【Objective】 To analyze the blood transfusion and adverse reactions in myelodysplastic syndroms (MDS) patients, so as to improve transfusion management in MDS patients. 【Methods】 The diagnosis and treatment information of MDS patients with blood transfusion in our hospital from January 2003 to December 2022 were collected, and the component transfusion and adverse reactions were investigated. 【Results】 The average infusion volume of red blood cells(RBCs) and platelets were respectively (27.46±43.11 ) and (16.41±24.81 ) in 799 MDS patients, which had no correlation with gender and blood type. The incidence of adverse reactions was 18.27% (146/799), with the most common adverse reactions as delayed serologic transfusion reaction (DSTR) (9.01%, 72/799), followed by non hemolytic fever reaction (4.76%, 38/799) and allergic reaction (4.38%, 35/799). Compared with all patients with transfusion, DSTR was more common in females (P<0.05), with elder age and had more RBCs consumption (all P<0.01). 86.11%(62/72) were Rh system, and 40.28% (29/72) had 2 or more antibodies. The occurrence time of DSTR in some patients was not related to the volume of RBCs trans infusion. 【Conclusion】 MDS patients, with more average transfusion volume and higher incidence of adverse reactions especially DSTR, were recommended a strictly limited transfusion schedule and Rh phenotype matching RBC products. The investigation of immune status of MDS patients at different periods is helpful to provide new aspects and therapeutic measures for the pathogenesis of DSTR, and the antibody screening time may adjusted appropriately.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objectives: To analyze the cardiac T2* value, liver iron concentration (LIC) , and related laboratory parameters in myelodysplastic syndrome (MDS) with iron overload and evaluate the changes of organ functions after iron chelation therapy. To explore the value of magnetic resonance imaging (MRI) T2* in making early diagnosis and assessing organs iron overload. Methods: Retrospective investigation was used to observe the cardiac T2* value, LIC, iron metabolism parameters and related laboratory parameters of 85 MDS patients from Nov 2014 to Jan 2018. Among them, 7 MDS patients with Low/Int-1 have received iron chelation therapy for 6 months during two MRI examinations. The above parameters were collected before and after iron chelation therapy for comparison. Results: Correlations were found between heart T2* value and age (rs=-0.290, P=0.007) and left ventricular ejection fraction (LVEF) (rs=0.265, P=0.009) . There was a significant negative correlation between heart T2* value and blood transfusion units (rs=-0.701, P<0.001) . There was a significant positive correlation between LIC and serum ferritin (SF) (rs=0.577, P<0.001) . There was also a correlation between LIC and ALT (rs=0.268, P=0.014) and blood transfusion units (rs=0.244, P=0.034) . There was no correlation between heart T2* and pro-BNP, SF (all P>0.05) , and no correlation between LIC and age (P>0.05) . The increase of heart T2* between the normal and abnormal groups was statistically significant (P=0.005) , but the iron overload ratio of the heart T2*<20 ms was not significant between the two groups. There was statistical significance in the proportion of severe liver iron overload (LIC>15 mg/g DW) (P=0.045) . After iron chelation therapy, the values of SF, transferrin saturation, ALT, AST, pro-BNP and LIC of 7 patients were decreased compared with values before iron chelation therapy, and the peripheral blood cell level was increased. However, the changes of LVEF and T2* values after iron chelation were not obvious. Conclusion MRI T2* may be a predictor of iron overload in patients with MDS in early stage, and may be more valuable compare with LVEF, SF and other laboratory indicators. The safety and repeatability of MRI cardiac T2* examination are recognized, and it can be used as an ideal detection for patients with iron overload.

Objective: To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms. Methods: The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment. Results: Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old (ranges: 17-85 years old) . According to the international prognostic scoring system (IPSS) , 46 cases were included in the relatively low risk group (low risk and intermediate-1 risk) , 63 in the relative high risk group (intermediate-2 and high risk) . There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4 (2-11) . A total of 74 patients achieved response (67.9%) and 30 (27.5%) achieved complete response (CR) . Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. (66.7%) , which was significantly higher than that of the patients without TP53 gene mutation (21.3%) (P=0.001) . Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor (OR=4.39, 95%CI, 1.20-16.06, P=0.026) . Conclusion TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.

OBJECTIVETo investigate the effect of human equilibrative nucleoside transporters 1 (hENT1) silencing on proliferation, apoptosis and demethylation of human myelodysplastic syndrome (MDS) derived cell line SKM-1 treated with 5-aza-2'-deoxycytidine (decitabine, DAC).

METHODShENT1 was silenced in SKM-1 cells mediated by lentivirus transfection. The infection efficiency was detected by flow cytometry, and the mRNA expression level of hENT1 was confirmed by qRT-PCR. The proliferation ratio of SKM-1 cells treated with different concentrations (0.5, 1, 5 mmol/L) of DAC for 24, 48 and 72 h was detected by CCK-8 method after hENT1 silencing. The apoptosis of SKM-1 cells was detected by Western blot for cleaved level of caspase-3 and evaluated by flow cytometry after staining with anti-Annexin V-PE and 7-AAD. The p15(INK4B) DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold™ Kit.

