Edit Bárdi

Cystatin C is a suitable marker of glomerular function in children with cancer

Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on nephrotoxicity in childhood cancer are scanty, in part because of the difficulties in obtaining reliable markers of glomerular function. We used serum cystatin C (cysC) to assess glomerular function. CysC was compared with serum creatinine concentration (SCr), the endogenous creatinine clearence ( C Cr), and the calculated Counahan formula ( C Counahan) in children with leukemia and solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay. Serum and urinary creatinine concentrations were determined by the Jaffé method. Samples were obtained from 258 children, including 92 receiving anticancer chemotherapy, 108 long-term survivors, 40 children without any renal disease, and 18 patients with chronic renal insufficiency. CysC of patients on current chemotherapy was assessed both before and after treatment. Significant correlations were found between cysC and SCr and between 1/cysC and C Counahan. CysC increased significantly after cisplatin, methotrexate, cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest that cysC measurement can be used to characterize glomerular function in children with cancer.

Late effects on renal glomerular and tubular function in childhood cancer survivors

Late nephrotoxicity among childhood cancer survivors is poorly documented.

Prevention and treatment of hyperuricemia with rasburicase in children with leukemia and non-Hodgkin's lymphoma

To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin’s lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 μmol/L to 58 μmol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.

Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer

Experimental evidence suggests that anthracyclines, widely used in cancer chemotherapy, may impair kidney function. We assessed kidney function by serum creatinine, urinary N-acetyl-β-D-glucosaminidase activity indices (NAGi) and microalbuminuria (MA) in 160 serum and urine samples obtained from 66 children with cancer. The effect of dexrazoxane was analyzed in 6 children on dexrazoxane supportive therapy in conjunction with daunorubicin (DNR) treatment, as compared with 6 children not receiving this agent. NAG; was significantly (p<0.05) elevated after treatment by DNR, doxorubicin, epirubicin (EPI) and idarubicin (IDA). MA proved to be a less sensitive indicator of kidney damage than NAGL DNR resulted in a progressive deterioration of proximal tubular function as determined by linear regression analysis. The mean NAG1 in the dexrazoxanetreated group was significantly (p<0.005) lower than in children not receiving dexrazoxane prior to DNR treatment. In conclusion, our study demonstrated that DNR, EPI and IDA induced an acute renal tubular damage similar to known tubulotoxic agents as cisplatin, carboplatin, cyclophosphamide and ifosfamide. The damage was clinically mild and only a minor proportion of patients can be expected to develop long-lasting tubulopathy with negative impact on the quality of life.

Practices of pediatric oncology and hematology providers regarding fertility issues: A European survey

Fertility is impaired in many survivors of childhood cancer following treatment. Preservation of fertility after cancer has become a central survivorship concern. Nevertheless, several doctors, patients, and families do not discuss fertility and recommendations for fertility preservation in pediatrics are still lacking. Recommendations based on scientific evidence are needed and before their development we wanted to assess the practice patterns of fertility preservation in Europe.

Combined local treatment and chemotherapy in the management of bilateral retinoblastomas in Hungary

This retrospective study supports that brachytherapy combined with cytostatic therapy may effectively contribute to tumor control. The second eye of 13 patients with bilateral retinoblastoma was treated with plaque brachytherapy after the enucleation of the first eye. Eleven patients received systemic cytostatic therapy. The mean follow up was 60 (±42 SD) months. Twelve patients are alive and free of tumor, 8 of them with acceptable visual acuity. After cytostatic therapy, late nephropathy was observed in 2 patients. In conclusion, brachytherapy combined with cytostatic therapy will be an option in the management of bilateral retinoblastoma after the enucleation of the first eye.

Polymorphism of angiotensin converting enzyme is associated with severe circulatory compromise in febrile neutropenic children with cancer.

Angiotensin converting enzyme (ACE) gene insertion(I)/deletion(D) polymorphism influences the outcome of a number of cardiovascular diseases. ACE I/D polymorphism was investigated by PCR in 207 pediatric cancer patients and 144 controls. ACE I/D distribution of patients and controls was similar. The frequency of the D allele and the prevalence of the deletion (DD) genotype were significantly (P < 0.05) higher among patients with severe circulatory compromise requiring treatment in the intensive care unit (ICU) than among the other patients and controls. Patients with the DD and ID genotypes spent significantly (P < 0.05) longer time in the ICU than patients with the II genotype.

P075 Analysis of complex chromosome aberrations in childhood acute lymphoblastic leukemia (ALL) using multicolor fluorescent in situ hybridization (M-FISH)

Chromosomal changes are an independent prognostic factor in childhood ALL. Patients are classified into risk groups for treatment according to karyotype. Conventional cytogenetic technique has limitations in the identification of complex chromosomal aberrations. Multicolor fluorescence in situ hybridization (M-FISH) allows simultaneous visualization of all human chromosomes in different colors. M-FISH is useful for detection of cryptic genetic aberrations, identification of marker chromosomes and complex chromosomal rearrangements. We used this technique to refine the diagnosis of five pediatric ALL patients previously characterized by conventional karyotyping and identify the disease-specific genetic alterations more accurately.