Background: Acute lymphoblastic leukemia (ALL) is a malignancy of the white blood cells characterized by its rapid and aggressive progress that needs immediate treatment. ALL could affect both adults and children. Various patient- and disease-related factors may be involved in ALL patients’ prognosis. Therefore, it is critical to identify important risk factors related to the competing outcomes of patients with ALL. Objectives: This study aimed to stratify the risk of outcomes of children with precursor B-cell ALL using demographic characteristics, laboratory characteristics, and extramedullary diseases. To achieve this goal, we used the best competing risks model to make an appropriate decision for children's treatment according to this classification. Methods: In this retrospective cohort study, 393 patients with ALL were included. ALL with B cell origins (CD20, CD19, CD10, and CD22 positive markers) was differentiated using flow cytometry. Complete remission was defined by a lymphoblast count of less than 5% in the bone marrow, presence of no blasts in cerebrospinal fluid (CSF), as well as complete disappearance of clinical symptoms. Patients with ALL were treated based on Berlin-Frankfurt-Münster (BFM). Competing outcomes were first-relapse and non-relapse mortality, respectively. Risk factors affecting competing outcomes were assessed based on a fully specified sub-distribution model. Results: Five-year estimates for overall survival and event free survival were 75% (95% CI: 69 - 79%) and 71% (95% CI: 66 - 75%), respectively. Five-year incidence rates for first-relapse and non-relapse mortality in children were 11.4% (95% CI: 8.32 - 15.16%) and 17.6% (95% CI: 13.98 - 21.67%), respectively. Moreover, according to the results, children with WBC > 50000, hemoglobin 8, and tumor lysis syndrome for the first-relapse outcome, and children with central nervous system (CNS) involvement and tumor lysis syndrome for the non-relapse mortality (NRM) outcome were considered as high-risk groups. Conclusions: We found that extramedullary diseases could have a crucial role in the risk stratification of children with precursor B-cell ALL. Therefore, for a targeted and effective treatment of high-risk children, in addition to chemotherapy, using appropriate PI3K pathway inhibitors, JAK2 pathway inhibitors, and antibody-based immunotherapy is recommended to reduce minimal residual disease and, consequently, mortality rate.
Several reports associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-haemophagocytic lymphohistiocytosis (sHLH) and proposed the HScore table for sCOVID-19 patients. We conducted a meta-analysis to found the possible association of HScore parameters with severity in COVID-19 patients. Systematic search was performed in Medline (PubMed), EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. Eighteen studies met the criteria and included in the meta-analysis (2459 patients). Significant higher levels of leukocyte, neutrophil, aspartate-transaminase (AST), ferritin, and fibrinogen, as well as lower level of lymphocyte, platelet, and hemoglobin were found in sCOVID-19 patients compared to non-severe ones. Fever was nearly associated with 2 times increased odds of sCOVID-19 (p-value = 0.051). Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 contrast with HScore. Conclusively, HScore parameters could be risk factors for the severity of COVID-19. However, some parameters’ roles are contradictory, suggesting further investigation and a new way of HScore interpretation for sCOVID-19 patients.
Background: Despite recent advances in hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) is still one of the most challenging post-transplant complications with a considerable mortality rate. Various strategies, including chemotherapy, depletion of T lymphocytes, monoclonal antibodies, corticosteroids, and other immunosuppressive drugs are used to reduce GVHD incidence, which usually increases the risk of cancer relapse and various infections in patients. The recently conducted studies have introduced oncolytic virotherapy as a promising solution to prevent GVHD and enhance the graft-versus-tumor effects. Oncolytic viruses are non-pathogenic viruses capable of selective lysis of cancer cells. These viruses can differentiate between allogeneic T lymphocytes and hematopoietic stem cells, and suppress allogeneic T cells. This review study aimed to discuss the mechanisms of oncolytic virotherapy in reducing the incidence of GVHD.
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