Clonal hematopoiesis is frequently observed in elderly people. To investigate the prevalence and dynamics of genetic alterations among healthy elderly individuals, a cohort of 50 people >80 years was genotyped for commonly mutated leukemia-associated genes by targeted deep next-generation sequencing. A total of 16 somatic mutations were identified in 13/50 (26%) individuals. Mutations occurred at low variant allele frequencies (median 11.7%) and remained virtually stable over 3 years without development of hematologic malignancies in affected individuals. With DNMT3A mutations most frequently detected, another cohort of 160 healthy people spanning all age groups was sequenced specifically for DNMT3A revealing an overall mutation rate of 6.2% (13/210) and an age-dependent increase of mutation prevalence. A significant difference (p = 0.017) in the DNMT3A expression pattern was detected between younger and healthy elderly people as determined by qRT-PCR. To evaluate the selection of clonal hematopoietic stem cells (HSCs), bone marrow of two healthy individuals with mutant DNMT3A was transplanted in a humanized mouse model. Xenografts displayed stable kinetics of DNMT3A mutations over 8 months. These findings indicate that the appearance of low-level clones with leukemia-associated mutations is a common age-associated phenomenon, but insufficient to initiate clonal selection and expansion without the additional influence of other factors.
Dear Editor,We report a case of disseminated Staphylococcus intermedius infection causing multiple spleen abscesses with consecutive splenectomy in a patient with acute lymphoblastic leukemia.A 49-year-old female patient underwent induction chemotherapy in accordance with the Germany Multicentre Study Group (GMALL) 08/2013 protocol for a precursor B-cell acute lymphoblastic leukemia (ALL). Fever episodes occurred during neutropenia, accompanied by intermittent left flank pain and increased inflammation parameters with a maximum C-reactive protein of 368.9 mg/l (normal range, < 5.0 mg/l). Extensive microbiological diagnostics including multiple blood and urine cultures did not reveal any relevant pathogens. Despite broad-spectrum antimicrobial therapy including a combination therapy of meropenem, linezolid, and fosfomycin, later ceftazidime, tigecycline, and liposomal amphotericin B, no improvement of clinical and laboratory parameters was achieved. Abdominal computed
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