Influence of early phase clinical trial enrollment on patterns of end‐of‐life care for children with advanced cancer

We conducted a retrospective cohort study of 125 pediatric oncology patients who died in 2010–2014 to explore how healthcare utilization, pediatric palliative care (PPC) receipt, and end‐of‐life care (EOLC) differed between patients enrolled in early phase clinical trials (EP) and those not enrolled (NEP). Baseline characteristics and healthcare utilization did not significantly differ between groups. EP patients received PPC consultation closer to death than NEP patients (median days before death = 58 [interquartile range = 16–84] vs. 85 [32–173]; P = 0.04). Our findings suggest that early phase trial enrollment does not substantially alter EOLC for children with advanced cancer but may contribute to later PPC engagement. Future studies should definitively assess the relationship between trial enrollment and PPC timing.     

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T-cell acute lymphoblastic leukemia

Background

The absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T‐cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T‐cell ALL.

Procedure

Forty‐five children with T‐cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q‐PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q‐PCR was defined as a fold‐change <0.35.

Results

ABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23–53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10–16.42).

Conclusions

The absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T‐cell ALL in Taiwan. Providing patients with T‐cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials. Pediatr Blood Cancer 2012; 58: 846–851. © 2011 Wiley Periodicals, Inc.     

Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia (ALL) after first bone marrow or extramedullary relapse

BACKGROUND: Approximately 25% of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse, with bone marrow being the most common site of recurrence. The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL. PROCEDURE: Thirty pediatric patients with relapsed medullary (n = 18) and extra-medullary (n = 12) ALL were enrolled at three pediatric institutions. Following receipt of induction and the first Block A and Block B of intensification, each patient was evaluated for toxicity, efficacy in achieving remission, and long-term survival. Additionally, minimal residual disease (MRD) detection by multidimensional flow cytometry (MDF) was performed. RESULTS: During induction, the major non-hematopoeitic toxicities were mucositis (30% of patients) and bacteremia (50% of patients). Two patients (7%) died of toxicity during induction. Toxicity during intensification Block 1A and 1B was markedly reduced. Eight-nine percent of patients with marrow disease achieved a remission following induction and intensification. The event-free survival (EFS) for all patients at 2 and 4 years were 60% (95% CI: 42-78%) and 49% (95% CI: 30-68%), respectively. CONCLUSIONS: This regimen for patients with relapsed ALL was successful in achieving a second remission for the majority of patients with acceptable toxicity.     

A medication diary‐book for pediatric patients with acute lymphoblastic leukemia in Indonesia

Background

Event‐free survival of pediatric patients with acute lymphoblastic leukemia (ALL) in Yogyakarta, Indonesia was low (20%). The aim of the study was to evaluate the effectiveness of using a medication diary‐book on the treatment outcome of childhood ALL.

Procedure

A randomized study was conducted with 109 pediatric patients with ALL in a pediatric oncology center in Yogyakarta, Indonesia. Both intervention and control groups received a structured parental education program and donated chemotherapy. The intervention group received a medication diary‐book to remind parents and families to take oral chemotherapy and present for scheduled appointments or admissions. Event‐free survival estimate (EFS) at 3 years was assessed.

Results

Among pediatric patients with ALL with highly educated mothers (senior high school or higher), the EFS‐estimate at 3 years of the intervention group was significantly higher than the EFS‐estimate at 3 years of the control group (62% vs. 29%, P = 0.04). Among pediatric patients with ALL with low‐educated mothers, no significant difference was found in the EFS‐estimates at 3 years between the intervention and control group (26% vs. 18%, P = 0.86).

Conclusions

We conclude that a medication diary‐book might be useful to improve the survival of pediatric patients with ALL in resource‐limited settings, particularly in patients with highly educated mothers. Pediatr Blood Cancer 2013;60:1593–1597. © 2013 Wiley Periodicals, Inc.     

