Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations.
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.
Department of Nephrology, University of Arizona Medical Center, Tucson, Ariz., USA.
Sangeetha
S
Murugapandian
Department of Nephrology, University of Arizona Medical Center, Tucson, Ariz., USA.
Babitha
B
Bijin
Department of Medicine, University of Arizona Medical Center, Tucson, Ariz., USA.
Iyad
I
Mansour
Department of Medicine, University of Arizona Medical Center, Tucson, Ariz., USA.
Sepehr
S
Daheshpour
Department of Nephrology, University of Arizona Medical Center, Tucson, Ariz., USA.
Biju G
BG
Pillai
Department of Nephrology, University of Arizona Medical Center, Tucson, Ariz., USA.
Bijin
B
Thajudeen
Department of Nephrology, University of Arizona Medical Center, Tucson, Ariz., USA.
Abdulla K
AK
Salahudeen
Gemcitabine; Ovarian cancer; Rituximab; Thrombotic microangiopathy