PURPOSE: Dried blood spot (DBS) is one of promising home sampling methods for therapeutic drug monitoring (TDM). However, the associated reliability and feasibility (including yield, adherence, and preference), which are criteria for the promotion of home-based DBS, remain unknown. This systematic review and meta-analysis aimed to evaluate the reliability and feasibility of TDM using DBS sampling. METHODS: In this study, a combination of MeSH and free terms for (dried blood spot*[title/abstract])AND ("Drug Monitoring"[Mesh])AND(home OR venous)was surveyed using EMBASE, PubMed, Cochrane Library, and Web of Science upon gathering published. we registered this study protocol with the International Prospective Registry of Systematic Reviews (CRD42021247559). RESULTS: Approximately half (35/75) of the evaluations reported good agreement between DBS and plasma, and the results for drugs with poor agreement may be improved using a haematocrit-based physiological equation. The yield and adherence to home-based DBS exceeded 87%, and questionnaire-based preference for DBS was 77%. CONCLUSIONS: DBS may be a reliable and feasible home sampling method; however, it requires intricate design and evaluation before implementation.
Dried Blood Spot Testing , Drug Monitoring , Humans , Drug Monitoring/methods , Reproducibility of Results , Feasibility Studies , Dried Blood Spot Testing/methods , Hematocrit
Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans , Child , Venous Thromboembolism/etiology , East Asian People , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Risk Factors , Thrombosis/chemically induced , China/epidemiology , Anticoagulants/adverse effects , Recurrence
Single-cell sequencing (SCS) sequences the genetic information of a single cell to better understand the differences amongst cells and reveal the unique changes of each cell type. The specific analysis of cell subsets at the single-cell level can accurately evaluate tumor cells and microenvironment cells to reveal the complexity of molecular components and the difference from the corresponding components in non-malignant tissues. Lymphoma is highly heterogeneous, some have unknown pathological types, etiology and poor prognosis. SCS is helpful to clarify the molecular mechanisms of lymphomagenesis and pathological staging, and guide clinical practice. This article reviews SCS and its application in lymphoma.
BackgroundSince late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. MethodsWe collected detailed information on 323 pediatric cases and their 951 household members in April 2022 during the Omicron outbreak. All household members received consecutively intensive RT-PCR testing for SARS-CoV-2 and routine symptom monitoring within 14 days after exposure to a confirmed case. We described the characteristics of study participants and estimated the transmission parameters. Both secondary infection attack rates (SARI) and secondary clinical attack rates (SARC) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. ResultsWe estimated the mean incubation period of SARS-CoV-2 Omicron variant to be 4.6 (median: 4.4, IQR: 3.1-6.0) days and the mean serial interval to be 3.9 (median:4.0, IQR: 1.4-6.5) days. The overall SARI and SARC among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. The estimated VEs of full vaccination was 14.8% (95% CI: 5.8%-22.9%) against Omicron infection and 21.5% (95% CI: 10.4%-31.2%) against symptomatic disease. The booster vaccination was 18.9% (95% CI: 9.0%-27.7%) and 24.3% (95% CI: 12.3%-34.7%) effective against infection and symptomatic disease, respectively. ConclusionsWe found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.
ObjectivesTo understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. MethodsThis study included local COVID-19 cases <18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. ResultsA total of 376 pediatric cases of COVID-19 (median age:6.0{+/-}4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children;3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35% (RR 0.65, 95% CI:0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration: 1.7{+/-}1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%), school (21.8%) and residential area (8.8%). ConclusionThe surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer protection against symptomatic infection and febrile disease.
Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.
