A Universal Room-Temperature 3D Printing Approach Towards porous MOF Based Dendrites Inhibition Hybrid Solid-State Electrolytes.

Hybrid solid-state electrolytes (HSSEs) provide new opportunities and inspiration for the realization of safer, higher energy-density metal batteries. The innovative application of 3-dimensional printing in the electrochemical field, especially in solid-state electrolytes, endows energy storage devices with fascinating characteristics. In this paper, effective dendrite-inhibited PEO/MOFs HSSEs is innovatively developed through universal room-temperature 3-dimensional printing (RT-3DP) strategy. The prepared HSSEs display enhanced dendrite inhibition due to the porous MOF filler promoting homogeneity of lithium deposition and the formation of C-OCO3 Li, ROLi, LiF mesophases, which further improve the migration of Li+ in PEO chain and comprehensive performances. This universal strategy realizes the fabrication of different slurry components (PEO with ZIF-67, MOF-74, UIO-66, ZIF-8 fillers) HSSEs at RT environment, providing new inspirations for the exploration of next-generation advanced solid-state batteries.

A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Vincristine and dexamethasone pulses in addition to maintenance therapy among pediatric acute lymphoblastic leukemia (GD-ALL-2008): An open-label, multicentre, randomized, phase III clinical trial.

The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we perform an open-label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10-year EFS was 82.6% (95% CI: 75.9-89.9) in the control group and 80.7% (95% CI: 74-88.1) in the treatment group (pnon-inferiority  = .0002). Similarly, patients with IR also demonstrated non-inferiority of the treatment group to the control group in terms of 10-year EFS (73.6% [95% CI: 67.6-80] vs. 77.6% [95% CI: 71.8-83.9]; pnon-inferiority  = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10-year EFS (61.1% [95% CI: 47.7-78.2] vs. 72.6% [95% CI: 55.6-94.7], p = .026) and a trend toward higher 10-year OS (73.8% [95% CI: 61.6-88.4] vs. 87.9% [95% CI: 579.2-97.5], p = .068). In the HR cohort, the total rate of drug-induced liver injury and Grade 3 chemotherapy-induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy-induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard-to-intermediate-risk patients could eliminate the pulses.

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol.

BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. METHODS: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. RESULTS: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). CONCLUSIONS: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

A Genetic Variant Ameliorates ß-Thalassemia Severity by Epigenetic-Mediated Elevation of Human Fetal Hemoglobin Expression.

A delayed fetal-to-adult hemoglobin (Hb) switch ameliorates the severity of ß-thalassemia and sickle cell disease. The molecular mechanism underlying the epigenetic dysregulation of the switch is unclear. To explore the potential cis-variants responsible for the Hb switching, we systematically analyzed an 80-kb region spanning the ß-globin cluster using capture-based next-generation sequencing of 1142 Chinese ß-thalassemia persons and identified 31 fetal hemoglobin (HbF)-associated haplotypes of the selected 28 tag regulatory single-nucleotide polymorphisms (rSNPs) in seven linkage disequilibrium (LD) blocks. A Ly1 antibody reactive (LYAR)-binding motif disruptive rSNP rs368698783 (G/A) from LD block 5 in the proximal promoter of hemoglobin subunit gamma 1 (HBG1) was found to be a significant predictor for ß-thalassemia clinical severity by epigenetic-mediated variant-dependent HbF elevation. We found this rSNP accounted for 41.6% of ß-hemoglobinopathy individuals as an ameliorating factor in a total of 2,738 individuals from southern China and Thailand. We uncovered that the minor allele of the rSNP triggers the attenuation of LYAR and two repressive epigenetic regulators DNA methyltransferase 3 alpha (DNMT3A) and protein arginine methyltransferase 5 (PRMT5) from the HBG promoters, mediating allele-biased γ-globin elevation by facilitating demethylation of HBG core promoter CpG sites in erythroid progenitor cells from ß-thalassemia persons. The present study demonstrates that this common rSNP in the proximal Aγ-promoter is a major genetic modifier capable of ameliorating the severity of thalassemia major through the epigenetic-mediated regulation of the delayed fetal-to-adult Hb switch and provides potential targets for the treatment of ß-hemoglobinopathy.

