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Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption. [ABSTRACT FROM AUTHOR]

Approximately half of patients diagnosed with essential thrombocythemia (ET) are older adults (aged ≥ 60 years), but to date, little is known about the clinical and molecular characteristics of older patients diagnosed according to the 2016 World Health Organization criteria. We retrospectively collected clinical and molecular data from 282 older (≥ 60 years) and 621 younger ET patients (18–59 years) in China from March 1, 2012 to November 1, 2021 and summarized the clinical characteristics and treatment of these older ET patients. Compared to younger patients, older patients had a higher incidence of the JAK2V617F mutation (P = 0.001), a lower incidence of CALR mutations (P = 0.033) and a higher rate of epigenetic mutations (P < 0.001), TP53 mutations (P = 0.005), and RNA splicing mutations (P < 0.001). Older patients had not only a higher incidence of thrombosis but also a higher incidence of bleeding events. Furthermore, older patients had a significantly higher mortality rate after disease progression (P = 0.050) or after thrombotic events (P = 0.013). Risk factors for thrombosis or prognosis were significantly different between older patients and the entire ET cohort. In older patients, non-driver mutations contributed significantly to thrombotic complications and a poor prognosis, while the JAK2V617F mutation was a risk factor for overall survival but not for thrombotic events. The application of interferon in older ET patients was not inferior to that of hydroxyurea in terms of efficacy and safety. Older patients presented unique characteristics different from those of younger patients, which could provide new information for formulating more appropriate treatment and follow-up strategies. [ABSTRACT FROM AUTHOR]

Chinese Gγ+(Aγδβ)0-thalassemia and SEA-HPFH are the most common types of β-globin gene cluster deletion in Chinese population. The aim of the study was to analyze clinical features of deletional Chinese Gγ+(Aγδβ)0-thalassemia and Southeast Asian hereditary persistence of fetal hemoglobin (SEA-HPFH) in South China. A total of 930 subjects with fetal hemoglobin (HbF) level ≥ 2% were selected on genetic research of Chinese Gγ+(Aγδβ)0-thalassemia and SEA-HPFH. The gap polymerase chain reaction was performed to identify the deletions. One hundred cases of Chinese Gγ+(Aγδβ)0-thalassemia were detected, including 90 cases of Chinese Gγ+(Aγδβ)0/βN-thalassemia, 7 cases of Chinese Gγ+(Aγδβ)0 /βN-thalassemia combined with α-thalassemia, 2 cases of Chinese Gγ+(Aγδβ)0-thalassemia combined with β-thalassemia, and 1 case of Chinese Gγ+(Aγδβ)0-thalassemia combined with β-gene mutation. One hundred nine cases of SEA-HPFH were detected, including 97 cases of SEA-HPFH/βN, 9 cases of SEA-HPFH/βN combined with α-thalassemia, 2 cases of SEA-HPFH combined with β-thalassemia, and 1 case of SEA-HPFH combined with β-gene mutation. Statistical analysis indicates significant differences in MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), and HbA2 and HbF levels between Chinese Gγ+(Aγδβ)0-thalassemia heterozygotes and SEA-HPFH heterozygotes (P < 0.001). There are statistical differences in hematological parameters between them. Clinical phenotypic analysis can provide guidance for genetic counseling and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

