Clinical features and prognostic analysis of lymphoma‑associated hemophagocytic syndrome: A report of 139 cases

Zhang,Qiaolei; Wang,Lulu; Zhou,De; Zhu,Lixia; Li,Li; Xie,Wanzhuo; Tan,Yamin; Ye,Xiujin

doi:10.3892/ol.2022.13599

Clinical features and prognostic analysis of lymphoma‑associated hemophagocytic syndrome: A report of 139 cases

Authors:
- Qiaolei Zhang
- Lulu Wang
- De Zhou
- Lixia Zhu
- Li Li
- Wanzhuo Xie
- Yamin Tan
- Xiujin Ye
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Affiliations: Department of Hematology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, P.R. China, Department of Hematology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: November 17, 2022 https://doi.org/10.3892/ol.2022.13599
Article Number: 13

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Abstract

Lymphoma‑associated hemophagocytic syndrome (LAHS) is characterized by rapid onset, rapid progression and a poor prognosis, and is easy to misdiagnose. In order to improve the clinical understanding, diagnosis and treatment of LAHS, the clinical characteristics and risk factors of LAHS were discussed by retrospective data analysis in the present study. The clinical characteristics of 324 patients with newly diagnosed hemophagocytic syndrome (HPS) were retrospectively investigated. The patients were divided into two groups: The LAHS group comprising 139 patients with LAHS and the non‑LAHS group comprising 185 patients with HPS that was not associated with lymphoma. The clinical features and prognosis of the two groups were compared. Patients in the LAHS group had higher levels of total bilirubin (P=0.005) and indirect bilirubin (P=0.006). In addition, patients in the LAHS group had a higher early mortality rate (50.4 vs. 34.6%; P=0.004), higher recurrence rate (30.2 vs. 15.1%; P=0.001), reduced 5‑year overall survival rate (OS; 21.5 vs. 52.4%; P<0.001) and reduced relapse‑free survival rate (RFS; 7.7 vs. 48.3%; P<0.001) compared with those in the non‑LAHS group. If patients with early mortality in the two groups were excluded, the 5‑year OS rates were improved and also significantly different (43.3 vs. 80.2%; P=0.041). The 5‑year OS and RFS of patients in the LAHS group who had received chemotherapy were significantly superior compared with those who had not received chemotherapy (P<0.001). Multivariate analysis showed that an activated partial thromboplastin time of >36.0 sec (P=0.020) and serum lactate dehydrogenase level of >1,000 U/l (P=0.045) were independent risk factors for a poor LAHS prognosis. The outcomes of the patients with LAHS were worse than those of those with other types of HPS due to the higher early mortality rate. Therefore, it may be concluded that the reduction of the early mortality rate of patients with LAHS is of great importance.

