Chimeric antigen receptor T cell immunotherapy‑associated hemophagocytic lymphohistiocytosis: Pathogenesis, clinical manifestation, diagnosis and management compared with cytokine release syndrome (Review)
- Authors:
- Jinglin Hu
- Cuicui Feng
- Lingbo He
- Yini Wang
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Affiliations: Department of Hematology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China, Department of General Practice, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China - Published online on: May 26, 2025 https://doi.org/10.3892/mmr.2025.13578
- Article Number: 213
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Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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|
Shimabukuro-Vornhagen A, Böll B, Schellongowski P, Valade S, Metaxa V, Azoulay E and von Bergwelt-Baildon M: Critical care management of chimeric antigen receptor T-cell therapy recipients. CA Cancer J Clin. 72:78–93. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Lin H, Cheng J, Mu W, Zhou J and Zhu L: Advances in universal CAR-T cell therapy. Front Immunol. 12:7448232021. View Article : Google Scholar : PubMed/NCBI | |
|
Cameron BJ, Gerry AB, Dukes J, Harper JV, Kannan V, Bianchi FC, Grand F, Brewer JE, Gupta M, Plesa G, et al: Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med. 5:197ra1032013. View Article : Google Scholar : PubMed/NCBI | |
|
Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM and Rosenberg SA: Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 18:843–851. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Brudno JN and Kochenderfer JN: Toxicities of chimeric antigen receptor T cells: Recognition and management. Blood. 127:3321–3330. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Owusu KA, Schiffer M and Perreault S: Chimeric antigen receptor T cells: Toxicity and management considerations. AACN Adv Crit Care. 33:301–307. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Freyer CW and Porter DL: Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies. J Allergy Clin Immunol. 146:940–948. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Major A, Collins J, Craney C, Heitman AK, Bauer E, Zerante E, Stock W, Bishop MR and Jasielec J: Management of hemophagocytic lymphohistiocytosis (HLH) associated with chimeric antigen receptor T-cell (CAR-T) therapy using anti-cytokine therapy: An illustrative case and review of the literature. Leuk Lymphoma. 62:1765–1769. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Hines MR, Knight TE, McNerney KO, Leick MB, Jain T, Ahmed S, Frigault MJ, Hill JA, Jain MD, Johnson WT, et al: Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Transplant Cell Ther. 29:438.e1–438.e16. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Sandler RD, Tattersall RS, Schoemans H, Greco R, Badoglio M, Labopin M, Alexander T, Kirgizov K, Rovira M, Saif M, et al: Diagnosis and management of secondary HLH/MAS following HSCT and CAR-T cell therapy in adults; A review of the literature and a survey of practice within EBMT centres on behalf of the autoimmune diseases working party (ADWP) and transplant complications working party (TCWP). Front Immunol. 11:5242020. View Article : Google Scholar : PubMed/NCBI | |
|
Lichtenstein DA, Schischlik F, Shao L, Steinberg SM, Yates B, Wang HW, Wang Y, Inglefield J, Dulau-Florea A, Ceppi F, et al: Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells. Blood. 138:2469–2484. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Hines MR, Keenan C, Maron Alfaro G, Cheng C, Zhou Y, Sharma A, Hurley C, Nichols KE, Gottschalk S, Triplett BM and Talleur AC: Hemophagocytic lymphohistiocytosis-like toxicity (carHLH) after CD19-specific CAR T-cell therapy. Br J Haematol. 194:701–707. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Shah NN, Highfill SL, Shalabi H, Yates B, Jin J, Wolters PL, Ombrello A, Steinberg SM, Martin S, Delbrook C, et al: CD4/CD8 T-cell selection affects chimeric antigen receptor (CAR) T-cell potency and toxicity: updated results from a phase I anti-CD22 CAR T-cell trial. J Clin Oncol. 38:1938–1950. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Debaugnies F, Mahadeb B, Ferster A, Meuleman N, Rozen L, Demulder A and Corazza F: Performances of the H-score for diagnosis of hemophagocytic lymphohistiocytosis in adult and pediatric patients. Am J Clin Pathol. 145:862–870. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Schubert ML, Schmitt M, Wang L, Ramos CA, Jordan K, Müller-Tidow C and Dreger P: Side-effect management of chimeric antigen receptor (CAR) T-cell therapy. Ann Oncol. 