Application value of nutritional intervention in children with acute lymphoblastic leukemia during maintenance treatment / 公共卫生与预防医学

Objective To observe the application value of nutritional intervention in children with acute lymphoblastic leukemia (ALL) during maintenance treatment. Methods A total of 75 children with ALL admitted to Hematology and Oncology Department of Children's Hospital Affiliated to Nanjing Medical University from January 2020 and January 2022 were enrolled as the research subjects. According to different intervention methods, the patients were divided into routine intervention group (n=35) and nutritional intervention group (n=40). The routine intervention group was given routine interventions and diet guidance, while the nutritional intervention group was additionally given continuous nutritional intervention. The nutritional status, anthropometry indicators [weight, upper arm circumference, triceps skin fold thickness (TSFT)], biochemical indicators (prealbumin, albumin) and incidence of complications were compared between the two groups. Results After intervention, the nutritional risk rate in the nutritional intervention group was lower than that in the routine intervention group (47.50% vs 71.43% , P<0.05), while the values of weight, upper arm circumference and TSFT were higher than those in the routine intervention group (P<0.05), the serum albumin level was higher than that in the routine intervention group (P<0.05), and the incidence of complications was lower than that in the routine intervention group (25.00% vs 48.57%, P<0.05). Conclusion Nutritional intervention is beneficial to maintain stable nutritional status, promote growth and development, and reduce the incidence of related complications in ALL children during maintenance treatment.

Application of immunotherapy in relapsed/refractory B-cell acute lymphoblastic leukemia / 中国药房

Immunotherapy， as an emerging treatment method， has been proven to improve the prognosis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia （B-ALL） and has good application prospects. Immunotherapy， including chimeric antigen receptor T cell immunotherapy （CAR-T） and monoclonal antibodies， has shown great potential for application， and has been approved for marketing. This article summarizes the application of the above two therapies in the treatment of relapsed/ refractory B-ALL， and concludes that CAR-T is a kind of personalized immunotherapy， and the selection of ideal targets is an important part of its action. Currently， the ideal targets in clinical studies include CD19， CD22 and CD19/CD22. Monoclonal antibodies， including blinatumomab and inotuzumab ozogamicin， have shown superior therapeutic efficacy for relapsed/refractory B- ALL. Immunotherapy has shown superior therapeutic effects compared to conventional chemotherapy， expanding the selection of treatment options for relapsed/refractory B-ALL.

Survival benefit of pediatric-based regimen for adults with acute lymphoblastic leukemia: A single-center retrospective cohort

ABSTRACT Introduction: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. Methods: Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. Results: The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p = 0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p = 0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p = 0.0007 and p = 0.004, respectively). Conclusion: ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.

Outcome of adolescents and young adults with acute lymphoblastic leukemia in a single center in Brazil

ABSTRACT Introduction: Acute lymphoblastic leukemia (ALL) presents a poor prognosis in adults. The adoption of pediatric protocols has been changing this scenario, especially for adolescents and young adults (AYA). Objective and method: We aimed to evaluate a consecutive series of patients treated at the State Institute of Hematology of Rio de Janeiro between 2012 and 2020, focusing on the AYA subgroup. Result: The B-ALL was the most frequent subtype (81.6%) and AYA, the predominant age group (57.7%). The median overall survival (OS) was 9.4 months. High early mortality was observed and sepsis was the main cause of death. Better OS results were noted in AYA, in comparison to over 39y (13.3 × 6.2 months, respectively), the Berlin-Frankfurt-Münster (BFM) being the protocol of choice in this group. Conclusion: The use of the pediatric protocol seems to improve the OS of AYA, however, high rates of deaths from infection were observed, demonstrating the need for advances in the Brazilian public system clinical support.

The prognostic values of the IL?10 (G1082A) and TNF?? (G308A) polymorphisms in Egyptian patients with acute lymphoblastic leukemia: A single?center study

Background: Interleukin?10 (IL?10) and tumor necrosis factor?alpha (TNF??) genes contribute to oncogenesis. We evaluated the influence of the IL?10 (G1082A) and TNF?? (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL). Materials and Methods: We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL?10 (G1082A) and TNF?? (G308A) polymorphisms using allele?specific polymerase chain reaction and polymerase chain reaction杛estriction fragment length polymorphism. Survival analyses were performed using the Kaplan朚eier estimator and the log?rank test. Results: In children with ALL, the A allele of TNF?? and IL?10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region朅belson (BCR?ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL?10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF?? A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL?10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR?ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003). Conclusion: A possible association exists between the A allele of IL?10 and TNF?? polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL?10 GG genotype may be associated with better survival in children with ALL.

