Antineoplastics
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Reactions 1237 - 31 Jan 2009 » Editorial comment: A search of AdisBase, Medline and Embase did not reveal any previous case reports of Epstein- ★ S Antineoplastics Barr virus-associated lymphoproliferative disorder associated with rituximab. The WHO Adverse Drug Reactions database EBV-associated lymphoproliferative disorder contained two reports of Epstein-Barr virus infection (first report with rituximab) and (MedDRA) and three reports of lymphoproliferative disorder haemophagocytosis: case report (MedDRA) associated with rituximab. A 35-year-old woman developed Epstein-Barr virus (EBV)-associated lymphoproliferative disorder, complicated with viral-induced haemophagocytosis, after receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The woman was diagnosed with follicular lymphoma (FL). Her serology was consistent with a previous EBV infection. She received 6 courses of R-CHOP [dosages not stated] every 21 days followed by rituximab 375 mg/m 2 alone for two cycles. One month after completion of therapy, all previously involved lymph nodes had regressed; however, bone marrow biopsy showed an infiltrate of small lymphoma cells. Five weeks after the last rituximab treatment, she had a circulating B-cell level of < 5/µL and moderate hypogammaglobulinaemia (3.41 g/L). Thirteen months after treatment, she presented with a fever (40°C) and right axillary and cervical lymphadenopathy; additionally, she rapidly developed jaundice. She had hepatosplenomegaly, pulmonary consolidation, multiple kidney nodules and enlarged mediastinal, axillary, hilar and mesenteric lymph nodes. She had a raised bilirubin level (149 µmol/L) and raised inflammatory markers. Her WBC count was 3.6 × 10 9 /mL with 83% neutrophils, a haemoglobin level of 8.4 g/dL and a platelet count of 79 × 10 9 /L. She had mild hypofibrinogenaemia, a mild prolongation of activated partial thromboplastin time, hypertriglyceridaemia and hyperferritinaemia. An IgG λ monoclonal protein was detected at a level of 8.7 g/L. She received antibiotics. Bone marrow biopsy showed haemophagocytosis and dysmyelopoiesis; a lymphoepithelioid infiltrate with a minor plasmacytosis and several large lymphoid cells was also observed. Cervical lymph node biopsy revealed a polymorphous B lymphoproliferation with an equal number of small and large cells, moderate plasmacytosis and the presence of macrophages. Lymphoid cells were positive for EBV- encoded RNA, particularly in areas rich in B cells and plasma cells. The plasma cells demonstrated λ light chain restriction, unlike those seen in the original FL. PCR confirmed the presence of a monoclonal B-cell population different from that seen in the original FL. Serology was suggestive of a past EBV infection; however, whole blood was PCR positive for EBV DNA at 40 000 copies/mL. She was diagnosed with EBV-induced polymorphous lymphoproliferation with a monoclonal B-cell population and virus-associated haemophagocytosis. The woman received high-dose corticosteroids without improvement. Subsequently, corticosteroids were tapered and she received rituximab. She became afebrile and liver function and pancytopenia improved. EBV DNA became undetectable and CT scan showed complete resolution. At last follow-up, 13 months after rituximab treatment she remained well without any relapse of FL or EBV-induced lymphoproliferative disease. Author comment: "[T]he possible contribution of rituximab. . . is uncertain but interesting. . . The development of moderate hypogammaglobulinaemia after immunochemotherapy might have contributed to an immunodeficient state. Other possibilities include an immunosuppressive effect of FL itself, of chemotherapy, or pure coincidence." Johnston A, et al. Epstein-Barr virus-induced lymphoproliferative disorder after rituximab combined with CHOP therapy. Clinical Lymphoma & Myeloma 8: 356-358, No. 6, Dec 2008 - France 801135328 1 Reactions 31 Jan 2009 No. 1237 0114-9954/10/1237-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
Transcript of Antineoplastics
Reactions 1237 - 31 Jan 2009
» Editorial comment: A search of AdisBase, Medline andEmbase did not reveal any previous case reports of Epstein-★ SAntineoplastics Barr virus-associated lymphoproliferative disorder associatedwith rituximab. The WHO Adverse Drug Reactions databaseEBV-associated lymphoproliferative disordercontained two reports of Epstein-Barr virus infection(first report with rituximab) and(MedDRA) and three reports of lymphoproliferative disorderhaemophagocytosis: case report (MedDRA) associated with rituximab.A 35-year-old woman developed Epstein-Barr virus
(EBV)-associated lymphoproliferative disorder,complicated with viral-induced haemophagocytosis, afterreceiving rituximab, cyclophosphamide, doxorubicin,vincristine and prednisone (R-CHOP).