We aimed to clarify the clinical characteristics, prognostic factors, and effectiveness of the HLH-94/2004 regimens and hematopoietic stem cell transplantation (HSCT) in pediatric patients with primary hemophagocytic lymphohistiocytosis (pHLH) in China. A retrospective analysis was performed on 38 patients with pHLH at Beijing Children's Hospital. PRF1 (34.2%) and UNC13D (31.6%) were the most common mutations in the pHLH. Thirty-eight patients were treated with the HLH-94/2004 regimens after diagnosis. Twenty-six patients (72.2%) responded to first-line treatment (complete response: 55.5%, partial response: 16.7%). The median survival time was 23 months. The overall survival (OS) rate at 3 years was 74.7%. There was no significant difference in the response rate (72% vs. 63.6%, P = 0.703) or 3-year OS (83.6% vs. 66.7%, P = 0.443) between the patients treated with the HLH-94 regimen and those treated with the HLH-2004 regimen. The incidences of all side effects in patients treated with the HLH-94 or HLH-2004 regimen were 32.0% and 18.2%, respectively (P = 0.394). Among 15 patients treated with HSCT, neither the preconditioning regimen nor the donor type affected patient prognosis (P = 0.205 and P = 0.161, respectively). The disease status (remission or nonremission) before preconditioning did not affect prognosis or the incidence of GVHD. Furthermore, a higher bilirubin level (≥ 30 μmol/L) was correlated with a poorer prognosis in pHLH patients (P = 0.026). The effectiveness rates of the HLH-94 and HLH-2004 regimens, chemotherapy, and HSCT were similar in pHLH patients. A bilirubin level ≥ 30 μmol/L might be an adverse prognostic factor in pHLH. [ABSTRACT FROM AUTHOR]

In October 2019, a viral infectious disease appeared in the city of Wuhan in China. A new betacoronavirus, SARS-CoV-2, has been recognized as the responsible pathogen in this infection. Although coronavirus disease is principally expressed as a pulmonary infection, critical SARS-CoV-2 infection is frequently complicated with coagulopathy, and thromboembolic events are recognizable in several patients. Dehydration, acute inflammatory condition, protracted immobilization during disease, existence of multiple cardiovascular risk factors such as diabetes, obesity or hypertension, previous coronary artery disease, ischemic stroke, peripheral artery disease are frequent comorbidities in SARS-CoV-2 hospitalized subjects, which possibly augment thrombo-embolic risk. However, other causal factors can still be identified such as unrestricted angiotensin II action, the use of immunoglobulins, an increased production of adhesion molecules able to induce vascular inflammation and endothelial activation, complement stimulation, excessive production of neutrophil extracellular traps (NETs), and increased platelet count. Low-molecular-weight heparin should be chosen as early treatment because of its anti-inflammatory action and its ability to antagonize histones and so defend the endothelium. However, several therapeutic possibilities have also been proposed such as fibrinolytic treatment, drugs that target NETs, and complement inhibition. Nevertheless, although the violence of the pandemic may suggest the use of heroic treatments to reduce the frightening mortality that accompanies SARS-CoV-2 infection, we believe that experimental treatments should only be used within approved and controlled protocols, the only ones that can provide useful and specify information on the validity of the treatments. [ABSTRACT FROM AUTHOR]

Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options. [ABSTRACT FROM AUTHOR]

Haemoglobin (Hb) H-constant spring (CS) alpha thalassaemia (- -/-αCS) is the most common type of nondeletional Hb H disease in southern China. The CRISPR/Cas9-based gene correction of patient-specific induced pluripotent stem cells (iPSCs) and cell transplantation now represent a therapeutic solution for this genetic disease. We designed primers for the target sites using CRISPR/Cas9 to specifically edit the HBA2 gene with an Hb-CS mutation. After applying a correction-specific PCR assay to purify the corrected clones followed by sequencing to confirm the mutation correction, we verified that the purified clones retained full pluripotency and exhibited a normal karyotype. This strategy may be promising in the future, although it is far from representing a solution for the treatment of HbH-CS thalassemia now. [ABSTRACT FROM AUTHOR]