Successful stem cell transplantation after nelarabine, pegylated asparaginase, vincristine, doxorubicin, and prednisone in refractory early T-cell precursor acute lymphoblastic leukemia: A case report

Early T-cell precursor Acute Lymphoblastic Leukemia (ALL) has a dismal prognosis. Nelarabine is a purine nucleoside analog that increases the apoptosis rate in T-cell lymphoblasts. We present a 30-year-old patient diagnosed with T-cell ALL. He was a high-risk patient because of an early precursor phenotype and a complex karyotype that had been refractory to three previous lines of treatment. He started a course of nelarabine (1500 mg/m for three days), pegylated-asparaginase, doxorubicin, vincristine, and prednisone (Nelarabine Peg-Asp AdmVP). He reached complete remission and received an allogeneic sibling hematopoietic stem cell transplant with fludarabine, total body irradiation, and cyclophosphamide as the conditioning regimen. He developed a pulmonary mycosis, which resolved, and grade-2 neurotoxicity in his upper and lower limbs. He was discharged after 40 days and to date remains with 23 months of complete remission. The Nelarabine Peg-Asp AdmVP regimen seems to be effective and safe. Further research is needed to establish it as an induction treatment in refractory early T-cell precursor acute lymphoblastic leucemia.

Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype / Miosina 1g como un marcador de alto riesgo en una paciente pediátrica con cambio de linaje de leucemia linfoblástica aguda a fenotipo mieloide

Abstract Background: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). Case report: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. Conclusions: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.

Resumen Introducción: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. Caso clínico: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. Conclusiones: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.

Infiltración del nervio óptico como forma inicial de recaída de la leucemia linfoblástica aguda / Optic nerve infiltration as an initial form of relapse of acute lymphoblastic leukemia

Introducción: La infiltración del nervio óptico como forma inicial de recaída de la leucemia linfoblástica aguda es rara, aunque altamente indicativa de que el sistema nervioso central está involucrado. Objetivo: Actualizar el conocimiento sobre infiltración del nervio óptico como forma inicial de recaída de la leucemia linfoblástica aguda. Métodos: Se realizó una revisión de las publicaciones más relevantes relacionadas con el tema durante los últimos años. La búsqueda y la localización de la información se apoyaron en la elección de palabras clave/descriptores que configuraron el perfil de búsqueda. Se utilizó el MeSH Database de PubMed. Se realizó una extensa revisión en Google Académico y otros megabuscadores de revisión sistemática mediante TripDatabase y Cochrane. Conclusiones: La infiltración directa de células tumorales y las alteraciones hematológicas propias de la enfermedad constituyen los mecanismos fundamentales de la fisiopatogenia. El edema del disco óptico es su signo oftalmoscópico más distintivo. La imagen por resonancia magnética de cráneo, el análisis citológico del fluido cerebroespinal y la biopsia de médula ósea negativas no deben excluir el diagnóstico. La terapia combinada que incluye la radiación localizada constituye una buena opción de tratamiento. Un número considerable de ojos recuperan su agudeza visual y muestran resolución del cuadro infiltrativo(AU)

Introduction: Optic nerve infiltration as an initial form of relapse of acute lymphoblastic leukemia is rare, although it is highly indicative of central nervous system involvement. Objective: To update the knowledge about optic nerve infiltration as an initial form of relapse of acute lymphoblastic leukemia. Methods: A review of the most relevant publications related to the subject during the last years was carried out. The search and localization of information was supported by the choice of keywords/descriptors that configured the search profile. The MeSH Database of PubMed was used. An extensive review was performed in Google Scholar and other systematic review mega search engines using TripDatabase and Cochrane. Conclusions: Direct tumor cell infiltration and disease-specific hematologic alterations are the fundamental mechanisms of pathophysiology. Optic disc edema is the most distinctive ophthalmoscopic sign. Negative cranial magnetic resonance imaging, cytologic analysis of cerebrospinal fluid and bone marrow biopsy should not exclude the diagnosis. Combination therapy including localized radiation is a good treatment option. A considerable number of eyes recover visual acuity and show resolution of the infiltrative picture(AU)

Potenciales biomarcadores moleculares de infiltración a sistema nervioso central en leucemia linfoblástica aguda / Central nervous system potential molecular biomarkers in acute lymphoblastic leukemia

Resumen La leucemia linfoblástica aguda es el tipo de leucemia más frecuente en niños entre los 2 y 3 años. A nivel internacional la población hispana es reportada como la más prevalente. En México se carece de información reciente, sin embargo, se conoce que es uno de los cánceres más frecuentes en niños. La infiltración de células linfoblásticas a sistema nervioso central es una complicación de pronóstico ominoso que puede presentarse en los pacientes con leucemia linfoblástica aguda, actualmente el diagnóstico se establece mediante citología de líquido cefalorraquídeo, sin embargo, es una prueba operador dependiente y que es afectada por el número de punciones realizadas en la toma de líquido cefalorraquídeo, con potencial contaminación con sangre. En distintos estudios se han caracterizado 6 genes que presentan una sobreexpresión en líquido cefalorraquídeo cuando se presenta dicha infiltración, en esta revisión analizamos estos nuevos marcadores y su potencial como herramientas de diagnóstico oportuno.

