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BACKGROUND: Fluid overload (FO) commonly occurs during hospitalization for allogeneic hematopoietic cell transplantation (HCT). Grade 2-4 FO is associated with day +100 non-relapse mortality.1 Post-transplant cyclophosphamide (PTCY) for graft-versus-host disease prevention requires aggressive IV hydration to prevent hemorrhagic cystitis. MATERIALS AND METHODS: This is a single-center, retrospective, observational study conducted at an academic medical center via electronic chart review. Included patients received allogeneic HCT followed by PTCY on days +3 and +4. Patients were excluded for age < 18 years or incarceration. Primary endpoints are incidence of Grade 2-4 FO and associated risk factors. Descriptive and inferential statistics (i.e., Fisher's exact test, multivariable regression analysis) were used. RESULTS: Of 97 patients screened, 95 were included and 2 were excluded due to absence of weight measurements needed to grade FO. Median age was 60 years, 66.3% were male, 91.6% received reduced-intensity conditioning, 72.6% received haploidentical HCT, 44.2% were ECOG 0, and 11.6% had diastolic dysfunction. Incidence of grade 2-4 FO was 33.7% (n = 32). Univariate analyses found age (continuous; p = 0.04) and BSA < 1.7 m2 (p = 0.006) as independent factors associated with grade 2-4 FO. Multivariable regression analysis found 3.3% higher risk with every 1-year increase in age ranging from f 20 to 78 years (OR 1.033, 95% CI 1.001, 1.006; p = 0.0453) and 82.8% lower risk with BSA ≥ 1.7 m2 (OR 0.172, 95% CI 0.051, 0.588; p = 0.005) after adjusting for co-variates. CONCLUSION(S): Increasing age and BSA < 1.7 m2 are risk factors associated with grade 2-4 FO during hospitalization for allogeneic HCT with PTCY.

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Developing a low-cost depyrogenation process is vital in extending medical applicability of polymers that can be used in medicine. We present an overview of the plasma-based depyrogenation literature and address the need to develop a non-thermal plasma-based depyrogenation process for delicate materials such as chitosan. We present a low-cost plasma apparatus to treat chitosan powder in hermetically sealed bags. We decouple the experiments into two; depyrogenation experiments for dried standard endotoxin on glass slides, and chitosan modifications analysis through FTIR spectroscopy. We demonstrate depyrogenation efficacy with up to a 4-log reduction in endotoxin levels and discuss minor changes observed in plasma-treated chitosan.

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Asparaginase administration has become a crucial component of front-line pediatric and pediatric-insipired multi-agent regimens for the treatment of acute lymphoblastic leukemia (ALL). The aim of this retrospective study was to assess the safety and feasibility of switching to Erwinia asparaginase after pegaspargase intolerance in adult ALL patients treated at Memorial Sloan Kettering Cancer Center. Our analysis included 10 patients, with a median age of 39 years (range 20-72), male predominance (90%), and a typical B-cell to T-cell ratio (70:30%) for ALL. Nine patients were switched to Erwinia asparaginase after pegaspargase hypersensitivity and one patient after grade 4 hyperbilirubinemia secondary to pegaspargase. With Erwinia asparaginase, no hypersensitivity reactions occurred and no patient developed other known clinical asparaginase-related toxicities. Laboratory adverse effects consisted of mostly mild elevation in liver enzymes. No morphologic relapses have occurred in any patient switched to Erwinia asparaginase in first remission at a follow up of 0.4-34.6 months. These findings are unique in that all of our patients received Erwinia asparaginase after hypersensitivity or intolerance to pegaspargase and 50% of them were older than 40 years of age, a population with very limited Erwinia asparaginase data. Our observations provide preliminary information that treatment with Erwinia asparaginase can proceed as scheduled in adult patients, despite pegaspargase hypersensitivity and possibly liver intolerance.

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OBJECTIVE: To review the clinical pharmacology, efficacy, and safety of blinatumomab for the treatment of pediatric and adult precursor B-cell acute lymphoblastic leukemia (B-ALL). DATA SOURCES: A literature search of EMBASE (1947 to April 2015), Medline (1946 to April 2015), PubMed (1996 to April 2015), the U.S. National Institutes of Health Clinicaltrials.gov, the Food and Drug Administration, and relevant meeting abstracts was conducted using the terms blinatumomab, BiTE, bispecific T-cell engager, MT103, MEDI-538, and Blincyto. STUDY SELECTION/DATA EXTRACTION: Human and animal studies describing the pharmacology, pharmacokinetics and pharmacodynamics, efficacy, and safety of blinatumomab for precursor B-ALL were identified. DATA SYNTHESIS: Blinatumomab is a first-in-class bispecific T-cell engager (BiTE) antibody derived from a B-lineage specific antitumor mouse monoclonal antibody that binds to both CD19 of B-cells and CD3 of T-cells. A pivotal phase II trial demonstrated that response rates were high in a refractory or relapsed patient population, with 43% achieving complete remission (CR). Median relapse-free survival was 5.9 months for those with CR or CR with incomplete hematological recovery. Median overall survival was 6.1 months, and 60% of patients achieved minimal residual disease (MRD) negativity. The most common adverse events included pyrexia, neurological events, headache, febrile neutropenia, peripheral edema, nausea, hypokalemia, constipation, and anemia. CONCLUSIONS: Blinatumomab is a novel BiTE therapeutic monoclonal antibody that has shown promising results in patients with relapsed or refractory ALL or those achieving a CR with persistent MRD. Phase III clinical trials should define the optimal place in therapy of blinatumomab.

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