Long-term Survival Of Children Research Articles

Chronic kidney disease in children: state of the art

composition of the blood or urine, with or without decreased GFR; and (b) GFR <60 ml/min/1.73 m 2 for ≥3 months, with or without the signs of kidney damage listed above [1]. The prevalence of CKD was as high as 11% in the adult population. 4.7% of the adult population from one study had a glomerular filtration rate (GFR) <60 ml/min (stages 3–5) [2]. Similar studies showed a higher prevalence (5.1%) of known stages 3–5 CKD in the general population, based on analysis of single serum creatinine results held on general practitioners computers [3]. The prevalence and epidemiological information on pediatric CKD is currently imprecise and flawed by methodological differences between the various data sources. The long-term survival of children with end-stage renal disease has improved in the last 25 years but the mortality is still very

Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children

Autologous hematopoietic stem cell transplant (AHSCT) has been advocated as a form of salvage therapy for children with high-risk or relapsed brain tumors but only limited data are available currently. We report the outcomes of pediatric brain tumors treated with AHSCT in a quaternary referral center in Hong Kong over 10 years (June 1996–May 2006). Thirteen patients with medulloblastoma (n = 9), cerebral primitive neuroectodermal tumor (n = 1), ependymoma (n = 1), germ cell tumor (n = 1) and cerebellar rhabdoid (n = 1) were transplanted because of tumor residual (n = 1) or recurrence (n = 12). Uniform upfront treatment protocols were adopted according to specific tumor types. Prior to AHSCT, 8 patients (61.5%) achieved complete remission and 5 (38.5%) were in partial remission. Conditioning employed thiotepa 300 mg/m2, etoposide 250 mg/m2 and carboplatin 500 mg/m2 daily for 3 days. Toxicity included mucositis and neutropenic fever in all patients, grade 4 hepatic toxicity in 4 patients (including hepatic veno-occlusive disease in 2 patients) and grade 4 renal toxicity in 1 patient. The 5-year event-free survival was 53.9%. Five patients died of disease recurrence or progression 8–21 months after transplant with a median disease-free period of 8 months post-transplant. One died of transplant-related complications in the early post-transplant period. Seven survived for a median of 5.4 years (maximum follow-up of 9.8 years), with six having Lansky-Karnofsky performance score above 80. All survivors had complete remission before transplant though 2 had leptomeningeal spread. We conclude that AHSCT can achieve long-term survival in children with recurrent brain tumor. However, those with macroscopic residual tumor before transplant cannot be salvaged.

Long-term survival in children under 3 years of age with low-grade astrocytoma

The purpose of this study is to analyze clinical aspects and disease-free survival (DFS) in children less than 3 years of age diagnosed with low-grade astrocytoma. In a period of 24 years (1980-2004), a total of 43 (5.4%) children were registered with these characteristics. Twenty-three patients had pilocytic astrocytoma, 18 diffused, and 2 mixed. Thirty-one (72.1%) children had incomplete surgical tumor resection and 12 (27.9%) had a complete tumor resection. Twelve (27.9%) patients had cranial radiotherapy and 17 (39.5%) received chemotherapy. Overall survival was recorded in 23 (53%). DFS was 50% at 250 months of follow-up for the whole group. DFS for the supratentorial group was 60% at 250 months, whereas, for the infratentorial, it was 22% at 120 months (p = 0.008). The only favorable prognostic pattern was the supratentorial presentation. Radiotherapy and chemotherapy did not alter the outcome.

Stereotactic Technique of Catheter Placement in the Stump of the Superior Vena Cava in Children with Impaired Venous Access

The long-term survival of children with irreversible intestinal failure is often dependent on adequate central venous access for the administration of parenteral nutrition. In children with occlusion of major central thoracic veins, innovative techniques to establish venous access have been described in the literature. The present report describes an innovative stereotactic technique of catheter insertion in children with occluded internal jugular and brachiocephalic veins. The catheter is inserted percutaneously from the neck into the distal patent stump of the superior vena cava communicating with the right atrium.

