Antineoplastics
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Reactions 1193 - 15 Mar 2008 S Antineoplastics Epstein-Barr virus lymphoproliferative disease in a child: case report A girl, aged approximately 4 years, developed Epstein-Barr virus (EBV) lymphoproliferative disease after receiving a number of high-dose immunosuppressive chemotherapeutic regimens [dosages not stated] for Langerhans cell histiocytosis. The girl initially received prednisone, vinblastine and mercaptopurine when she was aged 4 months. Three months later she received reinduction therapy with prednisone, vinblastine and etoposide for cranial disease recurrence. Two months later cladribine was administered for systemic disease relapse. Five months later her regimen was changed to vincristine and cytarabine. Over the next 2 years she received various combinations of methotrexate, asparaginase, mercaptopurine and cytarabine until disease remission. She then received 2 months’ maintenance therapy with oral mercaptopurine. Eight months after stopping maintenance therapy, she presented with fever, adenopathy, splenomegaly and interstitial lung disease. A chest CT scan revealed multifocal parenchymal pulmonary lesions, and a lung biopsy revealed a hypercellular mass of discohesive pleomorphic cells with large nucleoli, irregular nuclei, a variable nuclear-to cytoplasmic ratio and a high rate of mitosis. Immunohistochemical staining of lesional cells was positive for pan B-cells, and flow cytometric immunophenotyping was consistent with large B-cell lymphoma. The girl was initially treated with vincristine, doxorubicin and prednisone for presumed recurrence of her histiocytic disease. However, subsequent PCR for EBV revealed a viral load of 24 000 genomic copies/µg DNA. A Southern blot analysis suggested a population of clonal B-cells with a clonal EBV genome insertion. The antineoplastic agents were discontinued and treatment with rituximab was initiated. After her second weekly dose of rituximab she experienced an anaphylactic reaction. At that time, her viral load had become undetectable and rituximab treatment was stopped. However, 12 months later she developed recurrent pulmonary EBV lymphoma of her right lung lobe, and 5 weeks’ treatment with IV immunoglobulin and interferon therapy was started. Her lymphoma progressed and vincristine, doxorubicin and prednisone were restarted. However, she died soon after from complications associated with invasive pulmonary and sinus fungal infections. Author comment: "This patient’s protracted exposure to multiple courses of high dose immunosuppressive chemotherapy may have resulted in delayed immune reconstitution after chemotherapy was discontinued. In addition, the young age at which she was first exposed to high dose chemotherapy may have impaired initial development of her immune repertoire, further contributing to the development of EBV-LDP [EBV lymphoproliferative disease]." Lee DA, et al. EBV plus lymphoproliferative disease following prolonged chemotherapy for refractory LCH. Pediatric Blood and Cancer 50: 728-730, No. 3, Mar 2008 - USA 801103204 1 Reactions 15 Mar 2008 No. 1193 0114-9954/10/1193-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
Transcript of Antineoplastics
Reactions 1193 - 15 Mar 2008
SAntineoplastics
Epstein-Barr virus lymphoproliferative disease in achild: case report
A girl, aged approximately 4 years, developed Epstein-Barrvirus (EBV) lymphoproliferative disease after receiving anumber of high-dose immunosuppressive chemotherapeuticregimens [dosages not stated] for Langerhans cell histiocytosis.
The girl initially received prednisone, vinblastine andmercaptopurine when she was aged 4 months. Three monthslater she received reinduction therapy with prednisone,vinblastine and etoposide for cranial disease recurrence. Twomonths later cladribine was administered for systemic diseaserelapse. Five months later her regimen was changed tovincristine and cytarabine. Over the next 2 years she receivedvarious combinations of methotrexate, asparaginase,mercaptopurine and cytarabine until disease remission. Shethen received 2 months’ maintenance therapy with oralmercaptopurine. Eight months after stopping maintenancetherapy, she presented with fever, adenopathy, splenomegalyand interstitial lung disease. A chest CT scan revealedmultifocal parenchymal pulmonary lesions, and a lung biopsyrevealed a hypercellular mass of discohesive pleomorphic cellswith large nucleoli, irregular nuclei, a variable nuclear-tocytoplasmic ratio and a high rate of mitosis.Immunohistochemical staining of lesional cells was positivefor pan B-cells, and flow cytometric immunophenotyping wasconsistent with large B-cell lymphoma.
The girl was initially treated with vincristine, doxorubicinand prednisone for presumed recurrence of her histiocyticdisease. However, subsequent PCR for EBV revealed a viralload of 24 000 genomic copies/µg DNA. A Southern blotanalysis suggested a population of clonal B-cells with a clonalEBV genome insertion. The antineoplastic agents werediscontinued and treatment with rituximab was initiated. Afterher second weekly dose of rituximab she experienced ananaphylactic reaction. At that time, her viral load had becomeundetectable and rituximab treatment was stopped. However,12 months later she developed recurrent pulmonary EBVlymphoma of her right lung lobe, and 5 weeks’ treatment withIV immunoglobulin and interferon therapy was started. Herlymphoma progressed and vincristine, doxorubicin andprednisone were restarted. However, she died soon after fromcomplications associated with invasive pulmonary and sinusfungal infections.
Author comment: "This patient’s protracted exposure tomultiple courses of high dose immunosuppressivechemotherapy may have resulted in delayed immunereconstitution after chemotherapy was discontinued. Inaddition, the young age at which she was first exposed tohigh dose chemotherapy may have impaired initialdevelopment of her immune repertoire, further contributingto the development of EBV-LDP [EBV lymphoproliferativedisease]."Lee DA, et al. EBV plus lymphoproliferative disease following prolongedchemotherapy for refractory LCH. Pediatric Blood and Cancer 50: 728-730, No. 3,Mar 2008 - USA 801103204
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Reactions 15 Mar 2008 No. 11930114-9954/10/1193-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
