Cytoreductive agents

Hydroxyurea and busulfan are the agents most frequently reported as treatment choices in patients with diseases resembling aCML.62 Both can be used either on a daily schedule with the dose adjusted to the desired leukocyte blood count, or alternatively, on a cyclical schedule aiming initially for resolution of systemic symptoms and reduction of the leukocyte count. Due to its more rapid onset of action and lack of delayed effect on the bone marrow, hydroxyurea is more suitable for continuous, daily maintenance treatment. Busulphan's effects on the bone marrow are less predictable and may be delayed and cumulative, resulting in a prolonged bone marrow suppression. Therefore, its cyclical use is preferable. Although not formally documented in clinical studies, anemia and thrombocytopenia often persist in aCML patients with well-controlled leukocytosis, either as a consequence of the disease itself, treatment-associated myelosuppression, or both. Careful dose titration is therefore recommended for hydroxyurea and particularly for busulphan. An unfavorable response of these patients to busulfan has been considered by some a characteristic feature of aCML,62 and even treatment with hydroxyurea often yields only partial and transient disease control.62 63 The effectiveness of both agents is particularly limited in the management of organomegaly.

Analysis of the impact of the effects of various treatments after referral to a tertiary cancer center failed to document significant differences in the survival of treated and untreated patients.56

In patients with splenomegaly, splenectomy may result in a temporary alleviation of anemia and throm-bocytopenia, provided that the bone marrow remains functional and the cytopenias are not a consequence of disease evolution. Therefore, a bone marrow aspiration, biopsy, and karyotyping should be part of the preoperative evaluation. A recent report on the value of splenectomy in 12 patients with CMML showed improvement of thrombocytopenia in 4 of 11, and a modest improvement of anemia in 2 of 9 patients. None of the anemic patients achieved transfusion independence.64 There are no reports in aCML, but it is reasonable to expect similar results. Thus, splenectomy should be viewed as a palliative measure, particularly in patients with clinical symptoms, including pain due to splenomegaly. Of the remaining options to reduce splenomegaly, splenic irradiation is ineffective in myeloid malignancies and intensive intravenous chemotherapy using, e.g., cytarabine, although effective as a palliative treatment, it is invariably associated with bone marrow suppression. (M. Beran, unpublished observation, 2003).

The effectiveness of both oral drugs is particularly limited in control of hepatosplenomegaly. Analysis of the impact of treatment after referral to one tertiary cancer center failed to document significant differences in the survival between treated and untreated patients.

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