Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children's Cancer Group-ALL-2015 / 医学前沿

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.

Safety of Rituximab combined with intensive chemotherapy in the treatment of childhood aggressive mature B-cell lymphoma/leukemia / 中华实用儿科临床杂志

Objective:To investigate the safety of Rituximab combined with intensive chemotherapy in the treatment of aggressive mature B-cell lymphoma/leukemia in children.Methods:The clinical data of 77 patients with primary pediatric aggressive mature B-cell lymphoma/leukemia who were treated according to the Chinese Children Cancer Group(CCCG)-mature B-cell lymphoma(BNHL)-2015 protocol at Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiaotong University School from November 1, 2014 to July 31, 2018 were collected.A comparison was drawn on the adverse reactions and recovery of immune function indexes between patients in the Rituximab combined with intensive chemotherapy group (R4 group) and the chemotherapy alone group (R3 group).Results:Rituximab combined with AA was associated with a significantly lower platelet count [79.5%(35/44 cases) vs.54.5%(24/44 cases), χ2=6.223, P=0.011] and a higher incidence of infection [70.5%(31/44 cases) vs.36.4%(16/44 cases), χ2=10.275, P=0.001] compared with AA alone; Rituximab combined BB was associated with a higher incidence of mucositis and infection compared with BB alone [40.8%(20/49 cases) vs.29.3%(22/75 cases) and 85.7%(42/49 cases) vs. 72.0%(54/75 cases), respectively], but the differences were not statistically significant.A greater proportion of patients in the R4 group had a decrease in peripheral blood CD 19 positive cells (no statistically significant difference, P>0.05) and a greater proportion had a decrease in serum IgG ( P<0.05) compared to the R3 group, but there was no significant difference in treatment-related mortality between both groups.For patients in the R4 group, the average recovery time of IgG and IgM level was 13.1 months, and the longest recovery time was 31 months after the end of treatment. Conclusions:Rituximab combined with intensive chemotherapy is generally safe in the treatment of aggressive mature B-cell lymphoma/leukemia in children.However, it is often accompanied with prolonged immunoglo-bulin deficiency and the potential risk of secondary infection.Therefore, the strict control over the indications for its application is required, and the gamma globulin replacement therapy deserves to be investigated in the future.

Eight children with desmoplastic small round cell tumor and literature review / 中华实用儿科临床杂志

Objective:To analyze the clinical characteristics, therapeutic modalities and prognosis of desmoplastic small round cell tumor (DSRCT) in children, and to summarize the international research progress.Methods:A total of 8 children with DSRCT admitted to Shanghai Children′s Medical Center, Shanghai Jiaotong University, School of Medicine, from January 1999 to August 2019 were retrospectively studied.The clinical characteristics, consultation process and follow-up results were summarized, and the Kaplan-Meier survival analysis method was used to calculate the survival rate.Results:Among these 8 cases, there were 6 male children and 2 female children.Seven cases originated in the abdomen and pelvis, and 1 case originated in the sacral region.All cases had infiltrate surrounding tissues or viscera, and 4 cases(50%) had extra-peritoneal metastasis, including distant lymph node metastasis, liver, lung and bone metastasis.All patients received chemotherapy, among which 3 patients received radiotherapy, and 2 patients received autologous hematopoietic stem cell transplantation.The medical follow-up was continued to February 15, 2020, with the median follow-up period being 59 months.Three cases died and 5 cases survived (2 cases in complete remission, 1 case in recurrent relapse, 2 cases in partial remission still under treatment). The median relapse time was 14.5 months, the 3-year relapse-free survival rate was (30.0±17.5)%, and 3-year overall survival was (51.4±20.4)%.Conclusions:Half of DSRCT had distant metastasis; the prognosis was poor despite the aggressive multimodality therapeutic approaches, such as chemotherapy, cytoreductive surgery, and whole abdominopelvic radiotherapy and stem cell transplantation.

