Current prognostic models for myelodysplastic syndromes (MDS) do not allow the identification of patients with lower risk disease and poor prognosis that may benefit from early therapeutic intervention. We evaluated the characteristics of 856 patients with low or intermediate-1 disease by the International Prognostic Scoring System. Mean follow-up was 19.6 months (range 1-262). Of these patients, 87 (10%) transformed to acute myelogenous leukemia, and 429 (50%) had died. By multivariate analysis, characteristics associated with worse survival (Po0.01) were low platelets, anemia, older age, higher percent of marrow blasts and poor-risk cytogenetics. Although not included in the model, higher ferritin (P ¼ 0.007) and b2-microglobulin (Po0.001) levels were associated with worse prognosis. This allowed the development of a scoring system in which patients could be grouped in three categories: category 1 (n ¼ 182, 21%) with a median survival of 80.3 months (95% CI 68-NA); category 2 (n ¼ 408, 48%) with a median survival of 26.6 months (95% CI 22-32) and category 3 (n ¼ 265, 31%) with a median survival of 14.2 months (95% CI 13-18). In summary, this analysis indicates that it is possible to identify patients with lower risk MDS and poor prognosis who may benefit from early intervention.

Purpose: Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor.Experimental Design: Adult patients with advanced MM were entered on a multicenter phase II study.Results: Twenty-seven patients (median age 69, range 39 -79), median 4 (0 -10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m 2 twice weekly i.v. for a median of two 4-week cycles (range 0.2-9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for >4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n ‫؍‬ 7) compared with patients with progressive disease (n ‫؍‬ 5). Overall median survival was 42 weeks (range 3-92؉).Conclusions: Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.

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SUMMARY This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose-limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m2/day with cytarabine 2 g/m2/day, each for 5 days, and G-CSF 5 μg/kg, beginning the day before chemotherapy and continuing daily until neutrophil recovery. The complete remission (CR) rate among the 46 evaluable patients was 46% (95% confidence interval [CI] 31–61%) and the CR + CR but with a platelet count <100 x 109/l rate was 61% (95% CI 45–75%). Multivariate analysis showed that responses to GCLAC were independent of age, cytogenetic risk category, and number of prior salvage regimens. GCLAC is highly active in relapsed and refractory AML and warrants prospective comparison to other regimens, as well as study in untreated patients.

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