Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (7): 44-49.doi: 10.6040/j.issn.1671-7554.0.2019.507

Previous Articles    

Advances in the clinical treatment of hemophagocytic lymphohistiocytosis

WANG Zhao   

  1. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
  • Published:2022-09-27

Abstract: Hemophagocytic lymphohistiocytosis(HLH)is a life-threatening disease resulted from hereditary or acquired dysfunction of immune system characterized by pathologic inflammatory reaction. The therapeutic guideline for HLH published by the Histiocyte Society in 1994 was a milestone in HLH treatment, which has improved the clinical remission rate of HLH from less than 10% to 50%-70% and has become a first-line treatment. However, HLH is still a refractory disease, for which numerous clinical trials have been conducted in the past decade. The novel approaches of treatment include modified chemotherapy regimens and biologically targeted therapy. This paper reviews the recent advances in treatment of HLH in order to provide new insights.

Key words: Hemophagocytic lymphohistiocytosis, Clinical trial, Chemo-immunotherapy, Biotargeting therapy supplement

CLC Number: 

  • R733.4
[1] Trottestam H, Horne A, Aricò M, et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: longterm results of the HLH-94 treatment protocol [J]. Blood, 2011, 118(17): 4577-4584.
[2] Johnson TS, Terrell CE, Millen SH, et al. Etoposide selectively ablates activated T cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis [J]. J Immunol, 2014, 192(1): 84-91.
[3] Arca M, Fardet L, Galicier L, et al. Prognostic factors of early death in a cohort of 162 adult haemophagocytic syndrome: impact of triggering disease and early treatment with etoposide [J]. Br J Haematol, 2015, 168(1): 63-68.
[4] Bergsten E, Horne A, Arico M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study [J]. Blood, 2017, 130(25): 2728-2738.
[5] Ehl SA, von Bahr Greenwood T, Hines M, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantations for the treatment of HLH: consensus statements by the HLH steering committee of the histiocyte society [J]. J Allergy Clin Immunol Pract, 2018, 6(5): 1508-1517.
[6] Miyahara M, Sano M, Shibata K, et al. B-cell lymphoma-associated hemophagocytic syndrome: clinicopathological characteristics [J]. Annals of Hematol, 2000, 79(7): 378-388.
[7] Shin HJ, Chung JS, Lee JJ, et al. Treatment outcomes with CHOP chemotherapy in adult patients with hemophagocytic lymphohistiocytosis [J]. J Korean Med Sci, 2008, 23(3): 439-444.
[8] Hu Y, Xu J, Wang L,et al. Treatment of hemophagocytic lymphohistiocytosis with cyclophosphamide, vincristine, and prednisone [J]. Swiss Med Wkly, 2012, 142: 13512. doi: 10.4414/smw.2012.13512.
[9] Wang Y, Huang W, Hu L, et al. Multi-center study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis [J]. Blood, 2015, 126(19): 2186-2192.
[10] La Rosée P. First prospective clinical trial in adult HLH [J]. Blood, 2015, 126(19): 2169-2171.
[11] 噬血细胞综合征中国专家联盟,中华医学会儿科学分会血液学组. 噬血细胞综合征诊治中国专家共识[J]. 中华医学杂志, 2018, 98(2): 91-95.
[12] 中国抗癌协会淋巴瘤专业委员会. 淋巴瘤相关噬血细胞综合征诊治中国专家共识[J]. 中华医学杂志, 2018, 98(18): 1389-1393.
[13] Wang J, Wang Y, Wu L, et al. PEG-aspargase and DEP regimen combination therapy for refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis [J]. J Hematol Oncol, 2016, 9(1): 84.
[14] Mahlaoui N, Ouachée-Chardin M, de Saint Basile G,et al. Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients [J]. Pediatrics, 2007, 120(3): 622.
[15] Matsuda K, Toyama K, Toya T, et al. Reactivation of hemophagocytic lymphohistiocytosis triggered by antithymocyte globulin [J]. Intern Med, 2018, 57(4): 583-586.
