QuantiFERON‐TB Gold can help clinicians in the diagnosis of haemophagocytic lymphohistiocytosis

Merli, Pietro; Gentile, Leonarda; Quagliarella, Francesco; Cefalo, Maria Giuseppina; Strocchio, Luisa; Locatelli, Franco; Russo, Cristina; Gaspari, Stefania

doi:10.1111/bjh.17001

Cited by 6 publications

(7 citation statements)

References 10 publications

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“…Several groups have observed that IFN‐γ is essential for the development of HLH 18,22,41–43 ; moreover, other studies have found that levels of IFN‐γ and/or CXCL9 are markedly elevated in animal models and patients with HLH. Indeed, measurement of IFN‐γ in PB using a commercial IFN‐γ release assay (e.g., quantiferon‐TB) may help to diagnose HLH 44 . In a mouse model, IFN‐γ was found to be essential for the development of HLH‐like pathology 42 .…”

Section: Ifn‐γ In Hlhmentioning

confidence: 99%

The role of interferon‐gamma and its signaling pathway in pediatric hematological disorders

Merli

Quintarelli

Strocchio

et al. 2021

Pediatric Blood & Cancer

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Interferon‐gamma (IFN‐γ) plays a key role in the pathophysiology of hemophagocytic lymphohistiocytosis (HLH), and available evidence also points to a role in other conditions, including aplastic anemia (AA) and graft failure following allogeneic hematopoietic stem cell transplantation. Recently, the therapeutic potential of IFN‐γ inhibition has been documented; emapalumab, an anti‐IFN‐γ monoclonal antibody, has been approved in the United States for treatment of primary HLH that is refractory, recurrent or progressive, or in patients with intolerance to conventional therapy. Moreover, ruxolitinib, an inhibitor of JAK/STAT intracellular signaling, is currently being investigated for treating HLH. In AA, IFN‐γ inhibits hematopoiesis by disrupting the interaction between thrombopoietin and its receptor, c‐MPL. Eltrombopag, a small‐molecule agonist of c‐MPL, acts at a different binding site to IFN‐γ and is thus able to circumvent its inhibitory effects. Ongoing trials will elucidate the role of IFN‐γ neutralization in secondary HLH and future studies could explore this strategy in controlling hyperinflammation due to CAR T cells.

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Section: Ifn‐γ In Hlhmentioning

confidence: 99%

The role of interferon‐gamma and its signaling pathway in pediatric hematological disorders

Merli

Quintarelli

Strocchio

et al. 2021

Pediatric Blood & Cancer

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“…30 Moreover, previous studies found that indeterminate results of QFT-GIT (only one tube with specific peptides designed to stimulate CD4+ cells) or QFT Plus [two different tubes with specific peptides designed to stimulate CD4+ cells (TB1) and both CD4+ and CD8+ cells (TB2)], because of a high level of IFN-γ in the negative control tube, were obtained from patients with HLH, a not-so-rare (malignancy-associated HLH may occur in up to 1% of patients with HMs), lifethreatening, excessively inflammatory syndrome characterized by hyperactivation of macrophage and T-cells and causing fever, coagulopathy, cytopenia and liver function impairment, making it possible that QFT tests may help the diagnosis of HLH clinically, particularly in paediatric patients with primary HLH. 31,32 Our results together with these provide a fresh look at the role of high IFN-γ level of negative control result in the interpretation of QFT-GIT and the evaluation of progression to active TB in patients with HMs.…”

Section: Discussionmentioning

confidence: 67%

Features of indeterminate results of QuantiFERON-TB Gold In-Tube test in patients with haematological malignancies

