Objective:To explore the efficacy and feasibility of hypomethylating agent (HMA) as preventive therapy in children with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study. Data from 173 children who underwent allo-HSCT for high-risk AML at Children′s Hospital of Soochow University between August 2019 and April 2023 were analyzed. Participants were categorized into a trial group receiving HMA and a control group. Further classification was based on HMA courses:≥4 and <4 courses. The efficacy and safety of HMA preventive treatment after allo-HSCT were evaluated. Survival analysis was performed using the Kaplan-Meier method with Log-Rank testing, the Fine-Gray model was used to assess cumulative relapse rates and Cox regression was used to identify prognostic factors. Adverse events during HMA were descriptively analyzed.Results:Among 173 patients, there were 100 males (57.8%) and 73 females (42.2%), with the age of 81 (34,127) months. The starting time of HMA was 123 (91, 191) d post-transplant, continuing 4.0 (3.0, 6.5) courses and the follow-up period was 24 (13, 32) months. The trial group (53 cases) showed better 2-year overall survival (OS) rate ((88.6±5.6)% vs. (76.6±4.3)%, χ 2=5.00, P=0.025) and relapse-free survival (RFS) rate ((89.2±4.7)% vs. (56.2±4.8)%, χ 2=15.75, P<0.001) than control group (120 cases). The 2-year OS rates and RFS rates were similar between ≥4 courses group (31 cases) and <4 courses group (22 cases)(both P>0.05). The cumulative relapse rate in the trial group was significantly lower ((10.8±0.2)% vs. (35.2±0.2)%, χ 2=10.84, P=0.001) than control group. Among children with molecular relapse, 8 cases (8/30, 26.7%) in the control group had hematological relapse compared to 1 case (1/2) in the trial group ( χ 2=0.81, P=0.369). The differences in incidence of acute and chronic graft-versus-host disease (GVHD) were not statistically significant (all P>0.05). Cox regression analysis revealed that minimal residual disease (MRD) positivity detected by flow cytometry before allo-HSCT and chronic GVHD were independent risk factors for OS (both P<0.05).The HMA preventive treatment was an independent protective factor for RFS, while age ≥10 years and MRD positivity detected by PCR before allo-HSCT were independent risk factors for RFS (all P<0.05). In trial group, 38 cases experienced grade 3 to 4 adverse events (71.7%). Conclusion:HMA is safe as preventive treatment in post-transplant children with high-risk AML, which can reduce the relapse risk and doesn't increase the risk of GVHD.

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:To explore the efficacy and feasibility of hypomethylating agent (HMA) as preventive therapy in children with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study. Data from 173 children who underwent allo-HSCT for high-risk AML at Children′s Hospital of Soochow University between August 2019 and April 2023 were analyzed. Participants were categorized into a trial group receiving HMA and a control group. Further classification was based on HMA courses:≥4 and <4 courses. The efficacy and safety of HMA preventive treatment after allo-HSCT were evaluated. Survival analysis was performed using the Kaplan-Meier method with Log-Rank testing, the Fine-Gray model was used to assess cumulative relapse rates and Cox regression was used to identify prognostic factors. Adverse events during HMA were descriptively analyzed.Results:Among 173 patients, there were 100 males (57.8%) and 73 females (42.2%), with the age of 81 (34,127) months. The starting time of HMA was 123 (91, 191) d post-transplant, continuing 4.0 (3.0, 6.5) courses and the follow-up period was 24 (13, 32) months. The trial group (53 cases) showed better 2-year overall survival (OS) rate ((88.6±5.6)% vs. (76.6±4.3)%, χ 2=5.00, P=0.025) and relapse-free survival (RFS) rate ((89.2±4.7)% vs. (56.2±4.8)%, χ 2=15.75, P<0.001) than control group (120 cases). The 2-year OS rates and RFS rates were similar between ≥4 courses group (31 cases) and <4 courses group (22 cases)(both P>0.05). The cumulative relapse rate in the trial group was significantly lower ((10.8±0.2)% vs. (35.2±0.2)%, χ 2=10.84, P=0.001) than control group. Among children with molecular relapse, 8 cases (8/30, 26.7%) in the control group had hematological relapse compared to 1 case (1/2) in the trial group ( χ 2=0.81, P=0.369). The differences in incidence of acute and chronic graft-versus-host disease (GVHD) were not statistically significant (all P>0.05). Cox regression analysis revealed that minimal residual disease (MRD) positivity detected by flow cytometry before allo-HSCT and chronic GVHD were independent risk factors for OS (both P<0.05).The HMA preventive treatment was an independent protective factor for RFS, while age ≥10 years and MRD positivity detected by PCR before allo-HSCT were independent risk factors for RFS (all P<0.05). In trial group, 38 cases experienced grade 3 to 4 adverse events (71.7%). Conclusion:HMA is safe as preventive treatment in post-transplant children with high-risk AML, which can reduce the relapse risk and doesn't increase the risk of GVHD.

