About fifteen percent of patients with severe aplastic anemia (sAA) who undergo immunosuppression therapy (IST) develop clonal disease in the decade following treatment. Of 122 patients treated with horse ATG/CsA at NIH, 13 developed cytogenetic abnormalities (monosomy 7 in 9 patients, 7p deletion in one, and trisomy 8 in 2) (Rosenfeld et al: JAMA289:1130; 2003). Monosomy 7 usually occurs in patients with sAA who are unresponsive to IST. Factors responsible for clonal progression in bone marrow failure are still unclear. We and others have reported that monosomy 7 may be detected by fluorescent in situ hybridization (FISH) months before conventional cytogenetics and that high levels of GCSF foster preferential expansion of the monosomy 7 clone in vitro (Sloand E et al; Proc. Natl. Acad. Sci2006;103:14483). We hypothesized that a clone of monsomy 7 cells might indicate an underlying stem cell disorder unlikely to respond to immunosuppression or reflect more severe disease marked by higher endogenous GCSF levels. FISH was undertaken on 40 bone marrow samples obtained from aplastic anemia patients at presentation and before immunosuppressive treatment. Bone marrow mononuclear cells were hybridized with centromeric probes specific for chromosome 7 and chromosome 8 (to control for hybridization efficiency); samples were assessed on duplicate slides by three investigators who were unaware of the diagnoses and outcomes. Twenty-five healthy controls were tested concurrently. The upper limit of normal was set at 6% based on control data. Of twenty-one patients with > 6% monosomy 7 cells, response to IST was observed in 12 (57%), while 6 of 19 (84%) with normal FISH responded to IST (p=0.08). Thirteen patients had monosomy 7 frequencies of >10%. Of these 5 (38%) responded to IST, compared with 23/27 (85%) with ≤10% monosomy 7. The proportion of monosomy 7 cells in the bone marrow correlated with age (R2 =0.6, p<0.001). Two of the 23 non-responding patients later developed clonal progression with monosomy 7 or 7q-; both had >10% monosomy 7 by FISH at presentation, but normal cytogenetics. The two responding patients tested with >6% monosomy 7 prior to IST demonstrated <2% following successful IST, suggesting that the high endogenous levels of G-CSF present before IST response may have facilitated expansion of the clone. Significant monosmy 7 clones may reflect a stem cell disorder in patients not responding to IST.
Background – COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) is an emerging disease that presents with inflammation of multiple organs. The extracardiac radiographic manifestations of this syndrome are not well understood.Objective – We reviewed the radiologic findings of MIS-C in a cohort of children with a confirmed diagnosis of the syndrome.Materials and methods – In a retrospective study from 4/1/2020 to 5/22/2020, we reviewed imaging studies of 38 children with MIS-C, 21 females (55%) and 17 males (45%), with an average age of 9.2 years (range 1.3 – 20 years). Thirty six had chest radiographs, 6 had abdominal radiographs, 12 had abdominal sonograms or MRI, 2 had neck sonograms, and 3 had brain MRI.Results – 28 patients had pulmonary disease, with 24 (86%) having bilateral opacities, mostly diffuse (n=16, 57%). The most common abnormalities were peribronchial thickening (n=19, 68%), ground glass opacities (n=15, 54%) and consolidation (n=5, 18%). Pleural effusions were only present in children 10 years of age and under, and ground glass opacities were seen more often in older patients (59% vs. 26%, P<0.05). On abdominal imaging, small volume ascites was the most common finding (n=6, 50%). Other findings included right lower quadrant bowel wall thickening (n=3, 25%), gallbladder wall thickening (n=3, 25%), and cervical (n=2) or abdominal (n=2) lymphadenophathy. Of 3 patients with brain MRI, one had bilateral parietooccipital abnormalities and another papilledema.Conclusion – COVID-19 associated MIS-C causes a constellation of findings in the chest and abdomen, most often showing bilateral diffuse pulmonary abnormalities and small volume ascites.
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