ArticleBlood advances2020
Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00426101 (HLH-2004 Treatment Protocol), which is not on this map. Cited by 33 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
HLH-2004 Treatment Protocol
Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).Annals of the rheumatic diseases · 2023Pooled it
- The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).Arthritis & rheumatology (Hoboken, N.J.) · 2023Pooled it
- Prospective Study of Targeted Busulfan-Fludarabine Conditioning for Hematopoietic Stem Cell Transplantation in Genetic Rare Diseases.European journal of haematology · 2026Article
- Early management of hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a systematic literature review.EULAR rheumatology open · 2026Review
- Consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis in the Gulf Cooperation Council: a modified Delphi approach.Frontiers in immunology · 2026Article
- Disseminated mucormycosis leading to a fatal gastrointestinal perforation in a pediatric case of EBV-associated Hemophagocytic lymphohistiocytosis.Medical mycology case reports · 2025Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- Whole-genome sequencing reveals genetic backgrounds in Japanese patients with hemophagocytic lymphohistiocytosis treated with the HLH-2004 protocol.International journal of hematology · 2025Article
- Effect of genetic mutations on outcomes of stem cell transplantation in children with hemophagocytic lymphohistiocytosis.Bone marrow transplantation · 2025Article
- Beyond genotype: challenges in predicting disease risk for carriers of biallelic perforin variants.Blood · 2025Article
- Etiologies and long-term outcome of pediatric hemophagocytic lymphohistiocytosis and macrophage activation syndrome in Taiwan: a single-center retrospective study.Frontiers in immunology · 2025Article
- Chedíak-Higashi Syndrome: Hair-to-toe spectrum.Seminars in pediatric neurology · 2024Review
- A Non-targeted Proteomics Newborn Screening Platform for Inborn Errors of Immunity.Journal of clinical immunology · 2024Article
- Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity.Blood advances · 2024Article
- Early hematopoietic cell transplantation for familial hemophagocytic lymphohistiocytosis in a regional treatment network in Japan.International journal of hematology · 2024Article
- Sequential haplo-identical conditioning transplant regimen for pediatric patients with relapsed or refractory hemophagocytic lymphohistiocytosis.Bone marrow transplantation · 2024Article
- Ruxolitinib-based regimen in children with primary hemophagocytic lymphohistiocytosis.Haematologica · 2024Article
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Etoposide Therapy of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Other Immunomodulatory Treatment for Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
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Authors and funding
16 authors at 12 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P = .035). For children with verified FHL (family history/genetically verified, n = 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n = 53) was significantly lower (52%; 95% CI, 38-65) (P = .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival. This trial was registered at www.clinicaltrials.gov as #NCT00426101.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.