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Background: Clonorchis sinensisis a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensisinfection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown. Methods:Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples. Results:Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcusabundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensismay promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair. Conclusions:This study provides comprehensive insights into the pathological effects of C. sinensisinfection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensispathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions.

C-type lectin-like molecule-1 (CLL1) is preferentially expressed on acute myeloid leukemia (AML) stem cells and AML blasts, which can be considered as AML-associated antigen. Anti-CLL1-based CAR-T cells exhibited effective tumor-killing capacity in vitro and in AML-bearing mouse model. In this report, eight children with relapsed or refractory AML (R/R-AML) were recruited for a phase 1/2 clinical trial of autologous anti-CLL1 CAR-T cell immunotherapy. The objectives of this clinical trial were to evaluate the safety and the preliminary efficacy of anti-CLL1 CAR-T cell treatment. Patients received one dose of autologous anti-CLL1 CAR-T cells after lymphodepletion conditioning. After CAR-T treatment, patients developed grade 1–2 cytokine release syndrome (CRS) but without any lethal events. 4 out of 8 patients achieved morphologic leukemia-free state (MLFS) and minimal residual disease (MRD) negativity, 1 patient with MLFS and MRD positivity, 1 patient achieved complete remission with incomplete hematologic recovery (CRi) but MRD positivity, 1 patient with partial remission (PR), and 1 patient remained at stable disease (SD) status but had CLL1-positive AML blast clearance. These results suggested that anti-CLL1-based CAR-T cell immunotherapy can be considered as a well-tolerated and effective option for treating children with R/R-AML.

To identify the prognostic factors that are useful to improve central nervous system (CNS) control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on Chinese Children’s Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% confidence interval [CI], 78.9-81.7), and overall survival 91.1% (95% CI, 90.1-92.1). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5-2.3), and any CNS relapse 2.7% (95% CI, 2.2-3.2). The isolated CNS relapse rate was significantly lower in patients with B-cell ALL (B-ALL) than in those with T-cell ALL (T-ALL) (1.6%; 95% CI, 1.2-2.0 vs 4.6%; 95% CI, 2.9-6.3; P < .001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1-3.0; P = .03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0-7.3; P < .001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5-12.2; P = .007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and flow cytometry examination of diagnostic cerebrospinal fluid (CSF) (HR, 0.2; 95% CI, 0.06-0.6; P = .006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic CSF may improve CNS control in childhood ALL. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).

TCRαβ-Depleted HLA-haploidentical Stem Cell Transplantation represents a promising curative option for children with R/R-ALL. However, disease recurrence remains the primary cause of treatment failure. We developed a novel approach using CarT pre-HSCT and prophylactic haplo-DLI post-HSCT to decrease the relapse and improve transplant outcomes.

IMPORTANCE: A randomized clinical trial is needed to determine whether the second-generation Abl–tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL). OBJECTIVE: To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome–positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. DESIGN, SETTING, AND PARTICIPANTS: This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. INTERVENTIONS: Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. RESULTS: Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups. CONCLUSIONS AND RELEVANCE: Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome–positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IPR-14005706

Background

Objective:To compare the relationship among immune reconstitution, graft-versus-host disease (GVHD), and viral infections in three kinds of hematopoietic stem cell transplantation(HSCT) using different host sources for thalassemia major(TM) patients: matched unrelated donor (MUD) HSCT, haploidentical (Haplo) HSCT with post-transplant cyclophosphamide (PTCy)-based prophylactic therapy, and TCRαβ-T cell-depleted HSCT (TDH).