Stratified treatment of non-distant metastatic rhabdomyosarcoma in children: an analysis of its efficacy and prognostic factors / 中华实用儿科临床杂志

Objective@#To assess the efficacy of stratified treatment of pediatric non-distant metastatic rhabdomyosarcoma (RMS).@*Methods@#A retrospective review was conducted in 129 pediatric patients with non-distant metastatic RMS between January 2005 and December 2016 at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.According to their pathological types, TNM stages and postoperative pathologic staging, the 129 patients were grouped a low-risk group, an intermediate-risk group and a high-risk group.Multimodality therapies were applied to all patients including chemotherapy, surgery and radiotherapy.The overall survival (OS) and event-free survival (EFS) rates were analyzed by using the Kaplan-Meier method.@*Results@#Of 129 patients, 119 cases were included in this study.In 119 patients, the age of onset for the RMS ranged from 7 to 191 months, with the median onset age of 48 months.The median follow-up time was 40 months for event-free patients with RMS, and 36 months for all the 119 patients.The 5-year OS and EFS for all patients were (92.1±2.9)% and (76.5±4.4)%, respectively.While the 5-year EFS for patients in the low-risk group, intermediate-risk group and high-risk group were all above 70%, and the difference among the three groups was not statistically significant (χ2=2.679, P=0.262). A subsequent univariate analysis revealed that the onset age for RMS (≤1 year old or≥10 years old), TNM stage and postoperative pathologic stage were important predictors of EFS with statistical significance (all P<0.05), while gender, pathological type and primary site of RMS did not exhibit any significant impact on 5-EFS (all P>0.05). The 5-year EFS of RMS patients with Forkhead Box Protein O1(FOXO1)-positive was significantly lower than that of FOXO1-negative patients [(56.3%±14.8)% vs.(83.3±15.2)%], and the difference was statistically significant (χ2=4.588, P=0.028).@*Conclusions@#It is important that the stratification treatment should be strictly implemented on RMS patients.First, further improvement is necessary for the treatment of patients in the low-risk group due to their poorer prognosis compared to that of their intermediate-risk counterparts, for whom one feasible option is to reduce the dose of chemotherapy drug.Furthermore, FOXO1 can be used as an indicator for poor prognosis, where stratified treatment is necessary for pediatric patients with RMS.

Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia / 医学前沿

Homoharringtonine (HHT), a plant alkaloid from Cephalotaxus harringtonia, exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s. Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens. Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C), whereas patients in arm B were treated with HHT-containing regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT. From February 2009 to November 2015, 59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited. A total of 42 patients achieved a morphologic complete remission (CR) after the first course, with similar rates in both arms (70.6% vs.72.0%). At the end of the follow-up period, 40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR, which could not be considered as events but censors. The 5-year event-free survival (EFS) was 60.2%±9.6% for arm A and 88.0%±6.5% for arm B (P= 0.024). Patients in arm B experienced shorter durations of leukopenia, neutropenia, and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C. Consequently, the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.

Stratified treatment of non-distant metastatic rhabdomyosarcoma in children: an analysis of its efficacy and prognostic factors / 中华实用儿科临床杂志

Objective To assess the efficacy of stratified treatment of pediatric non-distant metastatic rhabdomyosarcoma (RMS).Methods A retrospective review was conducted in 129 pediatric patients with non-distant metastatic RMS between January 2005 and December 2016 at Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.According to their pathological types,TNM stages and postoperative pathologic staging,the 129 patients were grouped a low-risk group,an intermediate-risk group and a high-risk group.Multimodality therapies were applied to all patients including chemotherapy,surgery and radiotherapy.The overall survival (OS) and event-free survival (EFS) rates were analyzed by using the Kaplan-Meier method.Results Of 129 patients,119 cases were included in this study.In 119 patients,the age of onset for the RMS ranged from 7 to 191 months,with the median onset age of 48 months.The median follow-up time was 40 months for event-free patients with RMS,and 36 months for all the 119 patients.The 5-year OS and EFS for all patients were (92.1 ±2.9) ％ and (76.5 ± 4.4) ％,respectively.While the 5-year EFS for patients in the low-risk group,intermediate-risk group and high-risk group were all above 70％,and the difference among the three groups was not statistically significant (x2 =2.679,P =0.262).A subsequent univariate analysis revealed that the onset age for RMS (≤ 1 year old or ≥ 10 years old),TNM stage and postoperative pathologic stage were important predictors of EFS with statistical significance (all P ＜ 0.05),while gender,pathological type and primary site of RMS did not exhibit any significant impact on 5-EFS (all P ＞ 0.05).The 5-year EFS of RMS patients with Forkhead Box Protein O1 (FOXO1)-positive was significantly lower than that of FOXO1-negative patients [(56.3 ％ ± 14.8) ％ vs.(83.3 ± 15.2) ％],and the difference was statistically significant (x2 =4.588,P =0.028).Conclusions It is important that the stratification treatment should be strictly implemented on RMS patients.First,further improvement is necessary for the treatment of patients in the low-risk group due to their poorer prognosis compared to that of their intermediate-risk counterparts,for whom one feasible option is to reduce the dose of chemotherapy drug.Furthermore,FOXO1 can be used as an indicator for poor prognosis,where stratified treatment is necessary for pediatric patients with RMS.

