Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation

Böhm S, Wustrau K, Pachlopnik Schmid J, Prader S, Ahlmann M, Yacobovich J, Beier R, Speckmann C, Behnisch W, Ifversen M, Jordan M, Marsh R, Naumann-Bartsch N, Mauz-Körholz C, Hönig M, Schulz A, Malinowska I, Hines M, Nichols KE, Gil-Herrera J, Talano JA, Crooks B, Formankova R, Jorch N, Bakhtiar S, Kühnle I, Streiter M, Nathrath M, Russo A, Dürken M, Lang P, Lindemans C, Henter JI, Lehmberg K, Ehl S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

DOI: 10.1182/blood.2023022281

Abstract

Primary hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening hyperinflammatory syndrome that develops mainly in patients with genetic disorders of lymphocyte cytotoxicity and X-linked lymphoproliferative syndromes. Previous studies with etoposide-based treatment followed by hematopoetic stem cell transplantation (HSCT) resulted in 5-year survival of 50% to 59%. Contemporary data are lacking. We evaluated 88 patients with pHLH documented in the international HLH registry from 2016-2021. In 12 of 88 patients, diagnosis was made without HLH activity, based on siblings or albinism. Major HLH-directed drugs (etoposide, antithymocyte globulin, alemtuzumab, emapalumab, ruxolitinib) were administered to 66 of 76 patients who were symptomatic (86% first-line etoposide); 16 of 57 patients treated with etoposide and 3 of 9 with other first-line treatment received salvage therapy. HSCT was performed in 75 patients; 7 patients died before HSCT. Three-year probability of survival (pSU) was 82% (confidence interval [CI], 72%-88%) for the entire cohort and 77% (CI, 64%-86%) for patients receiving first-line etoposide. Compared with the HLH-2004 study, both pre-HSCT and post-HSCT survival of patients receiving first-line etoposide improved, 83% to 91% and 70% to 88%. Differences to HLH-2004 included preferential use of reduced-toxicity conditioning and reduced time from diagnosis to HSCT (from 148 to 88 days). Three-year pSU was lower with haploidentical (4 of 9 patients [44%]) than with other donors (62 of 66 [94%]; P < .001). Importantly, early HSCT for patients who were asymptomatic resulted in 100% survival, emphasizing the potential benefit of newborn screening. This contemporary standard-of-care study of patients with pHLH reveals that first-line etoposide-based therapy is better than previously reported, providing a benchmark for novel treatment regimes.

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitäts-Kinderspital Zürich Switzerland (CH) Universitätsklinikum Münster Germany (DE) Schneider Children's Medical Center Israel (IL) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Rigshospitalet Denmark (DK) Cincinnati Children's Hospital Medical Center United States (USA) (US) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Universitätsklinikum Ulm Germany (DE) St. Jude Children’s Research Hospital United States (USA) (US) IiSGM / Instituto de Investigación Sanitaria Gregorio Marañón Spain (ES) Medical College of Wisconsin (MCW) United States (USA) (US) IWK Health Centre Canada (CA) Motol University Hospital / Fakultní nemocnice v Motole Czech Republic (CZ) Universität Bielefeld Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Göttingen Germany (DE) Klinikum Kassel GmbH Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Universitätsklinikum Mannheim Germany (DE) Universitätsklinikum Tübingen Germany (DE) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Karolinska Institute Sweden (SE) Universitätsklinikum Freiburg Germany (DE)

How to cite

APA:

Böhm, S., Wustrau, K., Pachlopnik Schmid, J., Prader, S., Ahlmann, M., Yacobovich, J.,... Ehl, S. (2024). Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation. Blood. https://dx.doi.org/10.1182/blood.2023022281

MLA:

Böhm, Svea, et al. "Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation." Blood (2024).

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