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Resolution of chronic active EBV infection and coexisting pulmonary arterial hypertension after cord blood transplantation

Bone Marrow Transplantation volume 49, pages 1343–1344 (2014)Cite this article

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Chronic active Epstein–Barr virus (EBV) infection (CAEBV) is characterised by clonal proliferation of EBV-infected T or natural killer (NK) cells and inflammation.1, 2, 3, 4 Cardiovascular complications, such as arteritis and coronary artery aneurysm, are observed in about 20–60% of patients with CAEBV.1,5 The coexistence of pulmonary arterial hypertension (PAH) with CAEBV, which involves the very small arteries, is less common.1,6 PAH is a rarely curable disease despite recent advances in treatment.7 Here, we describe a patient with PAH in whom the disease developed after diagnosis of chronic active EBV infection (CAEBV) and resolved after cord blood transplantation (CBT).

The patient was a 36-year-old woman who had a 1-month history of fatigue, fever and skin rash. Laboratory studies showed an abnormal pattern of anti-EBV antibodies: antiviral capsid antigens IgG (5120 × ), anti-early antigen IgG (2560 × ) and anti-EB nuclear antigen (80 × ). Quantitative PCR showed an elevated copy number of EBV-DNA: 1.5 × 105 and 2.8 × 104 copies per microgram of DNA in fractionated peripheral blood CD4+ T cells and CD19+ B cells, respectively. EBV-DNA was not detected in CD8+ T cells or CD56+ NK cells. The CD4+/CD8+ T-cell ratio was elevated (6.3, normal 0.4–2.3). The clonality of EBV-infected CD4+ T cells was determined by southern blotting using EBV terminal repeats and the T-cell receptor gene. The Ig heavy-chain gene was determined to have the germline pattern. A diagnosis of CD4+ T cell-type CAEBV was made. Although allogeneic SCT (allo-HSCT) is the only curative therapy for CAEBV, we chose watchful waiting because of the lack of HLA-matched related or unrelated donors.

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References

  1. Kimura H, Hoshino Y, Kanegane H, Tsuge I, Okamura T, Kawa K et al. Clinical and virologic characteristics of chronic active Epstein-Barr virus infection. Blood 2001; 98: 280–286.

    Article  CAS  Google Scholar 

  2. Cohen JI, Kimura H, Nakamura S, Ko YH, Jaffe ES . Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008. Ann Oncol 2009; 20: 1472–1482.

    Article  CAS  Google Scholar 

  3. Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM et al. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood 2011; 117: 5835–5849.

    Article  CAS  Google Scholar 

  4. Kikuta H, Taguchi Y, Tomizawa K, Kojima K, Kawamura N, Ishizaka A et al. Epstein-Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease. Nature 1988; 333: 455–457.

    Article  CAS  Google Scholar 

  5. Muneuchi J, Ohga S, Ishimura M, Ikeda K, Yamaguchi K, Nomura A et al. Cardiovascular complications associated with chronic active Epstein-Barr virus infection. Pediatr Cardiol 2009; 30: 274–281.

    Article  Google Scholar 

  6. Hashimoto T, Sakata Y, Fukushima K, Maeda T, Arita Y, Shioyama W et al. Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection. Intern Med 2011; 50: 119–124.

    Article  Google Scholar 

  7. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Resp J 2009; 34: 1219–1263.

    Article  CAS  Google Scholar 

  8. Kawa K, Sawada A, Sato M, Okamura T, Sakata N, Kondo O et al. Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection. Bone Marrow Transplant 2011; 46: 77–83.

    Article  CAS  Google Scholar 

  9. Sato E, Ohga S, Kuroda H, Yoshiba F, Nishimura M, Nagasawa M et al. Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan. Am J Hematol 2008; 83: 721–727.

    Article  Google Scholar 

  10. Kato H, Onishi Y, Nakajima S, Okitsu Y, Fukuhara N, Fujiwara T et al. Significant improvement of Takayasu arteritis after cord blood transplantation in a patient with myelodysplastic syndrome. Bone Marrow Transplant 2014; 49: 458–459.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan

    Y Onishi, R Ohba & H Harigae

  2. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    K Sugimura & H Shimokawa

  3. Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo, Japan

    K Imadome

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  1. Y Onishi
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  2. K Sugimura
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Correspondence to Y Onishi.

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Onishi, Y., Sugimura, K., Ohba, R. et al. Resolution of chronic active EBV infection and coexisting pulmonary arterial hypertension after cord blood transplantation. Bone Marrow Transplant 49, 1343–1344 (2014). https://doi.org/10.1038/bmt.2014.129

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