Malignancy-associated hemophagocytic lymphohistiocytosis in children: a 10-year experience of a single pediatric hematology center

Huang, Zhizhuo; Jia, Yueping; Zuo, Ying‐Xi; Wu, Jun; Lu, Ai‐Dong; Zhang, Leping

doi:10.1080/16078454.2020.1833505

Cited by 17 publications

(21 citation statements)

References 32 publications

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“…Because of the ambiguity of diagnosis, the incidence might be greater than previously noted. In our study, the incidence of M-HLH in hematologic malignancy patients was 1.9%; however, in other studies, it was up to 8% [ 12 ]. Unrecognized HLH flare-ups could also contribute to some morbidity and mortality.…”

Section: Discussioncontrasting

confidence: 72%

Hemophagocytic Lymphohistiocytosis as Initial Presentation of Malignancy in Pediatric Patients: Rare but Not to Be Ignored

et al. 2021

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It is complicated to establish a consensus on the management and diagnosis of malignancy-triggered hemophagocytic lymphohistiocytosis (M-HLH) in children, as an initial presentation of malignancy is complicated. In this paper, we analyze the clinical characteristics and outcomes of eight pediatric patients in which M-HLH was the initial presentation of malignancy. All patients had hematologic malignancies: three subcutaneous panniculitis-like T-cell lymphomas, two acute lymphoblastic leukemias, two anaplastic large cell lymphomas, and a systemic EBV + T-cell lymphoma of childhood. The incidence rate of M-HLH among leukemia and malignant lymphoma patients in our institution was 1.9%. From the initial diagnosis of HLH, the median time taken to be diagnosed as a malignancy was about 1.3 months. The majority of patients received HLH-targeted immunosuppression and/or etoposide at first. The patients’ clinical response to treatment for HLH and malignancies were varied. Five out of the eight patients died, one of whom died due to HLH-related cerebral edema after the initiation of chemotherapy. The median overall survival was 1.6 years. In order to improve the survival rate, the early detection of M-HLH, rapid screening for malignancy, and complete control of M-HLH with HLH-directed therapy followed by a thorough response monitoring are required.

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Section: Discussioncontrasting

confidence: 72%

Hemophagocytic Lymphohistiocytosis as Initial Presentation of Malignancy in Pediatric Patients: Rare but Not to Be Ignored

et al. 2021

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“…In rheumatic patients, hepatomegaly is part of the diagnostic criteria for AOSD but not part of SLICC or ACR/EULAR diagnostic criteria for SLE. It is unclear what percentage of hepatomegaly is truly due to mHLH presentation as opposed to underlying malignancy, but multiple pediatric and adult population studies of HLH have shown hepatomegaly to be a key component of the disease [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

The spectrum of hemophagocytic lymphohistiocytosis: a retrospective study comparing adult macrophage activation syndrome to malignancy-associated hemophagocytic lymphohistiocytosis

2022

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Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening inflammatory syndrome that can be triggered by autoimmune diseases, malignancy, or infection. In rheumatologic patients, sHLH is referred to as macrophage activation syndrome (MAS). Differentiating between triggers is important for prompt treatment and prognosis. Data comparing subsets of sHLH are limited due to the rarity of this disease. We aim to explore differences in clinical features that may differentiate MAS from malignancy-associated HLH (mHLH) patients . We conducted a single-center retrospective study assessing clinical characteristics, laboratory parameters, treatment regimens and outcomes in 34 patients with sHLH over a 16 year period. We compared patients with MAS to those with mHLH. Hepatomegaly was not present in the MAS group but was present in the mHLH group (0 vs. 25%, p = 0.024). MAS patients had on average nearly double the concentration of platelets at 50.0 (IQR: 31.0–78.0 Kµ/L) vs. 29.0 Kµ/L (IQR: 14.0–37.5 Kµ/L), p = 0.003. Soluble IL-2R concentrations were four times lower in the MAS group with a median soluble IL-2R concentration of 6814.5 kU/L (IQR: 2101–2610 kU/L) vs. 27972.0 kU/L (IQR: 12,820–151,650 kU/L), p = 0.010. The MAS group fared better overall than the mHLH group but was not statistically significant (mortality 22 vs. 44%, p = 0.18). MAS and mHLH patients exhibited different laboratory parameters and clinical features, most notably differences in platelet counts, soluble IL-2R concentration and hepatomegaly, which may help differentiate these conditions early in their course.

