BACKGROUNDAberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters.METHODSA total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks.RESULTSPatients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate‐2/high‐risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment‐naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]).CONCLUSIONSDecitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further. Cancer 2006. © 2006 American Cancer Society.

In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. (Funded by Agios Pharmaceuticals; ClinicalTrials.gov number, NCT02074839 .).

Purpose Decitabine, a DNA-targeted hypomethylating agent, is approved by the United States Food and Drug Administration for treatment of patients with myelodysplastic syndromes (MDS) on a schedule of 15 mg/m2 administered via intravenous (IV) infusion every 8 hours for 3 days. This study assessed the efficacy and safety of an alternative dosing regimen administered on an outpatient basis in academic and community-based practices. Patients and Methods Patients were treated with decitabine 20 mg/m2 by IV infusion daily for 5 consecutive days every 4 weeks. Eligible patients were ≥ 18 years of age and had MDS (de novo or secondary) of any French-American-British (FAB) subtype and an International Prognostic Scoring System (IPSS) score ≥ 0.5. The primary end point was the overall response rate (ORR) by International Working Group (IWG 2006) criteria; secondary end points included cytogenetic responses, hematologic improvement (HI), response duration, survival, and safety. Results Ninety-nine patients were enrolled; the ORR was 32% (17 complete responses [CR] plus 15 marrow CRs [mCRs]), and the overall improvement rate was 51%, which included 18% HI. Similar response rates were observed in all FAB subtypes and IPSS risk categories. Among patients who improved, 82% demonstrated responses by the end of cycle 2. Among 33 patients assessable for a cytogenetic response, 17 (52%) experienced cytogenetic CR (n = 11) or partial response (n = 6). Conclusion Decitabine given on a 5-day schedule provided meaningful clinical benefit for patients with MDS, with more than half demonstrating improvement. This suggests that decitabine can be administered in an outpatient setting with comparable efficacy and safety to the United States Food and Drug Administration–approved inpatient regimen.

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Reduced-intensity conditioning HSCT to maintain remission in selected older patients with AML is relatively well tolerated and appears to provide superior outcomes when compared with historical patients treated without HSCT. GVHD and NRM rates were lower than expected. Future transplantation studies in these patients should focus on further reducing the risk of relapse.

The RABiTS™/MOD-YBCO (rolling assisted biaxially textured substrate/metal-organic deposition of YBa 2 Cu 3 O 7−δ ) route has been established as a low-cost manufacturing process for producing high performance second generation (2G) wire. American Superconductor Corporation (AMSC) has used this approach to establish a production scale manufacturing line based on a wide-web manufacturing process. This initial production line is currently capable of producing 2G wire in lengths to 500 m with critical currents exceeding 250 A cm −1 width at 77 K, in the self-field. The wide-web process, combined with slitting and lamination processes, allows customization of the 2G wire width and stabilizer composition to meet application specific wire requirements. The production line is currently supplying 2G wire for multiple cable, fault current limiter and coil applications. Ongoing R&D is focused on the development of thicker YBCO layers and improved flux pinning centers. This paper reviews the history of 2G wire development at AMSC, summarizes the current capability of the 2G wire manufacturing at AMSC, and describes future R&D improvements.

The potential prognostic value of quantitative real-time reverse transcriptionpolymerase chain reaction (RT-PCR [qrt-PCR]) measurements of PML-RAR␣ mRNA in acute promyelocytic leukemia was retrospectively assessed before treatment and at 3 posttreatment intervals in 123 patients on intergroup protocol 0129. The primary measure was the PML-RAR␣ GAPDH normalized quotient (NQ), that is, PML-RAR␣ mRNA copies divided by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA copies. Only samples with more than 2.5 ؋ 10 5 copies of the housekeeping gene GAPDH mRNA (detection sensitivity exceeding 10 4 ) were considered NQ evaluable. With RNA from low-density selected cells, paired peripheral blood (PB) and bone marrow samples (n ‫؍‬ 140) had comparable NQs (P < .001). Before treatment, high NQ was associated with short-form PML-RAR␣ (P < .001), but not with white blood cell count or clinical outcome. Following treatment, NQ was lower in all-trans retinoic acidinduced complete remission (CR) than chemotherapy-induced CR (P ‫؍‬ .018) and at first test after consolidation chemotherapy (P ‫؍‬ .037). After consolidation chemotherapy, patients with NQ exceeding 10 ؊5 had 4.1-fold increased relapse risk (P ‫؍‬ .008); however, 73% of patients who experienced relapse had NQ lower than 10 ؊5 . In the follow-up period (FUP), any NQ exceeding 10 ؊5 and 10 ؊6 had 17.5-fold and 7.6-fold increased relapse risk, respectively (P < .001), while no gradation of relapse risk (approximately 18%) could be identified at NQ lower than 10 ؊6 , including NQ ؊ .

Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure.