Growth impairment after ifosfamide-induced nephrotoxicity in children

BACKGROUND: The goal of this study was to analyze long-term consequences of ifosfamide-induced nephrotoxicity on growth and renal function in children treated for cancer. PROCEDURE: In a retrospective study, departments for pediatric oncology and nephrology in Germany, Austria, and Switzerland were asked to report patients with serious long-term nephrotoxicity after ifosfamide-treatment. Data at first appearance of renal dysfunction and at the last renal examination were collected using a standardized questionnaire. RESULTS: Fifty-nine patients with tubulopathy (35 severe, 24 moderate) following ifosfamide therapy were eligible for analysis of long-term outcome (median follow-up 4 years, range 1.1 to 12.9). Median height standard deviation score was significantly reduced at renal diagnosis, and at last renal examination (-1.7 and -2.1 respectively, P < 0.01 at each point in time). Patients with tubulopathy also had stunted growth in comparison with a control group of cancer patients without renal disease (mean difference at last examination: 7.3 cm (95% confidence interval: 2.5 to 12.1 cm). In patients with severe tubulopathy, glomerular filtration rate deteriorated significantly over time. End-stage renal disease was reported in one patient only, not solely caused by ifosfamide. CONCLUSION: Depending on the extent of tubular dysfunction, patients with ifosfamide-induced nephrotoxicity experienced significant growth impairment and a slow decline in glomerular filtration rate.     

Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: a report from the late effects surveillance system

BACKGROUND: Cisplatin and carboplatin are both nephrotoxic and can induce, to a different degree, impairment in glomerular function and hypomagnesemia. Prospective longitudinal studies on these renal impairments are rare in children and adolescents. PROCEDURE: Six hundred and fifty one sarcoma patients were investigated prospectively for nephrotoxicity in the Late Effects Surveillance System (LESS) network (median follow-up 2 years). Median cumulative dose was 360 mg/m(2) for cisplatin, and 1,500 mg/m(2) for carboplatin. Patients not treated with any platinum derivative were used as controls. Most patients (including controls) also received ifosfamide. Renal function was tested by serum magnesium, serum creatinine, and the GFR as estimated by the Schwartz formula. We evaluated incidence, dependencies, and the course of impairments. RESULTS: There was no observed platinum-induced reduction of glomerular function over time. After cessation of antineoplastic therapy, hypomagnesemia (<0.7 mmol/L) occurred in 12.1% (95% CI: 6.8%-19.4%) of patients after cisplatin therapy, and in 15.6% (95% CI: 5.3%-32.8%) after carboplatin therapy, in comparison with 4.5% (95% CI: 2.0%-8.7%) in patients without any treatment with platinum derivatives (P = 0.008). In all groups, the frequency of hypomagnesemia decreased with ongoing follow-up, but serum magnesium remained lower in platinum treated patients throughout the study period. CONCLUSION: Nephrotoxicity after treatment with cisplatin and carboplatin was mild in our study. Further studies have to show if serum magnesium is permanently decreased in platinum treated patients and if this will result in any clinically relevant impairment.     

Ifosfamide nephrotoxicity in children: Histopathological features in two cases

We report on two children with rhabdomyosarcoma who received ifosfamide as part of their chemotherapy schedule. Both children subsequently developed severe ifosfamide-induced nephrotoxicity, necessitating electrolyte supplementation. We describe the histopathological findings of renal biopsies performed in these children after the onset of renal dysfunction and comment on the possible mechanisms involved in ifosfamide nephrotoxicity. © 1996 Wiley-Liss, Inc.     

Ifosfamide nephrotoxicity in paediatric cancer patients

Ifosfamide is an alkylating agent which has been incorporated into frontline therapy for a number of malignant paediatric tumours. Recent data appears to suggest that tubular dysfunction may result from incorporation of this drug into chemotherapy schedules and that toxicity may be dose related. A detailed investigation of renal function was performed in a group of patients, ranging in age from 8 months to 15.9 years (median 8.6 years) with rhabdomyosarcoma (n=11) and Ewing's sarcoma (n=9) who were currently receiving (n=4) or had completed ifosfamide (n=16) therapy a mean of 16 months at the time of study. All but one patient demonstrated some degree of renal dysfunction and toxicity did not necessarily appear to be dose related. Implications for incorporation of this agent into future schedules for childhood sarcomas, which can expect to cure more than 60% of such children, must be addressed. The importance of ongoing monitoring is emphasised.     