A Study of Congenital Protein C Deficiency With Infancy Onset of CADASIL in a Chinese Baby.

OBJECTIVE: The main objectives of this article were to study a severe congenital protein C deficiency (PCD) in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and analyze the cause of this case. MATERIALS AND METHODS: We had recorded clinical manifestations of the patient, laboratory tests, imaging studies, and gene sequencing of the PROC gene and NOTCH3 gene to study the disease in this family. We checked the change of NOTCH3 protein by immunohistochemistry. RESULTS: Laboratory studies of the patient had revealed that his PC activity was 3%. Magnetic resonance imaging results showed hyperintense lesions in the cerebral white matter of the patient. PROC gene and NOTCH3 gene sequencing was performed among the family members. The patient was confirmed as homozygous for the (A-G)-12 at the transcription initiation site in the promoter region of the PROC gene and heterozygous mutation of the NOTCH3 gene. Immunohistochemical results showed that NOTCH3 protein was positive in the skin vascular smooth muscle of the patient. CONCLUSIONS: We studied a rare case of an infat boy diagnosed with both congenital PCD and CADASIL; congenital PCD was attributable to a compound that was homozygous for (A-G)-12 at the transcription initiation site in the promoter region of the PROC gene, and CADASIL was caused by missense mutation in exon 24 of NOTCH3. He was a sporadic patient with congenital PCD and CADASIL; it maybe that the deficiency of protein C led to early onset of CADASIL. The gene sequencing of PROC gene and NOTCH3 gene may have important value for fertility guidance and prenatal diagnosis.

[Serum level of soluble transferrin receptor in children with hemoglobin H disease].

OBJECTIVE: To investigate the serum level of soluble transferrin receptor (sTfR) and its association with the degree of anemia in children with hemoglobin H (HbH) disease. METHODS: A total of 55 children with HbH disease were enrolled as the HbH group, and 30 healthy children were enrolled as the control group. The HbH group was further divided into a deletional HbH disease group and a non-deletional HbH disease group. A retrospective analysis was performed for hematological parameters and serum sTfR level in all groups. RESULTS: Of the 55 children with HbH disease, 39 had deletional HbH disease and 16 had non-deletional HbH disease. Compared with the control group, the deletional and non-deletional HbH disease groups had significantly lower hemoglobin (Hb), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) and a significantly higher serum level of sTfR. Compared with the deletional HbH disease group, the non-deletional HbH disease group had significantly lower red blood cell count (RBC) and Hb level and significantly higher MCV, MCH, and serum sTfR level. In children with HbH disease, serum sTfR level was negatively correlated with RBC and Hb level (r=-0.739 and -0.667 respectively, P<0.05) and positively correlated with MCV and MCH (r=0.750 and 0.434 respectively, P<0.05). CONCLUSIONS: Serum sTfR level is associated the degree of anemia in children with HbH disease, and sTfR may be a target for the treatment of HbH disease.

Differences in frequency and regulation of T follicular helper cells between newly diagnosed and chronic pediatric immune thrombocytopenia.