Multicenter clinical trial of acute lymphoblastic leukemia in elder children and adolescents / 中华血液学杂志

Objective@#To analyze the clinical characteristics and long-term outcomes with multicenter study for acute lymphoblastic leukemia (ALL) in children over 10 years old and adolescents.@*Method@#Newly diagnosed ALL patients aged from 10 to 18 years old in three hospitals were included in the study from May 1st 2005 to April 30th 2015. They were received ALL-2005/2009 protocol following up to December 31st 2016. The clinical characteristics, outcomes and the prognostic analysis were evaluated between the two protocols.@*Results@#Totally, 237 patients were involved in the study, 76 cases for ALL-2005 and 161 cases for ALL-2009 protocol. Complete remission (CR) after induction therapy was 94.5%. 64 (28.6%) patients relapsed with a median time of 14.5 months and 70 (29.5%) patients passed away during the following time. In long-term follow-up, the 5-year event-free survival (EFS) and 5-year overall survival (OS) of ALL patients were (63.1±3.3)% and (68.4±3.2)%. The 7-year EFS and OS were (61.0±3.5)% and (67.6±3.3)%.The 5-year EFS of intermediate risk group in ALL-2005 and ALL-2009 protocol were (73.6±6.1)% and (71.7±4.3)% with no difference (χ2=0.064, P=0.801). The 5-year EFS of high risk group in two protocols were (27.6±9.6)% and (33.9±9.3)%, showing no significant difference (χ2=0.296, P=0.586). Five years relapsed rate of two protocols were (33.8±5.7)% and (32.6±4.1)% with no difference (χ2=0.055, P=0.815). The mortalities were 36.8% and 29.8% separately (χ2=2.869, P=0.090). Univariate analysis indicated that age, male, risk, BCR/ABL translocation/t(9;22) and resistant to induction were risk prognostic factors in long-term survival (χ2=4.764, 4.796, 46.410, 9.560, 25.450; P=0.029, 0.029, <0.001, 0.049, <0.001). Cox multivariate analysis showed male, risk and resistant to induction were independent risk prognostic factors (RR=1.790, 2.727, 2.719; P=0.021, 0.000, 0.012).@*Conclusion@#Protocol ALL-2009 enhanced the chemotherapy intensity in intermediate risk group with no benefit of survival. BCR-ABL fusion or t(9;22) translocation was still the risk factor of prognosis. TKI inhibitor used in these patients could improve survival. EFS rate was increased a little and death rate was decreased in ALL-2009 protocol with no significant lower relapsed rate comparing with ALL-2005 protocol.

Long-term results of multicenter study based on childhood acute lymphoblastic leukemia 2005 protocol / 中华儿科杂志

Objective@#To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study.@*Methods@#Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses.@*Results@#The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%.@*Conclusions@#In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

Long term follow-up of children with neuroblastoma without chemotherapy and radiotherapy / 临床儿科杂志

