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7043Background: Induction chemotherapy for AML results in prolonged neutropenia and a high risk of infection. CLT-008 is a human off-the-shelf allogeneic MPC preparation manufactured by ex vivo cul...

This prospective, randomized, multicenter, controlled trial was designed to evaluate the efficacy and safety of intravenous ganciclovir for the treatment of peripheral cytomegalovirus (CMV) retinitis in patients with AIDS. Patients were randomly assigned to receive either immediate treatment, intravenous ganciclovir, 5 mg/kg twice daily for 14 days followed by 5 mg/kg once daily for 14 weeks, or deferred treatment. Patients randomized to deferred treatment whose retinitis progressed were offered ganciclovir. Of the 22 patients randomized to deferred treatment who were included in the final analysis, 20 were found to have progressive CMV retinitis compared with 10 of the 13 randomized to immediate treatment. The median time to progression in the deferred treatment group, as determined by a masked fundus photography reading center, was 13.5 days compared with 49.5 days in the immediate treatment group (mean +/- SD, 19.3 +/- 4.1 vs. 66.4 +/- 14.0; P = .001, log rank test). These data indicate that ganciclovir delays the progression of CMV peripheral retinitis in persons with AIDS.

Study objective Inhaled bronchodilators are often used in the emergency department (ED) before a definitive diagnosis is made. We evaluated the association between inhaled bronchodilators and outcomes in acute decompensated heart failure patients without chronic obstructive pulmonary disease. Methods We conducted an analysis of the Acute Decompensated Heart Failure National Registry Emergency Module registry of patients with a principal discharge diagnosis of acute decompensated heart failure enrolled at 76 academic or community EDs. Dichotomous outcomes (mortality, ED discharges, ICU admission, ED IV vasodilator use, new dialysis, ED or in patient endotracheal intubation, ED BiPAP, and asymptomatic at discharge) in patients without a history of chronic obstructive pulmonary disease who were given bronchodilators were compared to those who were not given bronchodilators using logistic regression; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated; and propensity score adjustments were made. Results Of the 10,978 patients enrolled, 7299 (66.5%) did not have a history of chronic obstructive pulmonary disease. Bronchodilators were administered by the EMS or in the ED to 2317 (21%) patients. Patients without chronic obstructive pulmonary disease given bronchodilators were more likely to receive ED IV vasodilators (28.4% vs. 16.9%; propensity adjusted OR 1.40 [95% CI 1.18-1.67]) and in-patient mechanical ventilation (6.0% vs. 2.4%; propensity adjusted OR 1.69 [95% CI 1.21-2.37]) than patients without chronic obstructive pulmonary disease who were not given bronchodilators. Hospital mortality in patients without chronic obstructive pulmonary disease was similar regardless of bronchodilator treatment (3.4% vs. 2.6%, propensity adjusted OR 1.02 [95% CI 0.67, 1.56]). Conclusion Many acute decompensated heart failure patients without a history of chronic obstructive pulmonary disease receive inhaled bronchodilators. Bronchodilator use was associated with a greater need for aggressive interventions and monitoring, and this may reflect an adverse effect of bronchodilators or it may be a marker for patients with more severe disease.

Background: Current management of chemotherapy and radiation-induced neutropenia is unsatisfactory with frequent infection-related deaths. A novel allogeneic human myeloid progenitor cell product, CLT-008, that is culture-derived from G-CSF mobilized HSCs, can be cryopreserved and infused without HLA matching. Cells are intended to engraft transiently and produce mature myeloid effector cells that migrate to tissues and may mitigate the risk of bacterial or fungal infection for weeks, as has been demonstrated in murine models. Methods: To evaluate the safety of CLT-008, a phase 1 dose escalation study was conducted in subjects with AML, MDS or ALL during consolidation (n=18) or with AML or tAML during first or subsequent induction (n=31). Eligible subjects were age 18 or older and treated with a high-dose or standard-dose cytarabine-based regimen. All 18 consolidation subjects and 23 induction subjects received CLT-008. Subjects received CLT-008 on study day 6 (consolidation 106 or 107cells/kg) or on study day 9 (induction 107 or 3x107 cells/kg). G-CSF was given at 5 µg/kg daily from the day of CLT-008 until the ANC was 500/µL. During induction, 8 non-randomly selected controls received G-CSF without CLT-008. Dose limiting toxicities (DLT) were defined as any grade 3-5 infusion reaction, grade 4-5 organ toxicity (not due to the primary malignancy, infection, pre-existing condition, or initiation of new chemotherapy), any Grade III to IV GVHD, or failure of autologous neutrophil recovery at Day 42 not clearly attributable to another cause. All subjects were followed for 49 days and status was assessed at 6 months. Results: Among 41 currently evaluable subjects, 1 experienced a DLT of grade 3 allergic infusion-related reaction which resolved promptly with steroids and antihistamine. There were no other DLTs and no GVHD of any grade. Treatment-emergent adverse events occurring in 3 or more subjects included febrile neutropenia, infection, mucosal inflammation, fatigue, diarrhea, tachycardia and nausea but were not judged related to the product. Among the 23 induction subjects receiving CLT-008 with G-CSF, there was a reduction in mucositis (WHO grade 2 or greater) and in duration of febrile episodes when compared to the 8 control subjects. CLT-008-derived cells were detectable in the peripheral blood for 6 of 23 induction subjects at 2-10% of nucleated cells using STR-PCR; there was no clear effect on ANC from this chimerism. To date, 8 of 23 induction subjects went on to subsequent HSC transplant. Seven engrafted while one died on post-transplant day 10 from an unrelated cause. Conclusions: CLT-008 was safe and well tolerated in this phase 1 study. Only 1 DLT occurred and the pattern of AEs was as expected for this population. Among the induction subjects treated at 3x107 cells/kg, efficacy signals with respect to mucositis and duration of fever were found in the absence of high-level peripheral blood CLT-008 chimerism. These observations suggest that CLT-008-derived myeloid effector cells preferentially migrate to chemotherapy-damaged mucosal tissues where they could function to mitigate infection risk. Further clinical development is planned in a randomized phase 2 study using an enhanced potency iteration of CLT-008, assessment of tissue-level chimerism, and specific ascertainment of outcomes related to infection and chemotherapy sequellae. Figure 1 Figure 1. Disclosures Wieduwilt: Cellerant Therapeutics: Honoraria, Research Funding. Cerny:Cellerant Therapeutics: Honoraria, Research Funding. Akard:Cellerant Therapeutics: Research Funding. Ustun:Cellerant Therapeutics: Honoraria, Research Funding. Ravandi:Cellerant Therapeutics: Research Funding. Rossetti:Cellerant Therapeutics: Research Funding. Hill:Cellerant Therapeutics: Honoraria, Research Funding. Brown:Cellerant Therapeutics: Consultancy, Equity Ownership, Patents & Royalties. Kellerman:Cellerant Therapeutics: Employment, Equity Ownership. Van Syoc:Cellerant Therapeutics: Employment, Equity Ownership. Reed:Cellerant Therapeutics: Employment, Equity Ownership. Andreadis:Cellerant Therapeutics: Research Funding.