32:34–48. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, Chabannon C, Ciceri F, Corbacioglu S, Ellard R, et al: Management of adults and children receiving CAR T-cell therapy: 2021 Best practice recommendations of the European society for blood and marrow transplantation (EBMT) and the joint accreditation committee of ISCT and EBMT (JACIE) and the European haematology association (EHA). Ann Oncol. 33:259–275. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Ponnatt TS, Lilley CM and Mirza KM: Hemophagocytic lymphohistiocytosis. Arch Pathol Lab Med. 146:507–519. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Schram AM, Comstock P, Campo M, Gorovets D, Mullally A, Bodio K, Arnason J and Berliner N: Haemophagocytic lymphohistiocytosis in adults: A multicentre case series over 7 years. Br J Haematol. 172:412–419. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Henter JI: Hemophagocytic lymphohistiocytosis. N Engl J Med. 392:584–598. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Henter JI, Elinder G, Söder O and Ost A: Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand. 80:428–435. 1991. View Article : Google Scholar : PubMed/NCBI | |
|
Ravelli A, Minoia F, Davi S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, et al: 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: A European league against rheumatism/American college of rheumatology/paediatric rheumatology international trials organisation collaborative initiative. Ann Rheum Dis. 75:481–489. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA and Bosch X: Adult haemophagocytic syndrome. Lancet. 383:1503–1516. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
He L, Yang C and Wang Y: Biological therapies for hemophagocytic lymphohistiocytosis: Current knowledge and future perspectives. Expert Opin Biol Ther. 23:1005–1013. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Janka GE and Lehmberg K: Hemophagocytic syndromes-an update. Blood Rev. 28:135–142. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Griffin G, Shenoi S and Hughes GC: Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy. Best Pract Res Clin Rheumatol. 34:1015152020. View Article : Google Scholar : PubMed/NCBI | |
|
Filipovich A, McClain K and Grom A: Histiocytic disorders: Recent insights into pathophysiology and practical guidelines. Biol Blood Marrow Transplant. 16 (1 Suppl):S82–S89. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Arceci RJ: When T cells and macrophages do not talk: The hemophagocytic syndromes. Curr Opin Hematol. 15:359–367. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Niece JA, Rogers ZR, Ahmad N, Langevin AM and McClain KL: Hemophagocytic lymphohistiocytosis in Texas: Observations on ethnicity and race. Pediatr Blood Cancer. 54:424–428. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Löfstedt A, Jädersten M, Meeths M and Henter JI: Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: Incidence, clinical characteristics, and survival. Blood. 143:233–242. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Singh S, Khasbage S, Kaur RJ, Sidhu JK and Bhandari B: Chimeric antigen receptor T cell: A cancer immunotherapy. Indian J Pharmacol. 54:226–233. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Chong EA, Ruella M and Schuster SJ; Lymphoma Program Investigators at the University of Pennsylvania, : Five-year outcomes for refractory B-cell lymphomas with CAR T-cell therapy. N Engl J Med. 384:673–674. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al: Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 371:1507–1517. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Cappell KM, Sherry RM, Yang JC, Goff SL, Vanasse DA, McIntyre L, Rosenberg SA and Kochenderfer JN: Long-term follow-up of anti-CD19 chimeric antigen receptor T-cell therapy. J Clin Oncol. 38:3805–3815. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Feins S, Kong W, Williams EF, Milone MC and Fraietta JA: An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer. Am J Hematol. 94((S1)): S3–S9. 2019.PubMed/NCBI | |
|
Stone JD and Kranz DM: Role of T cell receptor affinity in the efficacy and specificity of adoptive T cell therapies. Front Immunol. 4:2442013. View Article : Google Scholar : PubMed/NCBI | |
|
Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, et al: Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b/2 open-label study: A phase 1b/2 open-label study. Lancet. 398:314–324. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang T, Tang Y, Cai J, Wan X, Hu S, Lu X, Xie Z, Qiao X, Jiang H, Shao J, et al: Coadministration of CD19- and CD22-directed chimeric antigen receptor T-cell therapy in childhood B-cell acute lymphoblastic leukemia: A single-arm, multicenter, phase II trial. J Clin Oncol. 41:1670–1683. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, et al: Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 377:2531–2544. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, et al: Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 380:45–56. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Frey NV, Shaw PA, Hexner EO, Pequignot E, Gill S, Luger SM, Mangan JK, Loren AW, Perl AE, Maude SL, et al: Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia. J Clin Oncol. 38:415–422. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, et al: Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 380:1726–1737. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Bupha-Intr O, Haeusler G, Chee L, Thursky K, Slavin M and Teh B: CAR-T cell therapy and infection: A review. Expert Rev Anti Infect Ther. 19:749–758. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Lei W, Xie M, Jiang Q, Xu N, Li P, Liang A, Young KH and Qian W: Treatment-related adverse events of chimeric antigen receptor T-cell (CAR T) in clinical trials: A systematic review and meta-analysis. Cancers (Basel). 13:39122021. View Article : Google Scholar : PubMed/NCBI | |
|
Zu C, Wu S, Zhang M, Wei G, Xu H, Cui J, Chang AH, Huang H and Hu Y: A distinct cytokine network distinguishes chimeric antigen receptor T cell (CAR-T)-associated hemophagocytic lymphohistiocytosis-like toxicity (carHLH) from severe cytokine release syndrome following CAR-T therapy. Cytotherapy. 25:1167–1175. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Y, Fang Y, Chen X, Wang Z, Liang X, Zhang T, Liu M, Zhou N, Lv J, Tang K, et al: Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol. 5:eaax79692020. View Article : Google Scholar : PubMed/NCBI | |
|
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, et al: Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 378:439–448. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Brudno JN and Kochenderfer JN: Current understanding and management of CAR T cell-associated toxicities. Nat Rev Clin Oncol. 21:501–521. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, et al: Chimeric antigen receptor T-cell therapy-assessment and management of toxicities. Nat Rev Clin Oncol. 15:47–62. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Fajgenbaum DC and June CH: Cytokine storm. N Engl J Med. 383:2255–2273. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Yan W, Xiong Y, Lv R, Du C, Yu T, Zhang S, Sui W, Deng S, Xiao J, Xu Y, et al: Uncommon biphasic CAR-T expansion induces hemophagocytic lymphohistiocytosis-like syndrome and fatal multiple infections following BCMA CAR-T cell therapy: A case report. J Immunother Cancer. 12:e0100802024. View Article : Google Scholar : PubMed/NCBI | |
|
Vandenhaute J, Wouters CH and Matthys P: Natural killer cells in systemic autoinflammatory diseases: A focus on systemic juvenile idiopathic arthritis and macrophage activation syndrome. Front Immunol. 10:30892020. View Article : Google Scholar : PubMed/NCBI | |
|
Weiss ES, Girard-Guyonvarc'h C, Holzinger D, de Jesus AA, Tariq Z, Picarsic J, Schiffrin EJ, Foell D, Grom AA, Ammann S, et al: Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome. Blood. 131:1442–1455. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kaplanski G: Interleukin-18: Biological properties and role in disease pathogenesis. Immunol Rev. 281:138–153. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Miao L, Zhang Z, Ren Z and Li Y: Reactions related to CAR-T cell therapy. Front Immunol. 12:6632012021. View Article : Google Scholar : PubMed/NCBI | |
|
Nichols KE and Hines MR: NK cells: Energized yet exhausted in adult HLH. Blood. 136:524–525. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Strati P, Ahmed S, Kebriaei P, Nastoupil LJ, Claussen CM, Watson G, Horowitz SB, Brown ART, Do B, Rodriguez MA, et al: Clinical efficacy of anakinra to mitigate CAR T-cell therapy-associated toxicity in large B-cell lymphoma. Blood Adv. 4:3123–3127. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Ahmed S, Furqan F, Strati P, Westin J, Fayad LE, Hagemeister FB, Lee HJ, Iyer SP, Nair R, Nastoupil LJ, et al: Haemophagocytic lymphohistiocytosis (HLH) in patients with large B-cell lymphoma treated with standard of care (SOC) axicabtagene ciloleucel (Axi-cel). J Clin Oncol. 38 (15 Suppl):S80572020. View Article : Google Scholar | |
|