Objective:To summarize the experience on accurate prevention and control of children′s emergency department during the epidemic of novel coronavirus Omicron variant.Methods:We retrospectively analyzed the strategies and management experience of emergency prevention and control of novel coronavirus infection in emergency department at Children′s Hospital of Fudan University from March to May 2022.Results:As a designated hospital for treating pediatric patients who contracted novel coronavirus in Shanghai, the emergency department in our hospital was confronted with the dual pressure of critical patients treatment and pandemic prevention and control.We carefully studied a series of laws and regulations, as well as the newest edition of Chinese clinical guidance for novel coronavirus pneumonia diagnosis and treatment, and combined with the characteristics of novel coronavirus infection in children, then formulated the independent emergency department, fever clinics and novel coronavirus clinics; Updated the emergency department pre-examination triage process, the precautions pratice of clinical stuffs and disfection strategy, and established the second emergency department.From the beginning of March to the end of May 2022, a total of about 12 000 patients were admitted to the emergency department in our hospital, including 704 patients in the resuscitation room, 652 patients in the observation room, and 164 patients in the emergency ward.There were six patients with novel coronavirus infection in the emergency department.Neither nosocomial infection nor occupational exposure occurred.Conclusion:After 3 months of practice, the results showed that it can fully guarantee the timely treatment of critically ill children and achieved zero cross-infection in the hospital, which has important reference significance for the treatment of children, epidemic prevention, control during the novel coronavirus epidemic.
Hematopoietic stem cell transplantation related thrombotic microangiopathy (TA-TMA) is a clinical syndrome characterized by microvascular hemolytic anemia, thrombocytopenia and involvement of end organ.The pathogenesis of TA-TMA involves vascular endothelial cell injury and abnormal activation of complement system.The risk factors include conditioning regimens, graft-versus-host disease, immunosuppressants, infection and HLA compatibility.Timely diagnosis and early initiation of appropriate treatment are essential to prevent multiple organ dysfunction and eventual death.At present, the lack of clinical evidence of TA-TMA has led to the fact that its diagnostic criteria and treatment have not been unified.The diagnosis and treatment suggestions put forward by domestic and foreign experts are intended to help clinicians evaluate potential TA-TMA, establish diagnosis in time, and give reasonable treatment and management.
Objective:To explore the clinical characteristics of Diamond-Blackfan anemia (DBA) in children caused by RPL5 gene mutation, thus improving the understanding of the etiology of DBA.Methods:The clinical data and sequencing results of a child with DBA caused by RPL5 gene mutation treated in the Children′s Hospital of Fudan University were analyzed.In addition, through literature review of reported DBA cases at domestic and home, summarized the clinical features of DBA.Results:The patient was an 8-year-old male child.Bone marrow puncture examination of the child showed DBA, and a heterozygous mutation of RPL5 gene c. 657C>G, p.Y219X was identified for the first time in the DBA case.A total of 47 cases of DBA were retrieved from the online databases plus the one reported in this study (48 cases in total), and their clinical features were summarized as follows: the incidence of DBA was similar in men and women.The number of DBA patients in Asia was lower than that in Europe and the United States.DBA was mainly a sporadic disease.Among the exon mutations in European and American cases of DBA, 43.0% of them had mutations in Exon3.The malformation rate of DBA patients with RPL5 mutation was 81.3% (39/48 cases, excluding short stature cases), which was higher than that of patients with other mutation types.The response rate of glucocorticoid therapy for DBA was 46.0%, which was lower than that of the overall response rate.Conclusions:chr1: 93303142(c.657 C>G, p.Y219X) is a newly detected mutation of RPL5 gene in the DBA case, which expands the pathogenic gene spectrum of DBA.Patients with RPL5 mutation have higher rates of teratogenicity and multiple teratogenicity, and a lower response rate to hormone therapy.
