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Constitutional mismatch repair deficiency (CMMRD) is caused by germline pathogenic variants in both alleles of a mismatch repair gene. Patients have an exceptionally high risk of numerous pediatric malignancies and benefit from surveillance and adjusted treatment. The diversity of its manifestation, and ambiguous genotyping results, particularly from PMS2, can complicate diagnosis and preclude timely patient management. Assessment of low‐level microsatellite instability in nonneoplastic tissues can detect CMMRD, but current techniques are laborious or of limited sensitivity. Here, we present a simple, scalable CMMRD diagnostic assay. It uses sequencing and molecular barcodes to detect low‐frequency microsatellite variants in peripheral blood leukocytes and classifies samples using variant frequencies. We tested 30 samples from 26 genetically‐confirmed CMMRD patients, and samples from 94 controls and 40 Lynch syndrome patients. All samples were correctly classified, except one from a CMMRD patient recovering from aplasia. However, additional samples from this same patient tested positive for CMMRD. The assay also confirmed CMMRD in six suspected patients. The assay is suitable for both rapid CMMRD diagnosis within clinical decision windows and scalable screening of at‐risk populations. Its deployment will improve patient care, and better define the prevalence and phenotype of this likely underreported cancer syndrome. [ABSTRACT FROM AUTHOR]

Anthracyclines are integral components of antileukemic treatment. Apart from cardiotoxicity, myelosuppression and infectious complications have been described for doxorubicin (DOX) and daunorubicin (DNR) as predominant side effects, but little is known about their differential toxicities. To address the question whether DNR is associated with a lower rate of infectious complications compared with DOX, 307 children with newly diagnosed acute lymphoblastic leukemia, enrolled in trial CoALL 08-09, were randomized to receive either DOX 30 mg/m2 (n = 153) or DNR 36 mg/m2 (n = 154) in delayed intensification. Hematologic toxicities and stomatitis were less frequent in the DNR group resulting in a significantly lower rate of infections in the DNR arm (27% vs. 59%, p < .0001). Survival was equal in both arms (95% SE 2%) (p = .55), with an insignificant difference in the relapse rate (RR 0.12 (SE = 0.03) in the DOX arm vs. 0.16 (SE = 0.04) in the DNR arm; p = .37; Hazard ratio 1.3; 95% confidence interval 0.7-2.6). In conclusion, DNR given in delayed intensification is associated with a lower incidence of infectious complications without loss of efficacy. [ABSTRACT FROM AUTHOR]

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Objectives: To analyse the development of MRI-guided vacuum-assisted biopsy (VAB) in Switzerland and to compare the procedure with stereotactically guided and ultrasound-guided VAB. Methods: We performed a retrospective analysis of VABs between 2009 and 2011. A total of 9,113 VABs were performed. Of these, 557 were MRI guided. Results: MRI-guided VAB showed the highest growth rate (97 %) of all three procedures. The technical success rates for MRI-guided, stereotactically guided and ultrasound-guided VAB were 98.4 % (548/557), 99.1 % (5,904/5,960) and 99.6 % (2,585/2,596), respectively. There were no significant differences ( P = 0.12) between the MRI-guided and the stereotactically guided procedures. The technical success rate for ultrasound-guided VAB was significantly higher than that for MRI-guided VAB ( P < 0.001). There were no complications using MRI-guided VAB requiring open surgery. The malignancy diagnosis rate for MRI-guided VAB was similar to that for stereotactically guided VAB ( P = 0.35). Conclusion: MRI-guided VAB is a safe and accurate procedure that provides insight into clinical breast findings. Key points: • Three vacuum-assisted breast biopsy (VAB) procedures were compared. • Technical success rates were high for all three VAB procedures. • Medical complications were relatively low using all three VAB procedures. • The use of MRI-guided vacuum-assisted breast biopsy is growing. [ABSTRACT FROM AUTHOR]