Category: Statistics

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1248-1254. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.044.

ABSTRACT

OBJECTIVE: To investigate the effect of acute graft-versus-host disease (aGVHD) mouse models established respectively by total body irradiation (TBI) and busulfan combined with cyclophosphamide (BU/CY) conditioning regimens after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODS: Bone marrow cells and splenic mononuclear cells were isolated respectively from femur, tibia, and spleen of C57BL/6 male mice (H-2Kb) which were selected as donors. After TBI pretreatment, BALB/c female mice (H-2Kd) were injected with donor bone marrow cells 1×10⁷/50 μl and splenic mononuclear cells 2×10⁷/100 μl through caudal vein, while CB6F1 female mice (H-2Kd/b) with donor bone marrow cells 2×10⁷/100 μl and splenic mononuclear cells 1×10⁸/500 μl after BU/CY pretreatment. The successful establishment of the aGVHD models were determined by post-transplant manifestations, rate of chimerism, target organ damage, etc. Results: After transplantation, mice of both groups showed listlessness, low activity, continued weight loss, and typical manifestations of aGVHD such as alopecia, hunched posture, diarrhea, and anal swelling. and died within 4 weeks. Flow cytometry detection showed complete chimerism in all the mice. Pathological examination of skin, intestines, liver, lung, and spleen tissues showed obvious aGVHD pathological changes. However, the weight loss, ruffled fur, and alopecia combined with severe scurf on those hair-free areas were significantly apparent in TBI group than BU/CY group, as well as higher aGVHD score, and the differences were statistically significant (P<0.05).

CONCLUSION: Both TBI and BU/CY as conditioning regimens can successfully establish stable mouse models of aGVHD after fully allo-HSCT and haploidentical HSCT for further research about mechanism of aGVHD. BU/CY conditioning regimen can more truly simulate physiological status in vivo of patients with chemotherapy based conditioning regimen, while TBI conditioning regimen shows significantly more typical aGVHD symptoms and easier to operate.

PMID:35981393 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.044

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1182-1187. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.032.

ABSTRACT

OBJECTIVE: To investigate the molecular epidemiological characteristics of common δβ-thalassemia/hereditary persistence of fetal hemoglobin(HPFH) in the prepregnant population in Huadu, and to provide a laboratory basis for prevention and control of thalassemia.

METHODS: Blood samples of childbearing age people in Huadu District of Guangzhou who participated in free thalassemia testing from January 2016 to July 2021 were collected for hematological parameters analysis and hemoglobin electrophoresis. Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia, ^SEA-HPFH and Taiwanese deletion β-thalassemia were detected by Gap-PCR in the samples with higher HbF(≥5%). Primers were designed for the proximal HBG1 and HBG2 promoter, and the point mutations in the proximal promoter region were detected by Sanger sequencing. Hematology parameters data were statistically analyzed.

RESULTS: Among 27 088 samples, Thirteen cases of Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia and thirty-three cases of ^SEA-HPFH were detected, which including 3 cases of Chinese ^Gγ⁺(^Aγδβ)⁰/β^N compounded with —^SEA/αα and three cases of ^SEA-HPFH/β^N compounded with —^SEA/αα. 6 carriers with ^Aγ-196 C>T were also detected; No Taiwanese thalassemia genetype was detected. The total detection rate of common δβ-thalassemia/HPFH was 0.19% (52/27 088). There were significant differences in the levels of MCV, MCH, HbA₂, and HbF among Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia, ^SEA-HPFH, ^Aγ-196 C>T (P<0.001). The hematological parameters of ^Aγ-196C>T combined with α⁰-thalassemia were similar to those of Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia carriers, and only HbA₂ was significantly lower than that of the latter, which was helpful for clinical identification.

CONCLUSION: δβ-thalassemia/HPFH should be included in the scope of thalassemia prevention program in the prepregnant population in Huadu District, and hematological parameters can provide some basis for identifying different types of δβ-thalassemia/HPFH.

PMID:35981381 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.032

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1150-1155. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.027.

