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

Merli, Pietro; Quintarelli, Concetta; Strocchio, Luisa; Locatelli, Franco

doi:10.1002/pbc.28900

Cited by 26 publications

(18 citation statements)

References 101 publications

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“…We have identified several serum biomarkers that can be used for an early diagnosis, 27,36 possibly allowing for preemptive interventions. In particular, since IFNg seems to play a central role in GF (which resembles HLH features), 37 emapalumab, a novel IFNg-neutralizing monoclonal antibody proven effective in resistant/relapsing HLH, 38 is being investigated as a preemptive treatment of GF in both malignant and nonmalignant settings [NCT04731298]. Since during the study period, busulfan, used for conditioning of patients with red blood cell disorders and HLH, was adjusted to maintain concentration at a steady state (Css) between 600 and 900 ng/mL, one may argue that increasing the target to 800-1050 ng/mL, as suggested by Bartelink and colleagues, 39 might result into higher engraftment rate.…”

Section: Discussionmentioning

confidence: 99%

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

et al. 2022

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Several non-malignant disorders (NMDs), either inherited or acquired, can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2012 and April 2020, 70 consecutive children affected by primary immunodeficiencies, inherited/acquired bone marrow failure syndromes, red blood cell disorders or metabolic diseases, lacking a fully-matched donor or requiring urgent transplantation, underwent TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative as part of a prospective study (#NCT01810120). Median age at transplant was 3.5 years (range 0.3-16.1); median time from diagnosis to transplant was 10.5 months (2.7 for SCID patients). Primary engraftment was obtained in 51 patients, while 19 and 2 patients experienced either primary or secondary graft failure (GF), the overall incidence of this complication being 30.4%. Most GFs were observed in children with disease at risk for this complication (e.g., aplastic anemia, thalassemia). All but 5 patients experiencing GF were successfully retransplanted. Six patients died of infectious complications (4 had active/recent infections at time of HSCT), the cumulative incidence of transplant-related mortality (TRM) being 8.5%. Cumulative incidence of grade I-II acute GvHD was 14.4% (no patient developed grade III-IV acute GVHD). Only one patient at risk developed mild chronic GvHD. With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In conclusion, TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment for children with NMDs. Prompt donor availability, low incidence of GvHD and TRM make this strategy an attractive option in NMDs patients.

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Section: Discussionmentioning

confidence: 99%

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

et al. 2022

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“…Tc or NK cells cannot remove activated macrophages, giving rise to enhanced macrophage activity and raising various cytokines levels. 31 The present case had normal Tc cells and abnormally low NK cell activity/count. As a subset of whole innate lymphoid cells, NK cells are currently defined as effector cells that are similar to Tc cells and exert natural cytotoxicity against primary tumor cells and metastasis by inhibiting proliferation, migration, and colonization to distant tissues.…”

Section: Discussionmentioning

confidence: 44%

Reactive Hemophagocytic Lymphohistiocytosis Secondary to Ovarian Adenocarcinoma: A Rare Case Report

Li¹,

Zhu²,

Li³

et al. 2022

JIR

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Background Hemophagocytic lymphohistiocytosis (HLH), a syndrome of immune hyperactivation and abnormal regulation that causes life-threatening inflammation, is mainly characterized by fever, hepatosplenomegaly, cytopenia, and other symptoms. Reactive HLH (rHLH) is typically secondary to immune deregulation caused by underlying rheumatologic, infectious, or malignant conditions. Malignancy-associated HLH (M-HLH) continues to be a critical health problem worldwide. Most malignancies associated with HLH are hematologic tumors, and M-HLH in non-hematologic tumors very rarely occurs. Case Report A 34-year-old Chinese woman had a history of persistent fever, acute dizziness, and bicytopenia. She was found to have developed bilateral ovarian cancer. Additional tests showed splenomegaly, hemophagocytes in the bone marrow, low natural killer activity, and hyperferritinemia, which met the diagnostic criteria put forth in the Histiocyte Society HLH-2004. The patient was treated with correcting anemia, increased platelets, and glucocorticoid therapy but showed no response. She progressively deteriorated and died 55 days later. Conclusion Hemophagocytic lymphohistiocytosis related to a solid tumor is extremely rare. To the best of the authors’ knowledge, the present case was the first to report rHLH secondary to ovarian adenocarcinoma. It is very significant for a better understanding of the disease mechanisms of HLH and should attract the attention of hematologists and other clinicians as the condition progresses and the cost of treating it increases.

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“…In particular, the levels of pro-inflammatory cytokines were shown to be significantly lower in COVID-19 patients than in critically ill patients with ARDS or sepsis [ 23 , 26 ]. Moreover, the profile of cytokine changes depends on the specific disease, with IFN-γ playing the key role in primary HLH [ 71 ], IL-18 in MAS [ 72 ], and IL-6 in CRS [ 73 ]. Even though it is caused by viral infections, the cytokine storm is characterized by different cytokine signatures in the cases of MERS [ 74 , 75 , 76 ], SARS [ 77 , 78 ], and influenza [ 20 , 79 , 80 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy

Lebedeva

Molodtsov

Anisimova

et al. 2022

IJMS

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Coronavirus disease 2019 (COVID-19) is characterized by immune activation in response to viral spread, in severe cases leading to the development of cytokine storm syndrome (CSS) and increased mortality. Despite its importance in prognosis, the pathophysiological mechanisms of CSS in COVID-19 remain to be defined. Towards this goal, we analyzed cytokine profiles and their interrelation in regard to anti-cytokine treatment with tocilizumab in 98 hospitalized patients with COVID-19. We performed a multiplex measurement of 41 circulating cytokines in the plasma of patients on admission and 3–5 days after, during the follow-up. Then we analyzed the patient groups separated in two ways: according to the clusterization of their blood cytokines and based on the administration of tocilizumab therapy. Patients with and without CSS formed distinct clusters according to their cytokine concentration changes. However, the tocilizumab therapy, administered based on the standard clinical and laboratory criteria, did not fully correspond to those clusters of CSS. Furthermore, among all cytokines, IL-6, IL-1RA, IL-10, and G-CSF demonstrated the most prominent differences between patients with and without clinical endpoints, while only IL-1RA was prognostically significant in both groups of patients with and without tocilizumab therapy, decreasing in the former and increasing in the latter during the follow-up period. Thus, CSS in COVID-19, characterized by a correlated release of multiple cytokines, does not fully correspond to the standard parameters of disease severity. Analysis of the cytokine signature, including the IL-1RA level in addition to standard clinical and laboratory parameters may be useful to define the onset of a cytokine storm in COVID-19 as well as the indications for anti-cytokine therapy.

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

Cited by 26 publications

References 101 publications

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

Reactive Hemophagocytic Lymphohistiocytosis Secondary to Ovarian Adenocarcinoma: A Rare Case Report

Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy

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