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:To establish an animal model of acute systemic cold injury in mice.Methods:There were 98 C57BL/6 mice, half male and half female, with body weight of 22-27 g and age of 10 weeks. The mice were randomly divided into 7 groups ( n=14) according to the changes of anal temperature in cold environment, namely, group A (38.5 ± 1) ℃, group B (35 ± 1) ℃, group C (30 ± 1) ℃, group D (25 ± 1) ℃, group E (20 ± 1) ℃, group F (15 ± 1) ℃, and group G (10 ± 1) ℃, among which, group A was the blank control group, and the rest groups were the experimental group. The mice in the blank control group were placed in the normal environment (20 ± 5) ℃, and the mice in the experimental group were placed in the low temperature artificial climate box at - 20℃. The anal temperature of the mice was measured intermittently (as the core temperature), and the time required for the core temperature of the mice to drop to groups B, C, D, E, F and G was recorded. The righting reflex was used to evaluate the consciousness state, the action ability and the general state of each organ of mice were observed, and the blood routine and HE staining of each organ were detected. Results:The lower the core temperature of the experimental group, the longer the time required. The consciousness state, action ability, general state of organs, blood routine, and HE staining of organs in groups B, C, and D were basically the same as those in group A, and there was no acute systemic cold injury. Therefore, the blood routine, general observation of organs, and HE staining of organs in groups B, C, and D were no longer displayed compared with those in group A. Compared with group A, mice in group E began to suffer from disturbance of consciousness and action ability. With the decrease of core body temperature, the damage was aggravated, and mice in group G died. Compared with group A, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group E began to decrease, and the univariate variance calculation showed that only WBC changes had statistical significance ( P<0.05). Compared with groups A and E, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group F were further reduced, and the changes of each index in univariate variance calculation were statistically significant ( P<0.05). The general observation results showed that compared with group A, the lung, liver and spleen surfaces of mice in group E began to darken, and compared with groups A and E, the lung, liver, spleen, kidney and heart of mice in group F were further deepened and darkened, with irregular edges. HE staining results of various organs showed that compared with group A, the mice in group E began to have partial alveolar structure destruction and a small amount of inflammatory cell infiltration, the central vein of the liver was slightly congested, and the red and white pulp of the spleen were indistinct. Compared with groups A and E, the pathological structure damage of the lung, liver, spleen, kidney, heart and brain tissues of the mice in group F was further aggravated. Conclusions:Detection of consciousness state, action ability, general state of organs, blood routine and HE staining indices of organs in mice under low temperature can simulate the progress of clinical acute cold injury, and the animal model of acute systemic cold injury was successfully prepared.

Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.

