Prognostic factors for CNS control in children with acute lymphoblastic leukemia treated without cranial irradiation.

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).

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial.

BACKGROUND: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia. METHODS: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m2) plus oral dexamethasone (6 mg/m2 per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706. FINDINGS: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060). INTERPRETATION: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia. FUNDING: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Improvement in cardiac morphology and function in young rats with dilated cardiomyopathy by recombinant human growth hormone].

OBJECTIVE: To investigate the effects of recombinant human growth hormone (rhGH) on the morphology and function of the left cardiac ventricle in young rats with dilated cardiomyopathy (DCM), and to evaluate the efficacy and safety of rhGH in the treatment of DCM. METHODS: Sixty male Sprague-Dawley rats were randomly and equally assigned to control group, DCM group, and rhGH group. Furazolidone (0.25 mg/g) was given by gavage for 12 weeks to prepare the DCM model. Rats in the rhGH group received an intraperitoneal injection of rhGH (0.15 U/kg) once per day for 12 weeks, while rats in the DCM group received an equal volume of normal saline instead. Rats in the control group did not receive any treatment. Cardiac indices, serum biochemical parameters, hemodynamic indices, cardiac histopathological changes, and levels of myocardial collagen fibrils in each group were determined using Doppler echocardiography, enzyme-linked immunosorbent assay, multi-channel physiological recorder, light and electron microscopy, and picrosirius red staining plus polarization microscopy, respectively. RESULTS: Compared with the control group, rats in the DCM group had significantly increased cardiac chamber size, significantly reduced ventricular wall thickness, and significantly decreased fractional shortening (FS) and ejection fraction (EF) (P<0.05). Rats in the rhGH group had significantly improved cardiac chamber size, ventricular wall thickness, FS, and EF compared with the DCM group (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05). There were significant differences in serum biochemical parameters and hemodynamic indices between the DCM and control groups (P<0.05). Compared with the DCM group, the rhGH group had significantly improved serum biochemical parameters and hemodynamic indices (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05), except for the levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. The DCM group had a significantly higher collagen type I/collagen type III (Col I/Col III) ratio in the myocardium than the control group (P<0.05), and there was no significant difference in the Col I/Col III ratio between the control and rhGH groups (P>0.05). CONCLUSIONS: rhGH plays a certain role in improvement in the morphology and function of the left cardiac ventricle in young rats with DCM.

[Clinical significance of skin prick test for inhalant allergens in 3085 children with allergic diseases].

OBJECTIVE: To investigate the main inhalant allergens and their distribution patterns in children with allergic diseases from Xi'an and the surrounding area and to provide evidence for the prevention and treatment of allergic diseases in children. METHODS: Skin prick test was performed using liquid with 13 standardized allergens (ALK-ABELL, Denmark) on 3085 children from Xi'an and the surrounding area who were treated for allergic diseases between July 2006 and July 2011, to detect inhalant allergens. RESULTS: Of the 3085 patients, 1368 (44.34%) had positive SPT results, with the most prevalent inhalant allergen being Dermatophagoides pteronyssinus (804 cases, 26.06%), followed by Dermatophagoides farinae (793 cases, 25.71%), Blomia tropicalis (440 cases, 14.26%), mugwort (282 cases, 9.14%), and cat hair (204 cases, 6.61%). The positive rates were 28.66% in the <4 years group, 41.85% in the 4-6 years group, and 58.61% in the 7-15 years group (P<0.01). Males had a significantly higher SPT positive rate than females (47.78% vs 38.50%；P<0.05). The SPT positive rate was highest in children with allergic rhinitis (72.41%), followed by bronchial asthma (62-25%), allergic dermatosis (45.83%), and allergic purpura (36.28%). CONCLUSIONS: In children from Xi'an and the surrounding area, the main inhalant allergens for allergic diseases include Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, mugwort and cat hair. The SPT positive rate increases with age. Male children have a higher SPT positive rate than female children. The SPT positive rate is highest in children with allergic rhinitis.

[Gene expression of Notch1 and Jagged1 in children with acute leukemia].

OBJECTIVE: To study the gene expression of Notch1 and Jagged1 in children with acute leukemia (AL) and their possible roles in the pathogenesis of AL. METHODS: Mononuclear cells from bone marrow or peripheral blood of 47 children with AL and 20 controls (normal children or children with nonmalignant hematologic disease) were collected from February 2009 to July 2011. A two-step method to semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression of Notch1 and Jagged1. Of the 47 children with AL, there were 26 cases of B-ALL, 6 cases of T-ALL and 15 cases of AML. RESULTS: The positive expression rate of Notch1 in the ALL and AML groups was higher than in the control group (P<0.05). The expression level of Notch1 in T-ALL children was higher than in B-ALL children (P<0.01). The positive expression rate of Jagged1 in the ALL and AML groups was not significantly different from the control group, however, the expression level of Jagged1 in the ALL and AML groups was higher than in the control group (P<0.05). CONCLUSIONS: There are significant differences in the gene expression of Notch1 between children with different types of ALL, and a higher expression of Notch1 relates to T-ALL. The activation of Notch1 signal is common in children with AL. The abnormal gene expression of Notch1 in children with AML shows the role of Notch1 in AML. The gene expression of Jagged1 in children with ALL or AML is abnormal, and this needs to be confirmed by further research.

