Browsing by Author "Abel, Melissa L"

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Open Access
Pulmonary toxicity after intraperitoneal mitomycin C: A case report of a rare complication of HIPEC
(World Journal of Surgical Oncology, 2017-02-20) Abel, Melissa L; Kokosis, George; Blazer, Dan G
© 2016 The Author(s). Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become a common treatment approach for disseminated appendiceal neoplasms. Systemic absorption of intraperitoneal chemotherapeutics may lead to drug-induced toxicity, most commonly neutropenia. Mitomycin C has been the most commonly used chemotherapeutic in HIPEC for the past several decades. Case presentation: Here, we describe a rare pulmonary complication secondary to intraperitoneal administration of mitomycin C. Conclusions: While rare, intraperitoneal mitomycin C has the potential to cause serious pulmonary toxicity that should be considered with administration. To our knowledge, this report represents only the second case described in the literature.
Open Access
Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma.
(Oncoimmunology, 2018-01) Suryadevara, Carter M; Desai, Rupen; Abel, Melissa L; Riccione, Katherine A; Batich, Kristen A; Shen, Steven H; Chongsathidkiet, Pakawat; Gedeon, Patrick C; Elsamadicy, Aladine A; Snyder, David J; Herndon, James E; Healy, Patrick; Archer, Gary E; Choi, Bryan D; Fecci, Peter E; Sampson, John H; Sanchez-Perez, Luis
Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for B-cell malignancies but has failed in some solid tumors clinically. Intracerebral tumors may pose challenges that are even more significant. In order to devise a treatment strategy for patients with glioblastoma (GBM), we evaluated CARs as a monotherapy in a murine model of GBM. CARs exhibited poor expansion and survival in circulation and failed to treat syngeneic and orthotopic gliomas. We hypothesized that CAR engraftment would benefit from host lymphodepletion prior to immunotherapy and that this might be achievable by using temozolomide (TMZ), which is standard treatment for these patients and has lymphopenia as its major side effect. We modelled standard of care temozolomide (TMZ^SD) and dose-intensified TMZ (TMZ^DI) in our murine model. Both regimens are clinically approved and provide similar efficacy. Only TMZ^DI pretreatment prompted dramatic CAR proliferation and enhanced persistence in circulation compared to treatment with CARs alone or TMZ^SD + CARs. Bioluminescent imaging revealed that TMZ^DI + CARs induced complete regression of 21-day established brain tumors, which correlated with CAR abundance in circulation. Accordingly, TMZ^DI + CARs significantly prolonged survival and led to long-term survivors. These findings are highly consequential, as it suggests that GBM patients may require TMZ^DI as first line chemotherapy prior to systemic CAR infusion to promote CAR engraftment and antitumor efficacy. On this basis, we have initiated a phase I trial in patients with newly diagnosed GBM incorporating TMZ^DI as a preconditioning regimen prior to CAR immunotherapy (NCT02664363).