Clinical Characteristics and Treatment Outcomes of Pediatric Patientswith Non-Hodgkin Lymphoma in East Asia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differfrom those of adults. This study delineated the characteristics and outcomes of pediatricNHL in East Asia. @*Materials and Methods@#Medical records of 749 pediatric patients with NHL treated at participating institutions inmainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 werereviewed. Demographic and clinical features, survival outcomes, and putative prognosticfactors were analyzed. @*Results@#Five hundred thirty patients (71%) were male. The most common pathologic subtypes wereBurkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases atdiagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%.The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphomawere 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheralT-cell lymphoma (PTCL) were 71% and 56% (p 250 IU/mL), and advanced disease at diagnosis( stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsedmore frequently than other pathologic subtypes (p < 0.001). @*Conclusion@#In East Asia, PTCL was more frequent than in Western countries, and bone marrow involvementdid not affect treatment outcome. This international study should motivate future collaborativestudy on NHL in East Asia.

Relationship between parental exposure to chemicals and risk of childhood acute leukemia / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between parental exposure to chemicals and the risk of childhood acute leukemia.</p><p><b>METHODS</b>An exploratory case-control study was conducted among 201 new cases of childhood acute leukemia under 15 years old who went to 3 children's hospitals in Shanghai, China from January 1, 2009 to December 31, 2010, as well as 201 sex- and age-matched children (as controls) who went to the child health care clinic or department of orthopedics in the above hospitals. A survey was performed by face-to-face interviews with children's mothers.</p><p><b>RESULTS</b>The risk factors for childhood acute leukemia might include maternal exposure to total chemicals (diesel oil, gasoline, paints, insecticides, pesticides, herbicides, and chemical fertilizers) from 3 months before pregnancy to the end of pregnancy (OR = 2.9, 95%CI = 1.1 ∼ 7.8), paternal exposure to insecticides (OR = 10.1, 95%CI = 1.2 ∼ 82.9) and chemical fertilizers (OR = 9.5, 95%CI = 1.1 ∼ 79.6) within 3 months before pregnancy, maternal working experiences in agriculture and forestry before pregnancy (OR = 8.4, 95%CI = 1.4 ∼ 50.2) and in spinning, leather processing, decoration, and vehicle repair before pregnancy (OR = 3.0, 95%CI = 1.2 ∼ 7.9) and during pregnancy (OR = 3.2, 95%CI = 1.1 ∼ 9.6), and paternal working experiences in agriculture and forestry (OR = 9.6, 95%CI = 2.1-44.8) and in spinning, leather processing, decoration, and vehicle repair (OR = 2.3, 95%CI = 1.1-5.0).</p><p><b>CONCLUSION</b>Parental exposure to chemicals may increase the risk of childhood acute leukemia in their offspring.</p>

Characteristics of RB1 gene mutations in Chinese patients with retinoblastoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the characteristics of RB1 gene mutations in Chinese patients with retinoblastoma.</p><p><b>METHODS</b>Peripheral blood samples of 35 patients with retinoblastoma were collected and genomic DNA was extracted. Multiplex PCR sequencing was carried out to identify RB1 gene mutations. Parents of 6 probands with RB1 mutations were also enrolled to identify the origins of mutations.</p><p><b>RESULTS</b>Fourteen patients were found to have carried germline mutations, among whom 11 had bilateral tumors and 3 had unilateral tumors. Sixteen germline mutations were identified, among which 13 were pathological, which included 5 nonsense mutations (c.1072C > T, c.1333C > T, c.1363C > T, c.1399C > T, c.2501C > A), 4 missense mutations (c.920C > T, c.1346G > A, c.1468G > A, c.1861C > A), 2 frameshift mutations (c.1947delG, c.2403delA) and 2 large fragment deletions (c.139_168 del30, exon 8 deletion). Three were non-pathological mutations, including 2 intronic mutations (c.540-23 dupT, c.2664-10T > A) and 1 silent mutation (c.2192T > A). One carrier was identified among the 6 parents of children carrying a RB1 mutation.</p><p><b>CONCLUSION</b>Screening for RB1 gene mutations in patients with bilateral or unilateral retinoblastoma can help to identify heritable mutations and provide important clues for genetic counseling and clinical management.</p>

Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy and toxicity of the CCCG-97 and BFM-90 protocols in the treatment of pediatric patients with B-cell non-Hodgkin's lymphoma (B-NHL) retrospectively, and to explore the optimal therapeutic strategy.</p><p><b>METHODS</b>Forty-five consecutive untreated patients (age of 18 years or less) with newly diagnosed B-NHL (including Burkitt Lymphoma and diffuse large B-cell lymphoma), treated in our hospital between July 1999 and December 2008 were enrolled in this study. The patients were classified into 2 groups by different protocols. From July 1999 to December 2004, twenty-one 3- to 13.8-year-old children were enrolled in the CCCG-97 group, with 1 in stage I/II, and 20 in stage III/IV(St Jude staging). From January 2005 to December 2008, twenty-four 2.8- to 14.1-year-old cases were enrolled in the BFM-90 group, with 3 in stage I/II, and 21 in stage III/IV (St Jude staging). The survival rates were evaluated by Kaplan-Meier analysis.</p><p><b>RESULTS</b>Forty of the 45 patients (88.9%) reached complete response (CR) after 2 courses of chemotherapy. In the CCCG-97 group, the CR rate was 95.2% (20/21 pts), while that in the BFM-90 group was 83.3% (20/24 pts). At a median follow-up time of 62 (17 to 131) months, the 5-year event-free survival (EFS) was 71.8% for all patients, and 69.1% for Stage III/IV, respectively. In the CCCG-97 group, the 3-year EFS was 76.2%. In the BFM-90 group, it was 75.0%. There was no significant difference in survival rates between the CCCG-97 and BFM-90 groups (P=0.975). Unfavorable events recorded were as follows: Death of progression before achieving CR during induction therapy in 4 cases, and relapse after achieving CR in 6 cases. The relapse rates were 19.0% (4/21 pts) in the CCCG-97 group and 8.3% (2/24 pts) in the BFM-90 group, with a non-significant statistical difference (P=0.292). Major toxicities were myelosuppression and mucositis, especially in the BFM-90 group, but were tolerable and manageable. five patients in the BFM-90 group received rituximab, 2 patients (Stage III) achieved CR, while the other 3 patients (Stage IV) had progressive disease or relapse.</p><p><b>CONCLUSIONS</b>Short-pulse and intensive chemotherapy, stratified according to stage of disease, can improve the survival rate of pediatric mature B-NHL. The efficacy of the CCCG-97 protocol and BFM-90 protocol is comparable and the toxicity is tolerable.</p>

Clinical characteristics of hepatic veno-occlusive disease in 6 children with hematologic neoplasm treated with 6-thioguanine / 中华儿科杂志

<p><b>OBJECTIVE</b>To improve the treatment of drug related childhood hepatic veno-occlusive disease (HVOD), clinical characteristics of 6 children with hematologic neoplasm from 2 hospitals of China Children's Leukemia Group (CCLG) treated with 6-thioguanine (6-TG) complicated with HVOD were analyzed.</p><p><b>METHOD</b>All the drug related HVOD patients were treated with CCLG acute lymphoblastic leukemia (ALL)-2008 protocol. They were from Children's Hospital of Fudan University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from April 2008 to April 2009. The diagnosis was made according to the modified Seattle criteria and Baltimore criteria, including 2 or 3 of the following clinical features: hepatomegaly and upper right abdominal pain, jaundice (bilirubin ≥ 35 µmol/L), ascites or confirmed by pathology. The 6 HVOD patients' clinical manifestations, laboratory finding, imageologic and pathologic data were collected and analyzed.</p><p><b>RESULT</b>Of the 6 patients, 2 were males and 4 females. Mean age of the 6 patients was 3.89 years (range from 3 years 1 month to 4 years 11 months). The original disease was acute lymphoblastic leukemia. HVOD occurred during chemotherapy protocols of CAM (CTX + Ara-C + 6-TG) or maintenance period (MTX + 6-TG). Most of 6 HVOD patients presented with pain in liver area, hepatomegaly on imaging, elevated aminotransferase and bilirubin (often ≥ 35 µmol/L), hydroperitonia was common, one with pleural fluid, illegible hepatic veins. All the patients recovered after being treated with hepatoprotective, jaundice-relieving and supportive therapeutics, some patients were treated with low molecular weight heparin. The prognoses were good.</p><p><b>CONCLUSION</b>HVOD was a serious complication of chemotherapy with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight heparin could improve the prognosis.</p>

Quantitative Detection of Translocation ETS Leukemia-Acute Myeloid Leukemia 1 Fusion Gene in Children with Acute Leukemia and Its Clinical Application in Minimal Residual Disease Monitoring / 实用儿科临床杂志

Objective To develop a method of real-time quantitative polymerase chain reaction (RQ-PCR) for detection of translocation ETS leukemia-acute myeloid leukemia 1(TEL-AML1) fusion gene in children with acute lymphoblast leukemia(ALL),and explore its clinical application in minimal residual disease (MRD) monitoring.Methods By reverse transcription and RQ-PCR,a quantifying of TEL-AML1 fusion gene was developed,and the expression levels of TEL-AML1 were detected in bone marrow (BM) samples obtained from 24 children with ALL at diagnosis and at the end of induction of remission,as well as at a series of follow-up. Moreover,the results of MRD detection by RQ-PCR were compared with that of detection by routine morphological examine of BM and cells differentiation mark analysis by flow cytometer(FCM),to evaluate the sensitivity of RQ-PCR in MRD monitoring. Results A method of RQ-PCR targeted at TEL-AML1 fusion gene was established. In 11 BM samples,which collected from TEL-AML1 positive children at the end of induction therapy and all of them achieved completely remission (CR) by routine morphological examine,5 samples were found to be MRD positive by RQ-PCR,positive ratio was 45%. There were 15 BM samples collected in maintenance therapy period,and all these samples were CR by routine morphological examine. However,by RQ-PCR,3 out of 15 samples were found to be MRD positive during maintenance therapy period. After intense and maintenance therapy,the MRD levels of the 3 children were declined to negative. In a recrudescent child,the expression of TEL-AML1 fusion gene was rose by a magnitude of 103 copies before relapse,and after induction therapy once again the patient was completely relaxed.Conclusions RQ-PCR targeted at TEL-AML1 has a higher sensitivity than conventional morphologic way and FCM. RQ-PCR can be used in the quantitative detection of MRD,and provide gist for early prognosticating a relapse and instructing clinical therapy.