Abstract
Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m2) and CY (120 mg/kg) or melphalan (210 mg/m2), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (∼180 mg/m2) and melphalan (140 mg/m2) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5±15.0% for MAST group and 85.0±8.0% for RIST group, and the 3-year OS rate was 54.5±15.0% for MAST group and 95.0±4.9% for RIST group (P=0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV.
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References
Kawa K . Epstein-Barr virus-associated diseases in humans. Int J Hematol 2000; 71: 108–117.
Cohen JI . Epstein-Barr virus infection. N Engl J Med 2000; 343: 481–492.
Kawa K . Diagnosis and treatment of Epstein-Barr virus-associated natural killer cell lymphoproliferative disease. Int J Hematol 2003; 78: 24–31.
Kimura H, Hoshino Y, Hara S, Sugaya N, Kawada J, Shibata Y et al. Differences between T cell-type and natural killer cell-type chronic active Epstein-Barr virus infection. J Infect Dis 2005; 191: 531–539.
Oshima K, Kimura H, Yoshino T, Kim CW, Ko YH, Lee SS et al. Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD. Pathol Int 2008; 58: 209–217.
Heslop H . How I treat EBV lymphoproliferation. Blood 2009; 114: 4002–4008.
Jones JF, Shurin S, Abramowsky C, Tubbs R, Sciotto C, Wahl R et al. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein Barr virus infections. N Engl J Med 1988; 318: 733–741.
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.
Ishihara S, Tawa A, Yumura-Yagi K, Murata M, Hara J, Yabuuchi H et al. Clonal T-cell lymphoproliferation containing Epstein-Barr (EB) virus DNA in a patient with chronic active EB virus infection. Jpn J Cancer Res 1989; 80: 99–101.
Kawa-Ha K, Ishihara S, Ninomiya T, Yumura-Yagi K, Hara J, Murayama F et al. CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA. J Clin Invest 1989; 84: 52–55.
Okano M, Kawa K, Kimura H, Yachie A, Wakiguchi H, Maeda A et al. Proposed guidelines for diagnosing chronic active Epstein-Barr virus infection. Am J Hematol 2005; 80: 64–69.
Ishihara S, Okada S, Wakiguchi H, Kurashige T, Morishima T, Kawa-Ha K . Chronic active Epstein-Barr virus infection in children in Japan. Acta Paediatr 1995; 84: 1271–1275.
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.
Kawa K, Okamura T, Yagi K, Takeuchi M, Nakayama M, Inoue M . Mosquito allergy and Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease. Blood 2001; 98: 3173–3174.
Okamura T, Hatsukawa Y, Arai H, Inoue M, Kawa K . Blood stem-cell transplantation for chronic active Epstein-Barr virus with lymphoproliferation. Lancet 2000; 356: 223–224.
Okamura T, Kishimoto T, Inoue M, Honda M, Yamashita N, Wakiguchi H et al. Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease. Bone Marrow Transplant 2003; 31: 105–111.
Kawa K, Okamura T, Yasui M, Sato E, Inoue M . Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease. Crit Rev Oncol Hematol 2002; 44: 251–257.
Henter JI, Horne A, Arico M, Egeler R, Filipovich A, Imashuku S et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48: 124–131.
Koyama M, Takeshita Y, Sakata A, Sawada A, Yasui M, Okamura T et al. Cytotoxic chemotherapy successfully induced durable complete remission in 2 patients with mosquito allergy resulting from Epstein-Barr virus-associated T-/natural killer cell lymphoproliferative disease. Int J Hematol 2005; 82: 437–440.
Shimoni A, Hardan I, Shem-Tov N, Rand A, Herscovici C, Yerushalmi R et al. Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia 2007; 21: 2109–2116.
Sakata N, Sato E, Sawada A, Yasui M, Inoue M, Kawa K . Chronic active Epstein-Barr virus infection treated with reduced intensity stem cell transplantation. Rinsho Ketsueki 2004; 45: 393–396.
Gotoh K, Ito Y, Shibata-Watanabe Y, Kawada J, Takahashi Y, Yagasaki H et al. Clinical and virological characteristics of 15 patients with chronic active Epstein-Barr virus infection treated with hematopoietic stem cell transplantation. Clin Infect Dis 2008; 46: 1525–1534.
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.
Kawa K, Sawada A, Koyama M, Inoue M . Epstein-Barr virus infection after unrelated cord blood transplantation: reactivation or reinfection? Int J Hematol 2007; 85: 267–269.
Brunstein CG, Weisdorf DJ, Defor T, Barker J, Tolar J, van Burik J et al. Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood 2006; 108: 2874–2880.
Acknowledgements
We are grateful to Dr Christopher P Fox for his advice and critical reading of the paper. We thank all patients and staffs included in this study for their participation.
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Kawa, K., Sawada, A., Sato, M. et al. Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection. Bone Marrow Transplant 46, 77–83 (2011). https://doi.org/10.1038/bmt.2010.122
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DOI: https://doi.org/10.1038/bmt.2010.122
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