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1	Canna SW and Marsh RA: Pediatric hemophagocytic lymphohistiocytosis. Blood. 135:1332–1343. 2020. View Article : Google Scholar : PubMed/NCBI
2	Liu P, Pan X, Chen C, Niu T, Shuai X, Wang J, Chen X, Liu J, Guo Y, Xie L, et al: Nivolumab treatment of relapsed/refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults. Blood. 135:826–833. 2020. View Article : Google Scholar : PubMed/NCBI
3	Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I, Yamamoto K, Horiuchi H, Takada K, Ohshima K, et al: Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol. 86:58–65. 2007. View Article : Google Scholar : PubMed/NCBI
4	Yao S, Jin Z, He L, Zhang R, Liu M, Hua Z, Wang Z and Wang Y: Clinical features and prognostic risk prediction of non-Hodgkin lymphoma-associated hemophagocytic syndrome. Front Onco. 11:7880562021. View Article : Google Scholar : PubMed/NCBI
5	Lin CH, Shih YH, Chen TC, Chou CW, Hsu CY and Teng CJ: A decade of lymphoma-associated hemophagocytic lymphohistiocytosis: Does the outcome improve? J Clin Med. 10:51142021. View Article : Google Scholar : PubMed/NCBI
6	Bigenwald C, Fardet L, Coppo P, Meignin V, Lazure T, Fabiani B, Kohn M, Oksenhendler E, Boutboul D, Uzzan M, et al: A comprehensive analysis of Lymphoma-associated haemophagocytic syndrome in a large French multicentre cohort detects some clues to improve prognosis. Br J Haematol. 183:68–75. 2018. View Article : Google Scholar : PubMed/NCBI
7	Giza A, Gałązka K, Jońca M, Raźny M, Zimowska-Curyło D, Wilk M, Goldman-Mazur S, Piątkowska-Jakubas B and Sacha T: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with probable mesentery involvement with associated hemophagocytic syndrome (HPS)-how to treat it? J Dermatolog Trea. 33:2674–2676. 2022. View Article : Google Scholar : PubMed/NCBI
8	Lehmberg K, Nichols KE, Henter JI, Girschikofsky M, Greenwood T, Jordan M, Kumar A, Minkov M, La Rosée P and Weitzman S; Study Group on Hemophagocytic Lymphohistiocytosis Subtypes of the Histiocyte Society, : Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. Haematologic. 100:997–1004. 2015.PubMed/NCBI
9	Tong H, Ren Y, Liu H, Xiao F, Mai W, Meng H, Qian W, Huang J, Mao L, Tong Y, et al: Clinical characteristics of T-cell lymphoma associated with hemophagocytic syndrome: Comparison of T-cell lymphoma with and without hemophagocytic syndrome. Leuk Lymphoma. 49:81–87. 2008. View Article : Google Scholar : PubMed/NCBI
10	Song Y, Yin Q, Wang J and Wang Z: Autologous hematopoietic stem cell transplantation for patients with lymphoma-associated hemophagocytic lymphohistiocytosis. Cell Transplant. 30:96368972110570772021. View Article : Google Scholar : PubMed/NCBI
11	Henter JL, Samuelsson-Horne AC, Aricò M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, et al: Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 100:2367–2373. 2002. View Article : Google Scholar : PubMed/NCBI
12	Birndt S, Schenk T, Heinevetter B, Brunkhorst FM, Maschmeyer G, Rothmann F, Weber T, Müller M, Panse J, Penack O, et al: Hemophagocytic lymphohistiocytosis in adults: Collaborative analysis of 137 cases of a nationwide German registry. J Cancer Res Clin Onco. 146:1065–1077. 2020. View Article : Google Scholar : PubMed/NCBI
13	Chang Y, Cui M, Fu X, Han L, Zhang L, Li L, Li X, Sun Z, Wu J, Zhang X, et al: Lymphoma associated hemophagocytic syndrome: A single-center retrospective study. Oncol Lett. 16:1275–1284. 2018.PubMed/NCBI
14	Liu YZ, Bi LQ, Chang GL, Guo Y and Sun S: Clinical characteristics of extranodal NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis. Cancer Manag Res. 11:997–1002. 2019. View Article : Google Scholar : PubMed/NCBI
15	Daver N, McClain K, Allen CE, Parikh SA, Otrock Z, Rojas-Hernandez C, Blechacz B, Wang S, Minkov M, Jordan MB, et al: A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer. 123:3229–3240. 2017. View Article : Google Scholar : PubMed/NCBI
16	Ren Q, Chan KW, Huang H, Wang Z, Fang X, Guo C, Li F, Zhang L, Yao Y, Chen Z, et al: Platelet-derived alpha-granules are associated with inflammation in patients with NK/T-cell lymphoma-associated hemophagocytic syndrome. Cytokine. 126:1548782020. View Article : Google Scholar : PubMed/NCBI
17	Meng G, Wang Y, Wang J and Wang Z: The DEP regimen is superior to the HLH-1994 regimen as first-line therapy for lymphoma-associated haemophagocytic lymphohistiocytosis. Leuk Lymphoma. 62:854–860. 2021. View Article : Google Scholar : PubMed/NCBI
18	Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J and Janka G: HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 48:124–131. 2007. View Article : Google Scholar : PubMed/NCBI
19	Jin Z, Wang Y, Wei N and Wang Z: Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis-a dangerous disease. Ann Hematol. 99:1575–1581. 2020. View Article : Google Scholar : PubMed/NCBI
