Comparison of Hemophagocytic Lymphohistiocytosis Diagnostic Criteria in Malignancy-Associated Hemophagocytic Lymphohistiocytosis Patients

Year 2022, Volume: 4 Issue: 4, 180 - 189, 29.10.2022

Hakkı Onur Kırkızlar , Tuğcan Alp Kırkızlar , Ufuk Demirci , Sedanur Karaman Gulsaran Volkan Bas Elif Umit , Ahmet Muzaffer Demir

https://doi.org/10.46310/tjim.1121064

Abstract

Background Fulfilling diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH) is challenging due to unavailable laboratory tests. Hence, we aimed to reveal malignancy-associated-HLH (M-HLH) patients in our center, which can not be reached in all tests.
Material and Methods Nine patients with M-HLH were analyzed retrospectively.
Results The median age was 59 years. The distribution of the underlying diseases was like diffuse large B cell lymphoma in 3 patients, acute myeloid leukemia in 2 patients, Hodgkin lymphoma in 2 patients, T cell non-Hodgkin lymphoma in 1 patient, and small cell lung cancer in 1 patient. According to HLH-2004 diagnostic criteria except for soluble CD25 and natural killer activity tests; one patient had 3/6, six patients had 5/6, two patients had 6/6 criteria while the median H-score was 258 at diagnosis. According to Tamamyan et al’s criteria; at the diagnosis, all patients had ≥7 (between 7-12) of 18 parameters. Patients fulfilled ≥5 parameters a median of 15 days (3-52 days) before the diagnosis and on that time six patients had 3/6 criteria of HLH-2004. 88.8% of the patients died. The median duration of survival was 8.5 days (1-18 days).
Conclusions Unavailability of the tests in some countries and centers as in ours results in complications to fulfill 5 of 8 criteria and being delayed in diagnosis and treatment. We need to develop more specific and accessible criteria, and grading systems for M-HLH diagnose.