儿童急性淋巴细胞性白血病微小残留病监测的预后意义

目的 研究儿童急性淋巴细胞性白血病(ALL)化疗过程中,不同时间点监测的不同微小残留病(MRD)水平的预后意义.方法 对102例ALL患儿进行MRD监测研究,分别在患儿诱导化疗开始后第15天、第29天、第3个月、第6个月、第12个月进行MRD监测.根据患儿初诊时免疫表型特征,采用流式细胞术检测不同的四色单克隆抗体组合.常用的抗体组合包括CD45CD19CD34CD10和CD45CD19CD34CD20等.结果 102例ALL患儿的5年总体生存(OS)率和无事件生存(EFS)率分别为(86.9±3.4)%和(79.9±4.0)%,共12例患儿复发.在第15天、29天、3个月、6个月和12个月,分别有14.3%、43.9%、39.1%、39.7%和45.6%的患儿处于MRD阴性(MRD<10~(-4)).其中MRD水平能在1年内达到阴性的患儿的长期存活率明显高于MRD持续阳性的患儿[5年EFS:(92.5±3.2)% vs. (58.3±8.6)%,P<0.001].各时间点上,化疗后第15天时MRD≥10~(-2)[(79.8±10.3)% vs.(28.6±17.1)%,P<0.001]、第29天时MRD≥10~(-3)[(88.3±4.9)% vs.(51.3±14.4)%,P<0.003]、第3个月[(92.4±5.1)% vs.(65.5±7.5)%,P<0.015]、6个月[5-year EFS rates(96.3±3.6)% vs.(65.4±7.5)%,P<0.003]及第12个月[(100.0±0.0)% vs.(67.7±8.4)%,P<0.002]时MRD≥10~(-4)的患儿的5年EFS率明显较差.而第15天时MRD≥10~(-2)是独立的不良预后因素.结论 采用流式细胞术动态监测MRD水平能有效地评估ALL患儿的预后,而不同时间点上具有预后意义的MRD水平并不相同.     

Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials

BACKGROUND: Adolescents with acute lymphoblastic leukaemia (ALL) have languished in the shadow of success of the outcome of therapy in childhood ALL. Their treatment has always been incorporated into either paediatric or adult clinical trials depending on the mode of referral and hence there is a need to address an age and risk specific strategy for improving the outcome of this neglected group of patients. This article has summarised the recent and updated retrospective comparative analysis of adolescents treated on the Medical Research Council (MRC) trials. This analysis adds further emphasis to the treatment approach and the merits and limitations of treatment of adolescents on paediatric and adult trials. METHODS: A retrospective comparative analysis of adolescents aged 15-17 years, treated on either MRC ALL97/revised 99 (n = 61), a randomised paediatric trial or UKALLXII/E2993 (n = 67), an adult trial, between 1997 and 2002 was undertaken. RESULT: Results suggest a trend towards a superior outcome on paediatric trials. The 5-year EFS on ALL97 was 65% (95% CI = 52-78%) and on UKALLXII/E2993 was 49% (95% CI = 37-61%; P = 0.01). Multivariate analysis allowing for age and Ph status, diminished the EFS difference, but confirmed a reduced rate of death in remission in patients managed on the paediatric protocol. CONCLUSIONS: Despite limitations in the methodology, comparative studies including our MRC study suggest a consistent advantage for adolescents managed intensively on paediatric trials. Redefining age limits with risk-based strategy and multi-centre collaboration should be considered to improve the survival of young adults.     