OBJECTIVE: This study aims to investigate the role of T follicular helper (TFH) cells in the immunopathogenesis of pediatric immune thrombocytopenia (ITP), as well as differences in TFH expansion and its regulation between newly diagnosed ITP (nITP) and chronic pediatric ITP (cITP). METHODS: Eighty-five children with ITP and 20 age-matched healthy controls were enrolled into this study. TFH cell frequencies and TFH cell-associated regulatory factors before and after treatment were analyzed by flow cytometry, RT-PCR and ELISA. RESULTS: The percentages of TFH cells were significantly elevated in both nITP and cITP compared with controls. RT-PCR revealed significant differences in Bcl-6, c-Maf, Blimp-1, ICOSL, TACI and BAFFR mRNA expression in CD4(+) T or CD19(+) B cells between patients and controls, and further between nITP and cITP, before and after treatment. Moreover, there were significant differences in serum IL-4, IL-21 and BAFF between patients and controls. CONCLUSION: The overactivation of TFH cells may contribute to the immunopathogenesis of pediatric ITP. IL-21 and IL-4 serum levels may affect the differentiation of TFH cells in ITP patients. The aberrant balance between BAFFR-BAFF/TACI-BAFF may be a factor that caused the persistent high expression of ICOSL in pediatric cITP, which consequently lead to the over activation of TFH cells in pediatric cITP.

[One-step multiplex RT-PCR for identifying common fusion transcripts in childhood acute lymphoblastic leukemia].

OBJECTIVE: To evaluate the efficiency of one-step multiplex RT-PCR for identifying four common fusion transcripts (TEL/AML1, E2A/PBX1, MLL/AF4 and BCR/ABL) in children with acute lymphoblastic leukemia (ALL). METHODS: Total RNA was extracted from bone marrow samples of 76 children who were newly diagnosed with ALL between January 2003 and December 2010. These RNAs were analyzed for TEL/AML1, E2A/PBX1, MLL/AF4 and BCR/ABL by one-step multiplex RT-PCR or common nested-multiplex PCR. The PCR products were confirmed by DNA sequencing. RESULTS: TEL/AML1 was found in 12 cases (the length of products was 298 bp in 9 cases and 259 bp in 3 cases), E2A/PBX1 was found in 3 cases (the length of products was 373 bp), BCR/ABL was found in 1 case (the length of products was 2 124 bp), and MLL/AF4 was found in 7 cases (the length of products was 427 bp in 1 case and 673 bp in 6 cases) using one-step multiplex RT-PCR combined with DNA sequencing. The results were consistent with those using common nested-multiplex PCR. CONCLUSIONS: One-step multiplex RT-PCR may be another alternative for detection of common fusion transcripts in children with ALL.

[Expression of leukocyte-associated Ig-like receptor-1 in children with immune thrombocytopenia].

OBJECTIVE: To study the expression of leukocyte-associated Ig-like receptor-1(LAIR-1) in children with immune thrombocytopenia (ITP), in order to explore the possible role of LAIR-1 in the pathogenesis of childhood ITP. METHODS: Expression levels of LAIR-1 on CD4(+) T cells, CD8(+) T cells and CD19(+)CD20(+) B cells of peripheral blood were measured in 40 children with ITP by flow cytometry. Serum level of solubility LAIR-1 (sLAIR-1) was measured using ELISA. Real-time PCR was used to measure LAIR-1 mRNA expression. Thirty-two healthy children served as the control group. RESULTS: The percentages of CD19(+)CD20(+) B cells in the ITP group were significantly higher than in the control group (P<0.05). In contrast, the percentage of CD4(+) T cells in the ITP group was significantly lower than in the control group (P<0.05). The expression levels of LAIR-1 on CD4(+) T cells and CD8(+) T cells were significantly lower in the ITP group than in the control group (P<0.05). Serum sLAIR-1 level and LAIR-1 mRNA expression in the ITP group significantly increased compared with the control group (P<0.05). CONCLUSIONS: LAIR-1 expression on CD4(+) and CD8(+) T cells decreases and serum sLAIR-1 level increases in children with ITP, suggesting that LAIR-1 may play an important role in immune imbalance in these children.

[Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia].

OBJECTIVE: To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL). METHODS: MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). RESULTS: The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes. CONCLUSIONS: MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.

Genetic polymorphism of γ-glutamyl hydrolase in Chinese acute leukemia children and identification of a novel double nonsynonymous mutation.