The woman was diagnosed with follicular lymphoma(FL). Her serology was consistent with a previous EBVinfection. She received 6 courses of R-CHOP [dosages notstated] every 21 days followed by rituximab 375 mg/m2
alone for two cycles. One month after completion oftherapy, all previously involved lymph nodes hadregressed; however, bone marrow biopsy showed aninfiltrate of small lymphoma cells. Five weeks after the lastrituximab treatment, she had a circulating B-cell level of< 5/µL and moderate hypogammaglobulinaemia (3.41 g/L).Thirteen months after treatment, she presented with a fever(40°C) and right axillary and cervical lymphadenopathy;additionally, she rapidly developed jaundice. She hadhepatosplenomegaly, pulmonary consolidation, multiplekidney nodules and enlarged mediastinal, axillary, hilar andmesenteric lymph nodes. She had a raised bilirubin level(149 µmol/L) and raised inflammatory markers. Her WBCcount was 3.6 × 109/mL with 83% neutrophils, ahaemoglobin level of 8.4 g/dL and a platelet count of79 × 109/L. She had mild hypofibrinogenaemia, a mildprolongation of activated partial thromboplastin time,hypertriglyceridaemia and hyperferritinaemia. An IgG λmonoclonal protein was detected at a level of 8.7 g/L. Shereceived antibiotics. Bone marrow biopsy showedhaemophagocytosis and dysmyelopoiesis; alymphoepithelioid infiltrate with a minor plasmacytosis andseveral large lymphoid cells was also observed. Cervicallymph node biopsy revealed a polymorphousB lymphoproliferation with an equal number of small andlarge cells, moderate plasmacytosis and the presence ofmacrophages. Lymphoid cells were positive for EBV-encoded RNA, particularly in areas rich in B cells andplasma cells. The plasma cells demonstrated λ light chainrestriction, unlike those seen in the original FL. PCRconfirmed the presence of a monoclonal B-cell populationdifferent from that seen in the original FL. Serology wassuggestive of a past EBV infection; however, whole bloodwas PCR positive for EBV DNA at 40 000 copies/mL. Shewas diagnosed with EBV-induced polymorphouslymphoproliferation with a monoclonal B-cell populationand virus-associated haemophagocytosis.
The woman received high-dose corticosteroids withoutimprovement. Subsequently, corticosteroids were taperedand she received rituximab. She became afebrile and liverfunction and pancytopenia improved. EBV DNA becameundetectable and CT scan showed complete resolution. Atlast follow-up, 13 months after rituximab treatment sheremained well without any relapse of FL or EBV-inducedlymphoproliferative disease.
Author comment: "[T]he possible contribution ofrituximab. . . is uncertain but interesting. . . The developmentof moderate hypogammaglobulinaemia afterimmunochemotherapy might have contributed to animmunodeficient state. Other possibilities include animmunosuppressive effect of FL itself, of chemotherapy, orpure coincidence."Johnston A, et al. Epstein-Barr virus-induced lymphoproliferative disorder afterrituximab combined with CHOP therapy. Clinical Lymphoma & Myeloma 8:356-358, No. 6, Dec 2008 - France 801135328
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Reactions 31 Jan 2009 No. 12370114-9954/10/1237-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
