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Central nervous system (CNS) relapse is uncommon in patients with acute myeloid leukemia (AML) with the use of high-dose cytarabine containing chemotherapy regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not well defined. We assessed the incidence and outcome of CNS relapses among 1245 patients with relapsed/refractory AML referred to our institution between 2000 and 2014. CNS leukemia relapse was observed in 51 patients (4.1%). Using a multivariate regression model and after adjusting for age, FLT3-ITD mutation (OR = 2.33; P = .02) and elevated LDH (>1000 IU/L, OR = 1.99; P = .04) were independent predictive factors for CNS relapse. Patients under 64 years of age with 0, 1, or 2 baseline adverse features had a probability of 3.8%, 7.0%-8.0%, and 13.9% for developing CNS disease, respectively. Our study identifies patients with AML at higher risk for CNS relapse in whom prophylactic CNS therapy may be warranted., (© 2017 Wiley Periodicals, Inc.)

We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.

A phase I study was performed to determine the safety and pharmacokinetics of XK469R in patients with refractory acute leukemia. The study aimed to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of XK469R given intravenously over 30 to 60 min on days 1, 3, and 5 of a 21 day cycle. Patients were treated in successive cohorts of six until DLT was observed. Once the MTD was determined, an additional cohort of six patients was enrolled at the previous dose level and that dose was considered the recommended phase 2 dose (RPTD). Forty-six patients were treated at dose levels of 1,400, 1,750, 2,200, and 2,750 mg. The DLTs were: mucositis, colitis and hyperbilirubinemia. Reversible myelosuppression was noted at all dose levels. One (2%) of 42 patients achieved a complete remission and five patients (11%) had hematologic improvement. The half-life of the drug was long with a mean value of 48 h. The mean clearance was 206 mL/h with a coefficient of variation of 32%. No correlation was observed between the development of DLT and pharmacokinetics. The RTPD is 1,750 mg. XK469R induced hematological responses in patients with refractory leukemia at tolerable doses.

Troxacitabine is a novel L-enantiomer nucleoside analog with unique properties in terms of its structure, pharmacokinetics, intracellular transport, and susceptibility to mechanisms of resistance. Troxacitabine has significant activity in patients with refractory myeloid leukemias, both as a single agent and when combined with standard anti-leukemia agents. In a cohort of 170 patients with refractory myeloid leukemia treated with troxacitabine-based regimens on Phase 1 or 2 studies, 10 (6%) had biopsy-proven extramedullary disease, either with or without bone marrow involvement. Six of these patients who received single-agent troxacitabine, 4 received a combination of troxacitabine and cytarabine. Complete response and disappearance of all extramedullary lesions were observed in 6 (60%) of these 10 patients. Two of the 6 responding patients relapsed within 3 months, 2 patients had remissions of 8 and 9 months duration, respectively, 1 patient is in on-going remission at 3, and 1 patient is lost to follow-up. Troxacitabine-based therapy had significant antileukemic activity in extramedullary myeloid leukemias and warrants further investigation in this clinical situation.

Purpose: To investigate the activity of a novel dioxolane L-nucleoside analog, troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia., Patients and Methods: Study participants were patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was provided as an intravenous infusion for more than 30 minutes daily for 5 days at a dose of 8.0 mg/m(2)/d (40 mg/m(2) per course). Courses were given every 3 to 4 weeks according to antileukemic efficacy., Results: Forty-two patients (AML, 18 patients; MDS, one patient; ALL, six patients; CML-BP, 17 patients) were treated. Median age was 51 years (range, 23 to 80 years); 22 patients were male. Stomatitis was the most significant adverse event, with three patients (7%) and two patients (5%), respectively, experiencing grade 3 or 4 toxicity. Ten patients (24%) had grade 3 hand-foot syndrome, and two patients (5%) had grade 3 skin rash. One patient (2%) had grade 3 fatigue and anorexia. Marrow hypoplasia occurred between days 14 and 28 in 12 (75%) of 16 assessable patients with AML. Two complete remissions and one partial remission (18%) were observed in 16 assessable patients with AML. None of six patients with ALL responded. Six (37%) of 16 assessable patients with CML-BP experienced a return to chronic-phase disease., Conclusion: Troxacitabine has significant antileukemic activity in patients with AML and CML-BP.

Objective: To determine the safety and cost-effectiveness of replacing the intravenous (IV) tubing sets in hospitalized patients at 4- to 7-day intervals instead of every 72 hours., Design: Prospective, randomized study of infusion-related contamination associated with changing IV tubing sets within 3 days versus within 4 to 7 days of placement., Setting: A tertiary university cancer center., Patients and Methods: Cancer patients requiring IV infusion therapy were randomized to have the IV tubing sets replaced within 3 days (280 patients) or within 4 to 7 days of placement (232 patients). Demographic, microbiological, and infusion-related data were collected for all participants. The main outcome measures were infusion- or catheter-related contamination or colonization of IV tubing, determined by quantitative cultures of the infusate, and infusion- or catheter-related bloodstream infection (BSI), determined by quantitative culture of the infusate in association with blood cultures in febrile patients., Results: The two groups were comparable in terms of patient and catheter characteristics and the agents given through the IV tubing. Intent-to-treat analysis demonstrated a higher level of tubing colonization in the 4- to 7-day group versus the 3-day group (median, 145 vs 50 colony-forming units; P=.02). In addition, there were three episodes of possible infusion-related BSIs, all of which occurred in the 4- to 7-day group (P=.09). However, when the 84 patients who received total parenteral nutrition, blood transfusions, or interleukin-2 through the IV tubing were excluded, the two groups had a comparable rate of colonization (0.4% vs 0.5%), with no catheter- or infusion-related BSIs in either group., Conclusion: In patients at low risk for infection from infusion- or catheter-related infection who are not receiving total parenteral nutrition, blood transfusions, or interleukin-2, delaying the replacement of IV tubing up to 7 days may be safe, as well as cost-effective

Purpose: To investigate the toxicity profile, activity, and pharmacokinetics of a novel L-nucleoside analog, troxacitabine (BCH-4556), in patients with advanced leukemia., Patients and Methods: Patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was given as an intravenous infusion over 30 minutes daily for 5 days. The starting dose was 0.72 mg/m(2)/d (3.6 mg/m(2)/course). Courses were given every 3 to 4 weeks according to toxicity and antileukemic efficacy. The dose was escalated by 50% until grade 2 toxicity was observed, and then by 30% to 35% until the dose-limiting toxicity (DLT) was defined., Results: Forty-two patients (AML: 31 patients; MDS: six patients [five MDS + one CMML]; ALL: four patients; CML-BP: one patient) were treated. Median age was 61 years (range, 23 to 79 years), and 29 patients were males. Stomatitis and hand-foot syndrome were the DLTs. The MTD was defined as 8 mg/m(2)/d. The pharmacokinetic behavior of troxacitabine is linear over the dose range of 0.72 to 10.0 m/m(2). Approximately 69% of troxacitabine was excreted as unchanged drug in the urine. Marrow hypoplasia occurred between days 14 and 28 in 73% of AML patients. Three complete remissions and one partial remission were observed in 30 assessable AML patients. One MDS patient achieved a hematologic improvement. A patient with CML-BP achieved a return to chronic phase disease., Conclusion: Troxacitabine has a unique metabolic and pharmacokinetic profile and significant antileukemic activity. DLTs were stomatitis and hand-foot syndrome. Troxacitabine merits further study in hematologic malignancies.