[16] Strout MP, Seropian S, Berliner N. Alemtuzumab as a bridge to allogeneic SCT in atypical hemophagocytic lymphohistiocytosis [J]. Nat Rev Clin Oncol, 2010, 7(7): 415-420.
[17] Keith MP, Pitchford C, Bernstein WB. Treatment of hemophagocytic lymphohistiocytosis with alemtuzumab in systemic lupus erythematosus [J]. J Clin Rheumatol, 2012, 18(3): 134-137.
[18] Marsh RA, Allen CE, McClain KL, et al. Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab [J]. Pediatr Blood Cancer, 2013, 60(1): 101-109.
[19] Wohlfarth P, Agis H, Gualdoni GA, et al. Interleukin 1 receptor antagonist Anakinra, intravenous immunoglobulin, and corticosteroids in the management of critically Ill adult patients with hemophagocytic lymphohistiocytosis [J]. J Intensive Care Med, 2017, 1: 885066617711386. doi: 10.1177/0885066617711386.
[20] Divithotawela C, Garrett P, Westall G, et al. Successful treatment of cytomegalovirus associated hemophagocytic lymphohistiocytosis with the interleukin 1 inhibitor-anakinra [J]. Respirol Case Rep, 2016, 4(1): 4-6.
[21] Savage E, Wazir T, Drake M, et al. Fulminant myocarditis and macrophage activation syndrome secondary to adult-onset Still's disease successfully treated with tocilizumab [J]. Rheumatology(Oxford), 2014, 53(7): 1352-1353.
[22] Teachey DT, Rheingold SR, Maude SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy [J]. Blood, 2013, 121(26): 5154-5157.
[23] Watanabe E, Sugawara H, Yamashita T, et al. Successful tocilizumab therapy for macrophage activation syndrome associated with adult-onset still's disease: a case-based review [J]. Case Rep Med, 2016, 2016: 5656320. doi: 10.1155/2016/5656320.
[24] Jordan MB, Hildeman D, Kappler J, et al. An animal model of hemophagocytic lymphohistiocytosis(HLH): CD8+ T cells and interferon gamma are essential for the disorder [J]. Blood, 2004, 104(3): 735-743.
[25] Canna SW, Wrobel J, Chu N, et al. Interferon-gamma mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice [J]. Arthritis Rheum, 2013, 65(7): 1764-1775.
[26] Kiu H, Nicholson SE. Biology and significance of the JAK/STAT signalling pathways [J]. Growth Factors, 2012, 30(2): 88-106.
[27] Das R, Guan P, Sprague L, et al. Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis [J]. Blood, 2016, 127(13): 1666-1675.
[28] Maschalidi S, Sepulveda FE, Garrigue A, et al. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice [J]. Blood, 2016, 128(1): 60-71.
[29] Broglie L, Pommert L, Rao S, et al. Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis [J]. Blood Adv, 2017, 1(19): 1533-1536.
[30] Sin JH, Zangardi ML. Ruxolitinib for secondary hemophagocytic lymphohistiocytosis: First case report [J]. Hematol Oncol Stem Cell Ther, 2017, 17: 30090. doi: 10.1016/j.hemonc.
[31] Wang J, Wang Y, Wu L, et al. Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause [J]. Ann Hematol, 2015, 94(5): 753-760.
[32] Carmo M, Risma KA, Arumugam P, et al. Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency [J]. Molecular Therapy, 2014, 23(4): 737-745.
[1] HAN Jing, JIA Chunling. Effects of periodontal basic therapy on postoperative pneumonia in patients with lung cancer before thoracic surgery [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 113-118.
[2] LEI Da-peng,LI Xue-zhong,XU Feng-lei,PAN Xin-liang,LIN Guo-jing,XUE Wei-guo,LI Chun-yang. Effect of fexofenadine hydrochloride sustained capsule for seasonal allergic rhinitis: a doubleblind, randomized, comparative multicenter trial [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(8): 819-822.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!