Objectives To analyze the clinical features and long-term follow-up results of neuroblastoma (NB) without chemotherapy and radiotherapy, and to provide evidence for further improvement of treatment. Methods The clinical data of children diagnosed with NB who received operation during January 2005 to December 2015 was retrospectively analyzed, and the long-term follow-up results were evaluated. Results In 57 cases of NB, 43 cases (81.1％) were in stage 1, 8 cases were in stage 2 and 2 cases were in stage 4S. The median age at diagnose was 7 months (11 days - 10 years and 11 months). There were 47/51 cases had the pathological type with a good prognosis (accounting for 92.2％). FISH was detected in 1/49 case which had the amplification at greater than 10 copies. 56/57 cases underwent surgical resection of the primary tumor, 50 cases of which were completely resected, and 3 cases had very good partial remission after tumor resection. The abdominal mass was found in the uterus in 1 case, and surgical operation was not performed and the imaging was regularly checked for follow-up , and the mass subsided completely at 7-month-old. The median follow-up time was 36 months (4 - 99 months). Five children were lost to follow-up and the median time of follow-up was 19 months (4 - 45 months). One child in stage 4S relapsed at 1 year of follow-up, 2 cases in stage 1 relapsed at 6 months of follow-up. Five years event free survival rates (EFS) in all patients were 94.6％, and overall survival rate (OS) of the 5 years was 100％. Conclusions Children younger than 18 months without MYCN amplification in the stages 1 and 2 are safe by surgical treatment alone with good prognosis. Simple surgical treatment can also be extended to all age groups of NB without MYCN amplification in the stages 1 or 2.

Survival and late effects of comprehensive treatment on children with neuroblastoma / 中华实用儿科临床杂志

Objective To investigate the organ function survival and late effects and secondary malignancy of childhood neuroblastoma (NB) with high intensity comprehensive treatment.Methods A total of 23 children with NB who received comprehensive treatment in Shanghai Children's Medical Center from December 1998 to October 2010 were enrolled.All tests were formulated according to the Children's Oncology Group (COG)'s guidelines with the approval of parents.The late side effects were graded by CTCAE v3.0,and hearing loss related to platinum was graded by Brock and Chang.Results The median follow-up was 96 (65-170) months.All the patients had at least one late side effect.The occurrence rate of 1-2 adverse effects was 100％,and 17.4％ (4/23 cases) of patients had grade 3-4 adverse effects.90.5％ of children (19/21 cases)developed hearing loss on both sides.Eleven children (52.4％,11/21 cases) developed dental abnormities,comprising microdontia,missing teeth,root stunting and enamel hypoplasia.9.5％ of children (2/12 cases) had scoliosis.42.8％ of children (9/12 cases) developed hypogonadism with the approval of parents or delayed growth.47.4％ of children (9/19 cases) had abnormal respiratory function.36.8％ of children (7/19 cases)had abnormal cardiac function.33.4％ of children (7/21 cases)developed renal damage.23.8 ％ of children (5/21 cases) had abnormal liver function.66.7％ of children (14/21 cases) had low level of cortisol,but adrenocorticotrophic hormone was normal.All children had normal function of thyroid.Three children developed secondary malignancy:leukemia,malignant fibroma and liver tumor.Conclusions The incidence of long-term adverse reactions of patients with neuroblastoma treated with high intensity comprehensive treatment is very high and the patients may have adverse effects,like hearing loss,dental abnormality,cardiopulmonary function abnormality,musculoskeletal problems and secondary malignancy.The upmost importance is to establish long-term follow-up program to detect the life quality of children and amend current therapeutic schemes improve life quality.

Study on the clinical outcomes of children with stage Ⅳ malignant extracranial germ cell tumors / 临床儿科杂志

Objective To evaluate the outcomes of children with stage Ⅳ malignant extracranial germ cell tumors. Methods Twenty-five patients were enrolled in the retrospective analysis. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method with SPSS 13.0. Results Of the 25 children, there were 13 males and 12 females. The mean age at diagnosis was 2 years old (ranged 1 to 11). Five patients receiving chemotherapy in another hospital before (n=1), or giving up treatment after confirmed diagnosis (n=1), or giving up effective treatment after received less than 2 cycles (n=3) were excluded from this analysis. Of the 20 patients, 90.0% (18/20) achieved complete remission and 5.0% (1/20) achieved partial remission after treatment. The 5-year EFS rate and 5-year OS rate were 70.0%±10.2% and 82.4%±9.2% respectively. There was no death occurred due to complications. Conclusions The effect of this treatment program is positive. The cumulative dose of the drugs is not high, compared with other schemes such as PEB, but there are more drugs involved. Whether these drugs may cause long-term adverse reactions needs further research.

