Additional key phrases: diabetes mellitus; nearpatient testing; accuracyVariations in haematocrit have been shown to be a source of error in several of the most commonly used reagent strip tests for glucose.l" In general, blood glucose measurements by these methods vary inversely with increasing sample haematocrit. Thus, patients with abnormally low haematocrits have spuriously high test strip measurements and vice versa.Haematocrit, however, is dependent on both the red blood cell count (RBC) and mean cell volume (MCV) of a sample, and are related as follows:Consequently, patients with variable MCV may have the same haematocrit but widely differing red cell counts. The corollary of this is that studies which use normal subjects (with similar MCVs) make it impossible to distinguish if the test strip error is due to haematocrit variations per se or to changes in the number of red cells. Therefore, we aimed to ascertain how variations in haematocrit, RBC and MCV affect strip glucose measurement. PATIENTS AND METHODSSamples were obtained from three groups, each comprising of three non-diabetic males: low MCV subjects (mean 70·4 [range 67-5-72' 5] Blood was collected in KzEDTA and had haematocrit, RBC and MCV measured using a Coulter S + 4 analyser (Coulter Corp, Hertfordshire,
The prognostic value of CD34 expression on leukaemic blast cells was assessed in 38 patients with acute myeloid leukaemia. Nineteen patients had more than 10% CD34 positive blast cells. Median survival for the CD34 positive patients was 125 days and for the CD34 negative patients the median survival has not yet been reached at day 575 (p = 0.06). Of those patients who received intensive chemotherapy, CD34 positive patients (n = 13) had a median survival of 150 days while for CD34 negative patients (n = 14) the median survival has not yet been reached (p = 0.01). Adjustment for age and pre-existing myelodysplastic syndrome did not affect the correlation of CD34 positivity with survival (p = 0.02). Over the period of observation (median 10 months, range 2-19 months) the relative risk of death was 5 times greater for the CD34 positive patients. This study suggests that CD34 expression is an adverse prognostic marker, independent of age and pre-existing myelodysplasia.
Background and Aims A platelet count ≤100,000/µL is regarded as an independent prognostic marker for the development of leukemia and is associated with inferior survival in myelofibrosis (MF) (Huang et al. 2008). The approved JAK2 inhibitor, ruxolitinib, is associated with treatment-emergent thrombocytopenia, and patients with platelets ≤100,000/µL were excluded from the phase III COMFORT trials. Efficacy and safety data are limited in patients with MF and platelets ≤100,000/µL treated with ruxolitinib. Pacritinib (SB1518), an oral JAK2/FLT3 inhibitor, did not appear to be associated with clinically significant treatment emergent anemia or thrombocytopenia during early phase studies in patients with myeloid and lymphoid malignancies. This integrated analysis was performed to further evaluate the safety and efficacy of pacritinib in MF patients with baseline platelet counts of ≤100,000/µL. Methods The databases from 2 phase I/II clinical trials of pacritinib in advanced myeloid malignancies and MF were integrated to evaluate the rate of adverse events (AEs) and favorable spleen responses in patients with MF and thrombocytopenia. Results One hundred twenty-nine patients with advanced myeloid malignancies and MF were treated with pacritinib in phase I and II clinical trials. Sixty-five patients with MF were treated with 400 mg orally once daily in 2 phase II studies. Of these, 28 patients with MF [21 primary MF (75%), 5 post-polycythemia vera-MF, 2 post-essential thrombocytosis-MF] had baseline platelet counts of ≤100,000/µL (median: 58,500/µL, range: 15,000/µL – 97,000/µL). The median age was 69 years. Twenty three (82%) patients had the JAK2V617F mutation. During the phase 2 studies, spleen volume responses were assessed by MRI and are shown for all patients (Figure 1) and for patients with platelets ≤100,000/µL (Figure 