ABSTRACT

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching.

METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up.

RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05).

CONCLUSION: Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.

PMID:35981376 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.027

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1129-1133. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.023.

ABSTRACT

OBJECTIVE: To investigate an improved culturing method for karyotyping analysis, and increase the detection rate of cytogenetic abnormalities in patients with multiple myeloma (MM), so as to provide more powerful information for the clinical diagnosis, prognosis stratification, and individualized treatment of MM patients.

METHODS: Eighty newly-diagnosed MM patients were enrolled and divided into two groups. In observation group, IL-6 (10 ng/ml) and GM-CSF (30 ng/ml) were supplemented in the culture medium, while no stimulating factor was added in control group. The samples from both groups were cultured for 72 hours under the same conditions, and their karyotypes were analyzed by G-banding. The detection rate of the cytogenetic abnormalities, as well as the corresponding characteristics were compared between the two groups.

RESULTS: The detection rate of the chromosome aberrations was greatly increased in the observation group compared with the control group, the overall detection rate was 72.5% and 22.5%, respectively, as well as 80.0% and 19.2% in the subgroup of ≤60 years old, 68.0% and 28.6% in the subgroup of > 60 years old, which showed significant statistical differences (P<0.05).

CONCLUSION: The modification of the culturing method with the addition of IL-6 (10 ng/ml) and GM-CSF (30 ng/ml) dual stimulating factors followed by incubation for 72 hours can effectively increase the detection rate of abnormal karyotypes in MM patients.

PMID:35981372 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.023

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1086-1093. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.017.

ABSTRACT

OBJECTIVE: To analyze the predictive value of acute phase proteins (APPs) on the prognosis of patients with acute myeloid leukemia (AML).

METHODS: 293 AML patients who met the study requirements from January 2015 to April 2021 were collected, their clinical characteristics and pre-treatment APPs levels ［including albumin (ALB), fibrinogen (FIB), C-reactive protein (CRP), Ferritin (FER)］ were followed up and investigated. Pearson correlation coefficient was used to analyze the correlation between APPs. Logistic regression was used to analyze the risk factors for mortality in AML patients. ROC curve was used to analyze the predictive value of APP for mortality in AML patients, and Kaplan-Meier survival analysis was used to compare the effect of APPs on complete remission (CR) rate, overall survival (OS), disease-free survival (DFS), and progression-free survival rate (PFS) of AML patients.

RESULTS: Pearson correlation analysis showed that there were negative correlations between ALB and CRP (r=-0.134, P=0002), as well as ALB and FER (r=-0.148, P=0.001). There were correlations between FER and CRP (r=0361, P＜0.001), as well as FER and FIB (r=0.293, P＜0.001). Logistic regression analysis showed that advanced age (>50 years) (OR=1.87, 95% CI=1.25-2.15, P＜0.001), relapse after treatment (OR=2.11, 95% CI=111-3.18, P=0.003), FLT3-ITD mutation (OR=2.59, 95% CI=1.10-4.12, P＜0.001), CRP≥524 mg/L (OR=1.21, 95% CI=1.02-2.14, P=0.024), CFA (CFA=CRP*FIB/ ALB)≥3 (OR=2.41, 95% CI=1.65-6.47, P＜0.001), and FER≥1145.58 mg/ml (OR=1.67, 95% CI=1.15-3.75, P＜0.001) were the risk factors for the survival of AML patients. ROC curve analysis showed that FER (AUC=0.752, 95% CI=0.681-0823, P＜0.001, the best cut-off value=1220.56 mg/ml) and CFA (AUC=0.804, 95% CI=0.741-0.868, P＜0.001, the best cut-off value=3.00) had higher predictive value for the survival of AML patients. The remission rate, PFS, DFS, and OS in the low CFA group (CFA≤3) were significantly higher than those in the high CFA group (CFA＞3), and the overall mortality rate was lower than that in the high CFA group; the remission rate, PFS, DFS, and OS in the low FER group (FER≤1220.56 mg/ml) were significantly higher than those in the high FER group (FER＞1220.56 mg/ml), while the overall mortality rate was lower than that in the high FER group, and the difference is statistically significant.

