Antineoplastics
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Reactions 1184 - 12 Jan 2008 ★ S Antineoplastics Immune reconstitution syndrome (first report with cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine and etoposide) and hepatosplenic candidiasis: case report A 17-year-old boy developed hepatosplenic candidiasis and immune reconstitution syndrome during chemotherapy for large B cell lymphoma. The boy received once cycle of chemotherapy with cyclophosphamide, vincristine and prednisone (COP), two cycles of COP with additional doxorubicin and methotrexate and one cycle of cytarabine and etoposide [dosages and duration of treatments not stated]. He showed aplasia with rapidly progressing fever on day 10 of the last cycle. The boy received empirical antibacterials and amphotericin B without improvement of his fever. His aplasia and fever had resolved on day 28; he showed no signs of infection, and antibacterials and antifungals were stopped. He was discharged 4 days later. On day 38, he was readmitted with fever of 39°C and upper abdominal pain. Laboratory investigations revealed the following levels: C-reactive protein 216 mg/L, ALP 615 IU/L, γ-glutamyl transferase 315 IU/L, bilirubin 33 µmol/L and conjugated bilirubin 18 µmol/L. On day 44, an abdominal scan showed multiple solid hypodense micronodules in his liver, and an ultrasound revealed four additional nodules in his spleen 10 days later. A liver node biopsy on day 45 showed unspecific granulomas; bacteriology, virology and parasitology were negative. He started receiving empirical broad-spectrum antibacterials and antifungals. On day 60, a repeat biopsy showed pseudomycelium filaments, but cultured were negative; hepatosplenic candidiasis was diagnosed. Anti-Candida antibody investigations were highly positive at 1/1280 on day 62, and caspofungin and voriconazole were initiated; however, fever of 39°C, inflammatory symptoms, signs of cholestasis and an elevated WBC count of 12 000/mm 3 persisted. Immune reconstitution syndrome was suspected and, on day 74 after chemotherapy, corticosteroid therapy was started. His fever subsided within 24 hours and his laboratory values improved within 1 week. On day 86, chemotherapy with rituximab, an anti-CD20 antibody, dexamethasone, cytarabine and cisplatin was restarted. His splenic lesions had disappeared 6 weeks after corticosteroid initiation, and his hepatic lesions were still regressing 2 and 5 months later. Author comment: A change of the intestinal mucosal barrier due to [cytarabine] treatment as well as the aplasia promoted fungal translocation from the intestinal tract . . . towards the liver. . . Our hypothesis is that the recovery from aplasia and the beginning of an immune reaction produced an excessive inflammatory reaction maintained by the persistence of the antigen in the tissues. Conter C, et al. Persistent fever and hepatosplenic candidiasis, efficiency of a corticoid therapy. Journal de Mycologie Medicale 17: 194-197, No. 3, Sep 2007 [French; summarised from a translation.] - France 801096011 » Editorial comment: A search of AdisBase, Medline and the WHO Adverse Drug Reactions database did not reveal any previous case reports of immune reconstitution syndrome associated with cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine or etoposide. 1 Reactions 12 Jan 2008 No. 1184 0114-9954/10/1184-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
Transcript of Antineoplastics
Reactions 1184 - 12 Jan 2008
★ SAntineoplastics
Immune reconstitution syndrome (first report withcyclophosphamide, vincristine, doxorubicin,methotrexate, cytarabine and etoposide) andhepatosplenic candidiasis: case report
A 17-year-old boy developed hepatosplenic candidiasis andimmune reconstitution syndrome during chemotherapy forlarge B cell lymphoma.
The boy received once cycle of chemotherapy withcyclophosphamide, vincristine and prednisone (COP), twocycles of COP with additional doxorubicin and methotrexateand one cycle of cytarabine and etoposide [dosages andduration of treatments not stated]. He showed aplasia withrapidly progressing fever on day 10 of the last cycle.
The boy received empirical antibacterials and amphotericinB without improvement of his fever. His aplasia and fever hadresolved on day 28; he showed no signs of infection, andantibacterials and antifungals were stopped. He wasdischarged 4 days later. On day 38, he was readmitted withfever of 39°C and upper abdominal pain. Laboratoryinvestigations revealed the following levels: C-reactive protein216 mg/L, ALP 615 IU/L, γ-glutamyl transferase 315 IU/L,bilirubin 33 µmol/L and conjugated bilirubin 18 µmol/L. Onday 44, an abdominal scan showed multiple solid hypodensemicronodules in his liver, and an ultrasound revealed fouradditional nodules in his spleen 10 days later. A liver nodebiopsy on day 45 showed unspecific granulomas;bacteriology, virology and parasitology were negative. Hestarted receiving empirical broad-spectrum antibacterials andantifungals. On day 60, a repeat biopsy showedpseudomycelium filaments, but cultured were negative;hepatosplenic candidiasis was diagnosed. Anti-Candidaantibody investigations were highly positive at 1/1280 onday 62, and caspofungin and voriconazole were initiated;however, fever of 39°C, inflammatory symptoms, signs ofcholestasis and an elevated WBC count of 12 000/mm3
persisted. Immune reconstitution syndrome was suspectedand, on day 74 after chemotherapy, corticosteroid therapy wasstarted. His fever subsided within 24 hours and his laboratoryvalues improved within 1 week. On day 86, chemotherapywith rituximab, an anti-CD20 antibody, dexamethasone,cytarabine and cisplatin was restarted. His splenic lesions haddisappeared 6 weeks after corticosteroid initiation, and hishepatic lesions were still regressing 2 and 5 months later.
Author comment: A change of the intestinal mucosalbarrier due to [cytarabine] treatment as well as the aplasiapromoted fungal translocation from the intestinaltract . . . towards the liver. . . Our hypothesis is that therecovery from aplasia and the beginning of an immunereaction produced an excessive inflammatory reactionmaintained by the persistence of the antigen in the tissues.Conter C, et al. Persistent fever and hepatosplenic candidiasis, efficiency of acorticoid therapy. Journal de Mycologie Medicale 17: 194-197, No. 3, Sep 2007[French; summarised from a translation.] - France 801096011
» Editorial comment: A search of AdisBase, Medline and theWHO Adverse Drug Reactions database did not reveal anyprevious case reports of immune reconstitution syndromeassociated with cyclophosphamide, vincristine, doxorubicin,methotrexate, cytarabine or etoposide.
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Reactions 12 Jan 2008 No. 11840114-9954/10/1184-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
