BACKGROUND: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease.
METHODS: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions.
RESULTS: Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p < .05).
CONCLUSIONS: Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients.
CONCLUSIONS: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.

Multiple myeloma (MM) is the second most common hematologic malignant tumor. Standard holistic treatment model and new drug-based regimens have greatly improved the survival of patients with MM; however, minimal residual disease (MRD) causes relapse in most patients. Therefore, combining MRD testing on the basis of traditional serological efficacy evaluation is necessary to achieve a more accurate assessment of the patient\'s disease status. At present, next-generation flow cytometry (NGF) and next-generation sequencing (NGS) are the mainstream technologies for detecting MRD based on bone marrow samples. To standardize and normalize MRD detection, the expert group discussed and formulated Chinese expert consensus on the application of NGF and NGS technology for bone marrow MRD detection in patients with MM.
多发性骨髓瘤（MM）是血液系统第二大常见恶性肿瘤，标准的整体治疗模式及以新药为主的方案极大地改善了MM患者的生存，但微小残留病（MRD）导致大多数患者复发。因此，需要在传统血清学疗效评估的基础上联合MRD检测，以更精准地评估患者的疾病状态。目前，二代流式细胞术（NGF）和二代测序（NGS）是基于骨髓样本检测MRD的主流技术。为使MRD检测标准化和规范化，专家组讨论制订了在MM患者中应用NGF和NGS技术进行骨髓MRD检测的中国专家共识。.

Background: Until now, limited clinical significance had been reported for disseminated tumor cells (DTCs) in gynecologic malignancies. DTCs were previously reported not to be associated with established risk factors, L1CAM immunoreactivity, and outcome in endometrial carcinoma (EC). This study\'s primary objective was to investigate potential correlations of DTCs in the bone marrow (BM) of EC patients with disease-related survival, and a secondary objective was to evaluate associations between molecular classification of EC and DTCs. Methods: Patients treated for primary EC at Tuebingen University women\'s hospital between 2003 and 2016 were identified. A total of 402 patients with a complete set of BM cytology, molecular, and clinical data were evaluable. Results: DTC occurrence was distributed equally among all four molecular groups (p = 0.651). DTC positivity was associated with a less favorable disease-free survival (HR: 1.86, 95% CI: 1.03-3.36, p = 0.036) and progression-free survival (HR: 1.86, 95% CI: 1.01-3.44, p = 0.045). Presence of DTCs was associated with a higher frequency of distant disease recurrence (p = 0.017). Conclusions: In line with our previous findings, tumor cell dissemination is not associated with molecular features in our large cohort of primary EC patients. Since DTCs seem to be associated with survival and location of disease recurrence, further studies are needed to decisively define their role in EC survival.

In the recent decade, analysis of circulating tumor DNA (ctDNA) has improved cancer care by allowing for rapid detection of actionable molecular targets. A new generation of circulating DNA tests is now becoming available commercially. These tests are characterized by a superior limit of detection of 0.01% vaF or better, allowing for the detection of radiologically occult molecular residual disease (MRD). MRD tests have the potential to revolutionize neoadjuvant and adjuvant treatment. In addition, these tests can be used as tumor markers to assess disease response. We reviewed the current evidence for the use of high-sensitivity MRD assays with particular focus on the genitourinary tumors. Multiple studies have now been reported in urothelial, renal, and recently testicular carcinoma. We find that the sensitivity varies across tumor types in the adjuvant setting and may reach a high of 100% in urothelial cancer. Specificity in tumor-informed MRD appears to be preserved across tumor types (98%-100%). Several trials are now prospectively validating MRD testing in biomarker integral studies, mainly in urothelial carcinoma.

Multiparameter flow cytometry (MPF) is an essential component of the diagnostic workup of hematologic malignancies. Recently developed tools have expanded the utility of MPF in detecting T-cell clonality and myelomonocytic dysplasia. Minimal/measurable residual disease analysis has long been established as critical in the management of B-lymphoblastic leukemia and is emerging as a useful tool in myeloid malignancies. With the continued increased complexity of MPF assays, emerging tools for data collection and analysis will allow users to take full advantage of MPF in the diagnosis of hematologic disease.

