Thrombotic Microangiopathy and Acute Kidney Injury: Navigating the Differential Diagnosis

bin 8,3g/dl, and platelet 73,000/mm3) occured although the blood count was initially normal. Olaparib was stopped, but grade 2 hematological toxicity did not resolve despite 4 weeks of interruption, and therefore, bone marrow biopsy and cytogenetic analysis were performed. RAEB type 2 myelodysplastic syndrome and complex karyotype were diagnosed. She is taking Azacytidine right now, and allogenic bone marrow transplantation is going to be performed. According to the Naranjo Adverse Drug Reaction Probability Scale, this myelodysplastic syndrome is a probable adverse drug reaction caused by olaparib (Table 1), so it was treatment related. Exposure to prolonged or high levels of toxic and chemotherapeutic agents, particularly alkylating agents and topoisomerase inhibitors, and radiation increases the risk of this clonal abnormality. These agents may cause DNA damage, impair DNA repair enzymes, and induce loss of chromosome integrity and result in dysplasia. Most cases of secondary or posttreatment Myelodysplastic Syndrome (MDS) occur in patients treated for a lymphoma or a solid tumor. Therapy-related MDS are increasing in frequency as the use of intensive chemotherapy and radiation increases in solid tumors. Treatment-relatedMDS/AcuteMyelogenous Leukemia has been announced as a serious adverse event of olaparib treatment. In a phase II study of olaparib, 2 patients developed leukemia and 1 patient developed MDS.4 All 3 patients had been heavily pretreated with previous chemotherapy before olaparib exposure similar to our patient (34 cycle). During the natural course of ovarian cancer, many leukemogenic therapies might be given because of recurrences. These therapies might play a role in the development of MDS/Acute Myelogenous Leukemia, but also might increase the risk of developing a treatment-related leukemia from PARP inhibitors, especially in populations similar to our patient. So, patients with prolonged cytopenia should be considered for hematological evaluation. Our case emphasizes the importance of publishing treatment response data. In this way, long-term safety data of these agents will be accumulated.