To study the genetic characteristics of primary hemophagocytic lymphohistiocytosis (pHLH) in China, we investigated the genetic data and clinical features of Chinese HLH patients. We retrospectively reviewed the genetic and clinical data of patients with HLH from November 2015 to June 2018. As a result, 26 patients were diagnosed with pHLH. The median age at diagnosis was 2.8 years (range 0.1-13.7 years). The probable overall survival at 12 and 24 months was 87.6% and 62.6%, respectively. Mutations in PRF1 (38.4%) and UNC13D (26.9%) were the most common genetic abnormalities. Furthermore, we identified 19 novel mutations that had not been previously reported and were predicted to likely be pathogenic. In addition to HLH-associated genes, there were 27 other genes identified. Genotype-phenotype analysis showed that patients with disruptive mutations were significantly younger at diagnosis than those with other mutation types (2.9 years vs. 6.4 years, P = 0.036). Familial HLH patients were more prone to central nervous system involvement and seizures compared with other patients (83.3% vs. 37.5%, P = 0.019; 55.6% vs. 12.5%, P = 0.04, respectively). In summary, numerous new mutations in HLH-related genes and other genes were identified in Chinese children with pHLH. Significantly, disruptive mutation types were more likely to be found in younger patients, and familial HLH patients tended to exhibit central nervous system involvement and seizures. [ABSTRACT FROM AUTHOR]

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. [ABSTRACT FROM AUTHOR]

The purpose of our study is to compare the 7-year response to imatinib monotherapy as an initial treatment and re-treatment in Chinese patients with chronic myelogenous leukemia-chronic phase (CML-CP) patients in a single center in Beijing. A retrospective study of 171 CML-CP patients receiving imatinib monotherapy was done with 73 in the initial treatment group (disease course ≤6 months) and 98 in the re-treatment group (disease course >6 months). Cumulative rates of complete cytogenetic response (CCyR) at 6, 12, and 36 months after imatinib treatment in the initial and re-treatment groups were 75%, 89%, and 96%, and 48%, 77% and 84% ( p = 0.0002), respectively. The median time to CCyR in the initial and re-treatment groups was 6 months (95% CI, 3.3-8.3) and 9 months (95% CI, 6.4-11.6), respectively ( p = 0.0002). Cumulative rates of major molecular responses at 9, 12, and 18 months after imatinib treatment in the initial and re-treatment groups were 31%, 48%, and 60%, and 15%, 25% and 37% (p = 0.017), respectively. The median time to the major molecular response in the initial and re-treatment groups was 15 months (95% CI, 12.3-17.7) and 36 months (95% CI, 25.9-46.0), respectively ( p = 0.017). Progression-free survival at 84 months in the initial and re-treatment groups was 97% and 85%, respectively ( p = 0.09). Event-free survival at 84 months in the initial and re-treatment groups was 92% and 70%, respectively ( p = 0.049). Only two of the 171 patients discontinued imatinib therapy for grade 3/4 adverse events. Our study revealed that CML-CP patients would benefit from early treatment with imatinib. [ABSTRACT FROM AUTHOR]

The beta-thalassemia is one of the most common autosomal recessive disorders in Southern China. The point mutation of beta-globin gene is the commonest molecular pathogenic mechanism. In Chinese population, over 30 mutations have now been identified. In this paper, we describe a novel beta(++)-thalassemia mutation of -73(A-->T) within the conserved CCAAT box at position -76 to -72 from the cap site of the beta-globin gene. The proband, an 8-year-old Chinese boy, was a compound heterozygote of this promoter mutation and a common beta(0)-thalassemia mutation of codon 41/42(-TCTT). He had a mild thalassemia intermedia phenotype and was transfusion independent with a hemoglobin (Hb) level of 9.4 g/dl, mean corpuscular volume (MCV) of 55.2 fl, and mean corpuscular hemoglobin (MCH) of 17.5 pg. His mother and two maternal uncles were carriers of -73(A-->T) mutation in beta-globin gene with hematological phenotype of silent beta-thalassemia. Real-time quantitative reverse transcript polymerase chain reaction (RT-PCR) analysis showed a slightly reduced beta-globin messenger RNA (mRNA) level (19.35%) in three heterozygotes compared with that in normal subjects. In restriction fragment length polymorphism (RFLP) haplotype analysis, the results indicated that this promoter mutation might be linked to the absence of BamHI-3'beta restriction site.