Prospective multicenter registration of major late sequelae in sarcoma patients using the Late Effects Surveillance System (LESS)

BACKGROUND: Late effects become progressively more important for the evaluation of therapeutic success in paediatric oncology. Thus, in 1998, the Late Effects Surveillance System (LESS) started to register and assess multicentrally, prospectively and longitudinally late effects of treatment for the group of Ewing's, soft tissue- and osteosarcoma patients. PATIENTS AND METHODS: The yearly results of the follow-up examinations of 785 Ewing's, soft tissue- and osteosarcoma patients, who were treated from 1.1.1998 until 31.12.2001, were prompted and assessed conforming to the guidelines developed by the LESS-study. RESULTS: 136/181 (75 %) of follow-up institutions take part in the LESS-study. Only 8 % of patients eligible for the LESS-study were cared for in non-cooperating facilities. Questionnaire return could be raised to 73-78 % and data completeness could also be significantly improved in the course of the study. Departments of internal medicine had a lower questionnaire return percentage than departments of paediatrics. Data availability for the nephrologic after-care was not satisfactory. CONCLUSIONS: The LESS project has been well established. Thus, the basis has been set for the development of risk-oriented strategies for intervention and for the further improvement of the follow-up of major late effects in sarcoma patients.     

Incidence and etiology of ifosfamide nephrotoxicity: Report of a meeting held in Rhodes,Greece, October 3, 1991, sponsored by Asta Medica,Frankfurt, Germany

The nephrotoxic potential of Ifosfamide is now clearly recognized but the true incidence is unknown and risk factors are uncertain. There are, as yet, few studies which systematically explore these issues although many centers have collected data from patients receiving Ifosfamide. These support the need for collaborative studies to look at the influence of probable risk factors such as age, cumulative dose, schedule, and exposure to other nephrotoxic drugs. The ability to detect acute subclinical changes in renal function may provide the opportunity to predict subsequent clinical toxicity. The consensus of opinion recorded so far provides the basis of recommendations for future studies. © 1993 Wiley-Liss, Inc.     

Renal late effects in patients treated for cancer in childhood: a report from the Children's Oncology Group

Improvements in childhood cancer therapy have led to increasing numbers of long-term survivors. These survivors are at risk for a variety of late effects due to the disease itself, treatment exposures (surgery, chemotherapy, and radiotherapy), underlying medical problems, and health behaviors. The COG LTFU Guidelines are risk-based, exposure-related recommendations for the identification and management of late effects due to therapies utilized in the treatment of childhood cancer, and are designed for asymptomatic survivors presenting for routine medical follow-up 2 or more years after completion of cancer therapy. The COG Guidelines Task Force on Urinary Tract Complications conducted an extensive review of the medical literature via MEDLINE. Specific treatment exposures which were reviewed include nephrectomy, chemotherapy regimens known to be nephrotoxic (cisplatin, carboplatin, ifosfamide, and methotrexate), and renal irradiation. Literature sources were ranked according to the strength of evidence and are cited in the review. This review summarizes the literature that supported the recommendations for cancer survivors at risk for nephrotoxicity previously outlined in the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers (COG LTFU Guidelines).     

Tubular function and histological findings in ifosfamide-induced renal Fanconi syndrome — a report of two cases

Two patients developed renal Fanconi syndrome (RFS) after intensive long-term chemotherapy for metastatic Ewing sarcoma and disseminated neuroblastoma. Whereas RFS was diagnosed in patient 1 before he developed osteomalacia, patient 2 experienced severe rickets and growth retardation. Renal function studies revealed slight glomerular impairment and severe tubular defects leading to increased excretion of glucose, amino acids, inorganic phosphate and low molecular weight proteins, indicating proximal tubular damage. Patient 2 additionally showed distal tubular dysfunction with acidosis and diminished concentrating capacity. Renal biopsy in patient 1 revealed marked proximal tubular defects without interstitial lymphocytic infiltration. In both patients renal damage could most likely be ascribed to previous ifosfamide (IFOS) therapy. Our patients showed no improvement in renal function after cessation of IFOS treatment, indicating a poor prognosis of once established RFS after IFOS therapy. Measurement of tubular reabsorption capacities provides exact information on the extent of tubular toxicity induced by IFOS and may be used to monitor IFOS treated patients.     

应用关节镜治疗儿童膝关节滑膜皱襞综合征30例临床分析

目的探讨关节镜对儿童滑膜皱襞综合征的诊断价值和治疗效果。方法对30例38膝膝关节滑膜皱襞综合征患儿进行关节镜检查,同时行滑膜皱襞松解切除术;采用Lysholm评分标准评价术前及术后膝关节功能的变化。结果该组平均随访时间3.8a（10个月～5年4个月）;术前平均Lysholm评分（52.57±5.26）分,术后平均Lysholm评分（93.00±4.04）分,平均改善41分,术前与术后功能评分差异有统计学意义（t=15.393,P〈0.01）。结论关节镜技术是治疗儿童滑膜皱襞综合征的一项安全、可靠、有效的措施。     

Prospective longitudinal evaluation of doxorubicin-induced cardiomyopathy in sarcoma patients: a report of the late effects surveillance system (LESS)