儿童急性淋巴细胞白血病南方ALL99方案临床疗效分析

目的对82例儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)治疗结果进行分析,探讨如何提高儿童ALL无病生存率。方法应用南方ALL99方案治疗82例ALL患儿。该方案引进德国BFM95和香港-新加坡ALL97方案,作了少许改动,形成南方ALL99方案。改动方面包括将三联鞘注中的氢化可的松换成地塞米松,将外院不规则化疗过的标危患者按中危治疗,将每一疗程开始时的中性粒细胞和血小板的标准提高到中性粒细胞≥1×109/L,血小板≥100×109/L。采用SPSS软件进行寿命表法分析。结果对1999年4月至2003年9月收治的82例ALL患儿按南方ALL99方案进行治疗,78例获完全缓解(completeremission,CR),CR率为95%;13例患者因经济困难或其他原因失访。其中按南方ALL99方案坚持治疗的69例,预期2年无病生存率91%,预期5年以上无病生存率75%;因感染死亡3例(死亡率为4%),复发死亡6例。结论引进德国BFM95和香港-新加坡ALL97方案而成的南方ALL99方案治疗儿童ALL疗效好,化疗相关死亡率低,该方案对中国人耐受性好,值得推广应用。     

Treatment‐related mortality in relapsed childhood acute lymphoblastic leukemia

1 Background

Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment‐related toxicity impacts survival.

2 Procedure

In this retrospective population‐based study, we described the causes of death and estimated the risk for treatment‐related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL‐92 and ALL‐2000 trials.

3 Results

Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment‐related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment‐related mortality were as follows: high‐risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3–3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3–9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17–9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment‐related causes.

4 Conclusions

Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.     

Unrelated cord blood and bone marrow transplantation in pediatric leukemia

To investigate the role of cord blood as an alternative stem cell source for hematopoietic stem cell transplantation for pediatric acute leukemia, we retrospectively analyzed the outcomes of 35 unrelated cord blood transplantations (UCBT) and 56 unrelated bone marrow transplantations (UBMT) with myeloablative conditioning. The 5 year overall survival (OS) probability was 49.8% (95% confidence interval [95%CI]: 35.6–62.4%) for UBMT and 53.8% (95%CI: 34.0–70.1%) for UCBT (P = 0.92). The 5 year event‐free survival (EFS) probability was 47.3% (33.6–59.8%) for UBMT and 33.0% (15.9–51.2%) for UCBT (P = 0.38). OS and EFS were not significantly different between the groups. On multivariate analysis there was no significant difference between the groups. In conclusion, UCBT can have a role as important as that of UBMT in pediatric acute leukemia.     

Hepatoblastoma in children aged less than six months at diagnosis: A report from the SIOPEL group

1 Background

The purpose of this study was to evaluate clinical characteristics, treatment, and survival of children, who were diagnosed with hepatoblastoma (HB) in their first 6 months of age, enrolled in the SIOPEL 2 and 3 protocols.

2 Methods

Seventy‐nine patients, treated between 1994 and 2006, were analyzed after stratification into three age groups: <1 month, between 1 and 3 months, and between 3 and 6 months. All received preoperative chemotherapy.

3 Results

Clinical characteristics were similar in both trials: 4 patients had pulmonary metastases at diagnosis, 4 had α‐fetoprotein <100 ng/ml, 68 were operated by partial hepatectomy, and 7 received liver transplant. Chemotherapy courses were delayed in 8.5%, 8.4%, and 11.8% of cycles in the three groups. Doses were calculated according to weight for children <5 and 5–10 kg, and further reduced in 18.1%, 6.8%, and 5.9% of cycles. Acute toxicity was manageable. Long‐term hearing loss was the major problem at follow‐up occurring in two‐thirds of children. Ten patients experienced progression or relapse, and 5 of 10 died. After a median follow‐up of 5.6 years, the 5‐year overall survival (OS) and event‐free survival (EFS) were 91% (95% confidence interval [CI]: 84–96%) and 87% (95% CI: 78–92%), respectively.

4 Conclusions

The 5‐year OS and EFS of children <6 months of age affected by HB seem to be similar to those documented in the elder children. Dose reduction does not seem to jeopardize the long‐term outcome and may explain the lower toxicity profile. Ototoxicity though appears as high as in the whole population of SIOPEL 2 and 3. The treatment for these children should be further explored in international studies, particularly focusing on prevention of hearing loss.     