Background: Hematopoietic stem cell transplantation (HSCT) can ultimately cure various hematological disorders. Building upon the basis of post-transplant cyclophosphamide (PT-cy) haploidentical HSCT, we innovatively employed a combination of haploidentical related donors and unrelated cord blood donors for complementary transplantation to treat pediatric leukemia and severe thalassemia. This approach has been successful, and complementary transplantation has become an important option in haploidentical HSCT. However, with the development of haploidentical HSCT and the long-term use of immunosuppressive agents, viral infections have gained increasing attention, and human herpesvirus 6 (HHV-6) is one of the concerning viruses. HHV-6 exists in two variants, HHV-6A and HHV-6B, with HHV-6B being the common infection in HSCT. HHV-6B is characterized by a preference for lymphocytes and neurons and can easily reactivate in patients with compromised immune systems after HSCT, leading to severe and irreversible brain and nerve damage, and in severe cases, death. In this study, we aim to identify the susceptible factors for HHV-6B infection in cases of complementary transplantation, with the goal of improving the safety of complementary transplantation in HSCT.

Background:Venetoclax, in combination with hypomethylating agents or low-dose cytarabine, is approved for newly diagnosed acute myeloid leukemia (AML) patients who are over 75 years of age or not eligible for intensive chemotherapy, while the efficacy of venetoclax-based regimens in young fit AML patients still needs to be further explored. Although the combination of anthracycline and cytarabine has achieved a remission rate of about 70% in these patients, the low complete response rate in adverse-risk patients, strong adverse reactions, and long duration of myelosuppression limited the clinical benefit. We presumed that venetoclax plus azacitidine in combination with low-intensity regimens CAG (G-CSF priming, low dose cytarabine, and aclarubicin) could have a better composite complete remission with an acceptable safety profile.

We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P< .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P< .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available.

We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available.

To provide a detailed insight into the early biological process of tobacco mosaic disease, transcriptomic changes in tobacco leaves were surveyed at 1, 3 and 5 days after mono-infected by Tobacco mosaic virus(TMV) and co-infected by Cucumber mosaic virus(CMV) and TMV. At the three different stages, there were 2372, 3168 and 2045 differentially expressed genes (DEGs) in mono-infected leaves, and 2388, 3281 and 3417 DEGs were identified in co-infected leaves. There were 836, 1538 and 1185 common DEGs between the mono-infection and co-infection at the three time points, respectively. These common DEGs were enriched in the pathways, such as photosynthesis, biosynthesis of secondary metabolites, plant–pathogen interaction, porphyrin and chlorophyll metabolism, phenylalanine metabolism and phenylpropanoid biosynthesis. Photosynthesis pathway was observably down-regulated, and defense response pathways were markedly up-regulated. These pathways have been found to be related to tobacco mosaic disease. Of these common DEGs, the changes in expression of argonaute proteins, thioredoxins and peroxidases showed that the activation of RNA silencing and the destruction of redox balance can be induced by tobacco mosaic virus infection, resulting in the reset of biology process and damage in tobacco plants. Additionally, the occurrence of symptoms in co-infected tobacco plants was more early and serious than mono-infection, indicating that there is synergy between TMV and CMV in co-infected tobacco plants. The timely usage of antiviral agents and plant resistance inducers can decrease the incidence of tobacco mosaic disease through changing the expression of some DEGs, indicating that these genes can be used to screen novel plant resistance inducers and antiviral agents. Overall, our results were helpful in clarifying the mechanism of tobacco mosaic disease and provided novel strategies for the prevention of tobacco mosaic disease.

ObjectivesBefore 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children’s Cancer Group ALL protocol between 2015 and 2016.MethodsDemographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government.ResultsAt a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications.ConclusionsThe rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment.Clinical trial registration numberChiCTR-IPR-14005706, pre-results.