Advances in Treatment of Pediatric Brain Tumors

The long-term survival of children with brain tumor has improved considerably in the last three decades, owing to advances in neuroimaging, neurosurgical, and radiation therapy modalities, coupled with the application of conventional chemotherapy. MRI, MR spectroscopy and diffusion-weighted MRI have contributed to more accurate diagnosis, prognostication and better treatment planning. Neurosurgical treatment has been advanced by the use of functional MRI, and intraoperative image-guided stereotactic techniques and electrophysiologic monitoring. The use of 3-D conformal and intensity-modulated radiation therapy, stereotactic radiosurgery, and radiosensitizing agents has made radiation therapy safer and more effective. Conventional chemotherapy, administered either alone or combined with radiation therapy has improved survival and quality of life of children with brain tumors. These improved outcomes have also occurred, due, in part, to their treatment on collaborative national and international studies. Recent promising diagnostic and therapeutic strategies have resulted from advances in understanding molecular brain tumor biology. Important new approaches include the refinement of drug-delivery strategies, the evaluation of biologic markers to stratify patients for optimal treatment and to exploit these molecular differences using "targeted" therapeutic strategies. These approaches include blocking tumor cell drug resistance mechanisms, immunotherapy, inhibition of molecular signal transduction pathways important in tumorigenesis, anti-angiogenic therapy, and gene therapy. The thrust of such approaches for children with brain tumors is especially directed at reducing the toxicity of therapy and improving quality-of-life, as well as increasing disease-free survival.

Prediction of target CD34 positive cells following leukopheresis in children with neuroblastoma

Myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) may improve long-term survival in children with disseminated neuroblastoma. In children it is important to be able to ascertain when to start the leukopheresis in order to keep the number of procedures to a minimum. Twenty-three children with high-risk neuroblastoma with a median weight of 13 kg (range 8-16 kg). Stem cell collection was planned to start at day 14 after the start of the preceding induction standard chemotherapy and after 4 days of G-CSF treatment at 10 microg/kg body weight once daily subcutaneously. Normal volume leukopheresis (median 2.2 times the blood volume of the child) was carried out using a CS-3000 Plus Blood Cell Separator. A pre-collection peripheral blood CD34+ count of >20/microl was a prerequisite for initiating the stem cell collection. Timely leukopheresis was carried out in 19/23 patients. In 17 (74%) of the patients the target number of CD34+ cells/kg body weight was obtained in one procedure; in the remaining the target number of stem cells was obtained after leukopheresis on the following day. A highly significant correlation was found between the pre-harvest CD34+ count from the peripheral blood and the total number of collected CD34+ cells/kg (r = 0.79, P < 0.001). When the pre-harvest CD34+ count was >40/microl, a sufficient number of CD34+ stem cells was collected in a single procedure in 15 out of 16 cases.

Long-term outcomes of children with end-stage renal disease

Long-term survival of children with end-stage renal disease (ESRD) has increased in the last 20 years, but the mortality rate remains high. Cardiovascular disease accounts for 40 to 50% of all deaths, infectious disease for about 20%. A prolonged period of dialysis versus having a renal graft and persistent hypertension are mortality risk factors. The prevalence of the various morbidities is high among those who have reached adulthood. Nearly 50% of all these patients suffer from left ventricular hypertrophy and life-threatening vascular changes; nearly one third has clinical signs of metabolic bone disease. This accounts for both dialysis and transplant recipients. The chance of getting cancer is increased ten times compared to the general population; skin cancer and non-Hodgkin lymphomas are most commonly reported. A long period of dialysis at childhood is associated with impairment of both cognitive and educational attainment. However, despite all these negative outcomes, the health perception of young adults with childhood onset ESRD is positive. Research and therapy in children with ESRD should focus not only on prevention of graft failure, but also on prevention of co-morbidity, especially cardiovascular disease, life-threatening infections and malignancies. Early transplantation, more extended forms of frequent hemodialysis in those who can not be transplanted, a more rigorous treatment of hypertension, avoidance or at least dosage reduction of calcium-containing phosphate binders, reduction of the chronic inflammatory state, and tailor made anti-rejection therapy after transplantation may all be targets to improve the outcome in future patients.