Abstract Acute lymphoblastic leukemia is the most common type of leukemia in children between 2 and 3 years of age. Internationally, hispanic population is reported as the most prevalent. In Mexico there is few recent information, however, it is known that it is one of the most frequent cancers in children. Infiltration of lymphoblastic cells into the central nervous system is an ominous prognostic complication that can occur in patients with acute lymphoblastic leukemia. Currently, diagnosis is established by cerebrospinal fluid cytology, however, this technique is affected by the number of punctions done while obtaining the fluid. In several research studies, 6 genes have been identified to be overexpressed in cerebrospinal fluid when infiltration occurs. In this review we analyzed these new molecular biomarkers and their potential as tools for timely diagnosis.

The association of hyperglycemia with the development of infectious complications in adult Filipino patients with acute lymphoblastic leukemia

Abstract Introduction Hyperglycemia occurs in Acute Lymphoblastic Leukemia (ALL) due to chemotherapeutic agents and may be stress-induced. Given the potential impact of hyperglycemia on the clinical outcomes of ALL patients, we sought to determine the association of hyperglycemia with the development of infectious complications. Methods This is a retrospective cohort involving adult Filipino ALL patients admitted at a tertiary referral center. Patients were stratified according to blood glucose levels and infections were classified into microbiologically and clinically defined infections. Logistic regression was performed to determine whether hyperglycemia was associated with the development of infectious complications. Results Of the 174 patients admitted for ALL, only 76 patients (44%) underwent blood glucose monitoring and were thus included in this study. Hyperglycemia was observed in 64 patients (84.21%). Infectious complications were seen in 56 patients (73.68%), of whom 37 patients (48.68%) had microbiologically defined infections and 19 (25%) had clinically defined infections. The respiratory tract was the most common site of infection and gram-negative bacteria were the predominant isolates. Hyperglycemia significantly increased the likelihood of infectious complications, particularly at blood glucose levels ≥ 200 mg/dL. Conclusion Hyperglycemia is associated with an increased likelihood of infectious complications in Filipino ALL patients. With sepsis being one of the main causes of mortality in this population, our study provides compelling evidence for us to consider routine blood glucose monitoring in order to manage and potentially decrease the occurrence of infections in these patients.

Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia / 中华血液学杂志

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.

Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

Integrated Traditional Chinese and Western Medicine Treatment for Acute Lymphoblastic Leukemia Complicated with Severe COVID-19 in Recovery Stage： A Case Report / 中医杂志

This paper reported a case of severe COVID-19 in the recovery stage with acute lymphoblastic leukemia treated by integrated traditional Chinese and western medicine， with the intention of shedding light on the clinical diagnosis and treatment of similar conditions. The patient， who had acute lymphoblastic leukemia， developed COVID-19 infection during the bone marrow suppression period after chemotherapy. Treatment with western medicine was mainly anti-infection， symptomatic management， and supportive care. During the recovery stage， considering the patient's chemotherapy history and disease progression， the overall syndrome was identified as deficiency of both qi and yin and binding of phlegm and blood. Based on the “state-target” combined treatment strategy， herbal prescriptions were selected and modified to address the “deficiency state”， “disease target”， and “symptom target”. In addition to western medicine， the patient was administered with Shengmai Powder （生脉散） and Compound Zhebei Granules （复方浙贝颗粒） in its modifications to boost qi， nourish yin， and reinforce healthy qi， nourish and cool the blood， ultimately achieving satisfactory therapeutic effects.

The Exploration of Glymphatic System Alteration in Pediatric Acute Lymphoblastic Leukemia Using DTI-ALPS Method / 中山大学学报(医学科学版)

