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7. Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations

Author

Murugapandian, Sangeetha, Bijin, Babitha, Mansour, Iyad, Daheshpour, Sepehr, Pillai, Biju G, Thajudeen, Bijin, and Salahudeen, Abdulla K

Subjects
Cancer, Rare Diseases, Ovarian Cancer, Kidney Disease, Patient Safety, Hematology, Orphan Drug, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Gemcitabine, Thrombotic microangiopathy, Rituximab, Ovarian cancer
Abstract

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.

Published
2015

9. List of Contributors

Author

Abramovitz, Blaise, primary, Adu, Dwomoa, additional, Afshinnia, Farsad, additional, Agarwal, Anupam, additional, Andrews, Sarah C., additional, Appel, Gerald, additional, Bailey, James L., additional, Bakris, George L., additional, Bauer, Carolyn A., additional, Baxi, Pravir V., additional, Berns, Jeffrey S., additional, Birks, Peter, additional, Bomback, Andrew, additional, Bose, Anirban, additional, Brosius, Frank C., additional, Brown, Lee K., additional, Bushinsky, David A., additional, Busse, Laurence W., additional, Campbell, Ruth C., additional, Canney, Mark, additional, Cathro, Helen, additional, Chávez-Iñiguez, Jonathan, additional, Chawla, Lakhmir S., additional, Chen, Sheldon, additional, Chertow, Glenn M., additional, Chew, Emily Y., additional, Chonchol, Michel, additional, Clegg, Deborah J., additional, Clive, David M., additional, Clive, Pia H., additional, Cohen, Scott D., additional, Collins, Ashte' K., additional, Cooper, James E., additional, Correa-Rotter, Ricardo, additional, Cukor, Daniel, additional, Dalal, Monica, additional, Davenport, Andrew, additional, Davis, Scott, additional, Davison, Sara N., additional, Delanaye, Pierre, additional, de Zeeuw, Dick, additional, Dobre, Mirela A., additional, Drawz, Paul, additional, Ebert, Natalie, additional, Eggers, Paul, additional, Ferrè, Silvia, additional, Freedman, Barry I., additional, Furth, Susan L., additional, Gao, Bixia, additional, García-García, Guillermo, additional, Gashti, Casey N., additional, Germino, Gregory G., additional, Goldsmith, David, additional, Golestaneh, Ladan, additional, Goligorsky, Michael S., additional, Greenberg, Arthur, additional, Gregg, L. Parker, additional, Guay-Woodford, Lisa M., additional, Hamm, Lee, additional, Hart, Allyson, additional, Haselby, Danielle, additional, Hedayati, S. Susan, additional, Heerspink, Hiddo J.L., additional, Herzog, Charles A., additional, Hostetter, Thomas H., additional, House, Andrew A., additional, Hruska, Keith A., additional, Ishani, Areef, additional, Isom, Robert T., additional, James, Matthew T., additional, Jhaveri, Kenar D., additional, Johansen, Kirsten, additional, Johnson, Richard J., additional, Kang, Duk-Hee, additional, Kanno, Hiroko, additional, Kanno, Yoshihiko, additional, Karambelkar, Amrita D., additional, Karet Frankl, Fiona E., additional, Khoury, Charbel C., additional, Kimmel, Paul L., additional, Kopp, Jeffrey B., additional, Korbet, Stephen M., additional, Kruzel-Davila, Etty, additional, Kummer, Andrew, additional, LaFave, Laura, additional, Lakkis, Jay I., additional, Lerman, Lilach O., additional, Levin, Adeera, additional, Lew, Susie Q., additional, Luyckx, Valerie A., additional, Mattoo, Tej K., additional, Maynard, Sharon E., additional, McCullough, Peter A., additional, Mehrotra, Rajnish, additional, Meyer, Timothy W., additional, Mitch, William E., additional, Moe, Orson W., additional, Mohandes, Samer, additional, Moss, Alvin H., additional, Moxey-Mims, Marva, additional, Murugapandian, Sangeetha, additional, Nath, Karl A., additional, Neugarten, Joel, additional, Neyra, Javier A., additional, Nissenson, Allen R., additional, Nobakht, Ehsan, additional, Nolin, Thomas D., additional, Norris, Keith C., additional, Norton, Jenna M., additional, Nowak, Kristen L., additional, Ojo, Akinlolu O., additional, Pahl, Madeleine V., additional, Paller, Mark S., additional, Palmer, Biff F., additional, Palmer, Nicholette D., additional, Patel, Samir S., additional, Pecoits-Filho, Roberto, additional, Peitzman, Steven J., additional, Peixoto, Aldo J., additional, Pham, Phuong-Thu T., additional, Pham, Phuong-Chi T., additional, Piraino, Beth, additional, Pisoni, Roberto, additional, Rabelink, Ton, additional, Radhakrishnan, Jai, additional, Rahman, Mahboob, additional, Raj, Dominic S., additional, Ramírez-Sandoval, Juan C., additional, Rangaswami, Janani, additional, Reckelhoff, Jane F., additional, Regunathan-Shenk, Renu, additional, Reule, Scott, additional, Ronco, Claudio, additional, Rosenberg, Mark E., additional, Rosner, Mitchell H., additional, Rovin, Brad, additional, Roy-Chaudhury, Prabir, additional, Ruebner, Rebecca, additional, Rule, Andrew D., additional, Sands, Jeff M., additional, Schlanger, Lynn E., additional, Schrauben, Sarah J., additional, Seliger, Stephen, additional, Shah, Maulin, additional, Sterns, Richard H., additional, Stites, Erik, additional, Sugatani, Toshifumi, additional, Textor, Stephen C., additional, Thadhani, Ravi, additional, Thajudeen, Bijin, additional, Thakar, Surabhi, additional, Thomas, George, additional, Townsend, Raymond R., additional, Turner, Jeffrey, additional, Unruh, Mark L., additional, Urquhart, Bradley L., additional, Vassalotti, Joseph A., additional, Vaziri, Nosratola D., additional, Velasquez, Manuel T., additional, Ver Halen, Nisha, additional, Waddy, Salina P., additional, Wang, Jinwei, additional, Weber, Marc, additional, Weir, Matthew R., additional, White, Christine A., additional, Whittier, William L., additional, Williams, Matthew J., additional, Wiseman, Alexander C., additional, Wymer, David C., additional, Wymer, David T.G., additional, Yee, Jerry, additional, Zhang, Luxia, additional, Zhuang, Shougang, additional, and Ziyadeh, Fuad N., additional