37% long-term survival of children with ALL relapse by risk-stratified salvage therapy - Results of trial ALL-REZ BFM 87 after 15 years of follow-up

Cure rates of childhood ALL improved distinctly in the past decades. Nevertheless, ca. 20% of the patients relapse, and their prognosis is clearly worse. We describe design and long term results of the multicenter trial ALL-REZ BFM 87 for children with first relapse of ALL. Patients (n=207) were stratified into three risk-groups (RG, A: early bone marrow (BM) relapse, B: late BM relapse, C: isolated extramedullary relapse), alternatively, patients with a poor prognosis (very early BM relapse or any relapse of T-ALL) could be enrolled to an experimental pilot regimen (P88). Treatment consisted of multiagent chemotherapy, cranial irradiation, and conventional maintenance therapy, or stem cell transplantation (SCT) in a subset of patients. The pEFS and pSRV at 15 years was .30±.03 and .37±.03, respectively, and differed significantly with regard to RG (A: .18±.05 and .20±.05; B: .44±.05 and .52±.05; C: .34±.05 and .42±.10; P88: .0 and .04±.04). In univariate and multivariate analyses, time to relapse, immunophenotype, and SCT proved to be significant predictors of EFS. SCT was effective in a subset of patients.

Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden.

The survival for patients with atrioventricular septal defect has improved markedly over the last decades and, during the same period, the survival of children with Down's syndrome has also increased. The aim of our study was to investigate long-term survival in patients having atrioventricular septal defect with common valvar orifice, but without associated significant congenital heart defects, in the setting of Down's syndrome, comparing the findings to those in chromosomally normal children with the same malformation. In a population-based retrospective study, we scrutinised the medical records from 801 liveborn children with atrioventricular septal defect born in Sweden during the period 1973 through 1997. Data on gender, presence or absence of Down's syndrome, associated congenital heart defects, date of birth, operation and death were recorded and followed up until 2001. An isolated atrioventricular septal defect with common atrioventricular valvar orifice was present in 502 children, of whom 86% had Down's syndrome. We found a significant reduc tion over time in age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using a multiple logistic regression model, we found no significant differences in mortality between genders, nor between those with or without Down's syndrome. Early corrective surgery could not be identified as a significant independent factor for survival. The 5-year postoperative survival in patients with Down's syndrome increased from 65% over the period from 1973 through 1977, to about 90% in the period 1993 through 1997, and the same trend was observed in chromosomally normal patients. Survival in uncomplicated atrioventricular septal defect with common atrioventricular valvar orifice has greatly increased, and surgical correction is now equally successful in patients with Down's syndrome and chromosomally normal patients, and for both genders. Death in connection with surgery is no longer the major threat, and focus must now be on long-term follow-up.

Long term survival of children with Burkitt lymphoma in Malawi after cyclophosphamide monotherapy.

Between 1991 and 1997, limited funding at times restricted available treatment for children with Burkitt lymphoma (BL) to cyclophosphamide (CPM) monotherapy at Lilongwe Central Hospital, Malawi. Our objective was to assess long-term survival in Malawian children with Burkitt lymphoma (BL) who had received one or more treatments with intravenous CPM at 40 mg/kg/dose at 14-day intervals. The study population consisted of 92 children in whom BL had been confirmed on fine needle aspirates (FNA), a home address had been documented on discharge from hospital, and the treatment records could be verified. Only the clinical site(s) of disease had been recorded. The M:F ratio was 1.4 and median age 8 years. A clinical officer on motorcycle attempted to locate the given addresses and interview parents or other sources. In 19 patients, the address was incorrect. Of 73 evaluable patients, 40 children are alive at a mean follow-up time of 59 (range: 29-104) months. The survival rate was 63.5% in 52 children with BL of the head only, and 33.3% in 21 children with primary disease involving the abdomen or other sites. Survivors had received a median number of 6 (range: 1-12), non-survivors 4 (range: 1-12), and untracable children 3 (range: 1-11) courses of CPM. We confirmed that CPM could cure children with facial and abdominal BL. The unavoidable bias in the selection of patients and the variable amount of CPM given, precludes accurate survival estimates. A prospective study with proper staging, assessment of FNA, marrow and cerebrospinal fluid with modern techniques, a standard treatment protocol, and adequate follow-up will better define the current therapeutic value of CPM monotherapy. CPM can be purchased at about 3 US dollars per 500 mg.

