Aggressive NK-cell leukemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[3] Maria Fernanda Villarreal, M.D. [4]
Synonyms and Keywords: ANKL

Overview

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course. There is no classification system for aggressive NK-cell leukemia. The pathogenesis of aggressive NK-cell leukemia is characterized by the proliferation of natural killer cells. Aggressive NK-cell leukemia is very uncommon, and is most commonly seen among middle aged adults. The most common risk factors in the development of aggressive NK-cell leukemia is the Epstein-Barr virus (EBV) infection. The majority of patients with aggressive NK-cell leukemia are symptomatic at diagnosis. Early clinical features include fatigue, night sweats, and fever. Physical examination among patients with aggressive NK-cell leukemia may be remarkable for hepatosplenomegaly. Aggressive NK-cell leukemia may also be diagnosed using bone marrow biopsy, findings of which can include extensive marrow replacement by leukemic cells and reactive histiocytes displaying hemophagocytosis. The mainstay of therapy for aggressive NK-cell leukemia is anthracycline-containing chemotherapy.

Historical Perspective

  • In 1986, Dr. Fernandez and his colleagues reported the first case of aggressive NK-cell leukemia.[1]
  • In 1989, Dr. Kawa and his colleagues first reported the association between EBV virus and aggressive NK-cell leukemia.[2]

Classification

Pathophysiology

Status Antigens
Positive CD2, CD3ε, CD56, perforin, granzyme B, TIA-1, CCR5
Negative CD57

Causes

  • There are no established causes for aggressive NK-cell leukemia.

Differentiating Aggressive NK-cell Leukemia from Other Diseases

Epidemiology and Demographics

  • Aggressive NK-cell leukemia is a rare disorder.[7][8]
  • Aggressive NK-cell leukemia is more commonly observed among young adults with median age of 42 years old.
  • Aggressive NK-cell leukemia affects men more frequently than women.
  • Aggressive NK-cell leukemia usually affects individuals of the Asian race.[9]

Risk Factors

Screening

  • There is insufficient evidence to recommend routine screening for aggressive NK-cell leukemia.

Natural History, Complications, and Prognosis

Diagnosis

Staging

  • The table below shows the staging system for aggressive NK-cell leukemia according to the Ann Arbor staging system.[11]
Stage Staging Criteria
Stage I
Stage II
Stage III
Stage IV

Symptoms

Physical Examination

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of aggressive NK-cell leukemia include:[14]

Peripheral Blood Smear may show large granular lymphocyte (LGL), fine or coarse azurophilic granules and nucleoli of varying prominence, and nuclei may be irregular and hyperchromatic.

Electrocardiogram

  • There are no ECG findings associated with aggressive NK-cell leukemia.

X-ray

There are no x-ray findings associated with aggressive NK-cell leukemia.

Echocardiography or Ultrasound

CT scan

  • There are no CT scan findings associated with aggressive NK-cell leukemia.

MRI

  • There are no MRI findings associated with aggressive NK-cell leukemia.

Other Imaging Findings

  • There are no other imaging findings associated with aggressive NK-cell leukemia.

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

  • Surgery is not recommended among patients with aggressive NK-cell leukemia.