Reduced Dose Intensity of Daunorubicin During Remission Induction for Low-Risk Patients With Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of the Chinese Children's Cancer Group.

It is urgently necessary to reduce the adverse effects of chemotherapy while maintaining their cure high rates for children with acute lymphoblastic leukemia (ALL). The present study aimed to determine whether the dose intensity of daunorubicin during the remission-induction phase could be reduced for low-risk patients with ALL. A total of 2396 eligible patients, who participated in CCCG-ALL-2015 study and were provisionally assigned to the low-risk group, were included and divided into single-dose group and double-dose group according to the dosage of daunorubicin during the remission-induction phase. For patients with ETV6-RUNX1 positive ALL or hyperdiploidy ALL, there were no significant differences in outcomes between the two groups. For other patients, the 5-year event-free survival rate was significantly better and the 5-year cumulative risk of any relapse was significantly lower in the double-dose group compared with the single-dose group. Both the 5-year overall survival rate and the risk of early deaths were not significantly different between the two groups. Our results suggested that only B-lineage ALL patients with ETV6-RUNX1 positivity or hyperdiploidy who achieved an early negative minimal residual disease status were suitable candidates for dosage reduction of daunorubicin during the remission-induction phase. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=10115, identifier ChiCTR-IPR-14005706.

[Therapeutic effects of erythropoietin on hypoxic-ischemic encephalopathy in neonates].

OBJECTIVE: To study the efficacy of erythropoietinin (EPO) in the treatment of moderate or severe hypoxic-ischemic encephalopathy (HIE) in neonates. METHODS: Seventy neonates with moderate or severe HIE were randomly assigned to two groups: EPO treatment and control (n=35 each). The EPO treatment group included 22 cases of moderate HIE and 13 cases of severe HIE. The control group included 24 cases of moderate HIE and 11 cases of severe HIE. Thirty-five healthy full-term infants served as normal group. The control group received a conventional treatment. Beside the conventional treatment, the EPO treatment group was intravenously injected with EPO of 200 IU/kg•d, 3 times weekly. Routine blood test was performed every 6 days. EPO dose was adjusted based on the results of the routine blood test. The course of EPO treatment was 2 to 4 weeks. Neonatal Behavioral Neurological Assessment (NBNA) was performed at age of 28 days. The infant development test of Child Development Centre of China (CDCC) was performed at ages of 3 months and 6 months. RESULTS: The percentage of normal NBNA scores in the EPO treatment group was significantly higher than that in the control group at age of 28 days (P<0.05), but was significantly lower than that in the normal group (P<0.01). The CDCC test including physical development index (PDI) and physical development index (MDI) showed the percentage of normal results in the EPO treatment group was significantly higher than in the control group at age of 3 months (P<0.05), but was significantly lower than in the normal group (P<0.01). The CDCC test including PDI and MDI showed that the percentage of normal results in the EPO treatment group was significantly higher than in the control group at age of 6 months. The MDI test results in the EPO treatment group were not significantly different from those in the normal group at age of 6 months, but the percentage of normal results in the PDI test in the EPO treatment group was still significantly lower than that in the normal group (P<0.05). CONCLUSIONS: EPO treatment has neuroprotective effects against moderate or severe HIE and improves long-term behavioral neurological developments in neonates.

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 109/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.

Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.

PURPOSE: Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS: We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS: We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION: Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

Septicemia after chemotherapy for childhood acute lymphoblastic leukemia in China: A multicenter study CCCG-ALL-2015.

BACKGROUND: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied. METHODS: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected. RESULTS: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. CONCLUSION: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.

Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

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.

[Roles of serum and urinary interleukins 13Ralpha2 and other cytokines in pediatric Henoch-Schonlein purpura].