γ-Glutamyl hydrolase (GGH) plays a central role in folate metabolism and antifolate action. Polymorphism in the human GGH gene (GGH) was associated with efficacy and side effects of methotrexate for treatment of acute lymphoblastic leukemia (ALL). This study aimed to identify polymorphisms of GGH in Chinese. Seventy-one children with ALL, 25 children with acute myeloid leukemia (AML), and 132 children with nonmalignancy as control were included. Human GGH cDNAs were prepared and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR)-denaturing gradient gel electrophoresis. The detected variants were further confirmed by DNA sequencing. Novel variant GGH cDNA was cloned, expressed, and characterized. Allelic frequency of GGH 452C→T polymorphism was determined as 9.2% (CT, 11/71; TT, 1/71) in the ALL group, 8.0% (CT, 4/25; TT, 0/25) in the AML group, and 9.1% (TT, 4/132; T/C, 16/132) in the controls, respectively. The total allelic frequency in the Chinese population (9.0%) was higher than those reported in Japanese (5.6%) and African Americans (4.4%), and was similar to Caucasians (10.0%). Association of 452TT+TC with increased rate of hepatotoxicity and mucositis was observed in the ALL patients. Two novel mutations were determined in the coding region of GGH in 2 boys with ALL: one of the mutations was a double nonsynonymous heterozygote (841AG+845AG, K257E/N258S), the other was a nonsynonymous heterozygote (797AG, K242R). The corresponding double-mutant protein showed unchanged enzymatic activity by functional analysis. Allele frequency of GGH C452T polymorphism is determined for the first time among Chinese. A novel double nonsynonymous mutation of GGH was identified in a boy with ALL.

[Effect of methylation inhibitor on EphB4 gene expression, proliferation and apoptosis in CEM cells].

OBJECTIVE: To study the regulation of methylation inhibitor 5-aza-2'-deoxycytidine on transcription of EphB4 gene and effects on the proliferation and apoptosis of human acute lymphocyte leukemia cell line CEM. METHODS: Bisulfite sequencing PCR was used to detect CpG island methylation density in EphB4 promoter. The expression of EphB4 mRNA and protein was determined by Q-PCR and Western blot. MTS assay and flow cytometry were used to detect the apoptosis of CEM cells after treatment with different concentrations of 5-aza-2'-deoxycytidine (1.0, 2.5 and 5 µmol/L). RESULTS: Methylation of EphB4 gene promoter was detected in CEM cells (31.4%). The methylation level of EphB4 gene was down-regulated after treatment with various concentrations of 5-aza-2'-deoxycytidine. The EphB4 mRNA and protein expression in CEM cells increased after 5-aza-2'-deoxycytidine treatment. 5-Aza-2'-deoxycytidine significantly inhibited the cell growth in dose and time dependent manners. Early apoptosis rates of CEM cells increased from 4.1% to 24.8% 96 hrs after 5-aza-2'-deoxycytidine treatment. CEM cells in G1 phase decreased from 62.4% to 46.8%, cells in G2 phase increased from 2.1% to 16.2%, and CEM cells were arrested in G2 phase after treatment with 5 µmol/L 5-aza-2'-deoxycytidine for 96 hrs. CONCLUSIONS: 5-Aza-2'-deoxycytidine, an inhibitor of specific methylation transferase, can induce expression of the silent EphB4 gene in CEM cells, inhibit the proliferation of leukemia cells and induce cell apoptosis.

[Evaluation of heart and liver iron deposition status in patients with ß- thalassemia intermedia and major with MRI T2* technique].