Retrospective analysis in 13 children with Kasabach-Merritt phenomenon and review of literature / 临床儿科杂志

Objective To improve understanding of the clinical manifestations, diagnosis and treatment of childhood Kasabach-Merritt phenomenon (KMP). Methods The clinical data of 13 patients admitted for KMP to XXX from January 2010 to January 2016 was retrospectively analyzed, with a review of relevant literature. Results The patients were 10 males and 3 females. The age of presentation varied from newborn to 5 months. 12 patients had cutaneous manifestations, like petechiae, ecchymosis, jaundice, skin masses, etc, 1 patient had pleural effusion. The location of lesions varied. The laboratory hallmark consists of profound thrombocytopenia and hypofibrinogenemia with elevated D-dimers. The median time from initial presentation to diagnosis was 60 days. After approaches like surgery, corticosteroids, propranolol, interferon, sirolimus, etc, 10 patients got remission while 3 patients died. 6 patients treated with sirolimushad complete response. Conclusions KMP is characterized with vascular tumor, severe thrombocytopenia and consumptive coagulopathy. Clinically, KMP often presents with early-onset and delay in diagnosis. Surgery is an effective approach for KMP. Sirolimus appears to be a promising treatment for KMP.

Long-term follow-up of neuroblastoma in children less than 18 months of age / 中华儿科杂志

Objective@#To assess the clinical features and long-term outcomes of neuroblastoma (NB) in children less than 18 months of age, so as to provide evidence for further improvement of treatment.@*Method@#Clinical data(sex, age, stage, risk group, treatment response, follow-up, etc.) of 155 NB patients under age of 18 months from June 2000 to December 2015 in Shanghai Children′s Medical Center were analyzed retrospectively. The clinical features were summarized and the long-term follow-up results were evaluated. The overall survival (OS) and event-free survival (EFS) were analyzed by using Kaplan-Meier method. Factors including age, stage, risk group, bone marrow and bone metastasis, N-MYC status and dehydrogenase(LDH) level were analyzed by Log-Rank test.@*Result@#Totally 155 eligible patients (96 males, 59 females) were included. The median age of disease onset was 7 months (11 days to 18 months). There were 31 cases of stage 1, 19 cases of stage 2, 45 cases of stage 3, 38 cases of stage 4 and 21 cases of stage 4S. The median follow-up time was 36 months (range 4 to 189 months), the 3-year and 5-year EFS rate were 89.6% and 85.2% respectively and the 3-year and 5-year OS rate were 96.2% and 94.1%, respectively. A total of 15 recurrent or progressed cases were observed. The median time to first recurrence was 11 months (range 3 to 39 months), 6 cases eventually died. Second malignancy occurred in one patient. The patients who had relapsed disease within 12 months from initial diagnosis have much lower 3-year OS rate than those in whom the disease recurred 12 months later (25.7% vs. 83.3%, P=0.020). Although the number of chemotherapy courses in median-high risk group reduced from 8.6 courses to 7.5 courses after the revision in 2008, the survival rate showed no significant difference between before and after (5-year EFS 74.4% vs. 84.3%, 5-year OS 89.0% vs. 92.9%, both P>0.05). In patients with stage 1 and stage 2, the 3-year EFS of 34 cases with surgery alone and 16 cases accepted chemotherapy were both 100%. Age at diagnosis, stage, risk group, MYCN status, LDH level, bone marrow involvement and bone infiltration had significant impacts on prognosis(all P<0.05).@*Conclusion@#Satisfactory outcomes could be achieved in neuroblastoma in children aged within 18 months; the prognosis was better in children at age less than 12 months compared with 12-18 months. MYCN amplification, LDH more than 5 times upper limit of normal range, bone marrow and bone infiltration were associated with worse prognosis.Excellent survival rates could be achieved in children with stage 1 and 2 disease within 18 month′s old accepted surgery alone, chemotherapy or radiotherapy could be avoided in these patients so as to reduce long-term adverse reactions.