OBJECTIVE: To study the roles of serum and urinary interleukins (IL)-13Ralpha2, IL-4, IL-6, IL-8 and tumor necrosis factor-alpha(TNF-alpha) in pediatric Henoch-Schonlein purpura (HSP). METHODS: Serum and urinary levels of IL-13Ralpha2, IL-4, IL-6, IL-8 and TNF-alpha were examined using ELISA in 52 children with HSP and 45 healthy children. The results were compared between the two groups. RESULTS: Serum levels of IL-13Ralpha2, IL-4, IL-6, IL-8 and TNF-alpha in HSP patients with or without renal lesions were higher than those in the control group (p<0.01 or 0.05). Urinary levels of IL-6 and TNF-alpha in HSP patients without renal lesions were higher than those in the control group (p<0.05). Except for urinary levels of IL-6 and TNF-alpha, urinary IL-13Ralpha2 levels in HSP patients with renal lesions (HSPN) were higher than those in the control group (p<0.05). CONCLUSIONS: Cytokines IL-13Ralpha2, IL-4, IL-6, IL-8 and TNF-alpha may play roles in the pathogenesis of pediatric HSP/HSPN.

Treatment abandonment in childhood acute lymphoblastic leukaemia in China: a retrospective cohort study of the Chinese Children's Cancer Group.

OBJECTIVES: Before 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. METHODS: Demographic, 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. RESULTS: At 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. CONCLUSIONS: The 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 NUMBER: ChiCTR-IPR-14005706, pre-results.

[Research progress on the donor cell sources of pancreatic islet transplantation for treatment of diabetes mellitus].

Objective: To summarize the research progress on the source and selection of donor cells in the field of islet replacement therapy for diabetes mellitus. Methods: Domestic and abroad literature concerning islet replacement therapy for diabetes mellitus, as well as donor source and donor selection was reviewed and analyzed thoroughly. Results: The shortage of donor supply is still a major obstacle for the widely clinical application of pancreatic islet transplantation (PIT). Currently, in addition to the progress on the allogeneic/autologous donor islet supply, some remarkable achievements have been also attained in the application of xenogeneic islet (from pig donor), as well as islet like cells derived from stem cells and islet cell line, potentially enlarging the source of implantable cells. Conclusion: Adequate and suitable donor cell supply is an essential prerequisite for widely clinical application of PIT therapy for type 1 diabetes mellitus (T1DM). Further perfection of organ donation system, together with development of immune-tolerance induction, gene and bioengineering technology etc. will possibly solve the problem of donor cell shortage and provide a basis for clinical application of cellular replacement therapy for T1DM.

Selection of Implantation Sites for Transplantation of Encapsulated Pancreatic Islets.

Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. To develop a clinically implantable BAP, some key aspects need to be taken into account: encapsulation material, capsule design, and implant site. Among them, the implant site exerts an important influence on the engraftment, stability, and biocompatibility of implanted BAP. Currently, an optimal site for encapsulated islet transplantation may include sufficient capacity to host large graft volumes, portal drainage, ease of access using safe and reproducible procedure, adequate blood/oxygen supply, minimal immune/inflammatory reaction, pliable for noninvasive imaging and biopsy, and potential of local microenvironment manipulation or bioengineering. Varying degrees of success have been confirmed with the utilization of liver or extrahepatic sites in an experimental or preclinical setting. However, the ideal implant site remains to be further engineered or selected for the widespread application of encapsulated islet transplantation.

[ALA-PDT alleviates graft-versus-host disease in mice following allogenic bone marrow transplantation].

OBJECTIVE: This study investigated the hypothesis that 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) might alleviate acute graft-versus-host disease (GVHD) following allogenic bone marrow transplantation (allo-BMT) in mice. METHODS: Acute GVHD model following allo-BMT was established in 40 recipient BALB/C mice. Fifty C57BL/6J mice were used as donors and another 10 BALB/C mice as blank control without any intervention. Recipients received a lethal dose of 8.5 Gy (60)Co radiation for 10 minutes before transplantation and then were randomly divided into four groups of 10 mice (A-D). Group A was injected with normal saline injection and served as controls. Group B received pure donor bone marrow and spleen cell infusion. Group C received donor bone marrow and mixed donor-recipient spleen cell infusion. Group D was administered with an infusion of donor bone marrow cells and mixed donor-recipient spleen cells treated with ALA-PDT. The 28th day survival rate, incidence of acute GVHD and hematological and pathological changes after transplantation were examined. RESULTS: All the mice from the Blank control group survived. The survival rates for Groups A-D on the 28th day were 0, 0, 10% and 60% respectively. Group D showed a significantly higher survival rate than the other three groups (P < 0.01). Most of the mice in Groups B and C developed GVHD but only two developed in Group D. Moreover Group D had less severe hematological and pathological changes when compared with Groups B and C. CONCLUSIONS: ALA-PDT significantly alleviated GVHD and increased the 28th day survival rate for allo-BMT mice. ALA-PDT may be a promising therapy for GVHD following allo-BMT. Future studies should focus on the underlying mechanism of its therapeutic effect.