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, et al: ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 25:625–638. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Meireles AM, Iacoboni G, Moço LM, Ramos I, Brás G, Azevedo J, Rodrigues Â, Moreira C and Mariz M: Hemophagocytic lymphohistiocytosis in a patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy. Immunotherapy. 16:1105–1111. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Khurana A, Rosenthal AC, Mohty R, Gaddam M, Bansal R, Hathcock MA, Nedved AN, Durani U, Iqbal M, Wang Y, et al: Chimeric antigen receptor T-cell therapy associated hemophagocytic lymphohistiocytosis syndrome: Clinical presentation, outcomes, and management. Blood Cancer J. 14:1362024. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P and Hejblum G: Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 66:2613–2620. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Takagi S, Masuoka K, Uchida N, Ishiwata K, Araoka H, Tsuji M, Yamamoto H, Kato D, Matsuhashi Y, Kusumi E, et al: High incidence of haemophagocytic syndrome following umbilical cord blood transplantation for adults. Br J Haematol. 147:543–553. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Porter TJ, Lazarevic A, Ziggas JE, Fuchs E, Kim K, Byrnes H, Luznik L, Bolaños-Meade J, Ali SA, Shah NN, et al: Hyperinflammatory syndrome resembling haemophagocytic lymphohistiocytosis following axicabtagene ciloleucel and brexucabtagene autoleucel. Br J Haematol. 199:720–727. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Turtle CJ, Hanafi LA, Berger C, Hudecek M, Pender B, Robinson E, Hawkins R, Chaney C, Cherian S, Chen X, et al: Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 8:355ra1162016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Zhou F, Wu Z, Li Y, Li C, Du M, Luo W, Kou H, Lu C and Mei H: Timing of tocilizumab administration under the guidance of IL-6 in CAR-T therapy for R/R acute lymphoblastic leukemia. Front Immunol. 13:9149592022. View Article : Google Scholar : PubMed/NCBI | |
|
He J, Xu N, Zhou H, Zhou Y, Wu D, Zhao R, Lin T, Xu J, Cao R, Li P and Liu Q: Case report: Chimeric antigen receptor T cells induced late severe cytokine release syndrome. Front Oncol. 12:8939282022. View Article : Google Scholar : PubMed/NCBI | |
|
Sigha OB, Mbono Betoko R, Nkoro GA, Fossi Happi M, Ekoube CE, Kelbaba BB, Mandeng Ma Linwa E and Kouotou EA: Bart's syndrome associated with a disorder of sexual differentiation: An atypical presentation in a Cameroonian newborn. Clin Case Rep. 10:e052342022. View Article : Google Scholar : PubMed/NCBI | |
|
Maus MV, Alexander S, Bishop MR, Brudno JN, Callahan C, Davila ML, Diamonte C, Dietrich J, Fitzgerald JC, Frigault MJ, et al: Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events. J Immunother Cancer. 8:e0015112020. View Article : Google Scholar : PubMed/NCBI | |
|
Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, et al: Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline. J Clin Oncol. 39:3978–3992. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Henter JI, Aricò M, Egeler RM, Elinder G, Favara BE, Filipovich AH, Gadner H, Imashuku S, Janka-Schaub G, Komp D, et al: HLH-94: A treatment protocol for hemophagocytic lymphohistiocytosis. HLH study group of the histiocyte society. Med Pediatr Oncol. 28:342–347. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, et al: Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med. 382:1811–1822. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Ge J, Zhang Q, Ma H, Wang D, Zhao Y, Zhu T, Wang W, Zhou C, Wei A, Lian H, et al: Ruxolitinib-based regimen in children with primary hemophagocytic lymphohistiocytosis. Haematologica. 109:458–465. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Rejeski K, Subklewe M, Aljurf M, Bachy E, Balduzzi A, Barba P, Bruno B, Benjamin R, Carrabba MG, Chabannon C, et al: Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations. Blood. 142:865–877. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, Kovac SH, Spettell CM and Saag KG: Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 55:420–426. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Kim JY, Kim M, Park JK, Lee EB, Park JW and Hong J: Limited efficacy of tocilizumab in adult patients with secondary hemophagocytic lymphohistiocytosis: A retrospective cohort study. Orphanet J Rare Dis. 17:3632022. View Article : Google Scholar : PubMed/NCBI | |
|