2). Thirty-seven percent and 43% of all evaluable patients and patients with ≤100,000/µL platelets, respectively, had ≥35% reduction in spleen volume from baseline (Table). Among the 21 informative patients with allelic JAK2V617F quantification at more than 1 study visit, 3, including 2 patients with homozygous mutations, had ≥35% reduction in spleen volume and substantial reductions in allelic burden from baseline (mean reduction 64%, range 44 to 88%). In the 11 (17%) patients with MF and baseline platelet counts ≤50,000/μL, overall spleen volume reduction was 38% (3/8) in evaluable patients and the median decline in platelet count observed at study end was 6,000/µL. Integrated safety analysis for all 129 patients with advanced myeloid malignancies showed the most common adverse events (AEs) were gastrointestinal (GI), predominantly diarrhea, and most of these were grade 1 (43%) and grade 2 (26%). The time to onset of diarrhea was ≤30 days in the majority of those affected, but only 2% had drug discontinuation as a consequence. Among the 129 patients in the phase 1 and 2 trials, 57 patients had ≤100,000 platelets; of these 26 (46%) had no CTC grade change in hemoglobin (Hb) and platelet counts from baseline values. Hb and platelet counts improved by one grade in 16% and 18% of patients, respectively. One grade worsening was seen in 28% and 30% in Hb and platelet counts, respectively. Conclusions Pacritinib was well-tolerated in patients with MF, regardless of their baseline platelet counts. Grade 1 or 2 GI toxicities, particularly diarrhea, were the most common AEs. Spleen responses were similar in patients regardless of baseline platelet counts (≥100,000/µL vs. ≤100,000/µL). Notably, even patients with initial platelet counts ≤50,000/µL tolerated therapy and the majority maintained stable hemoglobin and platelet counts. A phase III trial will evaluate pacritinib versus best available therapies in patients with MF and platelet counts ≤100,000/µL. Disclosures: Dean: Cell Therapeutics, Inc: Employment. Cernohous:Cell Therapeutics, Inc: Employment. Mesa:Incyte, CTI, Gilead, Celgene, Genetech, NS Pharma, Lilly: Research Funding. Campbell:Cell Therapeutics, Inc: Employment. Caldwell:Cell Therapeutics, Inc: Employment. Wang:Cell Therapeutics, Inc.: Employment. Myint:Cell Therapeutics, Inc: Employment.
Introduction: Mixed-phenotype acute leukemia (MPAL) accounts for 1.2% to 5% of acute leukemia across age groups with intermediate prognosis. We evaluated clinicoepidemiologic profiles and outcomes of MPAL. Methods: Records of children younger than 15 years of age with acute leukemia from January 2010 to December 2016 were reviewed on the basis of the MPAL WHO 2008 criteria. Treatment was uniform with a modified MCP-841 protocol. Descriptive analysis tools were used. Outcomes were measured by the Kaplan-Meier method on MedCalc, version 14.8.1. Results: Among 3830 children with acute leukemia in the study period, 2892 received treatment from our center, of whom 24 (0.83%) had MPAL, median age 9 years, with a male:female ratio of 3:1, and median white blood cell of 13.4×109/L. Common immunophenotypes were B/myeloid—12 (50%), T/myeloid—9 (37.5%), and B/T-lymphoid—3 (12.5%). Some B/myeloid cases had abnormal cytogenetics. Seventeen patients were evaluable for outcome. Sixteen patients underwent postinduction bone marrow and 13 (81%) achieved morphologic remission. Thirteen patients underwent flow cytometry–based minimal residual disease evaluation; 9 (69%) were <0.01% (4 postinduction, 5 postconsolidation), and 67% of these had sustained remission till the last follow-up. None underwent bone marrow transplant. The projected 3-year event-free and overall survival rates were 40% and 48%, respectively (median follow-up: 22 mo). Conclusion: MPAL represented <1% of childhood acute leukemia. acute lymphoblastic leukemia–type chemotherapy that incorporated high-dose cytarabine was effective in achieving an minimal residual disease–negativity rate of 69% in evaluated patients, which was also predictive of better outcome.
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