Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
37992218
DOI
10.1182/blood.2023022281
PII: S0006-4971(23)14448-X
Knihovny.cz E-resources
- MeSH
- Etoposide therapeutic use MeSH
- Humans MeSH
- Lymphohistiocytosis, Hemophagocytic * drug therapy diagnosis MeSH
- Lymphoproliferative Disorders * etiology MeSH
- Infant, Newborn MeSH
- Hematopoietic Stem Cell Transplantation * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Etoposide MeSH
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.
Center for Pediatric and Adolescent Medicine Frankfurt University Hospital Frankfurt Germany
Clinic for Children and Adolescents University Clinic Erlangen Erlangen Germany
Department of Pediatrics and Adolescent Medicine Mannheim University Hospital Mannheim Germany
Department of Pediatrics University Medical Center Ulm Ulm Germany
Department of Pediatrics University Medical Center Utrecht Utrecht The Netherlands
Division of Pediatric Hematology and Oncology Göttingen University Medical Center Göttingen Germany
Medical Faculty Martin Luther University of Halle Wittenberg Halle Germany
Paediatric Haematology Oncology IWK Health Centre Halifax NS Canada
Pediatric Hematology and Oncology Hannover Medical School Hannover Germany
Pediatric Hematooncology University Children's Hospital Giessen Giessen Germany
Pediatric Immunology University Children's Hospital Zurich Eleonorenstiftung Zürich Switzerland
Princess Máxima Center Utrecht The Netherlands
Schneider Children's Medical Center of Israel Petah Tikva Israel
Tel Aviv Medical School Tel Aviv University Tel Aviv Israel
Theme of Children's Health Karolinska University Hospital Stockholm Sweden
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