Keywords

hemophagocytic lymphohistiocytosis, malignancy, diagnosis, mortality

References

• Janka GE, Lehmberg K. Hemophagocytic syndromes--an update. Blood Rev. 2014 Jul;28(4):135-42. doi: 10.1016/j.blre.2014.03.002.
• George M. Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 2014 Jun 12;5:69-86. doi: 10.2147/JBM.S46255.
• Ehl S, Astigarraga I, von Bahr Greenwood T, Hines M, Horne AC, Ishii E et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1508-17. doi: 10.1016/j.jaip.2018.05.031.
• La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, Birndt S, Gil-Herrera J, Girschikofsky M, Jordan MB, Kumar A, van Laar JAM, Lachmann G, Nichols KE, Ramanan AV, Wang Y, Wang Z, Janka G, Henter JI. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019 Jun 6;133(23):2465-77. doi: 10.1182/blood.2018894618.
• Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I, Yamamoto K, Horiuchi H, Takada K, Ohshima K, Nakamura S, Kinukawa N, Oshimi K, Kawa K. Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol. 2007 Jul;86(1):58-65. doi: 10.1532/IJH97.07012.
• Machaczka M, Vaktnäs J, Klimkowska M, Hagglund H. Malignancy-associated hemophagocytic lymphohistiocytosis in adults: a retrospective population-based analysis from a single center. Leuk Lymphoma. 2011 Apr;52(4):613-9. doi: 10.3109/10428194.2010.551153.
• Daver N, McClain K, Allen CE, Parikh SA, Otrock Z, Rojas-Hernandez C, Blechacz B, Wang S, Minkov M, Jordan MB, La Rosée P, Kantarjian HM. A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer. 2017 Sep 1;123(17):3229-40. doi: 10.1002/cncr.30826.
• Kim YR, Kim DY. Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults. Blood Res. 2021 Apr 30;56(S1):S17-S25. doi: 10.5045/br.2021.2020323.
• Lehmberg K, Nichols KE, Henter JI, Girschikofsky M, Greenwood T, Jordan M, Kumar A, Minkov M, La Rosée P, 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. Haematologica. 2015 Aug;100(8):997-1004. doi: 10.3324/haematol.2015.123562.
• Noseda R, Bertoli R, Müller L, Ceschi A. Haemophagocytic lymphohistiocytosis in patients treated with immune check point inhibitors: analysis of WHO global database of individual case safety reports. J Immunother Cancer. J Immunother Cancer. 2019 May 2;7(1):117. doi: 10.1186/s40425-019-0598-9.
• Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039.
• Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014 Sep;66(9):2613-20. doi: 10.1002/art.38690.
• Tamamyan GN, Kantarjian HM, Ning J, Jain P, Sasaki K, McClain KL, Allen CE, Pierce SA, Cortes JE, Ravandi F, Konopleva MY, Garcia-Manero G, Benton CB, Chihara D, Rytting ME, Wang S, Abdelall W, Konoplev SN, Daver NG. Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes. Cancer. 2016 Sep 15;122(18):2857-66. doi: 10.1002/cncr.30084.
• Chen RL, Lin KH, Lin DT, Su IJ, Huang LM, Lee PI, Hseih KH, Lin KS, Lee CY. Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis. Br J Haematol. 1995 Feb;89(2):282-90. doi: 10.1111/j.1365-2141.1995.tb03302.x.
• La Rosée P. Treatment of hemophagocytic lymphohistiocytosis in adults. Hematology Am Soc Hematol Educ Program. 2015;2015:190-6. doi: 10.1182/asheducation-2015.1.190.
• Chellapandian D. Hemophagocytic lymphohistiocytosis lessons learned from the dark side. Immunol Allergy Clin N Am. Immunol Allergy Clin North Am. 2020 Aug;40(3):485-97. doi: 10.1016/j.iac.2020.04.003.
• Fadeel B, Orrenius S, Henter JI. Induction of apoptosis and caspase activation in cells obtained from familial haemophagocytic lymphohistiocytosis patients. Br J Haematol. 1999 Aug;106(2):406-15. doi: 10.1046/j.1365-2141.1999.01538.x.
• Birndt S, Schenk T, Heinevetter B, Brunkhorst FM, Maschmeyer G, Rothmann F, Weber T, Müller M, Panse J, Penack O, Schroers R, Braess J, Frickhofen N, Ehl S, Janka G, Lehmberg K, Pletz MW, Hochhaus A, Ernst T, La Rosée P. Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry. J Cancer Res Clin Oncol. 2020 Apr;146(4):1065-77. doi: 10.1007/s00432-020-03139-4.
• Delavigne K, Bérard E, Bertoli S, Corre J, Duchayne E, Demur C, Mansat-De Mas V, Borel C, Picard M, Alvarez M, Sarry A, Huguet F, Récher C. Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy. Haematologica. 2014 Mar;99(3):474-80. doi: 10.3324/haematol.2013.097394.
• Sano H, Kobayashi R, Tanaka J, Hashino S, Ota S, Torimoto Y, Kakinoki Y, Yamamoto S, Kurosawa M, Hatakeyama N, Haseyama Y, Sakai H, Sato K, Fukuhara T. Risk factor analysis of non-Hodgkin lymphoma-associated haemophagocytic syndromes: a multicentre study. Br J Haematol. 2014 Jun;165(6):786-92. doi: 10.1111/bjh.12823.
• Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014 Apr 26;383(9927):1503-16. doi: 10.1016/S0140-6736(13)61048-X.
• Zoref-Lorenz A, Murakami J, Hofstetter L, Iyer S, Alotaibi AS, Mohamed SF, Miller PG, Guber E, Weinstein S, Yacobovich J, Nikiforow S, Ebert BL, Lane A, Pasvolsky O, Raanani P, Nagler A, Berliner N, Daver N, Ellis M, Jordan MB. An improved index for diagnosis and mortality prediction in malignancy-associated hemophagocytic lymphohistiocytosis. Blood. 2022 Feb 17;139(7):1098-110. doi: 10.1182/blood.2021012764.
• Schram AM, Comstock P, Campo M, Gorovets D, Mullally A, Bodio K, Arnason J, Berliner N. Haemophagocytic lymphohistiocytosis in adults: a multicentre case series over 7 years. Br J Haematol. 2016 Feb;172(3):412-9. doi: 10.1111/bjh.13837.
• Schram AM, Campigotto F, Mullally A, Fogerty A, Massarotti E, Neuberg D, Berliner N. Marked hyperferritinemia does not predict for HLH in the adult population. Blood. 2015 Mar 5;125(10):1548-52. doi: 10.1182/blood-2014-10-602607.
• Wang H, Xiong L, Tang W, Zhou Y, Li F. A systematic review of malignancy-associated hemophagocytic lymphohistiocytosis that needs more attentions. Oncotarget. 2017 Jul 14;8(35):59977-85. doi: 10.18632/oncotarget.19230.
• Karlsson T. Secondary haemophagocytic lymphohistiocytosis: experience from the Uppsala University Hospital. Ups J Med Sci. 2015;120(4):257-62. doi: 10.3109/03009734.2015.1064500.