U.S. AGGREGATE AGRICULTURAL PRODUCTION ELASTICITIES ESTIMATED BY AN ARIMA FACTOR SHARE ADJUSTMENT MODEL

Production Economics,

VERIFICATION OF LINEAR PROGRAMMING SOLUTIONS, WITH EMPHASIS ON SUPPLY IMPLICATIONS

Demand and Price Analysis,

AN ADVANCED METHOD FOR ECONOMIC THRESHOLD DETERMINATION: A POSITIVE APPROACH

Research Methods/ Statistical Methods,

Dasatinib dose management for the treatment of chronic myeloid leukemia

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143669/1/cncr31232.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143669/2/cncr31232_am.pd

Meir Wetzler, MD

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111978/1/cncr29391.pd

Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study

Abstract Background Ruxolitinib improves splenomegaly and symptoms in patients with intermediate-2 or high-risk myelofibrosis; however, nearly half develop grade 3/4 anemia and/or thrombocytopenia, necessitating dose reductions and/or transfusions. We report findings from an open-label phase 2 study exploring a dose-escalation strategy aimed at preserving clinical benefit while reducing hematological adverse events early in ruxolitinib treatment. Methods Patients with myelofibrosis received ruxolitinib 10 mg twice daily (BID), with incremental increases of 5 mg BID at weeks 12 and 18 for lack of efficacy (maximum, 20 mg BID). Symptom severity was measured using the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS). Results Forty-five patients were enrolled, 68.9% of whom had a Dynamic International Prognostic Scoring System score of 1 to 2 (i.e., intermediate-1 disease risk). Median percentage change in spleen volume from baseline to week 24 was − 17.3% (≥ 10% reduction achieved by 26 patients [57.8%]), with a clear dose response. Median percentage change in MFSAF TSS from baseline at week 24 was − 45.6%, also with a dose response. The most frequent treatment-emergent adverse events were anemia (26.7%), fatigue (22.2%), and arthralgias (20.0%). Grade 3/4 anemia (20.0%) and dose decreases due to anemia (11.1%) or thrombocytopenia (6.7%) were infrequent. Conclusions A dose-escalation approach may mitigate worsening anemia during early ruxolitinib therapy in some patients with myelofibrosis. Trial registration ClinicalTrials.gov identifier, NCT01445769 . Registered September 23, 2011.https://deepblue.lib.umich.edu/bitstream/2027.42/145195/1/13045_2018_Article_642.pd

Clinical characteristics and whole exome/transcriptome sequencing of coexisting chronic myeloid leukemia and myelofibrosis

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCRâ ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera, or myelofibrosis or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent. In an effort to characterize the underlying genetic events that might contribute to the appearance of more than one MPN in a patient, we studied neoplastic cells from patients with dual MPNs by nextâ generation sequencing. We observed that most patients with two MPNs harbored mutations in genes known to contribute to clonal hematopoiesis through altered epigenetic regulation such as TET2, ASXL1/2, SRSF2, and IDH2 at varying frequencies (1%â 47%). In addition, we found that some patients also harbored oncogenic mutations in N/KRAS, TP53, BRAF, EZH2, and GNAS at low frequencies, which probably represent clonal evolution. These findings support the hypothesis that hematopoietic cells from MPN patients harbor multiple genetic aberrations, some of which can contribute to clonal dominance. Acquiring mutations in JAK2/CALR/MPL or the BCRâ ABL translocation probably drive the oncogenic phenotype towards a specific MPN. Further, we propose that the acquisition of BCRâ ABL in these patients is frequently a secondary event resulting from an unstable genome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136751/1/ajh24728.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136751/2/ajh24728_am.pd

A case of subdural hematoma in patient with chronic myeloid leukemia treated with high-dose imatinib mesylate

Imatinib mesylate (IM) is used to treat a wide range of diseases, including Philadelphia chromosome-positive chronic myeloid leukemia (CML), on account of its high tolerability and low incidence of minor adverse events. Hemorrhage is thought to be a rare complication of IM. Recently, IM has been associated with reduced α2-plasmin inhibitor and platelet dysfunction. We report here the case of a 33-year-old female patient with CML who experienced subdural hematoma after an incremental increase in IM dosage due to a loss of complete molecular response. This case indicates that physicians should be alert to this atypical cause of headache in patients taking high-dose IM