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Treatment of Epstein Barr virus‐induced haemophagocytic lymphohistiocytosis with rituximab‐containing chemo‐immunotherapeutic regimens
Open accessAbstract
Summary: Haemophagocytic lymphohistiocytosis ( HLH ) is a life threatening complication of E pstein– B arr virus ( EBV ) infection. The anti‐ CD 20 antibody rituximab depletes B cells, leading to improved outcomes for patients with EBV ‐associated B ‐lymphoproliferative disorders. To gather data on the use of rituximab in EBV ‐ HLH , we performed a retrospective investigation involving 42 EBV ‐ HLH patients who had received treatment with rituximab‐containing regimens. On average, patients received 3 rituximab infusions (range 1–10) at a median dose of 375 mg/m 2 . In all patients, rituximab was administered with other HLH ‐directed medications, including steroids, etoposide and/or ciclosporin. Rituximab‐containing regimens appeared well tolerated and improved clinical status in 43% of patients. Examination of laboratory data obtained prior to and within 2–4 weeks after the first rituximab dose revealed significant reductions in EBV load (median load pre‐rituximab: 114 200 copies/ml, median post‐rituximab: 225 copies/ml, P = 0·0001) and serum ferritin levels (median ferritin pre‐rituximab: 4260 μg/l, median post‐rituximab: 1149 μg/l, P = 0·001). Thus, when combined with conventional HLH ‐directed therapies, rituximab improves symptoms, reduces viral load and diminishes inflammation. These data support the incorporation of rituximab into future prospective clinical trials for patients with EBV ‐ HLH .
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“As with EBV-associated HLH,71 rituximab is highly effective in patients with HHV-8–associated multicentric Castleman’s disease, since B-cell depletion removes the primary reservoir for HHV-8.72”
From Cytokine storm (2020) · cites this paper as [71]
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HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis
Henter, J., Horne, A., Aricò, M., Egeler, R. M., Filipovich, A. H., Imashuku, S., Ladisch, S., McClain, K. L., Webb, D. K. H., Winiarski, J. H., et al. (2006) · Pediatric Blood & Cancer · doi:10.1002/pbc.21039 · Cited by 5,396
Perforin Gene Defects in Familial Hemophagocytic Lymphohistiocytosis
Stepp, S. E., Dufourcq-Lagelouse, R., Deist, F. L., Bhawan, S., Dogniaux, S., Mathew, P. A., Henter, J., Bennett, M., Fischer, A., Basile, G. D. S., et al. (1999) · Science · doi:10.1126/science.286.5446.1957 · Cited by 1,236 · cited 1×
“…that impair lymphocyte cytotoxic function or as a nonhereditary disorder triggered by infection, malignancy or autoimmune disease (Coffey et al, 1998; Nichols et al, 1998; Stepp et al, 1999; Feldmann et al, 2003; Zur Stadt et al, 2005, 2009; Rigaud et al, 2006; Cote et al, 2009; Janka, 2012).”
BackgroundFeldmann, J., Callebaut, I., Raposo, G., Dogniaux, S., Bacq, D., Dumont, C., Lambert, N., Ouachée-Chardin, M., Chédeville, G., Tamary, H., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00855-9 · Cited by 935 · cited 1×
“…that impair lymphocyte cytotoxic function or as a nonhereditary disorder triggered by infection, malignancy or autoimmune disease (Coffey et al, 1998; Nichols et al, 1998; Stepp et al, 1999; Feldmann et al, 2003; Zur Stadt et al, 2005, 2009; Rigaud et al, 2006; Cote et al, 2009; Janka, 2012).”
BackgroundCoffey, A. J., Brooksbank, R. A., Brandau, O., Oohashi, T., Howell, G. R., Bye, J. M., Cahn, A. P., Durham, J., Heath, P. D., Wray, P. W., et al. (1998) · Nature Genetics · doi:10.1038/2424 · Cited by 752
XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome
Rigaud, S., Fondanèche, M., Lambert, N., Pasquier, B., Mateo, V., Soulas-Sprauel, P., Galicier, L., Deist, F. L., Rieux‐Laucat, F., Revy, P., et al. (2006) · Nature · doi:10.1038/nature05257 · Cited by 703 · cited 1×
“…that impair lymphocyte cytotoxic function or as a nonhereditary disorder triggered by infection, malignancy or autoimmune disease (Coffey et al, 1998; Nichols et al, 1998; Stepp et al, 1999; Feldmann et al, 2003; Zur Stadt et al, 2005, 2009; Rigaud et al, 2006; Cote et al, 2009; Janka, 2012).”
