Anti-thymocyte globulin combined with post-transplantation cyclophosphamide reduce graft-versus-host disease in hematopoietic stem cell transplantation for pediatric leukemia.

This retrospective analysis evaluated the use of anti-thymocyte globulin (ATG) with or without post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis in children with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT). The study included 57 children, with 35 in the ATG-PTCy group and 22 in the ATG group. While overall incidence of acute and chronic GvHD did not differ significantly between groups, the ATG-PTCy group had lower rates of grade II-IV acute GvHD (p = 0.013) and moderate-to-severe chronic GvHD (p = 0.001) compared to the ATG group. Importantly, ATG-PTCy significantly improved GvHD/relapse-free survival (GRFS) compared to ATG (65.71% vs. 36.63%; p = 0.003). There were no differences in engraftment, infection rates, immune reconstitution, overall survival, leukemia-free survival, relapse rate, or non-relapse mortality between the two groups. Combining ATG with PTCy may reduce moderate-to-severe GvHD and improve GRFS in children undergoing HSCT for acute leukemia.

Unrelated umbilical cord blood transplantation with low-dose anti-thymocyte globulin for children with severe aplastic anemia: A case series.

OBJECTIVE: This study aimed to investigate the prognosis of unrelated umbilical cord blood transplantation (UCBT) using low-dose anti-thymocyte globulin (ATG) in children diagnosed with severe aplastic anemia (SAA). METHODS: This retrospective case series study was conducted involving pediatric SAA patients treated at the Capital Institute of Pediatrics from January 2020 to February 2023. All patients underwent a reduced-intensity conditioning (RIC) regimen alongside low-dose ATG. RESULTS: The study comprised nine patients (five males) with a median age of 5 years (range: 1.7 to 7 years). The median follow-up duration was 799 days (range: 367 to 1481 days), during which all patients survived. The median time interval from diagnosis to transplantation was 3 months (range: 1 to 9 months). The median dosage of ATG administered was 5 mg/kg (range: 2.5 to 7.5 mg/kg). The median durations for granulocyte and platelet engraftment were 15 days (range: 12 to 23 days) and 26 days (range: 12 to 41 days), respectively. Three patients experienced grade 2-4 acute graft-versus-host disease (aGVHD). Epstein-Barr virus (EBV) reactivation was observed in three patients, while cytomegalovirus (CMV) reactivation occurred in seven patients, with no cases of CMV disease or post-transplant lymphoproliferative disorder (PTLD). One patient experienced recurrence 15 months after transplantation due to influenza A infection. CONCLUSION: These findings indicate that SAA patients may attain a favorable prognosis following UCBT with a RIC regimen combined with low-dose ATG.

Clinical features and prognosis of pediatric acute lymphocytic leukemia with JAK-STAT pathway genetic abnormalities: a case series.

The objective of this study is to explore the clinical features and outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) harboring JAK-STAT signaling pathway genetic abnormalities. This retrospective case series examined the clinical data of pediatric patients diagnosed with ALL harboring JAK-STAT pathway genetic abnormality at the Children's Hospital of the Capital Institute of Pediatrics between January 2016 and January 2022. Bone marrow next-generation sequencing was used to reveal the JAK pathway abnormalities. Descriptive statistics were used. From 432 children with ALL during the study period, eight had JAK-STAT pathway genetic abnormalities. Regarding immunotyping, there were four patients with common-B cell types and one with pre-B cell type. The three patients with T-ALL had early T-cell precursor(ETP) type, pre-T cell type, and T cell type. Gene mutations were more common than fusion genes. There was no central nervous system involvement in eight patients. All patients were considered at least at intermediate risk before treatments. Four patients underwent hematopoietic stem cell transplantation (HSCT). One child had a comprehensive relapse and died. The child had a severe infection and could not tolerate high-intensity chemotherapy. Another child relapsed 2 years after HSCT and died. Disease-free survival was achieved in six children. JAK-STAT pathway genetic abnormalities in pediatric Ph-like ALL are rare. Special attention should be paid to treatment-related complications, such as infection and combination therapy (chemotherapy, small molecule targeted drugs, immunotherapy, etc.) to reduce treatment-related death and improve long-term quality of life.