CONCLUSION: The CFA value and FER level before treatment in AML patients can independently predict the prognosis of patients, and high levels of CFA and FER are associated with poor prognosis of AML patients.

PMID:35981366 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.017

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1071-1078. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.015.

ABSTRACT

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis.

METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient’s initial diagnosis, the relationship between the patient’s prognosis and CD47 was evaluated.

RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34⁺, CD38⁺, CD123⁺ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017).

CONCLUSION: The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.

PMID:35981364 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.015

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1063-1070. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.014.

ABSTRACT

AbstractObjective: To analyze the expression of FOSB in acute myeloid leukemia （AML） and its correlation with prognosis of the patient based on the large sample data.

METHODS: The genome, transcriptome, gene chip and clinical information from multiple public databases were statistical analyzed.

RESULTS: The expression of FOSB gene in AML patients was significantly higher than that in normal people. The prognostic analysis of the 163 patients showed that the patients with high FOSB expression showed longer OS and EFS than those with FOSB low expression. The patients were further divided into chemotherapy group and allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the treatment method, and then each group was divided into two subgroups (FOSBhigh, FOSBlow) according to the median expression level of FOSB. In the allo-HSCT group, the patients with FOSB high expression was longer event-free survival (EFS: P=0.017) and overall survival (OS: P=0029). At the same time, allo-HSCT in patients with high FOSB expression could improve the prognosis of the patients (Chemotherapy vs Allo-HSCT, OS: P<0.001, EFS: P=0.007). Multivariate analysis showed that the high expression of FOSB was an independent favorable prognostic factor for EFS and OS (EFS: HR=0.501， P=0.019; OS: HR=0.461， P=0.009) of the patients.

CONCLUSION: The high expression of FOSB indicated a good prognosis for acute myeloid leukemia.

PMID:35981363 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.014

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1056-1062. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.013.

ABSTRACT

OBJECTIVE: To observe the expression of helper T cells 17(Th17), interleukin 23 (IL-23) in peripheral blood in patients with acute myeloid leukemia (AML), to analyze the relationship between Th17, IL-23 in peripheral blood and immunophenotype.

METHODS: 105 patients with AML in the hospital from January 2019 to January 2021 were prospectively selected as the research subjects, the expression of Th17 and IL-23 in peripheral blood of patients with AML was detected by flow cytometry; immunophenotype was detected and counted. The relationship between the expression of Th17, IL-23 in peripheral blood and immunophenotype of AML patients was analyzed. Draw ROC curve and analyze the predictive value of Th17 and IL-23 expression in peripheral blood to immunophenotype.

RESULTS: The immunophenotype results of AML patients showed that myeloid antigen, lymphoid antigen and hematopoietic stem/progenitor cell marker antigen were positive expressed for various antigens in 105 AML patients, in myeloid antigens, CD13⁺ accounted for the highest proportion (93.33%), in lymphoid antigens, CD56⁺ accounted for the highest proportion (32.38%), and in hematopoietic stem/progenitor cell marker antigens, CD38⁺ accounted for the highest proportion (68.57%). The expression of Th17 in peripheral blood of AML patients with CD56⁺, CD7⁺, CD34⁺ and human leukocyte antigen DR⁺(HLA-DR⁺) were higher than that of AML patients with CD56^–, CD7^–, CD34^–, HLA-DR^–, the expression of IL-23 in peripheral blood of AML patients with CD56⁺, CD34⁺ and HLA-DR⁺ were higher than that of AML patients with CD56^–, CD34^–, HLA-DR^–, the differences were statistically significant (P<0.05); compared the expression of Th17 and IL-23 in peripheral blood between other antibody positive and negative patients, there was no statistical significant difference (P>0.05). Logistic regression analysis showed that the high expression of Th17 in patients with AML was related to the positive expression of CD56, CD7, CD34 and HLA-DR in the detection of immunophenotype, the high expression of IL-23 was related to the positive expression of CD56, CD34 and HLA-DR in the detection of immunophenotype. The ROC curve showed that the AUC of expression levels of Th17 and IL-23 in peripheral blood alone and in combination for predicting CD56⁺, CD34⁺, HLA-DR⁺ and Th17 in peripheral blood for predicting CD7⁺ were mostly 0.5-0.7, which had certain predictive value, but the predictive performance was low.

