Reversible posterior leukoencephalopathy syndrome after repeat intermediate‐dose cytarabine chemotherapy in a patient with acute myeloid leukemia

Abstract

A 56-year-old man was admitted to our hospital with leukocytosis, anemia, and thrombocytopenia. Acute monoblastic leukemia was diagnosed. Two subsequent courses of consolidation chemotherapy consisted of conventional doses of cytarabine and intermediate-dose cytarabine. Intermediate-dose cytarabine was infused intravenously every 12 hr for 6 days. On day 15 after the final infusion of cytarabine, the patient suffered headache, and on day 21, he experienced a decrease in sensation on the sole of his left foot. Magnetic resonance imaging (MRI) of the brain revealed widespread areas of white matter edema. Cerebrospinal fluid (CSF) examination revealed an increase in the number of cells to 31 mm À3; the majority were lymphocytes. No infiltration of leukemia cells was seen. After 2 months, brain MRI findings were normal. The clinicoradiologic features of the case were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). RPLS in the present case was unlikely to have been caused by direct neurotoxicity because (1) the doses of cytarabine (500 mg/m 2 ; total dose 9.2 g) were much smaller than those in reported cases and were repeatedly infused until RPLS developed; (2) the RPLS developed 21 days after the final infusion of cytarabine, a much longer period than previously reported; (3) the slight leukocytosis in the CSF observed on day 33 might also have been related to the cellular immune responses evoked by the infused cytarabine. These details suggest not only that direct cerebral neurotoxicity of cytarabine but also that some type of allergic response may have been involved in the development of RPLS. Am. J. Hematol. 82:304-306, 2007. Cytarabine is one of the key drugs in the treatment of acute myeloid leukemia (AML). Earlier studies showed that central nervous system (CNS) toxicity as well as several other adverse effects can occur with increased doses of cytarabine. The reaction is characterized by reversible cerebellar syndrome and cerebral dysfunction [1].Herein, we report a patient with AML who developed reversible posterior leukoencephalopathy syndrome (RPLS) after repeated treatment with intermediate-dose cytarabine. A 56-year-old man was admitted to our hospital with leukocytosis, anemia, and thrombocytopenia. Acute monoblastic leukemia was diagnosed. Complete remission was achieved after two courses of induction chemotherapy consisting of conventional doses of cytarabine (100 mg/m 2 of cytarabine for 7 days plus 12 mg/m 2 of idamycin for 3 days). During the induction therapy, skin erythema appeared over the patient's entire body, possibly due to an allergic response to the cytarabine.

Reversible posterior leukoencephalopathy syndrome following combinatorial cisplatin and pemetrexed therapy for lung cancer in a normotensive patient: A case report and literature review

“…In normotensive patients with RPLS, including the present case, another possible hypothesis is that damage to the endothelial cells of cerebral vessels by cytotoxic drugs destroys the blood-brain barrier, as proposed in a rat model (14). Numerous RPLS patients have demonstrated metabolic abnormalities, including fever, leukocytosis, hyponatremia, hypocalcemia and hypomagnesemia (2)(3)(4)(5)(6)(7)(8), implying that metabolic abnormalities may disturb the integrity of the blood-brain barrier and lead to cerebral edema. In a previous study, a postmortem examination of a patient with cisplatin-associated RPLS indicated severe nerve cell loss, gliosis and spongy changes to the bilateral occipital cortex, including the visual field; furthermore, mild to moderate demyelination in the subcortical white matter of the occipital cortex, gracile fasciculus and dorsal root ganglia was observed.…”

“…The list of common antineoplastic drugs that predispose patients to RPLS is expanding, and includes cisplatin, L-asparaginase, thalidomide, vinflunine, methotrexate, vincristine and cytarabine (2)(3)(4)(5)(6)(7)(8). Certain combination regimens have also been associated with RPLS, including a combination treatment of ziv-aflibercept with cisplatin and pemetrexed, the cyclophosphamide, hydroxydaunorubicin, Oncovin and Prednisone regimen, intrathecal methotrexate and intravenous ifosfamide, idarubicine and etoposide, bevacizumab/folinic acid, fluorouracil and irinotecan, and capecitabine and cyclophosphamide (9-13).…”

Reversible Posterior Leukoencephalopathy Syndrome in a Patient with Relapsed Hodgkin's Disease: A Case Report

“…4) Intravenous high dose MTX also has a strong tendency to cause leukoencephalopathy when combined with cranial radiation therapy. 10,11) Combined therapies are associated with more frequent and more rapid presentation than those using only a single agent. 12) In our specific case, the patient showed acute mental change, magnetic resonance imaging (MRI) showed hyper-intense signals on T2 weighted images and fluid attenuated inversion recovery (FLAIR) images of bilateral temporal, parietal, and occipital lobes.…”

Gemcitabine-Induced Reversible Posterior Leukoencephalopathy Syndrome: A Case Report and Review of the Literature

“…Both i.v. and intrathecal ara-C have been associated with RPLS, although the mechanism is not known [10].…”