Objective:To investigate the serum measles antibody in children with tumor and to provide the clinical evidence for measles vaccination strategy for this special population.Methods:From January 2016 to December 2018, the blood samples of children who were diagnosed with hematological malignancy or solid tumors and received chemotherapy in the Department of Hematology or Oncology Surgery of Children′s Hospital of Fudan University were collected. Enzyme-linked immunosorbent assay was used to quantitatively detect the level of measles IgG antibody, and dynamically monitor the changes of measles antibody level during chemotherapy. Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:A total of 441 children with tumors were enrolled, with the positive rate of measles antibody of 79.1%(349/441), and only 43.3%(191/441) of children had the protective level of IgG antibody. There was a statistically significant difference of the antibody protection rate in children aged<eight months old, eight months old to <two years old, two years old to <six years old, and ≥six years old ( χ2=15.647, P<0.01). There was no statistically significant difference of the protection rate of serum measles antibody between children aged two to <six years and≥six years (43.8%(95/217) vs 41.1%(58/141), P>0.05). The protection rate of serum measles antibody in children with hematological malignancy and solid tumor were 45.6%(78/171) and 41.9%(113/270), respectively, and there was no statistically significant ( P>0.05). There were 16.3%(16/98) of children who were observed to lose the pre-existing protective antibody during chemotherapy. There was no statistically significant difference of the protection rate of serum among children who had finished chemotherapy <six months, six months to <one year, one year to <two years, and ≥two years ( P>0.05). Conclusions:Serum measles antibody is below the protective level in more than 50% of children with malignancy after chemotherapy. Chemotherapy can compromise the protective antibody against measles. It is recommended for this special population to re-schedule measles vaccine after individualized evaluation to acquire the immuneprotection against measles.
Objective@#To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance.@*Methods@#Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis.@*Results@#A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ2=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ2=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ2=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ2=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ2=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL.@*Conclusion@#The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.
Objective@#To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance.@*Methods@#Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis.@*Results@#A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ2=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ2=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ2=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ2=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ2=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL.@*Conclusion@#The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.
Objective:To evaluate the treatment efficacy of children with T-cell acute lymphoblastic leukemia (T-ALL) and to explore the prognostic risk factors.Methods:The clinical and laboratory data of children with newly diagnosed T-ALL in Children's Hospital of Fudan University and Children's Hospital of Shanghai from January 2002 to December 2014 were retrospectively analyzed and compared with children with newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) in the same period. The treatment protocols were based on the combination of the Berlin-Frankfurt-Münster (BFM)-ALL regimen with chemotherapy. The treatment response and infection of the children were observed. Cox proportional hazard regression model single-factor and multifactor analysis were used to evaluate the prognostic factors.Results:Seventy-one children with T-ALL and 333 children with B-ALL were enrolled. The clinical features including gender, age, central nervous system leukemia as well as the white blood cell count at first diagnosis were significantly different between the two groups (all P < 0.05). The prednisone good response rates of children with T-ALL were lower than that of B-ALL [78.9% (56/71) vs. 93.4% (311/333), P < 0.01], and the complete remission rates were lower than that of [94.4% (67/71) vs. 99.1% (330/333), P= 0.023]. By the end of follow-up, the relapse rates of children with T-ALL and B-ALL were 20.9% (14/67) and 16.4% (54/330) ( P= 0.369). The children with T-ALL had a shorter time to relapse compared with children with B-ALL [64.3% (9/14) vs. 35.2% (19/54), P= 0.049]. The 5-year overall survival (OS) rates of children with T-ALL and B-ALL were (62.1±6.4)% and (81.3±2.4)% (P < 0.05), and the 5-year event free survival (EFS) rates were (61.0±6.3)% and (71.0±2.7)% (P < 0.05). There was no significant difference in OS and EFS among pro/pre T-ALL, cortical T-ALL and mature T-ALL (both P > 0.05). The difference of EFS curves between children with early T-precursor (ETP)-ALL and non-ETP ALL was statistically significant ( P= 0.044). The most common infection site was respiratory tract [63.9% (186/291)], and the gram-negative bacteria accounted for 43.5% (20/46). Cox univariate analysis showed that prednisone poor response, bone marrow non-remission on day 33 of induction-therapy, relapse and sepsis were prognostic risk factors for children with T-ALL (all P < 0.05), and Cox multivariate analysis showed that the latter three were independent prognostic risk factors (all P < 0.05). Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL, and T-ALL patients are prone to early relapse. The EFS of children with ETP-ALL is poor. Non-remission at the end of induction-therapy, relapse and sepsis are independent risk factors for prognosis.
