Identification of New Soluble Factors Correlated With the Development of Graft Failure After Haploidentical Hematopoietic Stem Cell Transplantation

Strocchio, Luisa; Bufalo, Francesca Del; Algeri, Mattia; Pagliara, Daria; Arnone, Claudia Manuela; Angelis, Biagio De; Quintarelli, Concetta; Locatelli, Franco; Merli, Pietro; Caruana, Ignazio

doi:10.3389/fimmu.2020.613644

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…The incidence of GF we observed is higher than that reported after T-replete haploHSCT with posttransplant cyclophosphamide (PT/Cy), 35 as expected after the removal of ab T cells that may counterbalance the lytic effect displayed by recipient lymphocytes against donor cells. 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].…”

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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“…The level of IFN-γ before HCT may influence the transplantation outcome ( 27 - 29 ). Higher levels of IFN-γ may indicate a more severe HLH disease with more intense inflammatory reactions and organ dysfunction.…”

Section: International Multidisciplinary Team (Imdt) Discussionmentioning

confidence: 99%

Case report: emapalumab treatment for a pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patient with cytokine storm enabling allogeneic hematopoietic cell transplantation

Jia,

Chen,

Luo

et al. 2024

Transl Pediatr

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Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by excessive immune activation and inflammatory response. Conventional immunotherapy and molecular targeted drugs demonstrate varying efficacy. Cytokine storm, the primary pathogenic mechanism of HLH, is driven by interferon-gamma (IFN-γ), interleukin (IL)-2, IL-18, etc., in which IFN-γ plays a critical role in the development of the disease. Emapalumab, a potent IFN-γ inhibitor, effectively reduces the occurrence of cytokine storms in refractory and relapsed HLH. Case Description A pediatric patient, 5 years old, female, with relapsed and refractory Epstein-Barr virus-associated HLH (EBV-HLH) showed no response to conventional chemotherapy or molecular-targeted drug treatment. However, after treatment with emapalumab, the patient achieved hematological remission. Subsequently, the patient underwent allogeneic hematopoietic cell transplantation (allo-HCT) and remains without HLH to date. Conclusions To the best of our knowledge, this is the first case report using emapalumab to control EBV-HLH before HCT in mainland China. This case highlights the potential efficacy of emapalumab for treating relapsed and refractory EBV-HLH and providing a stable physical status for HCT. Further research is necessary to confirm the efficacy and safety of emapalumab in this setting.

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“…Low concentrations of CCL7 (MCP3), a leucocyte chemoattractant, were also associated with reduced overall survival ( Figure 1H ). Elevated baseline levels have been associated with increased risk of graft failure after allo-HSCT ( 34 ) although the mechanisms that underlie its prognostic impact remain uncertain.…”

Section: Discussionmentioning

confidence: 99%

Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation

Verma,

Croft,

Greenwood

et al. 2024

Front. Immunol.

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Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy although graft versus host disease and relapse remain major complications. We measured the serum protein expression of 92 inflammation-related markers from 49 patients at Day 0 (D0) and 154 patients at Day 14 (D14) following transplantation and related values to subsequent clinical outcomes. Low levels of 7 proteins at D0 were linked to GvHD whilst high levels of 7 proteins were associated with relapse. The concentration of 38 proteins increased over 14 days and higher inflammatory response at D14 was strongly correlated with patient age. A marked increment in protein concentration during this period associated with GvHD but reduced risk of disease relapse, indicating a link with alloreactive immunity. In contrast, patients who demonstrated low dynamic elevation of inflammatory markers during the first 14 days were at increased risk of subsequent disease relapse. Multivariate time-to-event analysis revealed that high CCL23 at D14 was associative of AGvHD, CXCL10 with reduced rate of relapse, and high PD-L1 with reduced overall survival. This work identifies a dynamic pattern of inflammatory biomarkers in the very early post-transplantation period and reveals early protein markers that may help to guide patient management.

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Identification of New Soluble Factors Correlated With the Development of Graft Failure After Haploidentical Hematopoietic Stem Cell Transplantation

Cited by 7 publications

References 48 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

Case report: emapalumab treatment for a pediatric Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patient with cytokine storm enabling allogeneic hematopoietic cell transplantation

Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation

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