Analysis of Multiple Vitamins Serum Levels and Disease-Related Factors in Children with Acute Leukemia.

Objective: To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL). Methods: A total of 107 hospitalized children with AL were enrolled in this study and assigned to one group in each of the following categories: infected group (n = 52) and noninfected group (n = 55); treatment remission group (n = 56) and nonremission group (n = 51); high-risk (HR) group (n = 44), intermediate risk (IR) group (n = 53), and slight risk (SR) group (n = 8); cyclophosphamide + cytosine arabinoside+6-mercaptopurine + pegaspargase group (CAML, n = 15); methotrexate group (MTX, n = 9); and vindesine + daunomycin + L-asparaginasum + prednisone (VALP, n = 38). Hematological and serological parameters, hepatic and renal function, and changes in vitamins A, B1, B2, B6, B9, B12, C, D, and E serum content in children with AL were analyzed to investigate their relationship with AL disease-related factors. Results: The vitamin D level was significantly higher in the noninfected group than in the infected group (P < 0.05). Compared with the nonremission group, the level of vitamin B1 in the treatment remission group was significantly higher, while the levels of vitamin B6 and B12 were notably lower (P < 0.05). The levels of vitamins B6 and B12 were notably different among the treatment groups. Multivariate analysis showed that hemoglobin (Hb) and C-reactive protein (CRP) were predisposing factors of AL in children. The disease type (acute lymphoblastic leukemia/acute myelogenous leukemia) was the factor affecting remission in AL children. Abnormal kidney function and the occurrence of icterus were the influencing factors for the risk degree in AL children. Platelet (PLT) count, activated partial thromboplastin time (APTT), neutrophils (N), and immunophenotype were shown to affect the choice of therapeutic regimens. Conclusion: There are notable vitamins imbalances in children with AL. The imbalances influence disease-related factors and therefore provide some references for the prognosis and treatment of AL.

Clinical outcomes of individualized busulfan-dosing in hematopoietic stem cell transplantation in Chinese children undergoing with therapeutic drug monitoring.

To identify relationships between busulfan (Bu) exposure and outcomes of a cohort pediatric patients receiving hematopoietic stem cell transplantation (HSCT), along with a targeted busulfan-based conditioning regimen. We retrospectively evaluated targeted busulfan concentrations in 53 pediatric patients (age 0.4-16 years) who received busulfan 4 times daily according to recommended weight-based doses in a single-center analysis between 2018 and 2020. In this trial, individual busulfan pharmacokinetics were performed following dose 5 of the conditioning regimen. Twenty four of 53 patients (45.3%) studies did not require dose adjustments. Equal number of patients (24/53) required one dose adjustments while two-dose adjustment applied for 5 of 53 (9.4%). Twenty-one percent of the patients exhibited ll-lV aGVHD. The incidence of veno-occlusive disease (VOD) was in 3.8% of the 53 patients, while incidence of hemorrhagic cystitis (II-III) reached to 9.7%. Engraftment was successful in 98% of the 53 patients with relapse in 2% of cases. The probability of overall survival and disease-free survival at day 100 was 96% and 94%, respectively. In conclusion, therapeutic drug monitoring (TDM) and individualization of Bu dosage are essential to improve the efficacy and safety of busulfan-based regimen in Chinese pediatric HSCT recipients.

Evaluation of antitumor activity of survivin short interfering RNA delivered by lipid nanoparticles in colon cancer in vitro and in vivo.