Long-term survival of children with neuroblastoma prior to the neuroblastoma screening project in Germany.

In the last decades, prognosis of children with neuroblastoma has improved only slightly. Traditional estimates of survival reflect the survival experience of children diagnosed many years ago, and may thus not capture more recent progress in prognosis. We applied a new method of survival analysis, denoted period analysis, to provide more up-to-date estimates of long-term prognosis. We selected the cases diagnosed before the German neuroblastoma screening project in 1995, allowing to assess the method by comparing the 1994 projected survival estimates with the observations made today (2000). The data comes from the population based German Childhood Cancer Registry. We included all 1,353 children diagnosed with neuroblastoma below age 15 between 1980 and 1994. We derived 5-, 10-, and 15-year survival estimates using traditional analysis or period analysis as needed. Where possible we compared the period analysis estimates with the later obtained actual estimates. We showed trends in survival for the sample as a whole and for prognostic subgroups. Survival probabilities increased over time especially in the subgroups with poor prognosis. Short-term survival probabilities improved more than long-term survival probabilities. Evaluation of the period-analysis estimates showed them to provide accurate and timely projections of prognosis of newly diagnosed patients. The results suggest major improvements in prognosis of children with neuroblastoma, even prior to the start of the German neuroblastoma screening project, especially in advanced disease. This could have been disclosed with the application of the period analysis method in 1995 even then with considerable accuracy. We recommend a more widespread application of this method especially in population-based cancer registries.

Efficacy and outcome of intensive care in pediatric oncologic patients.

Because the long-term survival of children with cancer has dramatically improved because of multimodal treatment strategies, intensive care medicine has become more relevant for these patients. This study was performed to assess the efficacy of intensive care medicine in newly diagnosed pediatric oncologic patients and in patients under ongoing oncologic treatment. A retrospective analysis of children admitted to the pediatric intensive care unit (PICU) of the University Hospital Duesseldorf for life-threatening conditions between 1995 and 1999 was performed to identify those patients with an oncologic condition. University hospital. A total of 123 patients were identified. Children admitted for uncomplicated postoperative care and children admitted after bone marrow transplantation were excluded from this analysis. Forty-eight patients could be divided into two groups. Group A contained children admitted to the PICU at the time of cancer diagnosis and group B children receiving ongoing oncologic treatment. The evaluation included diagnosis, risk factors, complications leading to PICU admission, PICU therapy, and outcome. Statistical analysis included evaluation of Pediatric Risk of Mortality (PRISM) and Therapeutic Intervention Scoring System (TISS) scores. Respiratory insufficiency was the leading diagnosis for PICU admission, whereas in the remaining children cardiovascular insufficiency, renal failure, neurologic impairment, ileus, and tumor-associated complications led to PICU admission. The number of organ failures was correlated to outcome. All children but one of group A could be discharged from the PICU, whereas 12 of 35 children in group B died, despite intensive care treatment attempts. The PRISM and TISS scores at admission to the PICU were significantly higher in children who did not survive the period of intensive care treatment in group B. However, all patients with a PRISM score of >20 died. Diagnosis of cancer does not exclude potential benefit from intensive care medicine in these children, although severe complications might affect the prognosis.

Long-term survival of children with leukemia achieved by the end of the second millennium

The prognosis for patients with childhood leukemia has improved steadily over the last decades due to major progress in therapy. Much of this progress remains unaccounted for in traditional estimates of long-term survival rates, which essentially reflect the survival experience of patients who were diagnosed many years ago. The authors applied a new method of survival analysis, called period analysis, to provide up-to-date estimates of long-term survival rates. The analysis is based on data from the nationwide German Childhood Cancer Registry and includes 8059 children who were diagnosed with leukemia between 1981 and 1998. The most up-to-date 5-year, 10-year, and 15-year survival estimates were obtained by period analysis and were compared with to the most up-to-date survival estimates from traditional methods of survival analysis. Period estimates (95% confidence intervals) of 5-year, 10-year, and 15-year survival rates achieved by 1998 were 81% (79-83%), 77% (74-79%), and 73% (70-76%), respectively, for all patients with leukemia combined; 86% (84-88%), 81% (79-84%), and 77% (74-81%), respectively, for patients with acute lymphocytic leukemia; and 59% (53-65%), 59% (53-65%), and 57% (49-64%), respectively, for patients with acute nonlymphocytic leukemia. Substantially lower estimates would have been obtained with traditional methods of survival analysis. These results from one of the world's largest childhood cancer registries reveal that cure rates of childhood leukemia achieved by the end of the second millennium are higher than suggested by previous estimates based on traditional methods of survival analysis.