Huang

Teng

et al. 2021

Therapeutic Advances in Hematology

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Background and aims: The application of QuantiFERON-TB Gold in-Tube (QFT-GIT) in patients with haematological malignancies (HMs) has not been well studied. Therefore, we aimed to investigate the features of patients with HMs whose QFT-GIT results were indeterminate. Methods: This study enrolled patients with HMs for the analysis of QFT-GIT tests and additional 2-year follow-up. The characteristics and predictors of QFT-GIT indeterminate results were identified. Mycobacterium tuberculosis (TB) incidence rate (IR) and incidence rate ratio (IRR) were also investigated. Results: Of 89 participants, 27 (30.3%) had QFT-GIT indeterminate results. The QFT-GIT indeterminate patients were characterized with the diagnosis of leukaemia (63.0% versus 32.3%, p = 0.044), abnormal white blood count (WBC) (88.9% versus 14.5%, p = 0.001), abnormal lymphocyte percentage (81.5% versus 14.5%, p = 0.001) and lower lymphocyte count (×109/l) (0.5 versus 2.2, p = 0.000) when compared with those with determinate results. Meanwhile, abnormal WBC [odds ratios (OR): 15.18, p = 0.003] and lymphocyte percentage (OR: 6.90, p = 0.033) were predictors of indeterminate results. One patient with the QFT-GIT indeterminate status and high interferon-γ level of negative control result developed active TB with a TB IR of 18.5 per 1000 person-years and an IRR of 0.1 (95% confidence interval, 0.01–0.71) when compared with positive QFT-GIT patients without prophylaxis treatment. Conclusion: Abnormal ranges of WBC and lymphocyte differential count percentage were independent predictors useful to determine the optimal timing of implementing QFT-GIT test in patients with HMs.

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“…Recently, Merli et al described the use of an easy and widely available test, QuantiFeron-TB Gold (QFT-G) to detect patients with primary HLH. 36 As described before, IFN-γ play a key role in the pathogenesis of primary HLH (1, 10, 37). Merli et al showed that QFT-G test results were intermediate in all children with primary HLH.…”

mentioning

confidence: 84%

“…This was explained by the high serum IFN-γ levels, which characterized patients with primary HLH. 36 Even though some diseases, such as SLE and dermatomyositis may also present with high serum IFN-γ levels, this simple test may be a good diagnostic test to identify patients in whom a genetic mutation is suspected.…”

mentioning

confidence: 99%

Clinical Management of Relapsed/Refractory Hemophagocytic Lymphohistiocytosis in Adult Patients: A Review of Current Strategies and Emerging Therapies

Yıldız¹,

Bailly²,

Neste³

et al. 2021

TCRM

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Introduction Haemophagocytic lymphohistiocytosis (HLH) is a severe disorder with high mortality. The aim of this review is to update clinical management of relapsed/refractory HLH in adults, with a focus on current and new therapies. Methods We searched relevant articles in Embase and PUBMED with the MESH term “hemophagocytic lymphohistiocytosis; refractory; relapsing; adult.” Results One hundred eight papers were found; of these, 22 were retained for this review. The treatment of HLH in adult is based on the HLH-94 regimen. The response rate is lower than in pediatric patients, and 20–30% are refractory to this therapy. DEP regimen and allogenic hematopoietic stem cell transplantation (HSCT) are associated with complete response and partial response in 27% and 49.2%, respectively. However, many patients fail to achieve a stable condition before HSCT, and mortality is higher in them. New drugs have been developed, such as emapalumab, ruxolitinib, and alemtuzumab, and they may be used as bridges to the curative HSCT. They are relatively well tolerated and have few or mild side effects. With these agents, the rate of partial response ranges from 14.2% to 100%, while the rate of complete response is highly variable according to study and medication used. The number of patients who achieved HSCT ranged from 44.8% to 77%, with a survival rate of 55.9% to 100%. However, the populations in these studies are mainly composed of mixed-age patients (pediatric and adult patients), and studies including only adult patients are scarce. Conclusion Relapsed or refractory HLH in adult patients is associated with poor outcome, and consolidation with HSCT may be required in some cases. Mortality related to HSCT is mainly due to active HLH disease before HSCT and post HSCT complications. New drugs, such as empalumab, ruxolitinib, and alemtuzumab are interesting since these agents may be used as bridges to HSCT with increases in the numbers of patients proceeding to HSCT and survival rate.

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QuantiFERON‐TB Gold can help clinicians in the diagnosis of haemophagocytic lymphohistiocytosis

Abstract: CKG helped write the paper. S helped analyzed the genetic data. MGS provided patient history and clinical information. IR provided patient history and clinical information. HJM analyzed the data and wrote the paper.

Cited by 6 publications

References 10 publications

The role of interferon‐gamma and its signaling pathway in pediatric hematological disorders

The role of interferon‐gamma and its signaling pathway in pediatric hematological disorders

Features of indeterminate results of QuantiFERON-TB Gold In-Tube test in patients with haematological malignancies

Clinical Management of Relapsed/Refractory Hemophagocytic Lymphohistiocytosis in Adult Patients: A Review of Current Strategies and Emerging Therapies

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