20	Pasvolsky O, Zoref-Lorenz A, Abadi U, Geiger KR, Hayman L, Vaxman I, Raanani P and Leader A: Hemophagocytic lymphohistiocytosis as a harbinger of aggressive lymphoma: A case series. Int J Hematol. 109:553–562. 2019. View Article : Google Scholar : PubMed/NCBI
21	Li W, Zhong Y, Shuang Y, Huang H, Huang Y, Yu L and Huang X: High concentration of miR-133 is a useful marker for the diagnosis of lymphoma-associated hemophagocytic syndrome. Cancer Biomark. 20:159–164. 2017. View Article : Google Scholar : PubMed/NCBI
22	Yuan S, Wang Y, Luo H, Jiang Z, Qiao B, Jiang Y, Hu Y, Cheng Y, Chen X, Gong W, et al: Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma-associated hemophagocytic lymphohistiocytosis. Br J Haematol. 189:72–83. 2020. View Article : Google Scholar : PubMed/NCBI
23	Bin Q, Gao JH and Luo JM: Prognostic factors of early outcome in pediatric hemophagocytic lymphohistiocytosis: An analysis of 116 cases. Ann Hematol. 95:1411–1418. 2016. View Article : Google Scholar : PubMed/NCBI
24	George MR: Hemophagocytic lymphohistiocytosis: Review of etiologies and management. J Blood Med. 5:69–86. 2014. View Article : Google Scholar : PubMed/NCBI
25	Prokesch BC, Nagalla S, Ezzati F, Tujios SR, Dominguez A, Chen W, Kershaw C, Patel P, de la Flor C, Foster J, et al: What's in a name? The heterogeneous clinical spectrum and prognostic factors in a cohort of adults with hemophagocytic lymphohistiocytosis. Transfus Apher Sci. 57:779–784. 2018. View Article : Google Scholar : PubMed/NCBI
26	Li J, Wang Q, Zheng W, Ma J, Zhang W, Wang W and Tian X: Hemophagocytic lymphohistiocytosis: Clinical analysis of 103 adult patients. Medicine (Baltimore). 93:100–105. 2014. View Article : Google Scholar : PubMed/NCBI
27	Jin Z, Wang Y, Wang J, Wu L, Pei R, Lai W and Wang Z: Multivariate analysis of prognosis for patients with natural killer/T cell lymphoma-associated hemophagocytic lymphohistiocytosis. Hematology. 23:228–234. 2018. View Article : Google Scholar : PubMed/NCBI
28	Bhatt NS, Oshrine B and An Talano J: Hemophagocytic lymphohistiocytosis in adults. Leuk Lymphoma. 60:19–28. 2019. View Article : Google Scholar : PubMed/NCBI
29	Lee DE, Martinez-Escala ME, Serrano LM, Zhou XA, Kaplan JB, Pro B, Choi J and Guitart J: Hemophagocytic lymphohistiocytosis in cutaneous T-cell lymphoma. JAMA Dermatol. 154:828–831. 2018. View Article : Google Scholar : PubMed/NCBI
30	Takahashi N, Chubachi A, Miura I, Nakamura S and Miura AB: Lymphoma-associated hemophagocytic syndrome in Japan. Rinsho Ketsueki. 40:542–549. 1999.(In Japanese). PubMed/NCBI
31	Malkan UY, Albayrak M, Yildiz M, Maral S, Afacan Ozturk HB and Comert P: A rare case of diffuse large B-cell lymphoma-associated hemophagocytic lymphohistiocytosis. J Oncol Pharm Pract. 27:250–252. 2021. View Article : Google Scholar : PubMed/NCBI
32	Han L, Li L, Wu J, Li X, Zhang L, Wang X, Fu X, Ma W, Sun Z, Zhang X, et al: Clinical features and treatment of natural killer/T cell lymphoma associated with hemophagocytic syndrome: Comparison with other T cell lymphoma associated with hemophagocytic syndrome. Leuk Lymphoma. 55:2048–2055. 2014. View Article : Google Scholar : PubMed/NCBI
33	Signoff JK, Fitzgerald JC, Teachey DT, Balamuth F and Weiss SL: Hypofibrinogenemia is associated with poor outcome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome in pediatric severe sepsis. Pediatr Crit Care Med. 19:397–405. 2018. View Article : Google Scholar : PubMed/NCBI
34	Li N, Zhang L, Liu J, Zhang J, Weng HW, Zhuo HY and Zou LQ: A clinical study of 21 patients with hemophagocytic syndrome in 295 cases diagnosed with nasal type, extranodal nature killer/T cell lymphoma. Cancer Biol Ther. 18:252–256. 2017. View Article : Google Scholar : PubMed/NCBI
35	Jiang T, Ding X and Lu W: The prognostic significance of beta2 microglobulin in patients with hemophagocytic lymphohistiocytosis. Dis Markers. 2016:15239592016. View Article : Google Scholar : PubMed/NCBI
36	Pan H, Huo Y and Sun L: Comparison between clinical features and prognosis of malignancy- and non-malignancy-associated pediatric hemophagocytic lymphohistiocytosis. BMC Pediatr. 19:4682019. View Article : Google Scholar : PubMed/NCBI
37	Valade S, Mariotte E and Azoulay E: Coagulation disorders in hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Crit Care Clin. 36:415–426. 2020. View Article : Google Scholar : PubMed/NCBI
38	Jia J, Song Y, Lin N, Liu W, Ping L, Zheng W, Wang X, Xie Y, Tu M, Zhang C, et al: Clinical features and survival of extranodal natural killer/T cell lymphoma with and without hemophagocytic syndrome. Ann Hematol. 95:2023–2031. 2016. View Article : Google Scholar : PubMed/NCBI
39	Uni M, Yoshimi A, Maki H, Maeda D, Nakazaki K, Nakamura F, Fukayama M and Kurokawa M: Successful treatment with recombinant thrombomodulin for B-cell lymphoma-associated hemophagocytic syndrome complicated by disseminated intravascular coagulation. Int J Clin Exp Pathol. 6:1190–1194. 2013.PubMed/NCBI