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.

Bielefeld University University Clinic for Pediatrics Evangelisches Klinikum Bethel Bielefeld Germany

Bone Marrow Transplantation and Immune Deficiency Cincinnati Children's Hospital Medical Center Cincinnati OH

Center for Chronic Immunodeficiency Institute for Immunodeficiency Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Center for Pediatric and Adolescent Medicine Frankfurt University Hospital Frankfurt Germany

Center for Pediatric and Adolescent Medicine Pediatric Hematology Oncology University of Mainz Mainz Germany

Center for Pediatrics and Adolescent Medicine Hematology Oncology Heidelberg University Hospital Heidelberg Germany

Clinic for Children and Adolescents Department 1 Hematology Oncology Tübingen University Hospital Tübingen Germany

Clinic for Children and Adolescents University Clinic Erlangen Erlangen Germany

Clinic for Pediatrics and Adolescent Medicine Hematology Oncology Klinikum am Gesundbrunnen Heilbronn Heilbronn Germany

Department of Oncology Pediatric Hematology Clinical Transplantology and Pediatrics Medical University of Warsaw Warsaw Poland

Department of Pediatric Haematology and Oncology University Hospital Motol Prague Prague Czech Republic

Department of Pediatric Hematology and Oncology University Children's Hospital Münster Münster Germany

Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Pediatrics and Adolescent Medicine Mannheim University Hospital Mannheim Germany

Department of Pediatrics and Children's Cancer Research Center Klinikum rechts der Isar Technical University of Munich Munich Germany

Department of Pediatrics University Medical Center Ulm Ulm Germany

Department of Pediatrics University Medical Center Utrecht Utrecht The Netherlands

Department of Women's and Children's Health Childhood Cancer Research Unit Karolinska Institutet Stockholm Sweden

Division of Critical Care Department of Pediatric Medicine St Jude Children's Research Hospital Memphis TN

Division of Immunology and Children's Research Center University Children's Hospital Zürich Zürich Switzerland

Division of Pediatric Hematology and Oncology Faculty of Medicine Department of Pediatrics and Adolescent Medicine University of Freiburg Freiburg Germany

Division of Pediatric Hematology and Oncology Göttingen University Medical Center Göttingen Germany

Division of Pediatric Stem Cell Transplantation and Immunology University Medical Center Eppendorf Hamburg Germany

Immunology Hospital General Universitario and Instituto de Investigación Sanitaria Gregorio Marañón Madrid Spain

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 Hematology and Oncology Psychosomatics and Systemic Diseases Kassel Hospital Kassel Germany

Pediatric Hematology Oncology Blood and Marrow Transplant Division Medical College of Wisconsin Madison WI

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

Blood. 2024 Mar 7;143(10):836-838. doi: 10.1182/blood.2023023123. PubMed

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