中国实验血液学杂志最新文献

Objective: To analyze the genotypes and distribution of thalassemia in Xindu District of Chengdu, in order to provide reference for the prevention and treatment of thalassemia in this area.

Methods: A total of 3 679 samples screened for thalassemia gene in Xindu District People's Hospital of Chengdu from June 2021 to April 2024 were selected as the study objects. Blood related parameters were detected by blood analyzer, hemoglobin composition was analyzed by capillary electrophoresis, and routine thalassemia gene detection was performed by PCR + flow-through hybridization. For the samples whose hematologic characteristics did not match the conventional results of thalassemia genes, the genotypes were determined by gene sequencing technology and the results were analyzed.

Results: Among 3 679 samples, 540 carriers were detected, the total detection rate was 14.68%. Among them, 329 cases were α-thalassemia, with a total of 8 genotypes. The top 3 genotype in frequency were --^SEA/ αα (45.29%, 149/329), - α^3.7/ αα (38.91%, 128/329), and - α^4.2 / αα (6.08%, 20/329). There were 197 cases of β-thalassemia, with a total of 10 genotypes, and the top 3 genotype in frequency were β ^{CD41-42 (-TCTT)}/β ^N (29.95%, 59/197), β ^CD17(A>T)/β ^N (27.92%, 55/197), and β ^{IVSII-654(C>T)} /β ^N (24.87%, 49/197). There were 14 cases of αβ-thalassemia, with a total of 12 genotypes, and the main were - α^3.7/ αα, β ^{IVSII-654(C>T)} /β ^N and - α^3.7/ αα, β ^{CD41-42 (-TCTT)}/β ^N . There was a rare thalassemia genotype (--^SEA/ HKαα). In addition, three rare abnormal hemoglobin mutations and one unreported abnormal hemoglobin mutation (HBA1:c.300+13C>G site heterozygous mutation) were also found.

Conclusion: The detection rate of thalassemia gene in this area is high and the genotype is complex. In gene diagnosis, we should pay attention to the combination of multi-technology detection to avoid missing rare genotypes.

Objective: To investigate the bone marrow and peripheral blood cytological characteristics and prognosis in acute myeloid leukemia (AML) with FLT3-ITD mutation.

Methods: A total of 106 newly diagnosed AML patients who were hospitalized in the First Affiliated Hospital of Xi'an JiaoTong University from January 2021 to December 2023 were collected, and divided into mutation group and non-mutation group according to the results of high-throughput sequencing of bone marrow specimens. The cytological characteristics of bone marrow smears and peripheral blood smears of patients in the two groups were analyzed at the time of initial diagnosis. The differences in the degree of hyperplasia, the proportion of leukemic cells, and the erythroblasts and megakaryocytes were compared between the two groups. What's more, the relationship between FLT3-ITD mutation status and characteristics of bone marrow and peripheral blood cells was analyzed.

Results: AML patients with FLT3-ITD mutation accounted for 24.53% of the hospitalized AML patients during the same period. Patients with peripheral blood leukocyte counts >30×10⁹/L accounted for 53%, and >100×10⁹/L accounted for 15% in FLT3-ITD mutation group. Compared with non-mutation group, the peripheral blood leukocyte count was significantly higher in the mutation group ( P <0.001), and the degree of hemoglobin decline was milder (P <0.05). The level of platelet was not significantly different between the two groups (P >0.05). The highest proportion of FAB subtypes were M2a and M5a in mutation group, which accounted for 38% and 27%, respectively. The proportion of extreme hyperplasia of bone marrow in the mutation group was 38.46%, which was higher than 23.75% in the non-mutation group. The proportion of peripheral blood and bone marrow leukemic cells in patients with high-frequency mutation were significantly higher than those in patients with low-frequency mutation (both P <0.01). The complete remission (CR) rate after the first induction chemotherapy was 38.46% and 65.00% in the mutation group and non-mutation group, respectively, and the CR rate after 2 courses of induction chemotherapy was 50.00% and 73.75%, respectively.

Conclusion: The FLT3-ITD mutation results in high proliferation and rapid progression of the bone marrow feature in AML patients, with less suppression of normal erythropoiesis. Increased mutation frequency is accompanied by increased leukemic tumor burden in the bone marrow and circulation, and patients with FLT3-ITD mutation have a low response rate to early induction therapy.

Objective: To clarify the prognostic significance of 1q21 amplification in multiple myeloma (MM), and explore the efficacy and prognosis of ixazomib in the treatment of MM patients with 1q21 amplification.

Methods: A retrospective analysis of clinical data was conducted on 77 patients with newly diagnosed MM who were hospitalized in Zhongshan Hospital, Xiamen University from January 2010 to December 2022. To analyze the clinical features of MM patients with 1q21 amplification, evaluate the mitigation rate and survival treated with ixazomib-based regimens.