Published
2020
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14. EFFECTIVENESS OF CASIRIVIMAB-IMDEVIMAB AND SOTROVIMAB MONOCLONAL ANTIBODY TREATMENT AMONG HIGH-RISK PATIENTS WITH SARS-CoV-2 INFECTION: A REAL-WORLD EXPERIENCE

Author

Murugapandian, Sangeetha, primary, Gungor, Ahmet B., additional, Al-Obaidi, Mohanad, additional, Thajudeen, Bijin, additional, Wong, Ryan C., additional, Mansour, Iyad, additional, Zangeneh, Tirdad T., additional, Johnson, Katherine M., additional, Low-Adegbija, Nicole E., additional, Alam, Ruhaniyah, additional, Gonzalez-Negrete, Elvira, additional, Sandıkçı, Burhaneddin, additional, Gupta, Gaurav, additional, Bedrick, Edward J., additional, Saridogan, Turcin, additional, Mendoza, Katherine, additional, and Tanriover, Bekir, additional

Published
2022
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15. Lack of effectiveness of Bebtelovimab Monoclonal Antibody Among High-Risk Patients with SARS-Cov-2 Omicron During BA.2, BA.2.12.1 and BA.5 Subvariants Dominated Era

Author

Sridhara, Srilekha, primary, Gungor, Ahmet B., additional, Erol, Halil K., additional, Al-Obaidi, Mohanad, additional, Zangeneh, Tirdad T., additional, Bedrick, Edward J., additional, Ariyamuthu, Venkatesh K., additional, Shetty, Aneesha, additional, Qannus, Abd A., additional, Mendoza, Katherine, additional, Murugapandian, Sangeetha, additional, Gupta, Gaurav, additional, and Tanriover, Bekir, additional

Published
2022
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16. Effectiveness of Casirivimab-Imdevimab Monoclonal Antibody Treatment Among High-Risk Patients With Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617.2 (Delta Variant) Infection

Author

Al-Obaidi, Mohanad M, primary, Gungor, Ahmet B, additional, Nematollahi, Saman, additional, Zangeneh, Tirdad T, additional, Bedrick, Edward J, additional, Johnson, Katherine M, additional, Low-Adegbija, Nicole E, additional, Alam, Ruhaniyah, additional, Rangan, Pooja, additional, William Heise, C, additional, Ariyamuthu, Venkatesh K, additional, Shetty, Aneesha, additional, Qannus, Abd Assalam, additional, Murugapandian, Sangeetha, additional, Ayvaci, Mehmet M S, additional, Anand, Prince Mohan, additional, and Tanriover, Bekir, additional

Published
2022
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17. Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron during BA.2, BA.2.12.1 and BA.5 subvariants dominated era.

Author

Sridhara, Srilekha, Gungor, Ahmet B., Erol, Halil K., Al-Obaidi, Mohanad, Zangeneh, Tirdad T., Bedrick, Edward J., Ariyamuthu, Venkatesh K., Shetty, Aneesha, Qannus, Abd A., Mendoza, Katherine, Murugapandian, Sangeetha, Gupta, Gaurav, and Tanriover, Bekir

Subjects
COVID-19, SARS-CoV-2, SARS-CoV-2 Omicron variant, MONOCLONAL antibodies
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N = 1,091) compared to propensity score (PS) matched control (N = 1,091). The primary composite outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary composite outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p = 0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (<65 years or ≥65), and immunocompromised status (patients with HIV/AIDS or solid organ transplants or malignancy including lymphoproliferative disorder). The number needed to treat (1/0.026–0.022) with BEB MAb was 250 to avoid one hospitalization and/or death over 30 days. The BEB MAb use lacked efficacy in patients with SARS-CoV-2 Omicron subvariants (mainly BA.2, BA.2.12.1, and BA.5) in the Banner Healthcare System in the Southwestern United States. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Epidemiology of Glomerular Disease in Southern Arizona

Author

Murugapandian, Sangeetha, primary, Mansour, Iyad, additional, Hudeeb, Mohammad, additional, Hamed, Khaled, additional, Hammode, Emad, additional, Bijin, Babitha, additional, Daheshpour, Sepehr, additional, Thajudeen, Bijin, additional, and Kadambi, Pradeep, additional

Published
2016
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