Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia.

Optimization of post-remission therapies to maintain complete remission and prevent relapse is a major challenge in treating patients with acute myeloid leukemia (AML). Monitoring patients for measurable residual disease (MRD) is helpful to identify those at risk for relapse. Hypomethylating agents are being investigated as post-remission therapy. Identification of recurrent genetic alterations that drive disease progression has enabled the design of new, personalized approaches to therapy for patients with AML. Emerging data suggest that targeted post-remission therapy, alone or in combination with chemotherapy, may improve outcomes. Results of ongoing clinical trials will further define potential clinical benefits

Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy

Background: The phase 2 BRIGHT AML 1003 trial evaluated efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized patients to receive glasdegib + LDAC (n = 78) or LDAC alone (n = 38). The rate of complete remission (CR) was 19.2% in the glasdegib + LDAC arm versus 2.6% in the LDAC arm (P = 0.015). Methods: This post hoc analysis determines whether the clinical benefits of glasdegib are restricted to patients who achieve CR, or if they extend to those who do not achieve CR. Results: In patients who did not achieve CR, the addition of glasdegib to LDAC improved overall survival (OS) versus LDAC alone (hazard ratio = 0.63 [95% confidence interval, 0.41-0.98]; P = 0.0182; median OS, 5.0 vs 4.1 months). Additionally, more patients receiving glasdegib + LDAC achieved durable recovery of absolute neutrophil count (≥ 1000/μl, 45.6% vs 35.5%), hemoglobin (≥ 9 g/dl, 54.4% vs 38.7%), and platelets (≥ 100,000/μl, 29.8% vs 9.7%). Transfusion independence was achieved by 15.0% and 2.9% of patients receiving glasdegib + LDAC and LDAC alone, respectively. Conclusions: Collectively, these data suggest that there are clinical benefits with glasdegib in the absence of CR. Trial registration: ClinicalTrials.gov NCT01546038 (March 7, 2012

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations

partially_open16Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML). Patients and methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.partially_openembargoed_20230131Pollyea, Daniel A; DiNardo, Courtney D; Arellano, Martha L; Pigneux, Arnaud; Fiedler, Walter; Konopleva, Marina; Rizzieri, David A; Smith, B Douglas; Shinagawa, Atsushi; Lemoli, Roberto M; Dail, Monique; Duan, Yinghui; Chyla, Brenda; Potluri, Jalaja; Miller, Catherine L; Kantarjian, Hagop MPollyea, Daniel A; Dinardo, Courtney D; Arellano, Martha L; Pigneux, Arnaud; Fiedler, Walter; Konopleva, Marina; Rizzieri, David A; Smith, B Douglas; Shinagawa, Atsushi; Lemoli, Roberto M; Dail, Monique; Duan, Yinghui; Chyla, Brenda; Potluri, Jalaja; Miller, Catherine L; Kantarjian, Hagop

From Too Much to Too Little: How the central U.S. drought of 2012 evolved out of one of the most devastating floods on record in 2011

Table of Contents Section 1: Introduction....................................................................... 1 Section 2: Regional Drought Perspective................................. 2 Section 3: State Drought Perspectives........................................ 3 Section 3.1: Colorado........................................................................... 20 Section 3.2: Illinois.................................................................. 25 Section 3.3: Indiana................................................. 29 Section 3.4: Iowa...................... 36 Section 3.5: Kansas............................................................... 42 Section 3.6: Kentucky............................................................................ 46 Section 3.7: Michigan.............................. 52 Section 3.8: Minnesota............................................................ 58 Section 3.9: Missouri..................................................... 63 Section 3.10: Nebraska................................................. 67 Section 3.11: North Dakota............................................ 73 Section 3.12: Ohio................................................... 79 Section 3.13: South Dakota..................................... 85 Section 3.14: Wyoming........................................... 96 Section 4: Conclusions.............................................................. 9

Mapping the physiography of Michigan with GIS

Abstract: We present a new physiographic map of Michigan, that is also available interactively, online. Only four, small-scale physiographic maps of Michigan had been previously published. Our mapping project made use of a wide variety of spatial data, in a GIS environment, to visualize and delineate the physical landscape in more detail than has been done previously. We also examined many of the unit boundaries in the field, using a GIS running on a GPS-enabled laptop. Unlike previous physiographic maps, the online version of the map enables users to query the criteria used to define each of the 224 boundaries of its 10 major and 91 minor physiographic units. The interactive nature of the online version of the map is a unique enhancement to physiographic maps and mapping. Our study also provides data on the number and types of criteria used to define each of the 224 unit boundaries within the map. Most of our unit boundaries are based on data derived from 10-m raster elevation data and NRCS soils data, e.g., relief, soil wetness, escarpments, landscape fabric, and parent material characteristics. Data gleaned from NRCS SSURGO county-scale soil maps were a strength of the project