Antineoplastics
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Reactions 1292 - 13 Mar 2010 S Antineoplastics Aspergillus fumigatus and Absidia corymbifera invasive fungal infections and various other toxicities: case report A 14-year-old girl developed simultaneous Aspergillus fumigatus and Absidia corymbifera invasive fungal infections and various toxicities during treatment with antineoplastics [ALL BFM 2000 protocol; not all drugs in protocol stated; not all dosages stated]. The girl was diagnosed with acute lymphoblastic leukaemia and started receiving the ALL BFM 2000 protocol, which included dexamethasone 10 mg/m 2 /day for 30 days. On day 12, she developed severe chemotherapy- induced hepatopathy and cholestasis with reduced cholinesterase, elevated liver enzymes, a maximum bilirubin of 15 mg/dL, and hypoantithrombinaemia and hypofibrinogenaemia, which both required substitution. On day 14, she received low-dose fluconazole as antifungal prophylaxis. On day 27, chemotherapy was interrupted because of severe abdominal pain and febrile neutropenia. Fluconazole was replaced by caspofungin. A CT scan revealed enlarged kidneys and a cover plate thorax vertebral body 12 fracture. Following recovery of her neutrophil count, her fever resolved. She experienced severe intermittent abdominal pain crises and an MRT on day 46 revealed bilateral intrarenal abscesses involving up to 40% of the renal tissue. Respiratory symptoms prompted a repeat thoracic CT scan, which revealed a round-shaped pulmonary infiltrate in the peripheral right medial lobe. Chemotherapy was interrupted and the girl received liposomal amphotericin B. Renal biopsy revealed Aspergillus fumigatus and voriconazole was added. After 2 weeks, she underwent removal of the involved right medial lobe to decrease the risk of pulmonary haemorrhage and further spread during chemotherapy-induced neutropenia. PCR testing confirmed an infection with A. fumigatus and Absidia corymbifera. Her amphotericin B dosage was increased and voriconazole was discontinued; chemotherapy was continued. An attempt to replace amphotericin B with posaconazole was unsuccessful as sufficient trough levels could not be achieved. This was thought to be due to mucositis and pantoprazole therapy. In the second part of the cycle, the methotrexate dosage was decreased from 5g to 1 g/m 2 every 14 days in four cycles to avoid hepatopathic exacerbation. On day 144, she was rehospitalised with septic shock and pneumonia. A thoracic CT revealed multiple round-shaped infiltrates. Her amphotericin B dosage was increased and caspofungin was added. On day 162, her pulmonary infiltrates had nearly completely resolved. She completed the intensive reinduction protocol without dexamethasone to prevent any clinical consequences of vincristine-induced neuropathy and dexamethasone-induced myopathy, and because of the previous fungal infections; she was unable to walk unassisted. Subsequently, amphotericin B was replaced by posaconazole. Only after pantoprazole was discontinued, could reliable trough concentrations of posaconazole be achieved. At latest follow-up, she had completed maintenance therapy with methotrexate and mercaptopurine and was in complete remission. Author comment: "The attending physicians had to deal with disseminated [invasive fungal infections] in a clinical context of severe side effects of chemotherapy (mucositis, impairment of hepatic function) and possible interactions with supportive medication (posaconazole and pantoprazole)." Hasan D, et al. Successful management of a simultaneous Aspergillus fumigatus and Absidia corymbifera invasive fungal infection. Journal of Pediatric Hematology/Oncology 32: e22-4, No. 1, Jan 2010 - Germany 803006963 1 Reactions 13 Mar 2010 No. 1292 0114-9954/10/1292-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
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Transcript of Antineoplastics
Reactions 1292 - 13 Mar 2010
SAntineoplastics
Aspergillus fumigatus and Absidia corymbiferainvasive fungal infections and various othertoxicities: case report
A 14-year-old girl developed simultaneous Aspergillusfumigatus and Absidia corymbifera invasive fungalinfections and various toxicities during treatment withantineoplastics [ALL BFM 2000 protocol; not all drugs inprotocol stated; not all dosages stated].
The girl was diagnosed with acute lymphoblasticleukaemia and started receiving the ALL BFM 2000protocol, which included dexamethasone 10 mg/m2/day for30 days. On day 12, she developed severe chemotherapy-induced hepatopathy and cholestasis with reducedcholinesterase, elevated liver enzymes, a maximumbilirubin of 15 mg/dL, and hypoantithrombinaemia andhypofibrinogenaemia, which both required substitution.On day 14, she received low-dose fluconazole as antifungalprophylaxis. On day 27, chemotherapy was interruptedbecause of severe abdominal pain and febrile neutropenia.Fluconazole was replaced by caspofungin. A CT scanrevealed enlarged kidneys and a cover plate thoraxvertebral body 12 fracture. Following recovery of herneutrophil count, her fever resolved. She experiencedsevere intermittent abdominal pain crises and an MRT onday 46 revealed bilateral intrarenal abscesses involving upto 40% of the renal tissue. Respiratory symptoms prompteda repeat thoracic CT scan, which revealed a round-shapedpulmonary infiltrate in the peripheral right medial lobe.
Chemotherapy was interrupted and the girl receivedliposomal amphotericin B. Renal biopsy revealedAspergillus fumigatus and voriconazole was added. After2 weeks, she underwent removal of the involved rightmedial lobe to decrease the risk of pulmonary haemorrhageand further spread during chemotherapy-inducedneutropenia. PCR testing confirmed an infection with A.fumigatus and Absidia corymbifera. Her amphotericin Bdosage was increased and voriconazole was discontinued;chemotherapy was continued. An attempt to replaceamphotericin B with posaconazole was unsuccessful assufficient trough levels could not be achieved. This wasthought to be due to mucositis and pantoprazole therapy.In the second part of the cycle, the methotrexate dosagewas decreased from 5g to 1 g/m2 every 14 days in fourcycles to avoid hepatopathic exacerbation. On day 144, shewas rehospitalised with septic shock and pneumonia. Athoracic CT revealed multiple round-shaped infiltrates. Heramphotericin B dosage was increased and caspofungin wasadded. On day 162, her pulmonary infiltrates had nearlycompletely resolved. She completed the intensivereinduction protocol without dexamethasone to preventany clinical consequences of vincristine-inducedneuropathy and dexamethasone-induced myopathy, andbecause of the previous fungal infections; she was unableto walk unassisted. Subsequently, amphotericin B wasreplaced by posaconazole. Only after pantoprazole wasdiscontinued, could reliable trough concentrations ofposaconazole be achieved. At latest follow-up, she hadcompleted maintenance therapy with methotrexate andmercaptopurine and was in complete remission.
Author comment: "The attending physicians had to dealwith disseminated [invasive fungal infections] in a clinicalcontext of severe side effects of chemotherapy (mucositis,impairment of hepatic function) and possible interactionswith supportive medication (posaconazole andpantoprazole)."Hasan D, et al. Successful management of a simultaneous Aspergillus fumigatusand Absidia corymbifera invasive fungal infection. Journal of PediatricHematology/Oncology 32: e22-4, No. 1, Jan 2010 - Germany 803006963
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Reactions 13 Mar 2010 No. 12920114-9954/10/1292-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