Results: Among the 77 newly diagnosed MM patients, 40 patients had 1q21 amplification, while 37 didn't. Multivariate Cox regression analysis revealed that 1q21 amplification was an independent risk factor affecting the prognosis of MM patients (P < 0.05). Compared to patients without 1q21 amplification, those with 1q21 amplification had poorer progression-free survival (PFS) and overall survival (OS) (both P < 0.05). When the 1q21 amplification ratio exceeded 66.7%, both PFS and OS were worse (P < 0.05). There were no statistical differences in the deep remission rate (≥VGPR), overall response rate and PFS between the 1q21 amplification positive and negative groups treated with ixazomib-based regimens (P >0.05), but OS showed a significant difference (P < 0.05). Among the patients who switched to ixazomib treatment from bortezomib, there was a statistically significant difference in the complete response rate (P < 0.05). Compared to other treatment regimens, ixazomib-based regimens resulted in a significant reduction in adverse reactions such as peripheral neuropathy (P < 0.05).

Conclusion: Ixazomib-based chemotherapy regimens can overcome the poor prognosis associated with 1q21 amplification and improve mitigation rates and PFS in patients. Ixazomib has low incidence of adverse reactions, good safety profile and prolonged duration of therapy.

Objective: To investigate the mechanism of natural antigen B (nAgB) to protect Immune thrombocytopenia (ITP) mouse model by influencing autophagy.

Methods: Twenty-eight female BALB/c mice aged 8-10 weeks were randomly divided into four groups. 7 mice of each group were immunized intraperitoneally, the control group was treated with PBS as the control group; ITP group was treated with anti-CD41 monoclonal antibody (anti-CD41Ab) only; nAgB group was treated with nAgB intraperitoneal injection for 5d; nAgB+ITP group was treated with nAgB intraperitoneal injection for 5d, then treated with anti-CD41 Ab. The peripheral blood platelet count in each group was tested; and the spleen and liver should be isolated and weighed, the organ index was calculated; qRT-PCR was used to detect spleen microtubule-associated protein 1 light chain 3 ( LC3), p62, Beclin-1 mRNA expression levels. Western blot was used to detect the protein expression level of spleen LC3Ⅱ/LC3Ⅰ, p62, Beclin-1.

Results: Compared with the control group, mice in the ITP group showed a significant decrease in blood PLT count ［(102.1±17.9)×10⁹/L vs (485.4±185.2)×10⁹/L, P <0.01］, a significant increase in spleen index (P <0.01), mice in the nAgB group showed a significant increase in blood PLT count, rising to (1051±127.6)×10⁹/L on the 3 day after modeling. Compared with the ITP group, mice in the nAgB+ITP group showed a significant increase in PLT count on the 1 day of anti-CD41 Ab administration ［(428.6±131.6)×10⁹/L vs (102.1±17.9)×10⁹/L, P <0.05］, however, the spleen index was significantly decreased (P <0.05). qRT-PCR and Western blot results showed that compared with the control group, the mRNA and protein expression levels of spleen LC3, p62 and Beclin-1 were increased in the ITP group of mice (P <0.05, P <0.01). Compared with the ITP group, the nAgB+ITP group could significantly decrease mRNA levels of spleen LC3, p62 and Beclin-1 (P <0.05, P <0.01), and also significantly decrease the protein expression levels of LC3Ⅱ/LC3Ⅰ, p62 and Beclin-1 (P <0.05, P <0.01).

Conclusion: nAgB inhibits the transcription and expression levels of autophagy-related genes and regulates immune intolerance, thereby protecting ITP mouse models.

Objective: To explore the clinical value of plasma von Willebrand factor antigen (VWF:Ag) and VWF activity (VWF:GPIbM) based on ABO blood group in the risk assessment of deep vein thrombosis (DVT).

Methods: A total of 163 patients with DVT who sought medical treatment from March 2021 to December 2022 were selected as the case group, and 135 healthy volunteers during the same period were selected as the control group. The differences of ABO blood groups, plasma VWF:Ag and VWF:GPIbM levels between the two groups were compared. Receiver operating characteristic (ROC) curves were used to evaluate the clinical value of VWF testing in predicting DVT events. Logistic regression analysis was applied to identify risk factors for DVT.