Lung cancer is one of the most common malignancies worldwide, with non-small cell lung cancer (NSCLC) being the most common type. As understanding of precise treatment options for NSCLC deepens, circulating tumor DNA (ctDNA) has emerged as a potential biomarker that has become a research hotspot and may represent a new approach for the individualized diagnosis and treatment of NSCLC. This article reviews the applications of ctDNA for the early screening of patients with NSCLC, guiding targeted therapy and immunotherapy, evaluating chemotherapy and postoperative efficacy, assessing prognosis and monitoring recurrence. With the in-depth study of the pathogenesis of NSCLC, plasma ctDNA may become an indispensable part of the precise treatment of NSCLC, which has great clinical application prospects.
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Donor lymphocyte infusions (DLIs) are often recommended products after allogeneic hematopoietic stem cell transplant to increase graft - versus - leukemia effect. More success rate of DLI has been reported in relapsed posttransplant chronic myeloid leukemia. Whatever the indication for DLI, mortality related to post-DLI infusion is 5%-20%, and more than one-third of patients will develop acute and/or chronic graft versus host disease (GVHD) after DLI. We report two cases where DLIs were used for residual disease after posttransplant. Both of DLI went uneventful. None of the patient\'s developed signs of GVHD postinfusion. Although both patients expired with different causes, none were related to DLI infusion. Information from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with aggressive diseases may benefit from disease reduction before DLI. However, further evidence is required to evaluate its efficacy, especially in relapsed or residual hematological malignancies.

Circulating tumor DNA (ctDNA), a fragment of tumor DNA found in the bloodstream, has emerged as a revolutionary tool in cancer management. This review delves into the biology of ctDNA, examining release mechanisms, including necrosis, apoptosis, and active secretion, all of which offer information about the state and nature of the tumor. Comprehensive DNA profiling has been enabled by methods such as whole genome sequencing and methylation analysis. The low abundance of the ctDNA fraction makes alternative techniques, such as digital PCR and targeted next-generation exome sequencing, more valuable and accurate for mutation profiling and detection. There are numerous clinical applications for ctDNA analysis, including non-invasive liquid biopsies for minimal residual disease monitoring to detect cancer recurrence, personalized medicine by mutation profiling for targeted therapy identification, early cancer detection, and real-time evaluation of therapeutic response. Integrating ctDNA analysis into routine clinical practice creates promising avenues for successful and personalized cancer care, from diagnosis to treatment and follow-up.

BACKGROUND: The current standard of care for patients with inoperable stage III non-small cell lung cancer includes chemoradiotherapy (CRT) followed by 1 year of checkpoint inhibitor (CPI) therapy. Nevertheless, the optimal duration of consolidation CPI remains unknown. Here, we characterized the relationship between circulating tumor DNA (ctDNA) minimal residual disease (MRD) and clinical outcomes of patients with unresectable locally advanced non-small cell lung cancer treated on a phase 2 trial of short-course consolidation immunotherapy after CRT, with the goal of testing whether ctDNA may be able to identify patients who do not require a full year of treatment.
METHODS: Plasma samples for ctDNA analysis were collected from patients on the Big Ten Cancer Research Consortium LUN 16-081 trial after completion of CRT, before day 1 of cycle 2 (C2D1) of CPI (i.e., 1 mo after treatment start), and at the end of up to 6 months of treatment. Tumor-informed ctDNA MRD analysis was performed using cancer personalized profiling by deep sequencing. Levels of ctDNA at each time point were correlated with clinical outcomes.
RESULTS: Detection of ctDNA predicted significantly inferior progression-free survival after completion of CRT (24-mo 29% versus 65%, p = 0.0048), before C2D1 of CPI (24-mo 0% versus 72%, p < 0.0001) and at the end of CPI (24-mo 15% versus 67%, p = 0.0011). In addition, patients with decreasing or undetectable ctDNA levels after 1 cycle of CPI had improved outcomes compared with patients with increasing ctDNA levels (24-mo progression-free survival 72% versus 0%, p < 0.0001). Progression of disease occurred within less than 12 months of starting CPI in all patients with increasing ctDNA levels at C2D1.
CONCLUSIONS: Detection of ctDNA before, during, or after 6 months of consolidation CPI is strongly associated with inferior outcomes. Our findings suggest that analysis of ctDNA MRD may enable personalizing the duration of consolidation immunotherapy treatment.

Liquid biopsy is a minimally invasive method for biomarkers detection in body fluids, particularly in blood, which offers an elevated and growing number of clinical applications in oncology. As a result of the improvement in the techniques for DNA analysis, above all next-generation sequencing (NGS) assays, circulating tumor DNA (ctDNA) has become the most informing tumor-derived material for most types of cancer, including non-small cell lung cancer (NSCLC). Although ctDNA concentration is higher in patients with advanced tumors, it can be detected even in patients with early-stage disease. Therefore, numerous clinical applications of ctDNA in the management of early-stage lung cancer are emerging, such as lung cancer screening, the identification of minimal residual disease (MRD), and the prediction of relapse before radiologic progression. Moreover, a high number of clinical trials are ongoing to better define the impact of ctDNA evaluation in this setting. Aim of this review is to offer a comprehensive overview of the most relevant implementations in using ctDNA for the management of early-stage lung cancer, addressing available data, technical aspects, limitations, and future perspectives.