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“…HLA Class II plays a key role in EBV infection because it is required for the initial stages of viral infection of B cells, which are the sites of viral latency. Specific HLA Class II alleles are associated with increased or decreased susceptibility to EBV infection, which is also associated with their ability to bind to EBV gp42 9 . In contrast, although HLA Class I is not required for viral entry, polymorphisms in HLA Class I alleles are associated with the development and severity of infectious mononucleosis 10 .…”

Section: Discussionmentioning

confidence: 99%

“…The mortality rate of EBV‐associated HLH (EBV‐HLH) in children can be as high as 56%. In Asian countries, the prognosis of adults with EBV‐HLH is much worse: a previous study that included 61 patients of EBV‐HLH reported a 1‐year overall survival (OS) rate of only 25% 8,9 . CAEBV is the most common EBV infection in East Asia: in patients with EBV‐associated T/NK cell lymphoid tissue appreciation disease (LPD), which is associated with CAEBV, the survival rate is 44%.…”

Section: Introductionmentioning

confidence: 99%

“…In Asian countries, the prognosis of adults with EBV‐HLH is much worse: a previous study that included 61 patients of EBV‐HLH reported a 1‐year overall survival (OS) rate of only 25%. 8 , 9 CAEBV is the most common EBV infection in East Asia: in patients with EBV‐associated T/NK cell lymphoid tissue appreciation disease (LPD), which is associated with CAEBV, the survival rate is 44%. Currently, effective preventive measures against EBV infection do not exist, and available treatments for CAEBV and EBV‐HLH, mostly with rituximab, antiviral agents, and chemotherapeutic agents, remain unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

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EBV protection‐ and susceptibility‐related HLA alleles and EBV status in the Chinese population: A single‐center study

Suolitiken

Wang

Jin

et al. 2022

Immunity Inflam & Disease

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Background Although most adults are infected by Epstein‐Barr virus (EBV), some patients develop highly lethal diseases associated with EBV infection, including EBV‐hemophagocytic lymphohistiocytosis (EBV‐HLH), chronic active EBV infections (CAEBV), and lymphoma, the pathogeneses of which remain to be investigated. The human leukocyte antigen (HLA) complex may be associated with the viral infection pathway, and, therefore, HLA alleles may be associated with EBV‐related diseases and subpopulations of infected cells, studies related to EBV‐associated diseases, and subpopulations of infected cells that were conducted in China are scarce. Methods In this study, we analyzed the high‐resolution HLA genotypes of 269 patients with EBV‐associated diseases and 213 EBV‐seronegative hematopoietic stem cell donors using PCR‐SBT assay and elucidated the associations of HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1 alleles with EBV‐associated diseases in the Chinese population, Benjamini–Hochberg correction to adjust for multiple testing. HLA genotypes were also analyzed in patients with EBV‐associated diseases showing EBV‐infected lymphocyte subpopulations. Results We found that individuals carrying the following alleles showed the following levels of risks: HLA‐DRB1*11 allele, reduced risk of EBV‐related disease (OR [odds ratio]: 0.56; 95% confidence interval [95% CI]: 0.32–0.99; p < .05; Adjust p = .71); HLA‐DQB1*06:02 allele, reduced risk (OR: 0.5699; 95% CI: 0.3486–0.9317; p < .05; Adjust p = .57); and HLA‐B*15:01 allele, increased risk (OR: 1.763; 95% CI: 0.3486–0.9317; p < .05; Adjust p = .57). Patients with EBV‐associated diseases showing the B*15:01 genotype had a higher risk of T‐cell, NK‐cell, and multicell infections than those with other genotype subgroups. Conclusions These findings highlight the importance of HLA genotype for assessing EBV infectivity.

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Malignancy-associated hemophagocytic lymphohistiocytosis in children: a 10-year experience of a single pediatric hematology center

Cited by 17 publications

References 32 publications

Hemophagocytic Lymphohistiocytosis as Initial Presentation of Malignancy in Pediatric Patients: Rare but Not to Be Ignored

Hemophagocytic Lymphohistiocytosis as Initial Presentation of Malignancy in Pediatric Patients: Rare but Not to Be Ignored

The spectrum of hemophagocytic lymphohistiocytosis: a retrospective study comparing adult macrophage activation syndrome to malignancy-associated hemophagocytic lymphohistiocytosis

EBV protection‐ and susceptibility‐related HLA alleles and EBV status in the Chinese population: A single‐center study

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