First, there is a stepwise increase in cancer for each of the BI-RADS categories 3-5. Secondly, in BI-RADS 3 with microcalcifications, a biopsy is indicated according to our findings. Finally, the sensitivity of mammograms is 95% but the specificity is 19%.
To determine whether a lower imatinib dose could minimize toxicity while maintaining the molecular response (MR), imatinib dose was reduced to 300 mg daily in 43 patients with chronic myeloid leukemia (CML) in sustained deep molecular response to first-line imatinib 400 mg daily. At the time of dose reduction, median duration of the deep response was 4.1 (interquartile range (IQR) 2.2-5.9) years; molecular response was MR, MR, and MR of the international scale in 6, 28, and 9 patients, respectively. Toxicity grade was 1, 2, and 3 in 28, 8, and 1 patients, respectively; 6 patients underwent dose reduction without having side effects. With a median of 1.6 (IQR 0.7-3.2) years on imatinib 300 mg daily, only one patient lost the deep molecular response to MR. At the last follow-up, response was MR, MR, MR, and MR in 1, 3, 9, and 30 patients, respectively. Toxicity improvement was observed in 23 (62.2 %) of the 37 patients with side effects, decreasing to grade 0 in 20 of them. All but one anemic patients improved (p = 0.01), the median Hb increase in this subgroup of patients being 1 g/dL. In CML patients with sustained deep response to the standard imatinib dose, reducing to 300 mg daily significantly improves tolerability and preserves efficacy.
INTRODUCTION: The myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by dysplasia and cytopenias, especially anemia. There is no widely accepted standard therapy for MDS. Exogenous erythropoietin (EPO) seems to be able to raise Hb levels and/or decrease transfusion requirements in patients with MDS, with reported responses rates of 25–30%. In our center, EPO has been used since 1999, based on the published recommendations, assessing the therapeutic response after 12 weeks of therapy. OBJECTIVE: To analyze retrospectively the therapeutic response to EPO in 45 patients with MDS and anemia. PATIENTS AND METHODS: 45 consecutive patients with MDS and calculable IPSS score, showing low or intermediate-1 risk, were treated with EPO from 1999 to 2006. From the initial 45 patients, 5 were excluded from the analysis because of lack of follow-up. The 40 selected patients belonged to the following FAB subgroups: AR 20 (50%), ARS 12 (30%), AREB 3 (7%) and LMMC 5 (12%). Other criteria for treatment were Hb levels <10 g/dL or transfusion requirements ≥ 2U/month and/or serum EPO levels <500 U/L. Different commercially available EPO were used: 31 (77%) of the patients received EPO-alfa/beta (30,000 U/week sc) and 9 (23%) darbepoetin (150μg/week sc). Erythroid response criteria followed those of the International Working Group: complete response (CR) with a >2 g/dL Hb increase or transfusion independence, and partial response (PR) with a 1–2 g/dL Hb increase or 50% decrease in transfusion requirements. Sixteen patients with no response after 12 weeks of therapy, continued with double EPO dose for a median of 10 weeks. RESULTS: From the 40 patients selected, 22 (55%) were female with a median age of 76 years old (47– 86). Mean baseline Hb level was 8,4 g/dl (5,8–11). Serum EPO levels were measured in 33 patients: 23 (70%) presented <200 U/L and 10 (30%) between 200 and 500 U/L. Unexpectedly, as much as 19 (47,5%) of the 40 patients responded to treatment. 16 patients (40%) responded after twelve weeks: 7 of them (44%) showed CR and 9 (56%) PR. From the 24 patients who did not respond initially, 16 continued with double EPO dose and 3 (18%) of them responded after 8 weeks. Response rates in different FAB subgroups are shown in table 1. Median duration of all responses was 9 months (1–42 months), 12 months for CR and 5,5 months for PR. Interestingly, none of the subgroup with pretreatment EPO levels ≥200 responded (p=0,006). After an overall follow-up of 81 months, 7 selected patients died (3 due to blastic transformation and 4 due to causes not related to the disease). CONCLUSIONS: The response to EPO therapy of MDS-related anemia in our center was unexpectedly high (47,5%). Patients who do not show response after 12 weeks of initial therapy, seem to improve from switching to higher EPO doses since 18% of patients treated with this scheme responded. In our study, ARS subgroup showed an unexpected high rate of response (66%), although they were treated without association of granulocyte-stimulating colony factor. Remarkably, pretreatment serum EPO levels <200U/L seems to be a valuable predictor of response since none of the patients with levels ≥200 U/L and <500 U/L responded in our study. Table 1. Response rates in different FAB subgroups; N, number of patients; GR, global response; CR, complete response; PR, partial response FAB N GR (%) CR (%) PR (%) AR 20 35 20 15 ARS 12 66 16 50 AREB 3 33 33 0 LMMC 5 60 20 40
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