Pathogenesis of Hemophagocytic Lymphohistiocytosis

Filipovich, Alexandra H.; Chandrakasan, Shanmuganathan

doi:10.1016/j.hoc.2015.06.007

Cited by 86 publications

(53 citation statements)

References 15 publications

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“…Therefore, initiation of empiric therapy must be prompt and is often necessary before confirmatory genetic and diagnostic studies have resulted (12). Empiric therapy for FHL focuses on removing the infectious trigger in combination with cytoablative chemotherapy and broad-spectrum immunosuppression targeting T cell activation and proliferation (16, 17) (Level of evidence 1c). The first international treatment protocol for FHL was organized by the Histiocyte Society in 1994 (HLH-94) and consisted of an 8-week induction therapy using dexamethasone, etoposide, and intrathecal methotrexate (the latter of which is used for CNS involvement only) resulting in survival of 51% of FHL patients with a median follow-up of 3.1 years, and considered as a therapeutic bridge to HCT (17).…”

Section: Treatmentmentioning

confidence: 99%

“…Although FHL-related induction therapies can lead to disease remission, relapses in the hyperinflammatory response is exceedingly common making HCT the only curative treatment (12). HCT for FHL is most effective when patients have achieved complete remission in disease activity prior to initiation of the conditioning therapy for HCT (16, 20). Therefore, HLA typing should be initiated early in the course of treatment to ensure HCT can be initiated as quickly as possible once disease remission is achieved because of the high risk for disease recurrence, ongoing risk of secondary infections, and the long-term risk of leukemia and myelodysplastic syndrome from etoposide (12).…”

Section: Treatmentmentioning

confidence: 99%

“…Reduced intensity conditioning regimens have resulted in improvements in 5-year survival of FHL patients undergoing HCT compared to conventional myeloablative conditioning regimens (20). A full discussion of the complexities in diagnosis and treatment of FHL is outside the scope of this review, and we point interested readers to recent reviews on these topics (12, 13, 16, 21). …”

Section: Treatmentmentioning

confidence: 99%

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Weathering the Storm: Improving Therapeutic Interventions for Cytokine Storm Syndromes by Targeting Disease Pathogenesis

Weaver

Behrens

2017

Curr Treat Options in Rheum

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Opinion Statement Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

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Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Weathering the Storm: Improving Therapeutic Interventions for Cytokine Storm Syndromes by Targeting Disease Pathogenesis

Weaver

Behrens

2017

Curr Treat Options in Rheum

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“…İnfeksiyonların ailesel HLH'yi tetiklemenin yanı sıra akkiz HLH'ye de yol açtığı bilinmektedir. İnfeksiyöz etkenler çoğunlukla bir virüs, özellikle EBV olabilir (11,12) . Çalışmamızda da infeksiyona sekonder olgularımızdan 3'ünde geçirilmekte olan EBV belirlendi.…”

Section: Discussionunclassified

“…Günlük yineleyen ve persistan ateş erken bir bulgu olması dolayısıyla her yaş grubu hasta için önemlidir ve özellikle çocuk sağlığı ve hastalıkları uzmanlarının tanı koyması için her zaman bir baş-langıç noktası oluşturur (2,11) . Ferritin düzeyinin 500 mg/dl üzerinde olması tanı kriteri olarak kabul görürken, aynı zamanda tanıda 2000 mg/dl üzerin-deki değerlerin kötü prognozu işaret ettiği gösteril-miştir (4,9,15) .…”

Section: Discussionunclassified

Hemophagocytic Lymphohistiocytosis Single Center Experience

Töret¹,

Ay²,

Karapınar³

et al. 2018

BUCH

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ÖZAmaç: Hemofagositk Lenfohistiyositoz (HLH) sitokin fırtınası sonucu gelişen kontrolsüz hemofagositozun görüldüğü nadir bir hastalıktır. Ateş, splenomegali, hiperferritinemi ve sitopeni sendromun en iyi bilinen bulgularıdır. Ailesel (primer) tetikleyen altta yatan bir hastalığın olduğu akkiz (sekonder) HLH olmak üzere sınıflandırılır. Akkiz nedenler arasında infeksiyonlar, maliniteler, otoimmün hastalıklar ve bazı metabolik hastalıklar sayılabilir. Tedavinin temelini immünsüpresyon ve apopitotik kemoterapi oluşturmaktadır. Ailesel HLH veya ailesel olmayan persistan HLH'de küratif tedavi seçeneği kök hücre naklidir. Yöntem: Kliniğimizde tanı alan ve tedavi edilen 46 HLH olgusunu tanı kriterleri ve tedavi planları açısından retrospektif olarak irdeledik. Bulgular: Tanı kriteri olarak ateşin yanı sıra hiperferritinemi ve hemofagositozun en sık kaydedilen tanı kriterleri olduklarını belirledik. Olguların %46'sı dekzametazon, siklosporin A (CsA) ve etoposidden oluşan HLH-2004 tedavi kılavuzundaki üçlü tedaviye gereksinim duyduğunu saptadık. Sonuç: Sonuç olarak, hektik-persistan ateşle başvuran çocuklarda HLH aramanın erken tanı ve tedavi için önemli olduğunu düşünüyoruz.Anahtar kelimeler: Ateş, çocukluk çağı, hemofagositik lenfohistiyositoz, tedavi ABSTRACT Objective: Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder which develops as a result of cytokine storm syndrome due to uncontrolled hemophagocytosis. Fever, splenomegaly, hyperferritinemia and cytopenias are well-known clinical manifestations of the disease. Hemophagocytic lymphohistiocytosis is classified as familial (primary/genetic) and secondary (acquired) where an underlying disease is present. Among acquired causes infections, malignancies, autoimmune disorders and some metabolic disorders may be enumerated. The basis of treatment for HLH is immunosuppression and apoptotic chemotherapy. The curative treatment alternative for familial or non-familial persistent HLH is stem cell transplantation. Methods: We retrospectively analyzed 46 HLH cases diagnosed and treated in our clinic in terms of diagnostic criteria and treatment plans. Results: We identified the most frequently recorded diagnostic criteria as fever, hemophagocytosis and hyperferritinemia. We found that 46% of the cases needed treatment consisting of dexamethasone, cyclosporine (CsA) and etoposide according to HLH-2004 treatment guideline. Conclusion: As a result, we think that search for HLH in children who presented with hectic-persistent fever is important for the early diagnosis and treatment of HLH.

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