Prognostic values of increased B7 family proteins in haploidentical hematopoietic stem cell transplantation patients with aGVHD

Zhou, Biqi; Wang, Tanzhen; Lei, Lei; Lu, Yutong; Zhang, Li; Tang, Xiaowen; Qiu, Huiying; Sun, Aining; Zhang, Xueguang; Xu, Yang; Wu, Depei

doi:10.1007/s12185-019-02605-1

Cited by 7 publications

(8 citation statements)

References 47 publications

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“…Induction chemotherapy and consolidation chemotherapy in adolescent/adult patients were performed as previously described 17 . Details of the myeloablative allo‐HSCT procedure were described previously 18–20 . Humanized chimeric antigen receptor (CAR) T‐cell generation and infusion were performed as previously described 21 .…”

Section: Methodsmentioning

confidence: 99%

The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A‐PBX1: A 10‐year retrospective study

et al. 2021

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The clinical outcomes and genomic features of E2A‐PBX1 (TCF3‐PBX1)‐positive B‐cell acute lymphoblastic leukemia (B‐ALL) patients remain unclear. A total of 137 patients carrying E2A‐PBX1 among 3164 B‐ALL patients between 2009 and 2019 were retrospectively analyzed. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Age [DFS, p = 0.037; cumulative incidence of relapse (CIR), p = 0.005] and the level of minimal residual disease (MRD) after induction chemotherapy (OS, p = 0.020; DFS, p = 0.002; CIR, p = 0.006) were independent risk factors. In adolescents/adults, allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1) significantly improved the 5‐year prognosis (OS, p < 0.001; DFS, p < 0.001; CIR, p < 0.001). Haploidentical HSCT decreased the CIR compared with human leukocyte antigen‐matched HSCT in adolescents/adults (p = 0.017). Mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, nerve growth factor (NGF) signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children. Patients with multiple subclones at diagnosis tended to have unfavorable 3‐year prognoses (DFS, p = 0.010; CIR, p = 0.021). Leukemia clones with DNA repair gene mutations showed aggressive and treatment‐refractory phenotypes in this subtype of ALL. Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A‐PBX1‐positive B‐ALL outcomes. Allo‐HSCT, especially haploidentical HSCT, could improve the prognosis of adolescent/adult patients.

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Section: Methodsmentioning

confidence: 99%

The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A‐PBX1: A 10‐year retrospective study

et al. 2021

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“…B7 family Prognostic Increased post-transplantation serum B7H1/B7H3 serum in haplo-HSCT patients was associated with grade III to IV aGVHD. [35] sIL-27Ra Prognostic The probability of grade II to IV aGVHD and NRM was significantly higher in patients with low serum levels of sIL-27Ra compared with patients with high serum levels of sIL-27Ra.…”

Section: Cd30 Diagnosticmentioning

confidence: 99%

MicroRNAs as Potential Diagnostic, Prognostic, and Predictive Biomarkers for Acute Graft-versus-Host Disease

Motaei

Yaghmaie

Ahmadvand

et al. 2019

Biology of Blood and Marrow Transplantation

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Successful treatment of various hematologic diseases with allogeneic hematopoietic stem cell transplantation is often limited due to the occurrence of acute graft-versus-host disease (aGVHD). So far, there are no approved molecular biomarkers for the diagnosis and prediction of aGVHD at the clinical level due to our incomplete understanding of the molecular biology of the disease. Various studies have been conducted on animal models and humans to investigate the role of microRNAs in aGVHD pathogenesis to implicate them as biomarkers and therapeutic targets. Because of their high stability, tissue specificity, ease of measurement, low cost, and simplicity, they are excellent targets for biomarkers. In this review, we focused on microRNA expression profiling studies that were performed recently in both animal models and human cases of aGVHD to identify diagnostic and predictive biomarkers for this disease. The expression pattern of microRNAs can be specific to cells and tissues. Because aGVHD affects several organs, microRNA signatures in target tissues may help to understand the molecular pathology of the disease. Identification of organ-specific microRNAs in aGVHD can be promising to categorize patients for organ-specific therapies. Thus, microRNAs can be used as noninvasive diagnostic tests in clinic to improve prophylaxis, predict incidence and severity, and reduce morbidity.

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“…2 Previously published algorithms for severe aGVHD prognosis were usually based on peri-HSCT 'stationary' (i.e., not time-varying) parameters (including recipient, donor, and transplantation procedural characteristics) or 'landmark' analysis (designating a specific time point post-transplant for biomarker analysis) without modeling multidimensional time-series after HSCT. [3][4][5][6][7][8][9][10][11][12][13][14][15] These methods' discrimination capability was limited, especially for patients who develop severe aGVHD later; sizable dynamic clinical data have already accumulated for these patients, and yet much of this new information remains unused. AUCs of models using only stationary parameters were reported to be ≈0.62, even when data from > 20,000 patients were available.…”

Section: Main Textmentioning

confidence: 99%

“…[4][5][6]8 Attempts that tried to use biomarkers measured prior to the appearance of aGVHD signs to forecast severe aGVHD gave conflicting results. 7,10,11,13,14 ML research on dynamic risk monitoring has been active in intensive care, where blood samples and expert-rated scores are taken frequently and a plethora of devices are connected to the patient. 17,18 HSCT patients, however, have much lower data density and also higher heterogeneity in data collection than patients in intensive care.…”

Section: Main Textmentioning

confidence: 99%

Dynamic forecasting of severe acute graft-versus-host disease after transplantation

Liu

Cao

Guo

et al. 2021

Preprint

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To anticipate critical events, clinicians intuitively rely on multidimensional time-series data. It is, however, difficult to model such decision process using machine learning (ML), since real-world medical records often have irregular missing and data sparsity in both feature and longitudinal dimensions. Here we propose a nonparametric approach that updates risk score in real time and can accommodate sampling heterogeneity, using forecasting of severe acute graft-versus-host disease (aGVHD) as the study case. The area under the receiver operator characteristic curve (AUC) rose steadily after transplantation and peaked at >0.7 in both adult and pediatric cohorts. Various numerical experiments provided guidelines for future applications.

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Prognostic values of increased B7 family proteins in haploidentical hematopoietic stem cell transplantation patients with aGVHD

Cited by 7 publications

References 47 publications

The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A‐PBX1: A 10‐year retrospective study

The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A‐PBX1: A 10‐year retrospective study

MicroRNAs as Potential Diagnostic, Prognostic, and Predictive Biomarkers for Acute Graft-versus-Host Disease

Dynamic forecasting of severe acute graft-versus-host disease after transplantation

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