WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia.

We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracycline-AraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p = 0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age (p = 0.00009), NPM gene mutation (p = 0.002), and WT1 >75th percentile (>2365) (p = 0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients (p = 0.003 and p = 0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype (p = 0.008 and p = 0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30% vs. 6% in FLT3-ITD negative and FLT3 positive patients, respectively; p = 0.01) and OS (OS at 30 months: 38% vs. 20%, p = 0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.

Weekly standard doses of rh-EPO are highly effective for the treatment of anemic patients with low-intermediate 1 risk myelodysplastic syndromes.

For more than 20 years erythropoietin (rHEPO) has largely been used to treat anemia in myelodysplastic syndromes (MDS). Early clinical trials showed erythroid responses in no more than 15-25% of patients. In the last decade, a better selection of MDS patients suitable for a therapeutic challenge with rHEPO, alone or in combination with G-CSF, allowed for an increased response-rate, averaging around 40%. More recently, an even higher percentage of responses have been obtained using higher-doses of rHEPO (up to 80,000 IU/weekly) in lower-risk MDS patients. This treatment however, especially at such high doses, is costly and not easily affordable for prolonged periods. The aim of this study was to verify if the use of "standard" doses of rHEPO could induce a satisfying response-rate with a less expensive treatment schedule in IPSS-defined "lower-risk" MDS anemic patients. From January 2005 to December 2009 a total of 55 consecutive anemic (Hb ≤ 10 g/dL) patients (29 males, 26 females, median age 78 years) with low-intermediate-1 risk MDS were treated after informed consent with rHEPO (40,000 IU once a week subcutaneously) for at least 3 months; at the end of this period, erythroid response was assessed, and responders were allowed to continue the treatment indefinitely, whereas non-responders were considered "off study". Both efficacy and safety of the treatment were recorded and evaluated. After 3 months of treatment, 36 out of 55 (65.5%) patients achieved an erythroid response to rHEPO according to IWG 2006 criteria. Higher response-rates to rHEPO were related with both lower IPSS and particularly WPSS scores. Treatment was safe, and only 1 patient had to discontinue the treatment because of unmanageable side-effects. Among the 36 responders, 28 (77%) maintained the response after a median follow-up of 46 months. Our data indicate that standard doses of rHEPO are at least as effective as higher-doses for correcting anemia in lower-risk MDS patients; in this clinical scenario, this schedule allows for a consistent reduction of costs without precluding the achievement of a durable erythroid response.