HLH-94: A treatment protocol for hemophagocytic lymphohistiocytosis

Henter, Jan‐Inge; Aricò, Maurizio; Egeler, R. Maarten; Elinder, Göran; Favara, Blaise E.; Filipovich, Alexandra H.; Gadner, Helmut; Imashuku, Shinsaku; Janka‐Schaub, Gritta; Komp, Diane M.; Ladisch, Stephan; Webb, David

doi:10.1002/(sici)1096-911x(199705)28:5<342::aid-mpo3>3.0.co;2-h

Cited by 446 publications

(181 citation statements)

References 28 publications

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“…We analysed the data regarding underlying disease (or triggering factors), clinical characteristics, as well as outcome for 96 patients younger than 1 year of age who were registered in the Kyoto HLH study centre during the period of 1986 to 2002, including patients in the international HLH-94 protocol study [13]. The cohort consisted of 49 males and 47 females.…”

Section: Methodsmentioning

confidence: 99%

Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients

et al. 2005

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Section: Methodsmentioning

confidence: 99%

Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients

et al. 2005

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“…Two patients were treated according to the HLH-94 protocol because they attended our medical center in 2003 and 2005, respectively. The HLH-94 protocol consisted of initial therapy with dexamethasone 10 mg/m 2 per day and etoposide 150 mg/m 2 twice a week, followed by intravenous pulses of cyclosporin and dexamethasone to maintain a stable disease status [13]. The HLH-2004 protocol consisted of initial therapy with dexamethasone 10 mg/m 2 per day, etoposide 150 mg/m 2 twice a week, and cyclosporine followed by dexamethasone intravenous pulses [2].…”

Section: Treatmentsmentioning

confidence: 99%

“…"Treatment-refractory" was defined as clinical deterioration despite appropriate management. HLH protocol was defined as the HLH-94 or HLH-2004 protocol [2,13] and immunosuppressive treatment as treatment with an immunosuppressive agent only.…”

Section: Treatmentsmentioning

confidence: 99%

Clinical features of adult patients with secondary hemophagocytic lymphohistiocytosis from causes other than lymphoma: an analysis of treatment outcome and prognostic factors

et al. 2011

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Although hemophagocytic syndrome (HS) featuring secondary hemophagocytic lymphohistiocytosis (HLH) has a grave prognosis, little is known about the natural course of the disease. Patients who showed the clinical features of HLH as well as tissue-proven hemophagocytosis when seen at Asan Medical Center between 1999 and 2010 were included in this analysis. Patients with proven lymphoma were excluded. The median age of our 23 study patients was 49 years. Epstein-Barr virus was suspected to have caused HS in 16 (70%) patients and hepatitis A virus in one patient. Twenty-two patients were treated, 13 according to the HLH protocol and nine using immunosuppressive agents such as corticosteroid and/or cyclosporine. Five patients undertook allogeneic hematopoietic cell transplantation (HCT) during their treatment-dependent relapse (n = 4) or responsive status (n = 1). After the median follow-up of 180 days, 17 (74%) died and six (26%) were alive. The median time from initial presentation until death was 41 days among those patients who died. The serum fibrinogen level ≥166 mg/dL determined at the initial visit was significantly associated with the survival time according to univariate analysis. The low histiocyte proportion in bone marrow and early initiation of treatment tended to correlate with a favorable outcome. On multivariate analysis, serum fibrinogen ≥166 mg/dL (hazard ratio, 0.175, P = 0.018) was an independent clinical factor for determining the patient survival time. Despite appropriate patient management, the outcome of HS featuring HLH was grave. The serum fibrinogen level at the initial presentation was significant, and selected patients obtained some benefit from allogeneic HCT.

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“…Brain MRI with T2 intensity revealed spotty highdensity lesions in the white matter of the cerebrum, basal nuclei and cerebellum, which were thought to be central nervous system (CNS) involvements of HLH. He received chemotherapy according to the HLH-94 protocol, which consisted of dexamethazone, etoposide and cyclosporin A [9]. He subsequently underwent unrelated cord blood stem cell transplantation (SCT).…”

Section: Case Reportmentioning

confidence: 99%

Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: a case report

et al. 2006

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A 44-day-old male infant with familial hemophagocytic lymphohistiocytosis (FHL) associated with the MUNC13-4 mutation is reported. He presented with fever and poor feeding, lymphocytosis with thrombocytopenia and CSF pleocytosis without virological explanation. On the basis of progressive hyperferritinemia (1323 ng/ml), anemia (hemoglobin: 5.2 g/dl), hypertriglyceridemia (547 mg/dl) and increased LDH (1063 IU/l) with hemophagocytosis in the bone marrow, hemophagocytic lymphohistiocytosis was diagnosed. He showed a good response to corticosteroid therapy and the disease was stable for more than 5 months. Thereafter, he suffered from central nervous system complications, and successfully underwent unrelated cord blood stem cell transplantation. A remission was observed for more than 2 years, with mild mental retardation. Genetic analysis revealed that he had a compound heterozygous mutation of MUNC13-4; namely a novel 2163G>A mutation resulting in W721X, and 754-1G>C resulting in a premature stop codon in this gene. Western blot analysis showed the complete loss of the MUNC13-4 protein, whereas other molecules associated with the SNARE systems were detected at normal levels. Conclusion. FHL may have a broad clinical spectrum, and further analysis on its phenotype-genotype association is required to establish an appropriate treatment strategy, including immunochemotherapy and stem cell transplantation in the future.

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HLH-94: A treatment protocol for hemophagocytic lymphohistiocytosis

Cited by 446 publications

References 28 publications

Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients

Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 96 patients

Clinical features of adult patients with secondary hemophagocytic lymphohistiocytosis from causes other than lymphoma: an analysis of treatment outcome and prognostic factors

Familial hemophagocytic lymphohistiocytosis with the MUNC13-4 mutation: a case report

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