In our investigation, the fluoride content of surface water in northern China exceeds the standard, and accompanied by the problem of eutrophication. At present, there have been many studies on the coagulation treatment of pure fluoride-polluted waters, but the removal of fluoride in the waters containing algae has received little attention. In this paper, a typical type of cyanobacteria, M. aeruginosa, was chosen, and two coagulants (AlCl3and FeCl3) were selected to explore the difference and mechanism of algae on the coagulation removal of fluoride. Results indicated that when AlCl3dosage was between 1.0 mmol/L and 1.5 mmol/L, M. aeruginosacontributed to efficient fluoride removal because algae promoted the adsorption of F by increasing the distribution of Al(OH)3. In particular, M. aeruginosaincreased the F removal rate by 50.22% at 1.5 mmol/L AlCl3dosage. However, FeCl3showed unsatisfactory effects on fluoride removal. The residual Al/Fe in the coagulated effluent showed that M. aeruginosafixed large quantities of Fe, same with AlCl3, manifesting no selectivity in adhering metals. Besides, FeCl3had appeared to be more advantageous in removing organic matters. In particular, the high complexation capacity between HA and FeCl3caused the blockage and competition of the adsorption sites, which was why the presence of algal cells had no obvious promoting effect on fluoride removal by FeCl3. In addition, the HA flocs formed by using AlCl3also had an excellent ability to adsorb F-, suggesting that other substances in waters could promote the fluoride removal, not just M. aeruginosa.

No relevant conflicts of interest to declare.

Backgroud and purpose

No relevant conflicts of interest to declare.

We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with β-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TM-free survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat β-thalassemia patients in the absence of MSDs.

We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with ॆ-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TM-free survival were 92.37 and 90.47 in the UD-PBSCT group and 90.07 and 83.37 in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.97 and 9.67, respectively, in the UD-PBSCT group and 6.97 and 3.67, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.77 in the UD-PBSCT group and 10.07 in the MSD-HSCT group. In conclusion, UD-PBSCTs using the well-tolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat ॆ-thalassemia patients in the absence of MSDs.

Regarding children's patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), disease relapse remains the most common reason for transplant failure and patient death. We implemented a single center study to investigate hypomethylating agents (HMA) as maintenance treatment after HSCT for children AML or MDS. We retrospectively analyzed 30 patients with AML or MDS including 63 courses of azacytidine (AZA) and 69 courses of decitabine (DEC) from January 1, 2018 to June 30, 2021 (Figure 1A). Either AZA (37.5mg/m 2to 75 mg/m 2for consecutive 5-7 days) or DEC (5 mg/m 2for consecutive 5 days) was administrated 90 days post-transplantation as first course. Furthermore, the interval of HMA treatment was 1.5-month hereafter for in total of a year (Figure 1B). Patients that received at least one course of HMA treatment were included in this study. The patient characteristics was shown in Table 1. We found that the disease-free survival (DFS) and overall survival (OS) were 82.96±6.95% and 85.51±6.72%, respectively (Figure 1C, D). Based on Common Terminology Criteria for Adverse Events (CTCAE) criteria, only Grade 1 to 2 leukopenia (P<0.001), anemia (P=0.043), and thrombocytopenia (P=0.033) were found between complete blood count (CBC) of pre-treatment and post-treatment. Subgroup analysis indicated that the difference was mainly come from DEC group [leukopenia (P<0.001), anemia (P=0.001), and thrombocytopenia (P=0.190)] instead of AZA group [leukopenia (P=0.476), anemia (P=0.443), and thrombocytopenia (P=0.095)]. No nausea/vomiting, or elevated ALT, or elevated creatinine, or rash, or de novo/exacerbated GVHD were observed. Moreover, there were no difference of activation T cells populations (CD25 and HLA-DR) among 7 courses except CD3+HLADR+/CD3+ and CD8+HLADR+/CD8+ in course 1 vs course 4 (P= 0.0354 and P=0.0163, respectively, Figure 1E). Furthermore, a trend of increased percentage of CD3+HLADR+/CD3+, or CD4+HLADR+/CD4+, or CD8+HLADR+/CD8+ and decreased percentage of CD3+CD25+/CD3+, or CD4+CD25+/CD4+, or CD8+CD25+/CD8+ was found in relapsed group, despite there was no significant difference. Interestingly, DEC significantly reduced population of CD3+HLADR+/CD3+, or CD4+HLADR+/CD4+, or CD8+HLADR+/CD8+ compared to AZA (P<0.001, P<0.001, or P<0.001, respectively). In conclusion, both AZA and DEC as HMA maintenance treatment following HSCT in children AML or MDS was safe, and the outcome was encouraging. A further large cohort of randomization of AZA and DEC study is required.

