The Evaluation of Hematological Parameters and Their Correlation with Disease Prognosis in COVID-19 Disease in Iran.

Background: Since 2019, Coronavirus has been a highly contagious disease. The COVID-19 outbreak was declared a pandemic by the World Health Organization in March 2020. Variable laboratory findings are reported in COVID-19 patients, among which elevated levels of D-dimer, lactate dehydrogenase, as well as lymphopenia, have been reported to be associated with increased severity of disease symptoms requiring ventilator support, intensive care unit admission, and mortality. Materials and Methods: In the current study, inclusion criteria were: patient age above 18 years and hospitalization in the Imam Khomeini hospital with COVID-19 disease confirmed with nasopharyngeal swab polymerase chain reaction tests. Levels of white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, D-dimer, C-reactive protein, LDH, and ferritin were measured and their correlation with the final patients' outcome was evaluated. Results: A total of 208 patients were included in the present study. Higher neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, and D-dimer were significantly related to O2 dependency. Neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte and LDH were significantly related to higher rates of mortality. Higher Hb and lymphocyte count were significantly related to higher rates of survival. Conclusion: Hematological parameters including neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, D-dimer, Hb, and lymphocyte count were significantly related to the prognosis of patients with COVID-19 disease. This could help decide which COVID-19 patients have priority for hospitalization and intensive medical care, particularly when the pandemic disease causes limitations in healthcare service.

The T Cell Receptor Repertoire Diversity Following Hematopoietic Stem Cell Transplantation.

Immune reconstitution after hematopoietic stem cell transplantation (HSCT) with a conditioning regimen has appeared to be a promising treatment for autoimmune diseases and hematologic malignancies. This study aimed to assess the T cell receptor (TCR) repertoire diversity in CD4+ cells of patients with hematological malignancies who received allogeneic or autologous HSCT. The diversity of the TCR repertoire was evaluated in 13 patients with hematologic malignancies before and four months after HSCT. Amino acid changes in the 25 Vß families were evaluated using Spectratyping and data were presented as Hamming distance (HD). HD more than 20% was considered a change in TCR repertoire after HSCT. The mean HD was significantly changed after transplantation in all Vß gene families, with most amino acid changes in p4 and p22 families. There was a strong negative correlation between the HD as the index of TCR repertoire and age (r = -0.62,). The results revealed no association between HD mean and parameters such as sex, disease, conditioning regimen, and type of transplantation. Our data revealed that commonly used conditioning regimens in Iran could successfully cause TCR repertoire diversity in patients with hematologic malignancies in the short term. The amount of change in TCR repertoire was inversely correlated with the increasing age of patients.

Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study.

This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.

An in vitro assessment for evaluating the efficiency of ß-d-mannuronic acid (M2000) in myelodysplastic syndrome.

ß-d-Mannuronic acid (M2000), a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive properties, has been previously shown to exhibit potential therapeutic effects on autoimmune diseases. Immunosuppression therapy has been a standard approach for myelodysplastic syndrome (MDS) for many years. We evaluated the effect of M2000 on isolated peripheral blood mononuclear cells (PBMCs) from patients with MDS. The PBMCs were isolated from 13 patients with MDS and 13 normal donors. The cells were then treated with low, moderate, and high doses of M2000 and diclofenac as a control group. The level of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-3, granulocyte colony-stimulating factor (G-CSF) gene expression and the serum level of IL-6 and TNF-α production were evaluated by real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Our findings indicated a significant reduction in the production of IL-6 and TNF-α as inflammatory cytokines. Furthermore, the level of G-CSF gene expression was significantly increased. In conclusion, M2000, a newly designed NSAID, has a remarkable effect on isolated PBMC in patients with MDS, which might bring a potential hope for its oral administrations in these patients.