CONCLUSION: Myeloid antigen, lymphoid antigen and hematopoietic hematopoietic stem/progenitor cell marker antigen are positive expressed for various antigens in AML patients, the high expression of Th17 in peripheral blood of AML patients is related to the positive expression of CD56, CD7, CD34 and HLA-DR in detection of immunophenotyping, the high expression of IL-23 is related to the positive expression of CD56, CD34 and HLA-DR in the detection of immunophenotype.

PMID:35981362 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.013

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1034-1039. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.010.

ABSTRACT

OBJECTIVE: To investigate the effect of course delay of CCLG-ALL-2008 regimen on the relapse of paediatric B-cell acute lymphoblastic leukemia (B-ALL) patients.

METHODS: Paediatric B-ALL patients newly diagnosed and treated with CCLG-ALL-2008 regimen in the Children’s Hospital of Soochow University from January 2011 to December 2014 were retrospectively analyzed to clarify the relationship between chemotherapy course delay and relapse, and explore the causes of course delay which led to relapse. Patients were followed up until July 2019.

RESULTS: The correlation between treatment delay (number of weeks) and relapse rate was statistically significant (P=0.034), and hazard ratio indicated that longer than 4 weeks had a significant effect. The effect of positive minimal residual disease (MRD) (1×10^-4≤MRD≤1×10^-2) at the 12th week on the relapse rate was also statistically significant (P=0.041). Among the causes of treatment delay, the effect of myelosuppression on the relapse rate was statistically significant (P=0.01).

CONCLUSION: Treatment delay exceeding 4 weeks, positive MRD at the 12th week, and myelosuppression are independent prognostic factors for relapse.

PMID:35981359 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.010

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Aug;30(4):1022-1027. doi: 10.19746/j.cnki.issn.1009-2137.2022.04.008.

ABSTRACT

OBJECTIVE: To investigate the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the clinical efficacy and flow cytometry (FCM) minimal residual disease (MRD) of patients with acute myeloid leukemia (AML) after initial induction therapy in the real world.

METHODS: The clinical data of 44 AML patients who were diagnosed for the first time in the Department of Hematology, The Second Hospital of Anhui Medical University, and received the initial induction therapy were retrospectively analyzed. According to whether rhG-CSF was used after treatment, these patients were divided into control group and therapy group. The complete remission (CR) rate, duration of neutropenia, incidence of infection, duration of fever, cost of antibiotics drugs, length of hospital stay, FCM MRD, and relapse-free survival (RFS) time were compared between the two groups.

RESULTS: The CR rate in the control group was 60%, and 74% in the therapy group (P=0.3429). The duration of neutropenia was (21.28±7.91) days in the control group and (14.79±3.07) days in the therapy group (P=0.0016). The duration of fever was (12.80±7.31) days in the control group and (9.11±7.48) days in the therapy group (P=0.0136). While, there were no statistically significant differences between the two groups in the incidence of infection, cost of antibacterial drugs, length of hospital stay and RFS time (all P>0.05). In addition, it is particularly noteworthy that among the patients who finally obtained CR in the therapy group, 66% of them had myeloid precursor cells detected by peripheral blood FCM (accounting for 2.25%±0.99%) at the time of the first release of neutropenia, which was easy to be misdiagnosed as MRD positive.

CONCLUSION: rhG-CSF not only don’t affect the clinical remission rate after the initial induction treatment of AML, but also significantly shortens the time of duration of neutropenia and fever, however, it may affect the analysis of peripheral blood FCM MRD detection results when the neutropenia is released for the first time.

PMID:35981357 | DOI:10.19746/j.cnki.issn.1009-2137.2022.04.008