OBJECTIVE@#To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation.@*METHODS@#Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene.@*RESULTS@#The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree.@*CONCLUSION@#Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.
Humans , Chediak-Higashi Syndrome , Genetics , Exons , Heterozygote , Mutation , Pedigree , Sequence Analysis, DNA , Vesicular Transport Proteins , Genetics , Exome Sequencing
Burkitt lymphoma (BL) is a highly aggressive mature B﹣cell lymphoma originating from the germinal center, and accounts for 30%-50% of childhood non﹣Hodgkin lymphoma (NHL). The current dose﹣intensive, multi﹣agent chemotherapy has made great progress in the treatment of BL with the cure rate of 80%-90%; however, the relapse or death rate still remains 10%-20% due to toxicity of such therapy. Studies have shown that abnormal activation of PI3K﹣AKT﹣mTOR signaling pathway and abnormal expression of key regulatory genes are closely related to the pathogenesis, development, treatment and prognosis of BL. This article will review the abnormal activation mechanisms of PI3K﹣AKT﹣mTOR signaling pathway and targeted therapy of pediatric BL to further clarify the pathogenesis and potential targets for drug therapy of pediatric BL at the molecular and genetic levels.
Lymphoblastic lymphoma (LBL) is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia,which develops very fast with high morbidity.T-lymphoblastic lymphoma (T-LBL),accounting for 85％-90％ of LBL,develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum,whose diagnostic hallmark is the expression of a T-precursor cell immunophenotype.Recently many new diagnostic technologies,such as polymerase chain reaction,flow cytometry,fluorescence in situ hybridization and so on,have been used for the dignosis of LBL,which lay the foundation of the precision therapy for LBL.The adoption of pediatric-derived,intensive lymphoblastic leukemia-like protocols leads to significantly improved results,with event free survival about 75％-90％ in children.New clinical trials will introduce and confirm the value of new drugs and targeting agents,which may have more good effects.New minimal residual disease assessment methods(eg,next generation sequencing,NGS) make it possible to detect MRD in different subtype of childhood lymphomas.Now,the new advances in diagnosis and treatment of T-LBL were reviewed.
Rare diseases are very rare,but usually have severe symptoms.Some rare diseases are life-threatening.Most rare diseases cannot be cured.A very small part of these diseases can be cured by hematopoietic stem cell transplantation (HSCT).Umbilical cord blood transplantation(UCBT) is more suitable for children for the weak T cell immunity,the lower request for human leukocyte antigen (HLA) identity type and the lower incidence of graft versus host disease(GVHD).This article reviewed the published data in the treatment of UCBT in primary immunodeficiency disease,inherited metabolic disease,inflammatory bowel disease and bone marrow failure syndrome,in order to improve the level of rare disease treatment by HSCT,especially for UCBT.
Objective To investigate the efficacy and prognostic risk factors of ALL-R-2003 protocol in the treatment of relapsed childhood relapsed acute lymphoblastic leukemia (ALL) in single center. Methods A retrospective study of clinical data of 51 children with relapsed ALL from January 2004 to December 2014 was performed by using SPSS version 19.0 statistical software for statistical analysis. Results The median age at initial diagnosis of 51 patients was 5.5 years (range, 0.8-13.4 years). The median time from initial diagnosis to relapse was 25 months (range, 3-68 months) and follow-up time was 39 months (range, 3-116 months). The relapse rate in the standard-risk, intermediate-risk and the high-risk groups were 27.5 % (14/51), 29.4 %(15/51) and 43.1 % (22/51), respectively. The probability of 3-year overall survival (pOS) after relapse was (18.8±5.9)%and the probability of event free survival (pEFS) was (16.2±5.8)%. The 3-year pOS in very early relapse, early relapse and late relapse were 0, (11.7 ±7.7) % and (51.7 ±14.8) %, respectively (P= 0.000). There was no statistical difference in survival rate of different immunophenotype groups and sites of relapse (P> 0.05). The 3-year pOS of group S1, S2, S3, S4 were (50.0±35.4) %, (39.9±1.3) %, (10.0±9.5) % and 0, respectively (P=0.000). The 3-year pOS of bcr-abl and MLL gene positive groups were (25.0±21.7) %and 0, respectively, with no statistically significance compared with the negtive group [(24.1±12.0)%] (P>0.05). The 3-year pOS rates of children with bone marrow transplantation and without transplantation were (40.0 ±15.5) %and (13.0 ±5.9) % respectively (P= 0.038). Conclusions The children who in high risk group at initial diagnose are easily to meet earlier relapse and poorer prognosis. The survival period after relapse of bcr-abl or MLL gene positive cases is very short. Bone marrow transplantation can improve survival rate. Risk group at initial diagnose, relapse time and transplantation are the main factors influencing prognosis, and the relapse time and transplantation are the independent prognostic factors for relapsed childhood ALL.