Results: The levels of plasma VWF:Ag and VWF:GPIbM in the DVT group were significantly higher than those in the control group both overall and across ABO blood type subgroups (P < 0.01). Within the DVT group, the levels of plasma VWF:Ag and VWF:GPIbM in patients with non-O blood type were significantly higher than those with blood type O [VWF:Ag: 219.74%±63.64% vs 162.21%±56.03%, P < 0.01; VWF:GPIbM: 228.10% (185.15%, 249.10%) vs 148.25% (116.48%, 225.48%), P < 0.01]. The area under the ROC curve (AUC) of VWF:Ag for predicting DVT events was 0.855, with a cut-off value of 142.4%, sensitivity of 82.2% and specificity of 72.6%; the AUC of VWF:GPIbM was 0.861, with a cut-off value of 141.2%, sensitivity of 84.7%, and specificity of 71.1%. Univariate analysis showed that both VWF:Ag and VWF:GPIbM were influencing factors for DVT events (P < 0.05). Multivariate logistic regression analysis indicated that VWF:Ag>142.4% (OR=13.961, 95%CI : 7.654-25.464, P < 0.01) and VWF:GPIbM>141.2% (OR =17.615, 95%CI : 9.155-33.892, P < 0.01) were independent risk factors for DVT events.

Conclusion: Levels of VWF:Ag and VWF:GPIbM are significantly elevated in non-O blood type DVT patients. VWF:Ag>142.4% and VWF:GPIbM>141.2% are independent risk factors for DVT events. VWF testing based on ABO blood group aids in the precision prevention and control of DVT.

Objective: To explore the efficacy and drug-related toxicity of pediatric patients with recurrent and refractory Langerhans cell histiocytosis(LCH).

Methods: The clinical data of 38 children with refractory and recurrent LCH diagnosed in the Department of Hematology and Oncology of Wuhan Children's Hospital from January 2016 to June 2023 were retrospectively analyzed. The patients received three treatment regimens: regimen A was Cytarabine and Dexamethasone combined with Vindesine, regimen B was Cladribine with Cytarabine, and regimen C was Clofarabine monotherapy. The efficacy and safety of three second-line regimens were evaluated.

Results: Thirty-eight children with refractory and recurrent LCH included 22 males and 16 females, with an age at diagnosis of 2.4(0.4-11.5) years. The median follow-up time was 5.5(1.5-8.5) years. Twenty-one children without risk organ involvement were treated with regimen A, and the 5-year overall survival (OS) rate was 100%, and event-free survival (EFS) rate was (85.7±8.8)%. Among the 17 children with risk organ involvement, 11 cases were treated with regimen B, after 4 courses of treatment, 6 cases achieved no active disease (NAD) and 5 children achieved active disease better (ADB), and 5-year OS rate reached 100%, and 5-year EFS reached 81.8%±11.6%；6 cases were treated with regimen C, and after 6 courses of treatment, 4 cases achieved ADB and 2 cases achieved NAD. Children in group A had hematologic adverse reactions (WHO grade Ⅰ-Ⅲ), all children in group B had hematologic adverse reactions (WHO grade Ⅳ), and three cases had hepatobiliary adverse reactions (WHO grade Ⅱ), and children in group C had hematologic adverse reactions (WHO grade Ⅱ).

Conclusion: The second-line treatment regimens for children with recurrent and refractory LCH based on the involvement of organs at risk has significant efficacy, and further expansion of the sample size and optimization of the treatment regimens are still needed to reduce long-term recurrence rates and toxicity of the treatment.

Objective: To explore the correlation between serum ferritin (SF) levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.

Methods: Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected. The platelet corrected count increment (CCI) was used to evaluate the efficacy of platelet transfusion. The correlations between sex, age, disease type, transplantation history, red blood cell transfusion history, and SF level and the efficacy of platelet transfusion were analyzed.

Results: A total of 87 patients were included, with a cumulative 326 person-times platelet transfusions. As suggested by one-way analysis of variance, compared with the patients in the age groups of 24-45 years old and 46-66 years old, the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion (P =0.004, P =0.004). There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old (P =0.876). Compared with the patients who had a history of red blood cell transfusion within 3 days, the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion (P < 0.001). Compared with the groups with SF levels of 1.44-2.78 ng/L and >2.78 ng/L, the group with SF levels < 1.44 ng/L had a better efficacy of platelet transfusion (P =0.028, P < 0.001). Compared with the group with SF levels >2.78 ng/L, the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion (P =0.001). After adjusting for age and the history of red blood cell transfusion, the transfusion efficacy of the group with SF levels < 1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and >2.78 ng/L (P =0.021, P < 0.001); Compared with the group with SF levels >2.78 ng/L, the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion (P =0.001). Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion (P < 0.001).

Conclusion: There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases. Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.

Objective: To explore the expression level of m⁶A methyltransferase ZC3H13 gene in primary acute myeloid leukemia (AML) and its relationship with clinical features and prognosis.

