Epstein‐Barr virus associated pneumonia in an adult patient with severe aplastic anaemia: Resolution after the transient withdrawal of cyclosporine
Authors: Leonardo Potenza, Patrizia Barozzi, Mauro Codeluppi, Monica Morselli, Fabio Forghieri, Francesco Volzone, Giovanni Riva, Paola Pietrosemoli, Monica Pecorari, Giovanna Leonardi, Giuseppe Torelli, Mario Luppi
Journal: American Journal of Hematology (2007)

Itraconazole-enhanced vindesine neurotoxicity in adult acute lymphoblastic leukaemiaTo the Editor: Itraconazole, an azole with broad spectrum of fungal activity, has been used for the prevention and empirical therapy of invasive fungal infections (IFIs).Severe neurotoxicity following treatment with itraconazole and vincristine has been reported in 25 patients [1][2][3][4][5].Here we presented two adult acute lymphoblastic leukemia (ALL) patients developed neurotoxicity after treated with itraconazole and another vinca alkaloids, vindesine.Case 1: A 20-year-old male was admitted to our hospital because of fever and night sweat in December 2004.He was diagnosed as having ALL according to the FAB criteria.He was treated with one courses of DVP regimen and achieved complete remission.This patient was readmitted to our hospital for consolidation on August 2005.He was treated with hyper-CVAD chemotherapy and vindesine was used in day 4 and day 11, respectively.Because he has a history of pulmonary IFI, antifungal prophylaxis with itraconazole solution was started on day 2. Nine days after itraconazole was started, some symptom of paralytic ileus including abdominal pain, abdominal bloating, cramps, inability to pass flatus, or stool were presented.An X-ray of the abdomen shows bulging loops of intestine and some fluid levels were present.He was diagnosed to have paralytic ileus secondary to neurotoxicity caused by itraconazole and vindesine.After the itraconazole was stopped, his paralytic ileus was improved rapidly.This patient received autologous peripheral blood stem cell transplantation in February 2006 and remains in remission at present.Case 2: A 37-year-old female was admitted to our hospital because of fever and petechia in April 2005.A diagnosis of B-cell/T-cell biphenotypic acute leukemia was established based on the results of morphological assay and flow cytometry analysis.She was commenced on induction chemotherapy as for ALL (dexamethasone, Idarubicin, and vindesine).Among them, vindesine was used in day 1, day 8, and day 15, respectively.She presented as pulmonary infection with fever, cough, and expectoration in day 9. Emperical antifungal treatment with itraconazole injection was initiated.Five days after itraconazole was started, some symptom of neurotoxicity including limbs anesthesia, abdominal pain, abdominal bloating, cramps, inability to pass flatus, or stool were presented.An X-ray of the abdomen shows that some fluid levels were present.After the itraconazole and vindesine were discontinued, these symptoms were resolved rapidly.Unfortunately, she died of intracranial hemorrhage on day 28 of induction chemotherapy.Since Bo ¨hme first described enhanced severe vincristine neurotoxicity associated with itraconazole in four adults with ALL in 1995 [1], there are 21 cases that have been reported in children [2][3][4][5].The combined use of vinca alkaloids and itraconazole results in the enhanced neurotoxicity by the inhibition of cytochrome P450-mediated metabolism of vinca alkaloids and leading to increased plasma levels of the drug.The most frequent symptoms described were constipation, abdominal pain, paralytic ileus, and neuropathy.Here we presented two other adult ALL patients who developed neurotoxicity after coadministration of itraconazole and vindesine.Given the interaction of itraconazole with vinca alkaloids leading to severe and even potentially fatal toxicities, the combined use of these drugs should be avoided.