Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup

Background and Objectives Trisomy 8 (+8) is among the commonest genetic aberrations seen in acute myeloid leukemia (AML). However, the prognostic significance of this aberration and the best consolidation strategy for patients with it are still not resolved. Additional prognostic indicators are needed to further classify these patients and determine their appropriate management.Design and Methods Individual patient data-based meta-analysis was performed on 131 patients (median age 50 (18–60) years) with +8 as a sole aberration or +8 with one additional aberration treated between 1993 and 2002 in eight prospective German AML treatment trials. All patients received state-of-the-art treatment including high-dose cytarabine with the option for autologous or allogeneic hematopoietic stem cell transplantation (HSCT).Results In total, the 131 patients had a 3-year overall survival (OS) of 29% and a 3-year relapse-free survival (RFS) of 32%. Independent prognostic factors contributing to shorter OS were age ≥45 years, extramedullary disease, and a percentage of +8 positive metaphases ≥80%. Combining these three prognostic variables established a hierarchical model for OS. The 3-year OS was 13% for the high-risk group, 36% for the intermediate-risk group, and 55% for the low-risk group (

Clinical, epidemiological, and laboratory characteristics of mild-to-moderate COVID-19 patients in Saudi Arabia: an observational cohort study

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged from China in December 2019 and has presented as a substantial and serious threat to global health. We aimed to describe the clinical, epidemiological, and laboratory findings of patients in Saudi Arabia infected with SARS-CoV-2 to direct us in helping prevent and treat coronavirus disease 2019 (COVID-19) across Saudi Arabia and around the world. Materials and methods Clinical, epidemiological, laboratory, and radiological characteristics, treatment, and outcomes of pediatric and adult patients in five hospitals in Riyadh, Saudi Arabia, were surveyed in this study. Results 401 patients (mean age 38.16 ± 13.43 years) were identified to be SARS-CoV-2 positive and 80% of cases were male. 160 patients had moderate severity and 241 were mild in severity. The most common signs and symptoms at presentation were cough, fever, fatigue, and shortness of breath. Neutrophil and lymphocyte counts, aspartate aminotransferase, C-reactive protein, and ferritin were higher in the COVID-19 moderate severity patient group. Mild severity patients spent a shorter duration hospitalized and had slightly higher percentages of abnormal CT scans and X-ray imaging. Conclusions This study provides an understanding of the features of non-ICU COVID-19 patients in Saudi Arabia. Further national collaborative studies are needed to streamline screening and treatment procedures for COVID-19

Biglycan as a mediator of proinflammatory response and target for MDS and sAML therapy

ABSTRACTMyelodysplastic syndromes (MDS) and their progression to secondary acute myeloid leukemia (sAML) are associated with an altered protein expression including extracellular matrix (ECM) components thereby promoting an inflammatory environment. Since the role of the proteoglycan biglycan (BGN) as an inflammatory mediator has not yet been investigated in both diseases and might play a role in disease progression, its expression and/or function was determined in cell lines and bone marrow biopsies (BMBs) of MDS and sAML patients and subpopulations of MDS stem cells by Western blot and immunohistochemistry. The bone marrow (BM) microenvironment was analyzed by multispectral imaging, patients’ survival by Cox regression. ROC curves were assessed for diagnostic value of BGN. All cell lines showed a strong BGN surface expression in contrast to only marginal expression levels in mononuclear cells and CD34+ cells from healthy donors. In the MDS-L cell line, CD34−CD33+ and CD34+CD33+ blast subpopulations exhibited a differential BGN surface detection. Increased BGN mediated inflammasome activity of CD34−CD33+TLR4+ cells was observed, which was inhibited by direct targeting of BGN or NLRP3. BGN was heterogeneously expressed in BMBs of MDS and sAML, but was not detected in control biopsies. BGN expression in BMBs positively correlated with MUM1+ and CD8+, but negatively with CD33+TLR4+ cell infiltration and was accompanied by a decreased progression-free survival of MDS patients. BGN-mediated inflammasome activation appears to be a crucial mechanism in MDS pathogenesis implicating its use as suitable biomarker and potential therapeutic target.Abbreviations: Ab, antibody; alloSCT, allogenic stem cell transplant; AML, acute myeloid leukemia; BGN, biglycan; BM, bone marrow; BMB, bone marrow biopsy; casp1, caspase 1; CTLA-4, cytotoxic T lymphocyte-associated protein 4; DAMP, danger-associated molecular pattern; ECM, extracellular matrix; FCS, fetal calf serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HD, healthy donor; HSPC, hematopoietic stem and progenitor cell; HSC, hematopoietic stem cell; IFN, interferon; IHC, immunohistochemistry; IL, interleukin; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; MSI, multispectral imaging; NGS, next-generation sequencing; NLRP3, NLR family pyrin domain containing 3; OS, overall survival; PBMC, peripheral blood mononuclear cell; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1, PFS, progression-free survival; PRR, pattern recognition receptor; SC, stem cell; SLRP, small leucine-rich proteoglycan; TGF, transforming growth factor; TIRAP, toll/interleukin 1 receptor domain-containing adapter protein; TLR, toll-like receptor; Treg, regulatory T cell