Griscelli syndrome type Ⅱ (GS2) is a rare disease, and patients with GS2 are susceptible to secondary haemophagocytic lymphohistiocytosis (HLH). GS2 accompanied by secondary HLH has a dangerous clinical course, high mortality, and a high miss-diagnosis rate.In this paper, the pathogenesis and prognosis of a case confirmed as GS2 with secondary HLH by gene screening were reported, so as to improve diagnosis and treatment of this disease.The patient had clinical manifestations of silver hair and eye lashes, recurrent pulmonary infection, contiuning high fever, significantly increased ferroprotein levels and decreased fibrinogen levels.Besides, RAB27A gene homozygous mutations were found in the patient, originating from her parents (p.P126Qf3*3 frameshift mutation). This finding confirmed the diagnosis of GS2.The patient underwent transplantation of marrow stem cells from her father since the father-daughter HLA was 7/10.The follow-up results showed that the patient was still alive and healthy 2 years after transplantation.

Breast cancer is the most common cancer for Chinese women. Early screening is the best way to improve the rates of early diagnosis and early treatment of breast cancer. The peak ages of breast cancer in Chinese women are obviously different from those in the European and American countries. It is imperative to develop a guideline for breast cancer screening that is suitable for Chinese women. Based on the analysis and summary of breast cancer screening data in China, and the latest guidelines and consensus on breast cancer screening in Europe, the United States and East Asia, China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) has developed a population-based guideline for breast cancer screening in Chinese women. This guideline has provided detailed recommendations on the screening starting age, screening modalities, and screening interval in Chinese women with average risk and high risk of breast cancer, respectively. This article aims to interpret the above guideline, providing references for professionals in breast cancer screening.

Objective: To evaluate the efficiency and safety of low intensity conditional regimen for children with Fanconi anemia (FA) receiving allogenic hematopoietic stem cells transplantation (allo-HSCT). Methods: Four patients diagnosed as Fanconi anemia were enrolled in this study. One patient received HLA-identical sibling donor hematopoietic stem cell transplantation, two patients underwent unrelated donor matched (UD) HSCT, and one patient received unrelated cord blood transplantation. The conditional regimen consisted of Busulfan with low dose of cyclophosphamide. Results: All 4 cases succeeded in allo-HSCT. The median time for neutrophils engraftment was 11(9-15) day, median time to platelets (PLT) engraftment was 12 (8-28) day. One case occurred with grade I of aGVHD, 1 case with hemorrhagic cystitis. No patient happened with hepatic veno-occlusive disease (VOD). Conclusion Low intensity of conditional regimen is efficient and safe which should be recommended for FA patients with HSCT.

Objective To compare the efficacy and safety of induction therapy in 3+7 protocol and 3+10 protocol in children with acute myeloid leukemia (AML). Methods Two protocols were carried out in our hospital during January 2010 to January 2015, namely 3+7 protocol(AML-06,A group) and 3+10 protocol (modified AML protocol, B group). A total of 56 cases aged from 1 year-old to 13 year-old were enrolled in A group with male to female ratio at 31:25. Five of them were classified as FAB M1, 25 as M2, 11 as M4, 10 as M5, 2 as M6 and 3 as M7. Another 44 cases aged from 1 year to 12 years were enrolled in B group with a male to female ratio at 26:18, and 17 cases were classified as FAB M2, 14 as M4, 9 as M5, 2 as M6, and 2 as M7. Efficacy and adverse events were compared between the two groups. Results The complete remission rate (CR) of B group was 70.4%, while CR in A group was 48.2%. Considering the CR, 3+10 protocol showed higher efficacy than 3+7 protocol (P< 0.05). The major adverse event was bone marrow suppression. Treatment-related mortality (TRD) in A group was 1.8%, which was lower than that in B group (2.3%). The overall survival rate in A group was 75.0%, which was lower than that in B group (86.4%, P< 0.05). Conclusions The induction therapy of 3+10 protocol and 3+7 protocol showed effectiveness for AML treatment. The 3+10 protocol showed a higher CR than 3+7 protocol with no TRD increase, indicating that the 3+10 protocol should be recommended for AML treatment in children.