Park JH, Nath K, Devlin SM, Sauter CS, Palomba ML, Shah G, Dahi P, Lin RJ, Scordo M, Perales MA, et al: CD19 CAR T-cell therapy and prophylactic anakinra in relapsed or refractory lymphoma: Phase 2 trial interim results. Nat Med. 29:1710–1717. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Wohlfarth P, Agis H, Gualdoni GA, Weber J, Staudinger T, Schellongowski P and Robak O: Interleukin 1 receptor antagonist anakinra, intravenous immunoglobulin, and corticosteroids in the management of critically ill adult patients with hemophagocytic lymphohistiocytosis. J Intensive Care Med. 34:723–731. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Diorio C, Vatsayan A, Talleur AC, Annesley C, Jaroscak JJ, Shalabi H, Ombrello AK, Hudspeth M, Maude SL, Gardner RA and Shah NN: Anakinra utilization in refractory pediatric CAR T-cell associated toxicities. Blood Adv. 6:3398–3403. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Abedin S, McKenna E, Chhabra S, Pasquini M, Shah NN, Jerkins J, Baim A, Runaas L, Longo W, Drobyski W, et al: Efficacy, toxicity, and infectious complications in ruxolitinib-treated patients with corticosteroid-refractory graft-versus-host disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 25:1689–1694. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Bracaglia C, de Graaf K, Pires Marafon D, Guilhot F, Ferlin W, Prencipe G, Caiello I, Davì S, Schulert G, Ravelli A, et al: Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann Rheum Dis. 76:166–172. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Horne A, von Bahr Greenwood T, Chiang SCC, Meeths M, Björklund C, Ekelund M, Erensjö P, Berg S, Hagelberg S, Bryceson YT, et al: Efficacy of moderately dosed etoposide in macrophage activation syndrome-hemophagocytic lymphohistiocytosis. J Rheumatol. 48:1596–1602. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Zondag TCE, Lika A and van Laar JAM: The role of etoposide in the treatment of adult patients with hemophagocytic lymphohistiocytosis. Exp Hematol Oncol. 12:22023. View Article : Google Scholar : PubMed/NCBI | |
|
Song Y, Wang J, Wang Y, Wu L and Wang Z: Requirement for containing etoposide in the initial treatment of lymphoma associated hemophagocytic lymphohistiocytosis. Cancer Biol Ther. 22:598–606. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Henter JI, von Bahr Greenwood T and Bergsten E: Emapalumab in primary hemophagocytic lymphohistiocytosis. N Engl J Med. 383:596–598. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Bailey SR, Vatsa S, Larson RC, Bouffard AA, Scarfò I, Kann MC, Berger TR, Leick MB, Wehrli M, Schmidts A, et al: Blockade or deletion of IFNγ reduces macrophage activation without compromising CAR T-cell function in hematologic malignancies. Blood Cancer Discov. 3:136–153. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
McNerney KO, DiNofia AM, Teachey DT, Grupp SA and Maude SL: Potential role of IFNγ inhibition in refractory cytokine release syndrome associated with CAR T-cell therapy. Blood Cancer Discov. 3:90–94. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Verkamp B, Jodele S, Sabulski A, Marsh RA, Kieser P and Jordan MB: Emapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerism. Blood. 144:2625–2636. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Garonzi C, Chinello M and Cesaro S: Emapalumab for adult and pediatric patients with hemophagocytic lymphohistiocytosis. Expert Rev Clin Pharmacol. 14:527–534. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Y, Sun X, Kang K, Yang Y, Li H, Zhao A and Niu T: Hemophagocytic lymphohistiocytosis: Current treatment advances, emerging targeted therapy and underlying mechanisms. J Hematol Oncol. 17:1062024. View Article : Google Scholar : PubMed/NCBI | |
|
Roddie C, Lekakis LJ, Marzolini MAV, Ramakrishnan A, Zhang Y, Hu Y, Peddareddigari VGR, Khokhar N, Chen R, Basilico S, et al: Dual targeting of CD19 and CD22 with bicistronic CAR-T cells in patients with relapsed/refractory large B-cell lymphoma. Blood. 141:2470–2482. 2023.PubMed/NCBI | |
|
Schultz LM, Jeyakumar N, Kramer AM, Sahaf B, Srinagesh H, Shiraz P, Agarwal N, Hamilton M, Erickson C, Jacobs A, et al: CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia. 38:963–968. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Masih KE, Ligon JA, Yates B, Shalabi H, Little L, Islam Z, Ombrello AK, Inglefield J, Nussenblatt V, Manion M, et al: Consequences of hemophagocytic lymphohistiocytosis-like cytokine release syndrome toxicities and concurrent bacteremia. Pediatr Blood Cancer. 68:e292472021. View Article : Google Scholar : PubMed/NCBI | |
|
Service USDoHaH, Health NIo and Institute NC: National Cancer Institute, . Common terminology criteria for adverse events (CTCAE). Version 5.0.2017. |