A long-term follow-up report of pediatric relapsed Wilms tumor after retreatment / 中华儿科杂志

Objective@#To investigate the long-term efficacy and prognostic factors of pediatric relapsed Wilms tumor (WT) after retreatment.@*Method@#Sixteen children in Shanghai Children′s Medical Center with relapsed Wilms tumor were enrolled consecutively in this study between April 2006 and June 2016. All patients were diagnosed according to pathology, imaging and medical and surgical oncologist′s assistance. Relapse treatment included surgical excision, chemotherapy and selective radiation therapy. The clinical features, long-term outcomes and prognostic factors of patients were analyzed retrospectively.Survival data were analyzed by Kaplan-Meier.Log-Rank analysis was used for univariate analysis.@*Result@#One case was excluded because of giving up the therapy even though no disease progress was identified. A total of 15 cases (5 males and 10 females) were included in this study. The median age at diagnosis was 3.8 years (range 0.5-9.1 years). The tumor staging at diagnosis included one case of stageⅠ, 7 cases of stageⅡand 7 cases of stage Ⅲ. Among cases of stage Ⅲ, 6 cases had radiation therapy history. The pathology of all patients′ recurrent tumor was favorable histology (FH). The median follow-up time was 34.6 months (range 12.5-132.7 months) until March 21, 2017. The time from initial diagnosis to relapse was 7.9 months (range 3.1-17.9 months). Four cases experienced local recurrence, 9 cases relapsed with metastases (6 cases in lungs, 2 in livers, 1 in mediastinum) and 2 cases relapsed in both local site and with metastases. Except to 2 cases received irregular retreatment, 13 cases received regimen I (doxorubicin, vincristine, epoposide and cyclophosphamide for 25 weeks) as relapsed chemotherapy. Five cases received autologous bone marrow transplantation (ABMT). Until the last follow-up, 8 cases achieved continuous complete remission (range 6.7-104.3 months), 3 cases had relapse again or progressing and 4 cases died. The estimated 5-year overall survival (OS) rate and event free survival (EFS) rate were (70±15)% and (52±15)%. According to whether received ABMT or not, the 5-year EFS rate were 51% and 53%. According to whether relapsed within 6 months after diagnosis or not, the 5-year EFS rate were 38% and 56% respectively.@*Conclusion@#The 5-year EFS rate of pediatric relapsed FH WT have reached above 50% by multi-disciplinary treatment in our experience and we encourage patients and doctors to receive retreatment.

A follow-up report of childhood hepatoblastoma from 74 cases in a single center / 中华儿科杂志

Objective@#To investigate the efficacy and the prognostic factors in pediatric hepatoblastoma according to the standard diagnostic and therapeutic regimen.@*Method@#Eighty-four consecutive patients were enrolled in this study between June 2000 and June 2015. Diagnosis and staging was decided by the multi-disciplinary team including oncologists, surgeons, pathologists and sub-specialized radiologists refering to protocol of Children′s Oncology Group(COG) and International Society of Pediatric Oncology Liver Tumor Study Group (SIOPEL) in a case observational study. Univariate analysis was tested by the log-rank and multivariate analysis by COX regression. All consecutive cases were divided into low risk group and high risk group according to grouping criteria. Complete remission was defined as both imaging negative and α fetoprotein (AFP) normalization. Retrospective analysis was performed in clinical features, long-term outcomes and prognostic factors.@*Result@#Ten patients were excluded because of giving up after less than or equal to three cycles of treatment. A total of 74 cases were included in this study; 45 males and 29 females. The median age at diagnosis was 1.7 years(range 0.2-14.8 years). Untill August 30, 2016, the median follow-up time was 24.2 months (range 4.1-135.3 months); 59 cases achieved complete remission.The estimated five years overall survival (OS) and event free survival(EFS) were 90%(68/74)and 72%(58/74). AFP could be normalized after 5 circles of treatment or 2 circles of postoperation.In univariate analysis , the five years OS and EFS in low risk group were both 100%(18/18), and those in high risk group were 88%(50/56)and 68%(40/56), respectively. The five years OS rates were 75%(15/19) and 95%(53/55) in patients with or without distant metastasis (P=0.016). After 3 cycles of chemotherapy post tumor resection, we divided these patients into 2 groups according to AFP recover or not, the five years OS were 100%(43/43)and 81%(22/26), respectively (P=0.011).@*Conclusion@#The result of this protocol is reasonable when comparing with other worldwide research. Except for staging, metastasis, pathological subtypes, postoperative AFP recover or not is a prognostic factor after 3 cycles of chemotherapy.