OBJECTIVE: To study the status of iron deposition in patients with ß-thalassemia intermedia and major in mainland China. METHODS: The status of transfusion and chelation was examined in 39 patients with ß-thalassemia intermedia or major. Serum ferritin levels were measured. MRI T2* technique was used to detect cardiac and hepatic iron deposition. RESULTS: Serum ferritin levels ranged from the minimum of 1500 ng/mL up to a maximum of 11491 ng/mL. From liver MRI T2* measurement, 15 cases had severe hepatic iron deposition (38%) and moderate deposition was found in 15 cases (38%), mild in 7 cases (18%), and normal in 2 cases (5%). Heart MRI T2* showed severe heart iron deposition in 7 cases (18%), mild in 5 cases (13%), and normal in 27 cases (69%). One case had cardiac arrhythmia. Four cases were over 20 years of age, and presented with gonadal function hypoplasia. The majority of patients did not receive regular transfusion and they had delayed, suboptimal chelation due to financial problems. Serum ferritin level was closely related with timing and dosage of chelation. CONCLUSIONS: In patients with ß-thalassemia who do not receive early regular transfusion and iron chelation therapy, iron deposition may occur at an early age. Important organs and tissue functional lesions and related complications also result. Relevant agencies and family members should be aware of this trend and develop appropriate strategies to improve the medical condition and quality of life of patients with this disorder.

[Genetic factors in the occurrence of neonatal unconjugated hyperbilirubinemia].

OBJECTIVE: To study association of uridine-diphosphate-glucuronosyltransferase1A1 (UGT1A1) Gly71Arg, UGT1A1 promoter TATA-box and glucose-6-phosphate dehydrogenase (G6PD) gene mutations with the occurrence of neonatal unconjugated hyperbilirubinemia. METHODS: The TATA-box, exon 1 and exon 5 of the UGT1A1 gene and the exon 12 of G6PD gene were amplified by PCR. The products of PCR were analyzed by direct DNA sequencing. Clones for the mutations of the UGT1A1 gene and the G6PD gene were constructed in order to identify the results of the products of PCR. Seventy-two neonates with unconjugated hyperbilirubinemia (case group) and 65 healthy neonates (control group) were enrolled. The genotypes and allele frequencies of the polymorphisms of UGT1A1 Gly71Arg and UGT1A1 TATA-box were compared between the two groups. The effects of UGT1A1 Gly71Arg, UGT1A1 promoter TATA-box and G6PD gene mutations on the development of neonatal unconjugated hyperbilirubinemia were estimated using logistic regression models. RESULTS: There were significant differences in the genotype distribution of Gly71Arg polymorphism of UGT1A1 gene between the case and control groups (P<0.01). The Arg allele frequency of the polymorphisms of UGT1A1 gene in the case group was significantly higher than in the control group (P<0.01). There were no significant differences in the genotype distribution of the UGT1A1 promoter TATA-box between the two groups (P>0.05). The OR and 95%CI values of UGT1A1 Gly71Arg, UGT1A1 TATA-box and G6PD gene mutations associated with the development of neonatal unconjugated hyperbilirubinemia were 5.468 (2.274, 12.818), 0.688 (0.266, 1.778) and 5.081 (1.070, 24.133) respectively. CONCLUSIONS: UGT1A1 Gly71Arg and G6PD gene mutations may be involved in the development of neonatal unconjugated hyperbilirubinemia.

[Curative effects and safety of deferasirox in treatment of iron overload in children with ß-thalassemia major].

