Leukemia
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Clinical Trial
Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia.
Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. ⋯ Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.
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The cure rate of childhood acute lymphoid leukemia (ALL) has improved in the past 20 years due to improved treatment of T cell ALL, better infection control and availability of blood components, and more experience. Several these are proposed as treatment guidelines.
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Erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring the in vitro response of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors from 12 patients and from eight healthy donors to recombinant human erythropoietin (rhEPO), and by quantifying relationships between circulating EPO levels and progenitor cell frequencies in MDS marrow. Half-maximal growth of MDS CFU-E and BFU-E was detected at a 4-fold higher rhEPO concentration than required by control erythroid progenitors. Nine of the patients evaluated exhibited maximal growth of erythroid colonies at 5- to 20-fold higher than control saturating rhEPO concentrations. ⋯ The frequency of MDS marrow CFU-E and BFU-E was 57 +/- 42% and 18 +/- 9% of the mean control values, respectively. Correlation analysis of the relationships between MDS EPO levels and erythroid progenitors indicated that the anemia in MDS is not attributable to an abnormality in the capacity of EPO to induce the generation of CFU-E, but may be influenced by the BFU-E population, whose severe deficiency results in insufficient influx of EPO-responsive cells. Our findings therefore suggest that treatment of MDS patients with rhEPO may be of limited benefit, since the generation of BFU-E from more primitive ancestors and the initial growth requirements of these cells are not under the regulatory influence of this hormone.
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It has been suggested that abnormalities of chromosome 3 at bands q21 and q26 are associated with the presence of increased numbers of abnormal megakaryocytes in patients with hematologic malignancies. The pretreatment bone marrows of 287 patients with leukemia (acute myeloid leukemia (AML), 225 patients; acute lymphocytic leukemia (ALL), 36 patients; or chronic myelogenous leukemia in blast crisis (CML-B), 26 patients) were reviewed to identify those with normal or increased numbers of megakaryocytes. Thirty-two patients with AML, one with ALL, and 10 with CML-B had normal or increased numbers of megakaryocytes. ⋯ All five patients with abnormal chromosome 3 at bands q21 and q26 had additional cytogenetic abnormalities (Ph1 in two patients; -7 in three patients). Mean and median platelet counts were greater than 100,000/microliters for patients with marrow megakaryocytosis regardless of morphology, as well as for the patients with abnormalities involving 3q21 and 3q26. Abnormalities of megakaryocyte morphology, increases in the numbers of megakaryocytes, and normal to increased platelet counts are not uncommon in patients with acute leukemia and CML-B, and are not uniquely associated with changes involving chromosome 3.