Renal cell carcinoma in children under 14 years old: long-term survival.

To assess the treatment and long-term survival of children under 14 years old operated upon for renal cell carcinoma (RCC). The records of five patients (aged 2, 4, 6, 9 and 13 years) who had been treated for RCC between 1982 and 1993 were reviewed. All had undergone nephrectomy with (two) or without (three) regional lymphadenectomy. After surgery four patients received chemotherapy (vincristine with actinomycin-D, three, vinblastine, one), and two with advanced-stage disease received other agents (interferon alpha, interleukin-2). They were followed for 5 to 15 years. Three patients with stage I-II RCC were well at 13, 15 and 15 years after treatment. Of the two patients with regional lymph node involvement (stage III), one was well 5 years after surgery while the other developed hepatic, lung and bone metastases, and died 2 years after presentation. The prognosis and long-term survival of children under 14 years old with RCC is very good for those with low-stage tumours. Nephrectomy with complete tumour extirpation is the main mode of treatment. For advanced-stage tumours, the role of adjuvant chemotherapy and/or biological agents must be defined more clearly.

Duration of first remission predicts remission rates and long-term survival in children with relapsed acute myelogenous leukemia.

Although treatment of childhood acute myelogenous leukemia (AML) has substantially improved in the last 15 years, in nearly half of the patients disease recurs. The aim of this study was to establish the prognosis of relapsed childhood AML and to identify prognostic factors for achievement of second remission and survival. From February 1988 to July 1996, 134 children with first relapse of AML were reported to the study center of the AML-BFM group. 102 patients treated intensively to induce second remission were prospectively followed. With various regimens, complete remission was achieved in 52 of 102 patients (51%), 27 children were alive in median 2.5 years (range, 0.4-7 years) after relapse. Disease-free survival was observed in seven of 16 patients transplanted from a matched sibling donor, one of four after matched unrelated bone marrow transplantation, 10 of 22 after autologous transplantation and five of nine patients after chemotherapy alone (two patients were lost to follow-up). Time until relapse reflecting the duration of first remission is the only variable correlating CR and survival rates. Defining early relapse as less than 1.5 years from diagnosis to relapse resulted in a 5-year survival of 10%, s.e. 5% for early relapses and 40%, s.e. 10% for late relapses (P-logrank test, 0.0001). Duration of first remission is a strong predictor for achievement of second CR and survival. It should be considered in reporting results of experimental therapies.

Long-term survival of children and adolescents after traumatic brain injury

Objective: To obtain information on long-term mortality risk and life expectancy after traumatic brain injury (TBI), to improve planning and for counseling patients and their families. In contrast to the literature for spinal cord injury and other disabilities, there have been few such reports for TBI. Design: Records were reviewed on 946 persons aged 5 to 21 years who had sustained TBI. All were patients who subsequently received disability services in California, 1987 to 1995. Results: The chief predictors of mortality were basic functional skills such as mobility and self-feeding. After the initial high-risk period, mortality risk for TBI was much lower than for similarly functioning persons with cerebral palsy (a comparison group), although after 10 years the two sets of mortality rates had largely converged. For high-functioning persons, life expectancies were only 3 to 5 years shorter than for the general population. By contrast, the remaining life expectancy for those without mobility 6 months after injury was only 15 years.