BackgroundHighly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis
Allen, C. E., Yu, X., Kozinetz, C. A., & McClain, K. L. (2007) · Pediatric Blood & Cancer · doi:10.1002/pbc.21423 · Cited by 637
Stadt, U. Z. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi076 · Cited by 559 · cited 2×
“…that impair lymphocyte cytotoxic function or as a nonhereditary disorder triggered by infection, malignancy or autoimmune disease (Coffey et al, 1998; Nichols et al, 1998; Stepp et al, 1999; Feldmann et al, 2003; Zur Stadt et al, 2005, 2009; Rigaud et al, 2006; Cote et al, 2009; Janka, 2012).”
BackgroundFamilial and Acquired Hemophagocytic Lymphohistiocytosis
Janka, G. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-041610-134208 · Cited by 550
Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome
Nichols, K. E., Harkin, D. P., Levitz, S., Krainer, M., Kolquist, K. A., Genovese, C., Bernard, A., Ferguson, M. L., Zuo, L., Snyder, E., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13765 · Cited by 494
Self-citationTolerability and safety of rituximab (MabThera®)
Kimby, E. K. (2005) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2005.05.007 · Cited by 472 · cited 3×
“Immediate toxicities of rituximab include infusion-related fever, chills, hypotension and bronchospasm (Kimby, 2005).”
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Özen, S., & Esenboğa, S. (2019) · Springer eBooks · doi:10.1007/978-3-030-22094-5_34 · Cited by 1
Hemophagocytic Lymphohistiocytosis: an update to diagnosis and management
Ünal, Ş. (2014) · Acta Medica · Cited by 1
Yamaguchi, N., Miyamoto, A., Kuniya, K., Azuma, K., Osa, A., Goya, S., Kusu, T., Nishioka, K., Hirayama, K., & Sakai, S. (2020) · Haigan · doi:10.2482/haigan.60.423 · Cited by 1
Fauser, J., Koeck, S., Gunsilius, E., Chott, A., Peer, A., Ditlbacher, A., Fritsche, G., Joannidis, M., Wolf, D. G. F., & Pircher, A. (2021) · memo - Magazine of European Medical Oncology · doi:10.1007/s12254-021-00701-9 · Cited by 1
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Chitty-Lopez, M., Imanirad, D., & Leiding, J. W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-818731-9.00232-9 · Cited by 1
Alejandre, C., Calzada, Y., Hernández, L., Alsina, L., & Jordán, I. (2016) · Medicina Intensiva · doi:10.1016/j.medin.2016.02.002
Suggested Relationship Between Hemophagocytic Lymphohistiocytosis andBartonella henselae
Rokx, C., van Laar, J. A. M., & Rijnders, B. J. A. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/ciw301
Hemophagocytic Lymphohistiocytosis, Secondary
Yanagisawa, R., & Nakazawa, Y. (2017) · Springer eBooks · doi:10.1007/978-981-10-3886-0_13
Secondary Hemophagocytic Syndrome Associated with Herpes Virus Infections
Rodionovskaya, S. R., Alakaeva, I. B., & Tsymbal, I. (2015) · CHILDREN INFECTIONS · doi:10.22627/2072-8107-2015-14-4-64-67
“Через 2—4 недели от введения ритуксимаба у 43% больных определялось снижение вирусной нагрузки (от 114 200 копий до 225) и уровня ферритина (с 4260 до 1149 мкг/л), отражающего активность воспаления [12].”
Stem Cell Transplantation for Primary Immunodeficiency
Silva, J., Booth, C., & Veys, P. A. (2018) · Springer eBooks · doi:10.1007/978-3-319-77674-3_19
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Понежева, Ж. Б., Алексеевна, Г. А., & Плоскирева, А. А. (2019) · Immunopathology Allergology Infectology · doi:10.14427/jipai.2019.2.13
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Cui, X.-H., Gu, L. F., Yao, H., Cao, X., & Zhang, W. G. (2017) · PubMed Central · doi:10.3760/cma.j.issn.0253-2727.2017.01.017
Fenton, C., & Heo, Y. (2020) · Drugs & Therapy Perspectives · doi:10.1007/s40267-020-00746-6
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Wang, J., Wu, L., Fu, L., Wang, Y., Wei, N., & Wang, Z. (2015) · PubMed Central · doi:10.3760/cma.j.issn.0253-2727.2015.04.019
“[2] Chellapandian D, Das R, Zelley K, et al.”