Primary Prevention

Secondary Prevention

References

  1. Fernandez LA, Pope B, Lee C, Zayed E (April 1986). "Aggressive natural killer cell leukemia in an adult with establishment of an NK cell line". Blood. 67 (4): 925–30. PMID 3955237.
  2. 2.0 2.1 Kawa-Ha, K; Ishihara, S; Ninomiya, T; Yumura-Yagi, K; Hara, J; Murayama, F; Tawa, A; Hirai, K (1989). "CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA". Journal of Clinical Investigation. 84 (1): 51–55. doi:10.1172/JCI114168. ISSN 0021-9738.
  3. Ishida, Fumihiro (2018). "Aggressive NK-Cell Leukemia". Frontiers in Pediatrics. 6. doi:10.3389/fped.2018.00292. ISSN 2296-2360.
  4. Siu, Lisa L.P.; Wong, Kit-Fai; Chan, John K.C.; Kwong, Yok-Lam (1999). "Comparative Genomic Hybridization Analysis of Natural Killer Cell Lymphoma/Leukemia". The American Journal of Pathology. 155 (5): 1419–1425. doi:10.1016/S0002-9440(10)65454-5. ISSN 0002-9440.
  5. 5.0 5.1 [1] Chan JK. "Natural killer cell neoplasms." Anat Pathol. 1998;3:77-145. PMID 10389582
  6. Swerdlow, Steven (2017). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer. ISBN 9789283244943.
  7. 7.0 7.1 Suzuki, R; Suzumiya, J; Nakamura, S; Aoki, S; Notoya, A; Ozaki, S; Gondo, H; Hino, N; Mori, H; Sugimori, H; Kawa, K; Oshimi, K (2004). "Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells". Leukemia. 18 (4): 763–770. doi:10.1038/sj.leu.2403262. ISSN 0887-6924.
  8. Tang YT, Wang D, Luo H, Xiao M, Zhou HS, Liu D, Ling SP, Wang N, Hu XL, Luo Y, Mao X, Ao QL, Huang J, Zhang W, Sheng LS, Zhu LJ, Shang Z, Gao LL, Zhang PL, Zhou M, Zhou KG, Qiu LG, Liu QF, Zhang HY, Li JY, Jin J, Fu L, Zhao WL, Chen JP, Du X, Huang G, Wang QF, Zhou JF, Huang L (December 2017). "Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes". Blood Cancer J. 7 (12): 660. doi:10.1038/s41408-017-0021-z. PMC 5802497. PMID 29263371.
  9. 9.0 9.1 9.2 Lima, Margarida (2013). "Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis". Orphanet Journal of Rare Diseases. 8 (1): 95. doi:10.1186/1750-1172-8-95. ISSN 1750-1172.
  10. 10.0 10.1 Li, Chunrui; Tian, Ye; Wang, Jue; Zhu, Li; Huang, Liang; Wang, Na; Xu, Danmei; Cao, Yang; Li, Jianyong; Zhou, Jianfeng (2014). "Abnormal immunophenotype provides a key diagnostic marker: a report of 29 cases of de novo aggressive natural killer cell leukemia". Translational Research. 163 (6): 565–577. doi:10.1016/j.trsl.2014.01.010. ISSN 1931-5244.
  11. Lister, T A; Crowther, D; Sutcliffe, S B; Glatstein, E; Canellos, G P; Young, R C; Rosenberg, S A; Coltman, C A; Tubiana, M (1989). "Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting". Journal of Clinical Oncology. 7 (11): 1630–1636. doi:10.1200/JCO.1989.7.11.1630. ISSN 0732-183X.
  12. Song SY, Kim WS, Ko YH, Kim K, Lee MH, Park K (December 2002). "Aggressive natural killer cell leukemia: clinical features and treatment outcome". Haematologica. 87 (12): 1343–5. PMID 12495907.
  13. Sheridan W, Winton EF, Chan WC, Gordon DS, Vogler WR, Phillips C, Bongiovanni KF, Waldmann TA (November 1988). "Leukemia of non-T lineage natural killer cells". Blood. 72 (5): 1701–7. PMID 2846089.
  14. Nazarullah, Alia; Don, Michelle; Linhares, Yuliya; Alkan, Serhan; Huang, Qin (2016). "Aggressive NK-cell leukemia: A rare entity with diagnostic and therapeutic challenge". Human Pathology: Case Reports. 4: 32–37. doi:10.1016/j.ehpc.2015.08.001. ISSN 2214-3300.
  15. Wong, K. F.; Zhang, Y. M.; Chan, J. K. C. (2009). "Cytogenetic Abnormalities in Natural Killer Cell LymphomaLeukaemia - Is There a Consistent Pattern?". Leukemia & Lymphoma. 34 (3–4): 241–250. doi:10.3109/10428199909050949. ISSN 1042-8194.
  16. Loughran TP (July 1993). "Clonal diseases of large granular lymphocytes". Blood. 82 (1): 1–14. PMID 8324214.
  17. Morice WG, Kurtin PJ, Leibson PJ, Tefferi A, Hanson CA (March 2003). "Demonstration of aberrant T-cell and natural killer-cell antigen expression in all cases of granular lymphocytic leukaemia". Br. J. Haematol. 120 (6): 1026–36. doi:10.1046/j.1365-2141.2003.04201.x. PMID 12648073.
  18. Ishida F (2018). "Aggressive NK-Cell Leukemia". Front Pediatr. 6: 292. doi:10.3389/fped.2018.00292. PMC 6191480. PMID 30364049.
  19. Ishida F, Ko YH, Kim WS, Suzumiya J, Isobe Y, Oshimi K, Nakamura S, Suzuki R (June 2012). "Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase and allogeneic hematopoietic stem cell transplantation". Cancer Sci. 103 (6): 1079–83. doi:10.1111/j.1349-7006.2012.02251.x. PMID 22360679.
  20. Takami A, Nakao S, Yachie A, Kasahara Y, Okumura H, Miura Y, Sugimori N, Zeng W, Wang H, Kotani T, Shiobara S, Matsuda T (June 1998). "Successful treatment of Epstein-Barr virus-associated natural killer cell large granular lymphocytic leukaemia using allogeneic peripheral blood stem cell transplantation". Bone Marrow Transplant. 21 (12): 1279–82. doi:10.1038/sj.bmt.1701262. PMID 9674865.

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