Lymphoproliferative disorders (LPDs) are generally caused by uncontrolled B-cell proliferation induced by the Epstein-Barr virus (EBV) in the setting of impaired EBV-specific T-cell immunity, particularly when there is pharmacological immunosuppression including antithymocyte globulin. We herein present an unusual case of EBV associated with LPD (EBV-LPD) in which LPD occurred 3 weeks after the use of rabbit antithymocyte globulin administered for severe hepatitis-associated aplastic anemia; the patient died of fulminant leukemic lymphoma 5 days after the onset. We also review the pertinent literature on EBV-LPD after immunosuppressive therapy and document the efficacy of EBV viral load monitoring and the need for preemptive therapy.

van Esser JW, van der Holt B, Meijer E, Niesters HG, Trenschel R, Thijsen SF, van Loon AM, Frassoni F, Bacigalupo A, Schaefer UW, Osterhaus AD, Gratama JW, Lowenberg B, Verdonck LF, Cornelissen JJ: Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell-depleted SCT. Blood 2001;98:972–978.
Young NS, Calado RT, Scheinberg P: Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006;108:2509–2519.
Teramura M, Kimura A, Iwase S, Yonemura Y, Nakao S, Urabe A, Omine M, Mizoguchi H: Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan. Blood 2007;110:1756–1761.
Bacigalupo A: Antilymphocyte/thymocyte globulin for graft versus host disease prophylaxis: efficacy and side effects. Bone Marrow Transplant 2005;35:225–231.
Scheinberg P, Fischer SH, Li L, Nunez O, Wu CO, Sloand EM, Cohen JI, Young NS, John Barrett A: Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 2007;109:3219–3224.
Wondergem MJ, Stevens SJ, Janssen JJ, Oudejans JJ, Ossenkoppele GJ, Middeldorp JM, Zweegman S: Monitoring of EBV reactivation is justified in patients with aplastic anemia treated with rabbit ATG as a second course of immunosuppression. Blood 2008;111:1739, author reply 1739–1740.
Sillos EM, Shenep JL, Burghen GA, Pui CH, Behm FG, Sandlund JT: Lactic acidosis: a metabolic complication of hematologic malignancies: case report and review of the literature. Cancer 2001;92:2237–2246.
Dorr V, Doolittle G, Woodroof J: First report of a B cell lymphoproliferative disorder arising in a patient treated with immune suppressants for severe aplastic anemia. Am J Hematol 1996;52:108–113.
Sarangi JN, Kashyap R, Choudhry VP, Mishra DK, Saxena R, Gurbaxani S, Bhargava M: Severe aplastic anemia evolving into T cell acute lymphoblastic leukemia. Eur J Haematol 1999;63:269–271.
Takeuchi M, Soda R, Takahashi K, Kimura F, Lai M, Ueda Y: Philadelphia chromosome positive acute lymphocytic leukemia arising from aplastic anemia. Am J Hematol 2000;63:161–162.
Hirose Y, Masaki Y, Ebata K, Okada J, Kim CG, Ogawa N, Wano Y, Sugai S: T-cell type acute lymphoblastic leukemia following cyclosporin A therapy for aplastic anemia. Int J Hematol 2001;73:226–229.
Calistri E, Tiribelli M, Battista M, Michelutti A, Corbellino M, Viale P, Fanin R, Damiani D: Epstein-Barr virus reactivation in a patient treated with anti-thymocyte globulin for severe aplastic anemia. Am J Hematol 2006;81:355–357.
Suzuki Y, Niitsu N, Hayama M, Katayama T, Ishii R, Osaka M, Miyazaki K, Danbara M, Horie R, Yoshida T, Nakamura N, Higashihara M: Lymphoproliferative disorders after immunosuppressive therapy for aplastic anemia: a case report and literature review. Acta Haematol 2009;121:21–26.
Viola GM, Zu Y, Baker KR, Aslam S: Epstein-Barr virus-related lymphoproliferative disorder induced by equine anti-thymocyte globulin therapy. Med Oncol 2011;28:1604–1608.
Aalto SM, Juvonen E, Tarkkanen J, Volin L, Haario H, Ruutu T, Hedman K: Epstein-Barr viral load and disease prediction in a large cohort of allogeneic stem cell transplant recipients. Clin Infect Dis 2007;45:1305–1309.
Wagner HJ, Cheng YC, Huls MH, Gee AP, Kuehnle I, Krance RA, Brenner MK, Rooney CM, Heslop HE: Prompt versus preemptive intervention for EBV lymphoproliferative disease. Blood 2004;103:3979–3981.
van Esser JW, Niesters HG, van der Holt B, Meijer E, Osterhaus AD, Gratama JW, Verdonck LF, Lowenberg B, Cornelissen JJ: Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation. Blood 2002;99:4364–4369.
Dierksheide JE, Baiocchi RA, Ferketich AK, Roychowdhury S, Pelletier RP, Eisenbeis CF, Caligiuri MA, VanBuskirk AM: IFN-gamma gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice. Blood 2005;105:1558–1565.
Kojima S, Matsuyama K, Kodera Y, Okada J: Circulating activated suppressor T lymphocytes in hepatitis-associated aplastic anaemia. Br J Haematol 1989;71:147–151.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.