Clinical analysis of 14 cases of rare non-Hodgkin lymphoma in children / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and prognosis of 4 rare types of non -Hodgkin lymphoma(NHL)in children,and to discuss the progress in treatment.Methods Clinical data of 1 4 patients with rare types of NHL at Shanghai Children′s Medical Center,Shanghai Jiaotong University School of Medicine between January 2004 and December 201 4 were retrospectively analyzed,and their clinical features,treatment and prognosis were dis-cussed.Results Fourteen cases were reported including 6 subcutaneous panniculitis -like T -cell lymphoma (SPTCL),3 hydroa vacciniforme -like cutaneous lymphoma(HVLL),2 pediatric follicular lymphoma(PFL)and 3 ex-tranodal NK/T -cell lymphoma,and nasal type(ENKTL).Ten patients (71 .4%)primarily presented with skin lesions and underwent a long course of illness before they were finally diagnosed (the median was 1 0 months),71 .4%(1 0 /1 4 cases)of them associated with fever and 50.0%(7 /1 4 cases)with liver and spleen enlargement,and no evidence of central nervous system (CNS)and bone marrow (BM)involvement was observed,while 28.6% patients (4 /1 4 cases) had more than two lines′abnormalities in peripheral blood examination.Since there were no standard treatment guide-lines,most patients received CHOP (Cyclophosphamide +Adriamycin +Vincristine +Prednisone)and /or mature B -cell NHL -like therapy,and 50.0%(7 /1 4 cases)of them received interferon therapy in addition,while 1 patient re-ceived allogeneic hematopoietic stem cell transplantation after recurrence.The complete remission was achieved in 71 .4%(10 /14 cases)of all the patients.Two of them died,3 lost follow -up,and 1 relapsed.The 3 -year overall survi-val and event free survival rates were 0.84 and 0.57,respectively,after a median follow -up of 26 months (range 12 -64 months).Conclusions Pediatric rare types of NHL show atypical clinical manifestation,low incidence of CNS /BMinfil-tration and long course.It is hard to make pathological diagnosis and differentiation.It is also inappropriate to apply the commonly used staging system to these rare types of NHL.No standard treatment has been found by now.SPTCL,HVLL and PFL have relatively good outcomes when treated with mature B -cell NHL -type therapy plus interferon therapy.

Research progress in hereditary multiple exostoses / 临床儿科杂志

Hereditary multiple exostoses (HME) is an autosomal dominant genetic disease characterized by multiple benign cartilage-capped tumors primarily at the juxta-epiphyseal region of the long bone or on the lfat bones. Because the tumor can interfere with normal epiphysis, it causes bone deformities. The clinical features include short stature, the mechanical axis deviation, and function impairment. Recent studies showed that EXT gene mutation was associated with HEM. The EXT gene was involved in the biosynthesis of heparin sulfate. The gene mutations resulted in abnormal chondrocyte differentiation. This paper reviews the research progress in clinical manifestation, pathogenesis, biochemistry, the genotype-phenotype correlations, and treatment in HME.

Study on clinical prognosis among ETV6/RUNX1 positive childhood B-precursor acute lymphocyte leukemia / 临床儿科杂志