ObjectiveThe glymphatic system regulates cerebral spinal fluid and interstitial fluid transport which might be one of the pathways of central nervous system （CNS） leukemia at the early stage. This study aimed to investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space （DTI-ALPS） in pediatric acute lymphoblastic leukemia （ALL） without clinically diagnosed CNS infiltration. MethodsTwenty-five ALL and typically developing （TD） children were prospectively recruited， and all subjects underwent DTI. Group differences in brain water diffusivities and ALPS-index were evaluated using the analysis of covariance. The Spearman correlation analysis was used to evaluate the relationship between biological characteristics and significant parameters in pediatric ALL. ResultsCompared with TDs， decreased Dxassoc value （PFDR-corrected = 0.048） and increased Dzassoc value （PFDR-corrected = 0.033） were found in pediatric ALL. Hence， lower ALPS-index was found in children with ALL （PFDR-corrected < 0.001）. ALPS-index was negatively associated with the risk classification （rs = -0.47， P = 0.018） as well as immunophenotype （rs = -0.40， P = 0.046） in pediatric ALL. ConclusionsOur results show dysfunction of the glymphatic system is presented in pediatric ALL without clinically diagnosed CNS infiltration， which suggests that the glymphatic system might be one of pathway in the early-stage of ALL CNS infiltration. The DTI-ALPS method can be used to evaluate the change of glymphatic system， providing a new method for exploring the underlying mechanisms and early detection of pediatric ALL CNS infiltration.

Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Expression and Significance of Vitamin D Receptor Gene and NF-κB Pathway in Blood of Children with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression, clinical significance and prognosis of vitamin D receptor (VDR) gene and NF-κB pathway in children with acute lymphoblastic leukemia (ALL).@*METHODS@#Thirty children with definitive diagnoses of ALL from December 2018 to December 2021 were selected as ALL group, and 30 healthy children under physical examination were selected as control group. Peripheral blood of all study subjects was collected. The VDR and NF-κB mRNA and protein expressions were detected by real-time quantitative PCR and Western blot, respectively. The relationship between mRNA expression of the above genes and clinical characteristics of children was retrospectively analyzed.@*RESULTS@#The relative expression of VDR mRNA in peripheral blood of children with ALL was significantly lower than that in the control group (P < 0.05), while NF-κB mRNA was higher (P < 0.001). The expression of NF-κB mRNA in ALL children with peripheral blood white blood cell count (WBC) < 50×109/L at initial diagnosis was significantly higher than those with WBC≥50×109/L (P < 0.01). The expression of NF-κB mRNA in ALL children with infection was significantly higher than that those without infection (P < 0.05). There were no significant differences in NF-κB mRNA expression between children with different sex, age, hemoglobin at initial diagnosis, platelet, immunologic typing, risk and induced response (P >0.05).@*CONCLUSION@#The expression of NF-κB is of value to diagnosis and prognosis of ALL in children.

Effect of LncRNA GATA3-AS1 Targeting MiR-515-5p on Cell Proliferation and Apoptosis in Childhood Acute Lymphoblastic Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of long non-coding RNA (lncRNA) GATA3 antisense RNA 1 (GATA3-AS1) targeting miR-515-5p on the proliferation and apoptosis of childhood acute lymphoblastic leukemia (ALL) cells.@*METHODS@#RT-qPCR was used to determine the expression of GATA3-AS1 and miR-515-5p in the plasma of controls and ALL children. Human ALL cells Jurkat were divided into si-GATA3-AS1, si-NC, miR-NC, miR-515-5p, si-GATA3-AS1+anti-miR-NC and si-GATA3-AS1+anti-miR-515-5p groups. CCK-8 assay was used to detect the cell proliferation, and flow cytometry was used to detect the cell apoptosis. The targeting relationship between GATA3-AS1 and miR-515-5p was determined by dual-luciferase reporter assay.@*RESULTS@#The expression level of GATA3-AS1 in the plasma of ALL children was significantly higher than that of controls (P <0.001), while the expression level of miR-515-5p was significantly lower than that of controls (P <0.001). Compared with the si-NC group, the cell inhibition rate, apoptosis rate, and miR-515-5p expression level in si-GATA3-AS1 group were significantly increased (P <0.001). Compared with the miR-NC group, the cell inhibition rate and apoptosis rate in miR-515-5p group were significantly increased (P <0.001). GATA3-AS1 could directly and specifically bind to miR-515-5p. Compared with the si-GATA3-AS1+anti-miR-NC group, the cell inhibition rate and apoptosis rate in si-GATA3-AS1+anti-miR-515-5p group were significantly decreased (P <0.001).@*CONCLUSION@#Down-regulation of GATA3-AS1 can inhibit proliferation and induce apoptosis of childhood ALL cells by targeting up-regulation of miR-515-5p expression.

Expression of IGLL1 Gene and Its Clinical Significance in Pediatric T-ALL / 中国实验血液学杂志

OBJECTIVE@#To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients.@*METHODS@#A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed.@*RESULTS@#The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients.@*CONCLUSION@#In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.

Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area / 中国实验血液学杂志

OBJECTIVE@#To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area.@*METHODS@#The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes.@*RESULTS@#Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05).@*CONCLUSION@#The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.