Background:For patients without HLA matched donor, Haploid stem cell transplantation with PTCY method has relatively higher risk of relapse and graft-versus-host disease (GVHD). Umbilical cord blood (UCB) is readily available and has helped expand the donor pool to almost all patients requiring a transplant. Meanwhile UCB transplant improves EFS in leukaemia with lower risk of relapse and GVHD. However, the clinical application of UCB is limited due to lower implantation rate because of its low dose of stem cells than other sources of hematopoietic stem cells (HSC).

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Allogeneic stem cell transplantation is a cure for patients suffering from thalassemia major (TM). Historically, patients were limited by the selection of donors, while the advancement of haploidentical stem cell transplantation (haplo-SCT) has greatly expanded the donor pool. However, the outcomes of haplo-SCT in TM recipients vary between different programs. In this study, we retrospectively studied 73 pediatric TM patients (median age, 7 years; range, 3 to 14 years) who underwent haplo-cord transplantation. Both the estimated overall survival and transfusion-free survival were 95.26% (CI 95.77% to 96.23%). Neither primary nor secondary graft failures were observed. The median follow-up period was 811 days (range, 370 to 1433 days). Median neutrophil and platelet engraftment times were 22 days (range, 8 to 48 days) and 20 days (range, 8 to 99 days), respectively. Acute graft-versus-host disease (aGVHD) was observed in 52% of patients and of these, 25% developed grade III to IV aGVHD. Cord blood engraftment was associated with delayed immune recovery and increased aGVHD severity. Viral DNAemia occurred in a relatively high proportion of patients but only 7% of patients developed CMV disease, while another 7% of patients had post-transplantation lymphoproliferative disorder. Long-term complication outcomes were good. Only one patient developed extensive chronic GVHD. No surviving patients were reliant on blood transfusion by the time this manuscript was submitted. This is one of the largest studies on the outcomes of pediatric TM patients who received stem cell transplantations from alternative donors. The haplo-cord program is safe and practical for TM patients that do not have matched donors.

To identify the prognostic factors that are useful to improve CNS control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on China Children’s Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% CI, 78.9%–81.7%), and overall survival 91.1% (95% CI, 90.1%–92.1%). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5%–2.3%), and any CNS relapse 2.7% (95% CI, 2.2%–3.2%). The isolated CNS relapse rate was significantly lower in patients with B-ALL than in those with T-ALL (1.6%; 95% CI,1.2%–2.0% vs 4.6%; 95% CI 2.9%–6.3%; P< 0.001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1%–3.0%; P=0.03), the presence of BCR–ABL1fusion (HR, 3.8; 95% CI, 2.0%–7.3%; P< 0.001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5%–12.2%; P=0.007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04%–0.7%; P=0.02) and flow cytometry examination of diagnostic cerebrospinal fluid (HR, 0.2; 95% CI, 0.06%–0.6%; P=0.006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic cerebrospinal fluid may improve CNS control in childhood ALL.

Background

No relevant conflicts of interest to declare.

Objectives:At present, allogeneic hematopoietic stem cell transplantation is still the only way to cure thalassemia major (TM) patients. But in fact, less than half of the patients can find matched sibling or unrelated donors.Umbilical cord blood stem cells(UCB) is a potential source of stem cells.This paper was to explore effectiveness and compare the outcomes of sibling's and unrelated cord blood stem cell transplantation combined with PBSC in TM.

Objectives: The hematopoietic stem cells transplantation (HSCT) is the only curable treatment in current for thalassemia major (TM).The quantity of auto stem cell of TM patients are very important for rescue the patients in case of failure of HSCT, and auto stem cells of TM will be used as target cells for gene therapy (GT) in the near future. Iron overload (IOL) can damage the hematopoiesis of TM. How to collect the auto stem cells in TM patients? How about the affects of iron overload in the mobilization and collection of auto stem cell? The aim of this study was to analyze quantity of auto stem cells in the TM and the affects of iron overload (IOL).

No relevant conflicts of interest to declare.