Objective To investigate the incidence of the ETV6/RUNX1 fusion gene among Chinese pediatric patients with B-ALL and its effect on the prognosis. Methods A total of 723 patients with B-ALL from January 1, 2007 to December 31, 2014 were enrolled in this study. All patients were detected ETV6/RUNX1 fusion gene by FISH. Clinical data and ETV6/RUNX1 were combined to analyze the clinical prognosis. Results Among the 723 patients, 151 were with ETV6/RUNX1 positive B-ALL, accounting for approximately 20.89%(151/723) of B-precursor cases;91 patients were with recurrence, including 10 patients with ETV6/RUNX1 positive B-ALL, and the recurrence rate of ETV6/RUNX1 positive B-ALL was 10.99%(10/91). Among 10 recurrent patients with ETV6/RUNX1 positive B-ALL, 9 patients relapsed more than 300 days later after diagnosis, while the recurrence times among the patients with ETV6/RUNX1 negative was very different. Although the recurrence times between the two groups showed no signiifcant difference (P?=?0.09), the recurrence times of ETV6/RUNX1 positive patients were mainly found at the end of clinical chemotherapy, while the recurrence time of ETV6/RUNX1 negative patients were mainly at maintaining chemotherapy period, there was a signiifcant difference between the distribution of recurrence time (P?

Report of 14 cases with pancreatoblastoma / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze clinical features, outcomes and correlative prognostic factors of the disease.</p><p><b>METHOD</b>Totally 14 newly diagnosed children with pancreatoblastoma at Shanghai Children's Medical Center, Children's Hospital of Chongqing Medical University, Sun Yat-sen University Cancer Center and Beijing Children's Hospital were enrolled into this study between April 2003 and July 2013. The clinical features, surgery, chemotherapy protocol and prognostic factors of patients were retrospectively analyzed.</p><p><b>RESULT</b>The median age at diagnosis was 6.5 years (0.6 to 11 years). Four cases had local tumor, 9 cases had local invasion, and in 1 case lung and liver metastasis was found at diagnosis. Increased serum α-fetoprotein were found in 8 cases (66-54,000 μg/L). In 8 patients the tumor was resected at first. The remaining 6 patients had biopsy and in four of them the tumor was completely resected after 4-6 cycles of chemotherapy. Except for 2 patients who gave up treatment, all the other patients fulfilled the comprehensive treatment including surgery and chemotherapy. One patient received radiofrequency ablation. The median follow-up period was 26 months(16-140 months). The estimated 2 year event free survival was (66.7 ± 13.6)%.On univariate analysis, non-resectable tumor(χ(2) = 6.663, P = 0.010), progression and metastases during treatment(χ(2) = 14.927, P = 0.000), poor response to treatment(χ(2) = 12.293, P = 0.000)were independent predictors for poor prognosis.</p><p><b>CONCLUSION</b>Complete resection and complete remission after treatment were excellent prognostic factors. Some initially unresectable disease seems to be resectable after adjuvant chemotherapy, which may be a key point of treatment strategy.</p>

Treatment of children with highly suspected mature B-cell lymphoblastic leukemia / 中华实用儿科临床杂志

Objective To evaluate the outcomes of mature B-cell acute lymphoblastic leukemia(mature B-ALL) and to assess the safety and efficacy of the treatment protocol.Methods From February of 2003 to December of 2012,15 children were diagnosed as mature B-cell acute lymphoblastic leukemia/lymphoma possible (mature B-ALL/NHLp) in Shanghai Children's Medical Center(SCMC) were enrolled,and they were treated with SCMC-mature B-ALL/NHLp-2003 protocol.All of the clinical characteristics,therapeutic effects and long-term outcomes were analyzed.The statistical data were processed by SPSS 21.0.Results The median age on diagnosis was 8.7 years (1 year and 5 months to 14 years and 4 months).Among them,4 cases presented with local mass including maxillofacial tumors,neck and abdominal mass.The others had systemic manifestations such as fever and pale face.These neoplastic cells retained the expressions of surface membrane immunoglobulin M,terminal deoxynucleotidyl transferase,Cμ,CD10,CD19,cCD79 a differently.Follow-up was updated to November 30,2013.The median follow-up period was 80 months (39-128 months).Theestimated 5-year event free survival rate was (80.0 ± 10.3) ％.According to univariate analysis,increased lactate dehydrogenase level (＞ 4-times the normal value),increased serum ferritin level (＞ 2-times the normal value),no small residual disease markers were indepen-dent poor prognostic factors(x2 =5.49,4.89,5.49,all P ＜ 0.05).Conclusions SCMC-mature B-NHL/ALLp-2003 protocol is feasible and safe for children with mature B-ALL/NHLp,but more sample cases need to be investigated.