Retinoblastoma(RB) is the most common intraocular malignancy in children.The tumor can originate in one or both eyes.About 40％ of children with RB have inherited form of the disease.The treatment options available for RB include chemoreduction therapy,intra-arterial chemotherapy,radiotherapy,enucleation,genetherapy and focal therapies such as cryotherapy,laser photocoagulation,transpupillary thermotherapy.Currently,with the progress of early diagnosis and treatment,chemotherapy combined focal therapies play an important role in the treatment,which not only improve the survival rates of RB children,but also improve the children's life qualities with salvaging the eve and vision.
Background and purpose: L-asparaginase (L-Asp) is an important drug in the treatment of childhood lymphoid neoplasms at present, but a lot of adverse reactions of L-Asp were observed. Pegasparaginase (PEG-Asp) is available in China in recent years. This study aimed to explore efifcacy and side-effect of PEG-Asp as ifrst-line treatment in childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods:A total number of 211 ALL or LBL patients were treated with CCLG 2008 or BFM-90 protocol with PEG-Asp or L-Asp between Apr. 2008 and Mar. 2013;42 patients, among whom, were 35 ALL patients and 7 LBL patients, were treated with PEG-Asp as ifrst-line treatment;169 patients were treated with L-Asp as ifrst-line treatment (including 53 patients treated with L-Asp during induction protocol; with PEG-Asp during consolidate protocol). The clinical outcome and adverse reaction of PEG-Asp with L-Asp were observe and compared. Results: There were 35 ALL patients in PEG-Asp ifrst-line treatment group and the complete remission rate after 1 course of PEG-Asp was 97.1%,however, which was 83.3%of high risk ALL patients. The complete remission rate of 7 LBL patients of PEG-Asp ifrst-line treatment group was 57.1%. There was no signiifcant difference between 2 groups (P>0.05). Thirty-four patients relapsed including 5 patients of PEG-Asp ifrst-line treatment group, 16 patients of L-Asp ifrst-line treatment group and 13 patients treated with L-Asp during induction protocol and with PEG-Asp during consolidate protocol. Thirty-one patients died including 3, 18, 10 patients in 3 groups respectively. Twenty-two patients died of relapse, 4 died without remission, 5 died of complications. There was also no signiifcant difference between 2 groups (P>0.05). The incidence rates of adverse reactions were 47.6% and 63.3% respectively. Anaphylaxis, liver functions abnormalities, blood coagulation abnormalities, gastrointestinal reaction, hyperglycemia and pancreatitis were common in our patients. The incidence rate of anaphylaxis in PEG-Asp as ifrst-line treatment group was lower than other groups (P=0.03). But there was no signiifcant difference been observed in the incidence of other adverse reaction. Conclusion: The short-term efifcacy of PEG-Asp as the ifrst-line treatment in childhood leukemia and lymphoma was satisfactory and the incidence rate of anaphylaxis was lower. However, we will still pay much attention to adverse reaction monitoring of PEG-Asp.
