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Sustained CR of refractory aggressive natural killer cell leukemia following unrelated cord blood transplantation

Bone Marrow Transplantation volume 45, pages 1760–1762 (2010)Cite this article

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Aggressive natural killer (NK) cell leukemia (ANKL) is a rare malignant lymphoproliferative disorder characterized by systemic NK cell proliferation; it is most prevalent in East Asia.1 ANKL is highly refractory to conventional chemotherapy and has dismal outcomes.1, 2 Allo-SCT has been reported to be efficacious in treating ANKL;3, 4, 5 the efficacy of unrelated cord blood transplantation (uCBT), however, remains unknown. We report a case of successful uCBT for refractory ANKL, with long-term CR.

A 32-year-old Japanese man was referred to our hospital for persistent fever for more than 4 months and marked hepatosplenomegaly. He had no history of mosquito-bite allergy or chronic active EBV infection. Laboratory studies revealed a large granular lymphocyte (LGL) count of 3.78 × 109/L, which accounted for 63% of the WBC count; the immunophenotype of the LGLs was CD2+, CD3−, CD4−, CD5−, CD7+, CD8−, CD16+, CD19−, CD56−, cytoplasmic CD3−, CD3ɛ+ and NKp46 (CD335)+. The expression of NKp46, a member of the natural cytotoxicity receptor family, is strictly confined to NK cells.6 Although NK cell neoplasms rarely stain negative for CD56, this immunophenotype indicated that these cells belonged to the NK cell lineage. A BM smear showed that LGLs accounted for 13.3% of all nucleated cells. Serological studies showed elevated anti-EBV antibody titers: viral capsid antigen-specific (VCA)-IgG, 2560 × ; VCA-IgM, <10 × ; early antigen-specific IgG, 320 × and EBV nuclear antigen, 80 × . Clonal proliferation of EBV-infected NK cells was confirmed by Southern blot analysis performed using a terminal-repeat probe from the EBV genome. Computed tomography revealed marked hepatosplenomegaly with no lymphadenopathy. Liver needle biopsy revealed scattered infiltration of lymphocytes with EBV-encoded RNAs, indicating liver involvement in ANKL. The EBV-DNA load (determined by RQ-PCR) in the whole blood was 4.7 × 106 copies per 106 cells. Based on the above-mentioned findings, the diagnosis of ANKL was confirmed.

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References

  1. Suzuki R, Suzumiya J, Nakamura S, Aoki S, Notoya A, Ozaki S et al. Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia 2004; 18: 763–770.

    Article  CAS  PubMed  Google Scholar 

  2. Suzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H et al. Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol 2009; 21: 1032.

    Article  PubMed  Google Scholar 

  3. Teshima T, Miyaji R, Fukuda M, Ohshima K . Bone-marrow transplantation for Epstein-Barr-virus-associated natural killer cell-large granular lymphocyte leukaemia. Lancet 1996; 347: 1124.

    Article  CAS  PubMed  Google Scholar 

  4. Takami A, Nakao S, Yachie A, Kasahara Y, Okumura H, Miura Y et al. Successful treatment of Epstein–Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 1998; 21: 1279–1282.

    Article  CAS  PubMed  Google Scholar 

  5. Ito T, Makishima H, Nakazawa H, Kobayashi H, Shimodaira S, Nakazawa Y et al. Promising approach for aggressive NK cell leukaemia with allogeneic haematopoietic cell transplantation. Eur J Haematol 2008; 81: 107–111.

    Article  PubMed  Google Scholar 

  6. Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C et al. p46, a novel natural killer cell-specific surface molecule that mediates cell activation. J Exp Med 1997; 186: 1129–1136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yamamoto T, Iwasaki T, Watanabe N, Oshimi K, Naito M, Tsuruo T et al. Expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells of patients with granular lymphocyte-proliferative disorders. Blood 1993; 81: 1342–1346.

    CAS  PubMed  Google Scholar 

  8. Murashige N, Kami M, Kishi Y, Kim SW, Takeuchi M, Matsue K et al. Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms. Br J Haematol 2005; 130: 561–567.

    Article  PubMed  Google Scholar 

  9. Suzuki R, Suzumiya J, Nakamura S, Kagami Y, Kameoka JI, Sakai C et al. Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms. Bone Marrow Transplant 2006; 37: 425–431.

    Article  CAS  PubMed  Google Scholar 

  10. Hatsumi N, Saitoh T, Yokohama A, Uchiumi H, Matsushima T, Tsukamoto N et al. Ribosome–lamella complex of leukemic cells in a patient with aggressive NK cell leukemia. Ultrastruct Pathol 2002; 26: 415–417.

    Article  PubMed  Google Scholar 

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Acknowledgements

We acknowledge Metro Tokyo Red Cross Cord Blood Bank for supplying cord blood stem cells. We thank Dr Tuneo Yabusako (Higashisumiyoshi-Morimoto Hospital) for conducting liver needle biopsy. We also thank all the medical and nursing staff of Osaka Red Cross Hospital for providing excellent care to the patient.

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  1. Department of Hematology, Osaka Red Cross Hospital, Tennoji-ku, Osaka, Japan

    M Nishizawa, N Sugino, Y Matsui, H Kaneko, M Watanabe, Y Miura & M Tsudo

  2. Department of Hematology and Oncology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan

    M Nishizawa

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  1. M Nishizawa
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  2. N Sugino
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Correspondence to M Nishizawa.

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Nishizawa, M., Sugino, N., Matsui, Y. et al. Sustained CR of refractory aggressive natural killer cell leukemia following unrelated cord blood transplantation. Bone Marrow Transplant 45, 1760–1762 (2010). https://doi.org/10.1038/bmt.2010.189

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