Matched related donor hematopoietic stem cell transplantation results in a long‐term follow‐up of a pediatric acquired severe aplastic anemia subset: A stem cell source perspective

HSCT has substantially improved pediatric acquired SAA patients' outcomes. Retrospectively, we attempted to assess the outcome of MRD HSCT in 65 pediatric patients referred to a single center from 1992 to 2012. We were particularly interested to find out whether source of SC (PB, n = 40 and BM, n = 25) significantly impacts EFS and GVHD incidence. With a median follow‐up of 45 months, total EFS was 87.7%; EFS for PB and BM groups was 87.5% and 88%, respectively. Acute GVHD (grades 3–4) occurred in 13 patients (PB, n = 10 [25%] and BM, n = 3 [12%]), acute GVHD (grades 2–4) occurred in 24 (PB, n = 16 [40%] and BM, n = 8 [32%]). Extensive chronic GVHD occurred in five patients (PB, n = 3 [7.5%] and BM, n = 2 [8%]). Cox regression revealed that elapsed time of <10 months between diagnosis and HSCT is associated with improved survival (hazard ratio, 95% CI = 1.204, 1.010–1.434, p = 0.038). SC source did not significantly affect EFS, incidence of acute GVHD (grades 3–4), or extensive chronic GVHD (p = 0.938, 0.121, and 0.487, respectively). Based on our findings, pediatric acquired SAA patients are benefitted most if MRD‐HSCT is carried out early in disease process and SC source does not affect outcome of MRD‐HSCT in these patients.     

Acute myeloid leukemia in children: Current status and future directions

Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML‐DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all‐trans retinoic acid (ATRA)‐combined regimen with an 80–90% OS. Children with ML‐DS are treated with a less intensive regimen compared with non‐DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high‐risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials.     

Late events in pediatric patients with Ewing sarcoma/primitive neuroectodermal tumor of bone: the Dana-Farber Cancer Institute/Children's Hospital experience

The outcome for 82 pediatric patients with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Children's Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002); the overall survival (OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated.     

Treatment and biology of pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. In the past ALL was intractable but now the survival probability is as high as 80–90%. Improved supportive care, treatment stratification based on relapse risk, biological features of leukemic cells, and optimization of treatment regimens by nationwide and international collaboration have contributed to this dramatic improvement. While including traditional risk factors (e.g. age and leukocyte count at diagnosis), the treatment has been modified based on biological characteristics (aneuploidy and translocation) and treatment response (assessed by minimal residual disease). Treatment for pediatric ALL typically consists of induction therapy with steroids, vincristine, and asparaginase with or without anthracycline, followed by multi‐agent consolidation including high‐dose methotrexate and re‐induction therapy. After consolidation, less intensive maintenance therapy is required for 1–2 years to maintain event‐free survival. Recently, using advanced genomic analysis technology, novel sentinel genomic alterations that may provide more precise stratification or therapeutic targets, were identified. Moreover, in the last decade germline variations have been recognized as similarly important contributors to understanding the etiology and sensitivity of ALL to treatment. A more individualized approach based on genomic features (somatic and germline) and treatment response, the introduction of newly developed agents such as molecular targeted drugs or immunotherapy, and social support including long‐term follow up are required for further improvement.     

Obesity and survival in a cohort of predominantly Hispanic children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.     

The impact of clinical trial enrollment on specialty palliative care utilization in pediatric patients with high-grade gliomas

Background

Palliative care (PC) provides numerous benefits for children with cancer. Pediatric patients with high-grade glioma (HGG) are particularly well suited for early PC involvement given their high symptom burden and poor prognosis. However, studies continue to reveal that children with cancer, including HGG, have delayed PC involvement. We hypothesized that clinical trial enrollment may lead to a lack of or delay in PC involvement in this population.