RESULTSThe expression level of hENT1 silenced group (0.253±0.030) was statistically decreased compared with that in control group (1.000±0.091) (P<0.01). Compared with control, the proliferation inhibition rate of hENT1 silenced group was significantly decreased by different concentrations of DAC (0.5, 1, 5 μmol/L) treatment for 24, 48, 72 h (P<0.05), which was (49.41±4.02)% and (33.03±2.47)%, respectively (P=0.007) at 5 μmol/L DAC treatment for 72 h in hENT1 silenced group and the control group. Western blot showed that cleaved caspase3 of hENT1 silenced group was also significantly inhibited. The percentage of Annexin Ⅴ⁺ cells and demethylation status of p15(INK4B) were significantly decreased.

CONCLUSIONApoptosis of hENT1 silenced SKM-1 cells induced by DAC was decreased, and the susceptibility of these cells to demethylation treatment was also decreased.

Apoptosis ; Azacitidine ; analogs & derivatives ; Caspase 3 ; Cell Line ; DNA Methylation ; Drug Resistance ; Equilibrative Nucleoside Transporter 1 ; Humans ; Lentivirus ; Myelodysplastic Syndromes ; Sincalide

OBJECTIVECompare the characteristics of magnetic resonance imaging（MRI）liver T2*, cardiac T2* and serum ferritin on the assessment of iron overload.

METHODSA total of sixty-nine patients from November 2011 to June 2014 were enrolled in this study. Their cardiac and liver iron concentration levels were measured through MRI examination, with other clinical data were collected to perform statistical analysis.

RESULTSThe correlation between liver T2* and adjusted serum ferritin（ASF） was statistically significant（P=0.003）. However, no significant correlation was found between cardiac T2* and liver T2*, ASF, respectively. According to the statistical analysis of the 69 cases, it is found that the number of iron overload cases diagnosed by liver T2* was 62 and 20 cases were severe iron overload （32.26%）; the number of iron overload cases diagnosed by ASF was 47 and 14 cases were severe iron overload（29.79%）, while the number of iron overload cases diagnosed by cardiac T2* was only 25 and no severe iron overload cases.

CONCLUSIONSince SF was affected by other factors, it cannot reflect the level of iron overload in human body objectively. Now, liver T2* has become the gold standard for assessment of iron overload because of its good reliability and repeatability. However, cardiac T2* cannot correctly be used as assessment for iron overload, and it is only a method of evaluating the level of cardiac iron deposition.

Ferritins ; blood ; Hematologic Diseases ; diagnosis ; Humans ; Iron Overload ; diagnosis ; Liver ; Magnetic Resonance Imaging ; Myocardium ; Reproducibility of Results

Adult ; Aged ; Aged, 80 and over ; Agranulocytosis ; chemically induced ; Azacitidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Neutrophils ; drug effects ; Young Adult

Objective To study the clinical features and differential diagnosis of Langerhans cell histiocytosis (LCH).Methods A case of LCH was reported and the literatures were reviewed.Results The of multisystem LCH patient,presented with a diabetes insipidus (DI) and panhypopituitarism,was 44 years old,and developed costal,tibial and femoral multiple lesions.The final diagnosis as LCH was made based on biopsy of tibia and lymph nodes.The biopsy specimen showed that the cells were infiltrated exhibiting the characteristic morphologic features of Langerhans cell (LC) with a convoluted shape,elongated nuclei exhibiting longitudinal grooves,and immunohistochemistry results revealed positive LC for the S-100,CD1a and Langerin immunostaining.Conclusions LCH may range from a solitary lytic bone lesion (for example eosinophilic granuloma) with a favorable course to a fatal disseminated leukaemia-like form.LCH typically involves the bone,lesions almost can be found in all organs.DI and CNS involvement often present as a puzzling syndrome,which renders the diagnosis problematicly,and often delays the diagnosis of LCH.The damage to the pituitary/hypothalamus axis results in life-long hormonal replacement therapy.

Objective To study the effect of decitabine treating elderly patient with myelodysplastic syndrome-ring sideroblastic refractory anemia (MDS-RAS) and review the literatures. Methods Decitabine treated a patient with MDS-RAS four courses, at the dose of 25 mg everyday for 5 days per course. Observed the change of symptoms, peripheral blood cell counts, myelogram, T cell polarization, cellular immunity,chromosome. Determined the curative effect combined with efficiency standard of WHO 2008. Results The clinical symptoms got better after two courses. Peripheral blood cell counts began to get better after one course. The number of leukocyte, hemoglobin and platelet got nearly normal after four courses. After two courses, T cell polarization state got normal, the number of iron ring promyelocyticin bone marrow declined from 16 % to 0 and chromosome changed from complex karyotype to normal. Conclusion Decitabine is an effective drug to the old patient with MDS-RAS. But it needs to increase the number of cases and follow up long-term to observe the effective rate and long-term efficacy.