BackgroundEckstein, O. S., & Allen, C. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821671-2.00034-9
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Salamonowicz, M. (2022) · Acta Haematologica Polonica · doi:10.5603/ahp.a2021.0102
“Presence of EBV-HLH does not exclude lymphoma [15, 16].”
Nichols, K. E., & Marsh, R. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816768-7.00025-9
Self-citationMAS in der pädiatrischen Rheumatologie
Holzinger, D. (2022) · Springer Reference Medizin · doi:10.1007/978-3-662-60410-6_32
Xu, T., Xiong, L., & Tang, L. V. (2022) · Modern Rheumatology Case Reports · doi:10.1093/mrcr/rxac056
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Gans, H. A., & Lewis, D. B. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-75608-2.00012-4
Xu, T., Tang, L. V., & Xiong, L. (2022) · Research Square · doi:10.21203/rs.3.rs-2374660/v1
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“Besides plasma exchange and intravenous immunoglobulin, emerging therapies that warrant further clinical investigation include anti-IL-1, anti-TNF-α, anti-IFN-γ treatments [32] as well as kinase inhibitors [32], rituximab [38] and anti-virals [39].”
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Thiebaut, L., Pasquier, G., Theret, S., & Russello, J. (2023) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2023.10.440
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Movsisyan, A., Hambardzumyan, L., Badikyan, M., Petrosyan, M., Minasyan, M., Avagyan, A., Simonyan, J., Ivanenko, A., Bardakhchyan, S., & Tamamyan, G. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-15717-2.00021-4
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Handley, G. H. (2024) · Springer eBooks · doi:10.1007/978-3-031-57369-9_13
Goodman, A., Burns, A. J., & Tullberg, I. (2025) · Cureus · doi:10.7759/cureus.83720
“Some studies have proposed the use of B-cell-specific targets, such as rituximab or alemtuzumab, for the treatment of EBV-HLH [29,30], but insufficient data currently prevent broad recommendations.”
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“Rituximab and vincristine, administered to target AIHA, did not yield a significant clinical response for either AIHA or HLH [26,27].”
Потапенко, В. Г., Антонов, М. М., Авдошина, Д. Д., Aksenova, M. M., Baykov, V. V., Belogurova, M. B., Бехтерева, И. А., Glyzhina, L. V., Дулаева, Э. Н., Забутова, Ю. В., et al. (2025) · Clinical oncohematology · doi:10.21320/2500-2139-2025-18-4-355-371
Tahseen, M. M., & Pasangha, E. (2025) · Cureus · doi:10.7759/cureus.95534
“Rituximab is often considered in EBV-associated HLH, as EBV tends to replicate in B cells; this approach can improve symptoms, reduce viral load, and dampen inflammation [14].”
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Metadata
- Authors
- Chellapandian, D., Das, R., Zelley, K., Wiener, S. J., Zhao, H., Teachey, D. T., Nichols, K. E., & EBV‐HLH Rituximab Study Group
- Affiliations
- Department of Pediatrics Einstein Medical Center Philadelphia PA USA
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Nichols, Kim E.
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2013-05-21
- Volume
- 162
- Issue
- 3
- Pages
- 376-382
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- PMC
- PMC3776423
- OpenAlex
- W2029782045
- Cited by
- 251
- References
- 36
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 22 · 2023: 18 · 2022: 20 · 2021: 25 · 2020: 23 · 2019: 19 · 2018: 19 · 2017: 19 · 2016: 19 · 2015: 14 · 2014: 15 · 2013: 2
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL089745)
- National Cancer Institute (K12CA001727)
- Topics
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- Epstein-Barr virus, hemophagocytic lymphohistiocytosis, rituximab, anti-CD20 monoclonal antibody, B-cell depletion, EBV viral load, serum ferritin, etoposide, cyclosporine, corticosteroid therapy, chemoimmunotherapy, B-cell lymphoproliferative disorders
- MeSH terms
- Rituximab, Adolescent, Adult, Aged, Antiviral Agents, Child, Child, Preschool, Drug Administration Schedule, Drug Evaluation, Drug Therapy, Combination, Herpesvirus 4, Human, Female, Humans, Immunologic Factors, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Analysis, Treatment Outcome, Viral Load, Epstein-Barr Virus Infections, Lymphohistiocytosis, Hemophagocytic, Young Adult, Antibodies, Monoclonal, Murine-Derived
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