Procedure

For each patient in our cohort of 43 pediatric patients with HGG, demographic, diagnostic, therapeutic, clinical trial enrollment, and PC information were collected. Statistical analysis was performed comparing PC characteristics between patients who did and did not enroll in a clinical trial.

Results

Seventy-two percent of patients had at least one visit with a PC provider. Fifty-six percent of patients enrolled in a clinical trial with HGG-directed therapy. Seventy-one percent of patients who enrolled in a clinical trial received specialty PC compared to 74% of non-trial participants (p = 1.000). Patients who enrolled in clinical trials received PC earlier in their disease course measured in days before death (mean = 177 days) compared to those who did not enroll (mean = 113 days, p = .180), though not statistically significant.

Conclusions

The prevalence of clinical trial enrollment is high in patients with HGG and will likely increase as the genomic/epigenomic landscape of these tumors is better understood. As such, our data reassuringly suggest that trial participation does not interfere with the receipt of specialty PC in this population.     

Intensified chemotherapy without SCT in infant ALL: Results from COG P9407 (Cohort 3)

Background

Infants with acute lymphoblastic leukemia (ALL) present with aggressive disease and a poor prognosis. Early relapse within 6–9 months of diagnosis is common. Approximately 75% of infants have MLL‐rearranged (MLL‐R) ALL with event free survival (EFS) ranging from 20% to 30%. Children's Oncology Group (COG) P9407 used shortened (46 weeks), intensified therapy to address early relapse and poor EFS.

Procedure

P9407 therapy was modified three times for induction toxicity resulting in three cohorts of therapy. One hundred forty‐seven infants were enrolled in the third cohort.

Results

We report an overall 5‐year EFS and OS of 42.3 ± 6% and 52.9 ± 6.5% respectively. Poor prognostic factors included age ≤90 days at diagnosis, MLL‐R ALL and white cell count ≥50,000/μl. For infants ≤90 days of age, the 5‐year EFS was 15.5 ± 10.1% and 48.5 ± 6.7% for those >90 days (P < 0.0001). Among infants >90 days of age, 5‐year EFS rates were 43.8 ± 8% for MLL‐R versus 69.1 ± 13.6% for MLL‐germline ALL (P < 0.0001).

Conclusions

Age ≤90 days at diagnosis was the most important prognostic factor. Despite shortened therapy with early intensification, EFS remained less than 50% overall in MLL‐R ALL. Pediatr Blood Cancer 2015;62:419–426. © 2014 Wiley Periodicals, Inc.     

Early indicators of dysmetabolic syndrome in young survivors of acute lymphoblastic leukemia in childhood as a target for preventing disease

PURPOSE: To investigate the presence of early indicators of the dysmetabolic syndrome (DS) in young survivors with acute lymphoblastic leukemia (ALL) in childhood. PATIENTS AND METHODS: We enrolled 80 patients with ALL (50 males, median age 13.9 y, median interval since completion of chemotherapy 6.3 y). Sixty-two patients (group A) received chemotherapy only, whereas 18 patients (group B) received chemotherapy and cranial irradiation (18 Gy). RESULTS: Frank obesity [25%; confidence interval (CI) 95%, 16.7%-35.6%], increased blood pressure (21%; CI 95%, 13.6%-31.5%), increased serum triglycerides (21%; CI 95%, 13.6%-31.5%), reduced serum high-density lipoprotein cholesterol (12%; CI 95%, 6.7%-21.7%), increased fasting insulin (8%; CI 95%, 3.2%-15.7%), and osteopenia (71%; CI 95%, 60.5%-80.1%) were detected in groups A and B. Reduced IGF-1 (15%; CI 95%, 8.6%-24.6%) and thyroid hormone abnormalities (11%; CI 95%, 5.8%-20.2%) were detected only in group B. In group B, there was a statistically significant increase in the prevalence of obesity (P=0.024), hyperinsulinemia (P=0.004), and the full DS (22%; CI 95%, 8.6%-45.9% vs. 8%; CI 95%, 3.1%-18.0%; P=0.017) compared with group A. CONCLUSIONS: Young survivors of childhood ALL, especially those treated with cranial irradiation, are at risk for obesity, dyslipidemia, insulin resistance, hypertension, and the full DS early after the completion of therapy.     