Endocrine late effects of childhood cancers

Long-term survival in children with cancer has increased markedly in the past 15 years. However, impaired linear growth and thyroid dysfunction that vary according to the age at diagnosis and treatment and to the dose and duration of radiation and chemotherapy have been described in these patients. The impact of cranial irradiation on the hypothalamic-pituitary-adrenal axis and on pubertal maturation has been less well studied. A positive correlation between the age at diagnosis and the age at onset of puberty in children who have been treated with high-dose cranial radiation therapy for central nervous system (CNS) tumors has been found recently. Frank adrenal insufficiency is uncommon after high-dose CNS irradiation, but alterations in the hypothalamic-pituitary-adrenal axis do occur. Assessments of the effects of newer modes of radiation therapy such as hyperfractionated craniospinal radiation suggest a lower incidence of primary hypothyroidism in the long term. (J Pediatr 1997;131:S37-41)

Long-term survival of children's false memories: A review

We present a theory-based review of research on the persistence of children's false memories over extended time intervals. Fuzzy-trace theory predicts that the long-term persistence of memory reports, whether true or false, will depend on whether initial reports were supported by verbatim or gist memories. In studies of children's spontaneous false-memory reports, both true and false reports have displayed long-term persistence, with false reports exhibiting persistence levels that were equal to or greater than those for true reports under theoretically specified conditions (which challenges the familiar forensic rule that persistence over time is an index of a report's truth). In studies of children's implanted false reports, both true and false reports have again displayed long term persistence, but persistence levels for true reports have usually been higher than those for false reports.

48 FULMINANT HEPATIC FAILURE— A SINGLE CENTER EXPERIENCE

Advances in liver transplanation have made this therapeutic option for children with fulminant hepatic failure who otherwise carry a mortality of 75-90%. The purpose of our study was to evaluate the results of a pediatric liver transplant program on this disease entity. Methods: A retrospective analysis was performed on data collected from patients referred to our pediatric liver transplant program since its inception in September 1992. Results: 17 patients with fulminant hepatic failure were referred for transplant evaluation. The etiology of liver failure included Tylenol overdose (n=4), CMV hepatitis (n=1), EBV hepatitis (n=1), HSV hepatitis (n=1) and unknown etiology (n=10). Eight patients were in grade 4 encephalopathy at the time of presentation of which 6 had an intracranial pressure monitor placed, the remaining 9 were in grade 2-3 encephalopathy. The mean PT at the time of presentation was 49.6 ± 18.2 secs. Outcome: There were five deaths; two from lack of an organ donor, two were referred late and died of fungal sepsis and one died of disseminated herpes. All 4 patients with Tylenol overdose recovered uneverntfully. Two other patients recovered spontaneously. Six patients received a liver transplant (3 with a reduced size graft). All patients who received a transplant are alive 2-46 months posttransplant with no neurological sequale. One patient required a retransplant a year later for chronic rejection. Conclusion: Liver transplantation offers the best chance of long term survival in children with fulminant hepatic failure. Early referral, reduced size grafting decrease the pre transplant mortality. Intracranial monitoring is safe and can prevent post transplant morbidity. Children with Tylenol overdose tend to have a good response to medical management.

ECG and echocardiographic diagnosis of pulmonary thromboembolism associated with central venous lines.

The aim was to establish the prevalence of pulmonary embolism in 21 children (median age 12 months; range 5-132 months) with central venous lines in situ > 3 months (median 10 months; range 3-47). Twelve-lead electrocardiograms (ECGs) and echocardiograms were analysed in a retrospective study using ECG and echocardiographic criteria for pulmonary embolism-previously established and validated in adult patients- and standard paediatric ECG values as control data. Patients were scored as having definite (n = 7), probable (n = 5), or no pulmonary embolism (n = 9). Overall 57% of ECGs showed abnormalities compatible with pulmonary embolism. In two patients, serial ECGs obtained during an acute cardiorespiratory illness showed cumulative changes diagnostic of pulmonary embolism. Eight of 12 patients with abnormal ECGs had echocardiography; in seven of these (88%) the right ventricular end diastolic diameter was > 2SD above the mean value for age. Twelve of the patients included in this study have died; two died following an acute respiratory illness. There was postmortem evidence of pulmonary thromboembolism in both of the two children for whom necropsy information was available. The data suggest that pulmonary embolism is common in children who have central venous lines in situ for > 3 months. Serial studies are of value in some patients. Pulmonary embolism may compromise the long term survival of children with small bowel failure and preclude consideration for liver and small bowel transplantation.