and muscle cramps were the most common side effects of Grade 3-4, whereas in early CP patients, the most frequent events were nausea, weight gain and cutaneous rash. We have observed that hematological and non-hematological side effects during imatinib therapy are different among late and early CP patients and that severe hematological toxicity may influence cytogenetic response only in early CP patients.

From a retrospective analysis of our series of myelodysplastic patients, we found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB) according to FAB criteria, but later on (median time 4 months, range 2-8) developed a peripheral monocytosis >1 x 10(9)/L, leading to a disease re-classification into a dysplastic type of chronic myelomonocytic leukemia (MD-CMML). Analysis of clinical and prognostic aspects in this subgroup of patients as compared with those of primarily diagnosed MD-CMML patients, showed some significant differences in Hb level, platelet count, percentage of immature circulating precursor (IPC), bone marrow blastosis and trilineage dysplasia. Median survival for present group of patients was 33 months compared with 20 months for MD-CMML. Different prognostic scores were applied for evaluation of risk distribution and relative impact on survival prediction. We suggest on a possible atypical presentation of CMML and indicate a careful attention to be addressed to myelodysplastic patients who develop peripheral monocytosis, who might have a CMML variant, with more favourable prognosis and prolonged survival. Furthermore, we believe this is a further evidence for the arbitrary nature of current classification systems, which definitely exclude CMML from myelodysplastic syndromes.