The current status of pediatric liver transplantation in Mainland China

Zhou J, Shen Z, He Y, Zheng S, Fan J. The current status of pediatric liver transplantation in Mainland China.
Pediatr Transplantation 2010: 14:575–582. © 2010 John Wiley & Sons A/S. Abstract: The aim of this article is to study the current status of pediatric liver transplantation in Mainland China. A total of 337 cases of pediatric liver transplantation enrolled in CLTR between 1993 and May 2009 were analyzed retrospectively. The median transplant age was 8.7 yr (64 day–17.8 yr), and Wilson’s disease was the most common indication (35.4%). Liver transplantation for biliary atresia accounted for 49.3% and 54.2% in 2008 and 2009 and had become the most common indication nowadays. One‐ and three‐yr survival rates of children transplanted at age<1 yr were 69.2% and 59.3%, respectively, and were significantly worse than those transplanted at age≥1 yr (83.9% and 76.6%, p < 0.05).In 63.8% (208/326) of the patients, LDLT was used with an overall one‐ and three‐yr survival rates of 87.5% and 84.4%, respectively. The one‐ and three‐yr survival for DDLT was significantly lower (66.7% and 52.2%, p < 0.05). The one‐ and three‐yr survival rates for those transplanted in era 1993–2000 were 63.6% and 36.4%, respectively, and the one‐ and two‐yr survival rates in the latest era (2007‐2009) were markedly improved (81.9% and 79.0%, p < 0.05). Cox’s analysis identified DDLT (HR = 2.90, CI 95% 1.5–5.6), being transplanted in era 1993–2000(HR = 3.4, CI 95% 1.1–10.2), fulminant liver failure (HR = 6.0, CI 95% 2.0–17.5), and malignancy (HR = 3.8, CI 95% 1.4–10.3) as predictors of increased mortality, and children transplanted at age 8–17 yr have an better survival (HR = 0.2, CI 95% 0.1–0.6). We concluded that pediatric liver transplantation is gradually developing and would probably be a promising therapy for pediatric end‐stage liver diseases in Mainland China.     

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??Objective??To summarize the clinical characteristics and outcome of adolescent patients with acute lymphoblastic leukemia??ALL?? treated with Chinese Children’s Leukemia Group??CCLG??-2008 protocol over a 5-year period from 2008 to 2013. Methods??Clinical features??immunophenotypes??cytogenetic abnormalities and prognosis of adolescent patients aged 10 to 18 were compared with younger patients under 10 years old. Results??During 2008—2012??723 patients with ALL were enrolled in our study. About 14.11% of them were 10- to 18-year old patients. Compared to younger ones??adolescent patients demonstrated a higher incidence of T-cell lineage phenotype??14.71% vs 5.8%????t??9??22????8.82% vs. 4.99%????t??1??19????8.82% vs. 5.15%???? and significantly lower frequency of t??12??21????21.74% vs. 8.82%??. In intermediate group?? the 5-year overall survival rate??OS?? and event-free survival rate??EFS?? of adolescent patients was compatible with paediatric patients????92.88% vs. 90.86%?? and ??77.09% vs. 82.9%????respectively. However??the EFS of adolescent patients with high-risk ALL was worse than paediatric patients??42.78% vs. 54.12%??. Conclusion??Despite the increased incidence of adverse prognostic factors??the survival rate of adolescent patients has been improved when treated with paediatric ALL protocol. However??the poor prognosis of adolescent patients in the high-risk group remains to be the current challenge.