BACKGROUND: Prospective longitudinal examinations of anthracycline-induced cardiomyopathy in a homogeneous cohort are rare in pediatric oncology. We herein report the results of observations on the frequency of cardiomyopathy in doxorubicin-treated sarcoma patients in Germany, Austria, and Switzerland. PROCEDURE: The Late Effects Surveillance System (LESS) prospectively collects longitudinal data on late sequelae of antineoplastic therapy in Ewing-, soft tissue-, and osteosarcoma patients treated within the therapy trial protocols of the German Society of Pediatric Oncology and Hematology. Two hundred sixty-five relapse-free patients who had received doxorubicin for the treatment within the EICESS-92/EURO-E.W.I.N.G.-99, COSS-96, and CWS-96 therapy trials were serially examined by echocardiography. The analyzed population consisted of 142 males and 123 females. Their mean age at the end of therapy was 13 +/- 5 years. The mean follow-up time was 34 +/- 12 months. The mean cumulative doxorubicin dose was 290 +/- 91 mg/m(2). RESULTS: In this cohort, the total cumulative incidence of doxorubicin-induced cardiomyopathy was 7.5%. Four patients (1.5%) suffered from a symptomatic cardiomyopathy and 16 (6%) from a subclinical cardiomyopathy. Cardiomyopathy manifested in 11 cases already under antineoplastic therapy and in the remaining nine cases at a median of 26 days (range: 17-174 days) after stopping antineoplastic therapy. Univariate and multivariable analysis did not confirm any of the known risk factors for developing anthracycline-induced cardiomyopathy in our patient group within the described time interval. CONCLUSIONS: After a mean follow-up of 34 +/- 12 months, cumulative incidence of doxorubicin-induced cardiomyopathy in our pediatric sarcoma patients was at the lower end of that reported by other groups.     

Anaplastic sarcoma of the kidney: Case report and literature review

Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13‐year‐old boy with a large renal mass, underwent surgery. Pathological findings showed proliferation of short spindle‐shaped cells with anaplastic features including multiple foci in hyaline cartilage. Complex chromosomal abnormalities were detected in the tumor cells. Postoperative chemotherapy with the regimen for Ewing's sarcoma achieved complete remission but the tumor recurred and the patient died during re‐induction chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage. Because there were no viable tumor cells, the recurrent tumor was considered to have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown pathogenesis, and no standard treatment has yet been established, but the tumor cells may be responsive to chemotherapy. Further study is needed to establish the optimal treatment strategy.     

儿童可逆性后部脑病综合征2例报告并文献复习

目的提高对儿童可逆性后部脑病综合征(RPES)的认识。方法回顾性分析首都儿科研究所收治的2例可逆性后部脑病综合征患儿的临床资料,并结合文献进行分析。结果2例患儿原发病分别为系统性红斑狼疮和肾病综合征,均在病程中突然出现头痛、视觉异常、意识障碍、高血压和抽搐等症状。头颅MRI显示双侧大脑顶、颞、枕叶皮层或皮层下片状长T1/T2信号。经过及时降血压和对症治疗后,短期内症状很快缓解,2～3周内影像学异常完全消失。结论RPES的发病机制是多方面的,急剧增高的血压可能是发生RPES的主要原因之一,及时有效的降压治疗可使病情在短期内逆转。     

Multiagent chemotherapy for children with metastatic neuroblastoma: A report from childrens cancer study group

During the past 10-15 years there has not been a significant improvement in the overall survival of children with metastatic neuroblastoma. From 1971 through 1975, 104 eligible patients were entered on two clinical studies for newly diagnosed cases of stage IV neuroblastoma by the Childrens Cancer Study Group (CCSG). Patient data from both studies were evaluated for activity of cyclophosphamide, imidazole carboxamide, and vincristine and of these same agents plus adriamycin. Response was evaluated by serial measurements of tumor size. Eighty-four patients experienced a complete or partial response. The life-table estimate of median survival on both studies was 11–12 months for all patients and 13-18 months for responders, unchanged from the results of previous CCSG studies. Long-term survival, however, for patients on these studies demonstrates a significant increase compared with results reported from the three previous CCSG studies. Children less than 1 year or greater than 6 years of age at diagnosis showed a significantly improved survival pattern over the intermediate age group. It is suggested that there is a need to consider the induction response pattern and age at diagnosis when planning a maintenance program so that nonresponders can be identified early and considered for treatment with new agents or aggressive multimodal therapy.     

Successful living-related liver transplantation in a child with familial yellow nail syndrome and fulminant hepatic failure: report of a case

An 11-yr-old boy with familial YNS and FHF and who underwent LRLT is presented. LRLT was performed from his father with YNS. The findings of hepatic failure resolved immediately after LRLT, but severe respiratory complications and chylous ascites were observed during the follow-up. At 12 months after successful LT, the patient has good graft function, but findings of YNS including chronic cough, lymphedema and yellow nails are still present. To the best of our knowledge, this is the first case of YNS who underwent LRLT for FHF.