OBJECTIVE: To study the effectiveness and safety of deferasirox (DFX) in the treatment of iron overload in children with ß-thalassemia major. METHODS: Twenty-four ß-thalassemia major children with iron overload who received regular blood transfusion were randomly enrolled. The serum feritin (SF) levels were measured in the patients after different doses of DFX treatment. The DFX treatment-related adverse events were observed. The values of cardiac MRI T2* and liver MRI T2* were compared between the patients receiving DFX treatment for 5 years and the patients treated with deferoxamine and deferiprone. RESULTS: The patients with iron overload did not respond to DFX at the initial dose of 20-30 mg/kg•d. However, the SF level decreased significantly after the dose of DFX increased to 30-40 mg/kg•d (U=58, P<0.01). Serum liver transaminase elevation was the most common adverse effect, followed by non-progressive elevation in serum creatinine level. The mean SF level was significantly lower (1748±481 ng/mL vs 3462±1744 ng/mL; P<0.05), in contrast, the liver MRI T2* value was significantly higher (8.5±2.9 ms vs 2.7±1.9 ms; P<0.01) in patients receiving DFX treatment for 5 years than in the controls. There were no significant differences in the cardiac MRI T2* value between the two groups. CONCLUSIONS: DFX can reduce SF levels in a dose-dependent manner in children with ß-thalassemia major. It can significantly lower liver iron overload but not cardiac overload. Serum liver transaminase elevation and non-progressive elevation in serum creatinine level are major adverse effects in DFX treatment.

Identification of a De Novoc.1000delA ANK1 mutation associated to hereditary spherocytosis in a neonate with Coombs-negative hemolytic jaundice-case reports and review of the literature.

BACKGROUND: To strengthen the understanding of Hereditary Spherocytosis (HS) and determine the disease-causing mutation present with neonatal jaundice. HS is a hemolytic condition resulting from various erythrocyte membrane defects. Many different mutations result in HS, including mutations in ANK1. CASE PRESENTATION: A term neonate presented at ten hours with severe jaundice requiring exchange transfusion. At two months he was hospitalized due to repeated pallor and anemia requiring blood transfusions. Using next-generation sequencing, we discovered the responsible mutation in the proband but not in his parents; a heterozygous nucleotide variation of c.1000delA (p.1334Sfs*6) in ANK1. Thus hereditary spherocytosis was diagnosed. CONCLUSIONS: Genetic detection is an important means of discovering the cause of hemolytic anemia in neonates and infants where routine diagnostic tests are unrevealing. We found a novel de novo mutation, c.1000delA (p.1334Sfs*6) in ANK1 that might account for other cases of HS in the Chinese population.

Pharmacokinetics and complementary evaluation system-based guidance on prophylaxis of paediatric patients with haemophilia A in China with Kovaltry: protocol of the LEAP study.

INTRODUCTION: Haemophilia A is a rare inherited bleeding disease caused by the deficiency of coagulation factor VIII (FVIII). The main treatment protocol is to administer regular exogenous FVIII concentrate infusions. With the discovery of variability in individualised pharmacokinetics (PK) and bleeding phenotype, the previous weight-based approach needs to be replaced by more advanced PK-tailored prophylaxis with an accurate evaluation system. In this study, we combine individualised PK profiles and a complementary evaluation system to guide prophylaxis in paediatric patients with haemophilia A. METHODS AND ANALYSIS: This is a single-centre, prospective single-arm study. The aim of this study is to assess the effectiveness of a new strategy combining PK and a complementary evaluation system to treat haemophilia A in Chinese paediatric patients. Sixty paediatric patients with haemophilia will be recruited. After PK testing, they will receive a PK-guided stepup prophylaxis in the next 2 years. The dosing regimen will be determined according to individualised PK profiles and complementary evaluation findings. Related indicators at the end of the study will be compared with the values at treatment initiation to examine the effectiveness of this new strategy. The demographic data of the investigated patients will be summarised by descriptive statistics. Quantitative data will be described by summary statistics, including arithmetic median, range, mean and arithmetic SD. Analyses will use t-test to compare indicators such as bleeding rate and imaging score at both ends of the study as well as during follow-up. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of Beijing Children's Hospital (Number 2020-Z-095). The findings will be presented at international meetings such as World Federation of Hemophilia World Congress. Related manuscripts will be submitted to peer-review journals such as Blood and Hemophilia. TRIAL REGISTRATION NUMBER: ChiCTR2000037821; Pre-results.

Co-Transplantation of Haploidentical Stem Cells and a Dose of Unrelated Cord Blood in Pediatric Patients with Thalassemia Major.

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.