Methods: A total of 131 newly diagnosed AML patients and 12 controls were enrolled from July 1, 2018 to December 1, 2021 in the Hematology Department of the Second Hospital of Shanxi Medical University. RT-qPCR technology was used to detect the expression level of ZC3H13 mRNA in bone marrow (BM) samples. A retrospective analysis was conducted to examine the correlation between ZC3H13 expression level and clinical indicators, gene mutations, and prognosis.

Results: The expression level of ZC3H13 mRNA in primary AML patients was significantly higher than that in the control group ( P <0.001). The white blood cell count, proportion of BM blast cells, and relapse rate in the high ZC3H13 expression group were higher than those in the the low ZC3H13 expression group (all P <0.05), while the Th/Ts ratio was lower ( P <0.01). Univariate survival analysis showed that patients with high expression of ZC3H13 had shorter median overall survival (OS) and disease-free survival (DFS) than those with low expression of ZC3H13 (both P <0.05). The results of multivariate Cox regression analysis showed that high-risk stratification (OS:HR=1.612, 95% CI : 1.151-2.257, P =0.005; DFS:HR=1.551, 95% CI : 1.031-2.335, P =0.035) and high ZC3H13 expression (OS:HR=1.756, 95% CI : 1.028-2.999, P =0.039; DFS:HR=1.935, 95% CI : 1.018-3.678, P =0.044) were both independent risk factors for OS and DFS in AML patients.

Conclusion: The expression of ZC3H13 in AML patients may be related to tumor burden and immune function. Patients with high expression of ZC3H13 have poor prognosis, and high expression of ZC3H13 is an independent risk factor for the prognosis of AML patients.

Objective: To analyze the clinical characteristics and prognosis of children with hematological malignancies complicated by secondary hemophagocytic lymphohistiocytosis (HLH).

Methods: A total of 67 children with HLH admitted to Jinan Second Maternal and Child Health Hospital between June 2020 and June 2024 were selected. Children without hematological malignancies were divided into the non-combined group, and those with hematological malignancies were divided into the combined group. The clinical characteristics and prognosis of the two groups were analyzed.

Results: There were no significant differences in clinical characteristics such as WBC, Hb, PLT between the two groups (P ＞0.05). During the follow-up, the 1- and 2-year overall survival (OS) rates for all children were (88.6±4.1)% and (73.1±7.7)%, respectively. In the non-combined group, 43 children survived and 6 died, with 1- and 2-year OS rates of (95.2±3.3)% and (77.4±9.3)%, respectively. In the combined group, 12 children survived and 6 died, with 1- and 2-year OS rates of (71.8±10.7)% and (62.8±12.6)%, respectively. The OS rate of the combined group was significantly lower than that of the non-combined group (χ²=4.787, P =0.029). The 1- and 2-year event free survival (EFS) rates of the combined group were (61.1±11.5)% and (50.9±13.3)%, respectively.

Conclusion: Children with hematological malignancies complicated by secondary HLH exhibit complex and diverse clinical characteristics. Although favorable short-term therapeutic effects can be achieved, their long-term prognosis tends to be less optimistic.

Objective: To analyze the effect of high serum ferritin (SF) before transplantation on erythrocyte, granulocyte and platelet implantation in unrelated cord blood transplantation (UCBT) patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Methods: The medical records of 60 patients with MDS and AML who underwent UCBT in the First Affiliated Hospital of University of Science and Technology of China from January 2020 to December 2022 were retrospectively collected. According to the SF level before transplantation, they were divided into high SF group (SF≥1 000 μg/L, n=20) and non-high SF group (SF<1 000 μg/L, n=40). The red blood cell (RBC) infusion volume before transplantation, implantation time of RBC, granulocyte and platelet, implantation risk and prognosis were analyzed and compared between the two groups.

Results: There was no correlation between the level of SF before transplantation and RBC infusion. After transplantation, the median implantation time of RBC in the high SF group was 28.5(14-149) d, which was longer than 21(10-83) d in the non-high SF group ( P < 0.05). The median time of granulocyte engraftment in the high SF group was 16.5(12-63) d, while that in the non-high SF group was 16(12-49) d, with no statistical difference between the two groups (P >0.05). The median platelet engraftment time in the high SF group was 45(12-206) d, while that in the non-high SF group was 35.5(14-149) d, with no statistical difference between the two groups (P >0.05). Kaplan-Meier cumulative implantation probability analysis showed that the rate of erythroid implantation in the non-high SF group was higher than that in the high SF group ( P < 0.05), while there was no significant difference in the rates of granulocyte and platelet implantation between the two groups (P >0.05). The 1-year overall survival rates of the non-high SF group and high SF group were 95% and 90%, respectively, with no statistical difference between the two groups (P >0.05).

Conclusion: SF levels before cord blood transplantation in MDS and AML patients have an impact on post transplant erythroid implantation. Detecting and intervening of iron load in patients before transplant may be beneficial for improving implantation and prognosis.