Survivin has been overexpressed in numerous types of cancer and is associated with a poor clinical outcome. A number of various approaches have been used to counteract survivin in order to inhibit tumor growth or promote cell apoptosis. The present study aimed to evaluate the efficiency and antitumor effect of a survivin-targeted short interfering RNA (siRNA) delivery system using lipid nanoparticles for the treatment of colon cancer. Survivin siRNA (si-survivin) nanoliposomes were prepared and transfected into LoVo cells. The mRNA expression level of survivin was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell viability was evaluated by MTT assay. LoVo-bearing nude mice were treated with si-survivin intratumorally or intravenously. Tumor growth in LoVo-bearing mice was monitored and recorded, and tumor samples were obtained for evaluation of survivin expression levels using RT-qPCR, western blotting and immunohischemical staining. The expression level of survivin was significantly reduced by nanoliposomal si-survivin along with cell proliferation inhibition in vitro. Intravenous administration of si-survivin nanoliposomes may significantly inhibit tumor growth with less toxicity compared with doxorubicin hydrochloride treatment in LoVo-bearing mice. Nanoliposomal si-survivin may significantly reduce the expression level of survivin and inhibit cell proliferation of colon cancer cells in vitro and in vivo. si-survivin delivered by lipid nanoparticles may be a potential treatment approach for colon cancer.

Small interfering RNA targeting of the survivin gene inhibits human tumor cell growth in vitro.

The present study aimed to evaluate the impact of small interfering RNA (siRNA) targeting of the survivin gene in human tumor cells and the effect of decreased survivin expression on the proliferation and apoptosis of tumor cells. Human tumor cell lines (MSA-MB-231, SGC-7901, HeLa, A549, SK-OV-3 and Raji, PC-3) were cultured in vitro and divided into three groups: survivin siRNA-treated, scrambled negative control siRNA-treated and an untreated control group. The level of survivin mRNA and protein expression was subsequently determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell proliferation was also examined by an MTT assay following transfection and the apoptotic rate of cells was detected by Hoechst and Annexin V/propidium iodide staining. It was observed that relative to the control group, expression of survivin mRNA and protein in the survivin siRNA-treated group was significantly downregulated. Furthermore, siRNA targeting of survivin lead to the inhibition of tumor cell proliferation, as well as an increase in their apoptotic rate in vitro. These data suggest that survivin may be a potential tumor biomarker and a novel target for the treatment of cancer.

Survivin downregulation using siRNA nanoliposomes inhibits cell proliferation and promotes the apoptosis of MHCC-97H hepatic cancer cells: An in vitro and in vivo study.

At present, survivin is one of the most cancer-specific proteins that has been identified. The present study aimed to investigate the antitumor effects of novel survivin small interfering RNA (siRNA) nanoliposomes targeting survivin in human hepatocellular carcinoma MHCC-97H cells and xenograft mouse models. Survivin-targeted siRNA nanoliposomes were prepared and transfected into MHCC-97H cells and MHCC-97H-bearing nude mice. Survivin expression was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell viability was analyzed using an MTT assay and apoptosis was evaluated using Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide staining. Tumor growth in MHCC-97H-bearing mice was monitored following treatment and tumor samples were obtained for survivin expression analysis using RT-qPCR, western blotting and immunohistochemistry staining. Survivin expression levels were significantly downregulated by nanoliposome-mediated survivin siRNA delivery and this was associated with a significant inhibition of cell growth and an increase in the apoptosis of MHCC-97H cells. Downregulation of survivin expression using survivin siRNA nanoliposomes inhibited tumor growth in the MHCC-97H xenograft models without significant treatment-associated toxicity. Therefore, a cationic nanoliposome-based survivin siRNA delivery system was constructed and demonstrated to be efficient for survivin siRNA delivery in in vitro and in vivo studies. These results demonstrate that survivin downregulation was able to significantly attenuate cell proliferation and induce the apoptosis of MHCC-97H cells, as well as inhibit tumor cell growth in MHCC-97H xenograft models, indicating that survivin suppression using siRNA may contribute to the inhibition of tumor development by suppressing cell proliferation and promoting apoptosis.