Among patients with a hematological malignancy (HM) and among those who have undergone hematopoietic stem cell transplantation (HSCT), next-generation sequencing (NGS) of cell-free DNA may aid in treatment decision-making where infection is suspected, according to research published in Transplantation and Cellular Therapy.

Patients with HM or who have undergone HSCT are at a high risk of mortality in case of infection, owing to the higher likelihood they are immunocompromised. While prophylaxis for fungal infections is frequently used, the risk of both fungal and bacterial infection remains high, at 3.5% and up to 25%, respectively, in these populations.

Microbial infections are, furthermore, often difficult to diagnose among these patients, any may require time-consuming biopsies and blood tests to inform treatment decision-making. As NGS has shown promise in detection of microbial pathogens, researchers conducted a retrospective analysis to determine the results of cell-free DNA NGS, as well as the effects these results have on treatment decisions.

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Between 2018 and 2020, researchers reviewed 95 patient-samples. In the according patient group, 31, for whom there were 32 samples, had an HM or had undergone HSCT. Among patients who had NGS performed, all had either fever or imaging suggestive of infection. In the cohort, the median age was 56 years (range, 18-75), 18 (58%) were male, 11 (35%) had an HM treated with chemotherapy, and 20 (65%) had undergone HSCT.

Overall, the median number of days from appearance of fever to NGS sampling was 5 (range, 1-28), with a median number of days to NGS results of 2 (range, 1-6). In 9 of the 32 cases (28%), NGS results led to an increase in antibiotic use, while 10 (31%) had a decrease. Management of patient care was changed in 19 patients (59%) in the overall group.

Sensitivity and specificity for clinically relevant infection were 80% and 58%, respectively, though NGS correctly identified uncommon microbes, including Legionella and Toxoplasma.

“In conclusion, utilizing NGS to provide rapid identification of opportunistic pathogens in severely immunocompromised patients is advantageous for clinical management of life-threatening infection,” the authors wrote. “NGS has a high sensitivity and rapid turnaround time, resulting in better antimicrobial stewardship, prevention of over-treatment, and decrease length of hospital stay by better targeting appropriate therapies.”


Yu J, Diaz JDD, Goldstein SC, et al. Impact of next-generation sequencing cell-free pathogen DNA test on anti-microbial management in adults with hematological malignancies and transplant recipients with suspected infections. Transplant Cell Ther. Published online February 26, 2021. doi:10.1016/j.jtct.2021.02.0251038/nm4142