J.D. Beck

Risk-Adjusted Therapy of Acute Lymphoblastic Leukemia Can Decrease Treatment Burden and Improve Survival: Treatment Results of 2169 Unselected Pediatric and Adolescent Patients Enrolled in the Trial ALL-BFM 95.

The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and long-term toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups. Estimated 6-year event-free survival (6y-pEFS) for all 2169 patients was 79.6% (+/- 0.9%). The large standard-risk (SR) group (35% of patients) achieved an excellent 6y-EFS of 89.5% (+/- 1.1%) despite significant reduction of anthracyclines. In the medium-risk (MR) group (53% of patients), 6y-pEFS was 79.7% (+/- 1.2%); no improvement was accomplished by the randomized use of additional intermediate-dose cytarabine after consolidation. Omission of preventive cranial irradiation in non-T-ALL MR patients was possible without significant reduction of EFS, although the incidence of central nervous system relapses increased. In the high-risk (HR) group (12% of patients), intensification of consolidation/reinduction treatment led to considerable improvement over the previous ALL-BFM trials yielding a 6y-pEFS of 49.2% (+/- 3.2%). Compared without previous trial ALL-BFM 90, consistently favorable results in non-HR patients were achieved with significant treatment reduction in the majority of these patients.

Ifosfamide-induced nephrotoxicity in 593 sarcoma patients: A report from the Late Effects Surveillance System

Ifosfamide is widely used in paediatric oncology, but its use is limited by nephrotoxic side effects. The aim of this study was to evaluate the incidence and risk factors of tubulopathy, with special emphasis on the influence of age, where different findings have been published so far.

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

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.

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

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.

Humoral immunity against diphtheria, tetanus and poliomyelitis after antineoplastic therapy in children and adolescents : a retrospective analysis

Serum antibodies against diphtheria- and tetanus-toxin were measured in 71 children and against poliomyelitis viruses 1-3 in 65 children and adolescents 0-18 months after cessation of antineoplastic therapy. Non or marginally protective serum titers were found in 62% of patients against diphtheria, in 18% of patients against tetanus and in 72% of patients against one or more poliomyelitis virus serotypes. Of these patients, 55%, 46% and 75% were immunized adequately according to age against diphtheria, tetanus and poliomyelitis, respectively. In 50% or more of patients a lack of protective immunity against diphtheria, tetanus and poliomyelitis was found which could not be explained by an inadequate immunization status. This suggests that other factors (e.g. influence of underlying illness, antineoplastic therapy or both on lymphocytes) might be responsible for these findings and this deserves further investigation. Measurement of serum antibodies against vaccine-preventable illnesses and consecutive booster immunizations are an essential part of long-term follow up in pediatric patients after antineoplastic therapy.

Growth impairment after ifosfamide-induced nephrotoxicity in children

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.

Die Überlebenden einer Krebserkrankung im KindesalterNachsorge und Spätfolgen nach erfolgreicher Therapie

ZusammenfassungDurch die Erfolge bei der Behandlung krebskranker Kinder haben die Erkennung, Behandlung und, soweit möglich, auch die Vermeidung von Spätfolgen nach antineoplastischer Behandlung und die Verbesserung der Nachsorge besondere Bedeutung erlangt. Im Rahmen des “Late Effects Surveillance Systems (LESS)” der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) werden seit 1995 systematisch wesentliche Spätfolgen bei den Patienten der Therapieoptimierungsstudien erfasst, um so die Fragen nach Inzidenz, Zeitpunkt des Auftretens und der Prognose zu beantworten. Die wichtigsten bisher näher untersuchten Folgeschäden sind Kardiotoxizität vor allem nach einer Anthrazyklintherapie, Oto- und Nephrotoxizität nach Platinderivaten, Tubulopathien nach Ifosfamid und endokrine Störungen mit ihren Auswirkungen auf Wachstum, Pubertätsentwicklung und Fertilität. Darüber hinaus ist das im Vergleich zur übrigen Bevölkerung deutlich erhöhte Risiko, an einem Zweitmalignom zu erkranken, in der Betreuung dieser Patienten von besonderer Wichtigkeit. Dieser Frage geht das Deutsche Kinderkrebsregister nach. Die Kenntnis einer strukturierten Nachsorge im Rahmen einer vertikalen Vernetzung stellt für den Kinderarzt in Klinik und Praxis die Grundlage für die Betreuung ehemals krebskranker Kinder und Jugendlicher dar.AbstractWith increasing success of cancer therapy in childhood detection, treatment and possibly avoidance of long term sequelae after antineoplastic therapy and the aftercare of these patients are of great importance today. The “Late Effects Surveillance System (LESS)” of the GPOH, established in 1995, collects systematically data on major late effects of patients treated according to the therapy optimising studies to answer the questions about incidence and latency after first line treatment as well as prognosis. The most significant late effects known today are cardiotoxicity mainly after therapy with anthracyclines, oto- and nephrotoxicity after platinum derivatives, tubulopathy after ifosfamide and endocrine dysfunctions causing deficiencies in growth, pubertal development and fertility. Furthermore the risk of secondary neoplasia is an important issue in the management of these patients. This is investigated by the German Childhood Cancer Registry. Knowledge of a structured aftercare in the frame work of a vertical network provides the basis of efficient care and counselling of cancer survivors in childhood and adolescence.

Postnatal respiratory distress in a dichorial twin with congenital thoracic neuroblastoma after assisted reproduction by intracytoplasmatic sperm injection

We report on the case of a female twin with congenital thoracic neuroblastoma after conception via intracytoplasmatic sperm injection (ICSI). Birth occurred at 37 + 1‐week gestation per primary sectio caesarea. Acute respiratory distress necessitated intubation and mechanical ventilation. Ultrasound and magnetic resonance imaging (MRI) showed a mass in the right upper thorax compressing the trachea. The tumor was subtotally excised and histological analysis revealed neuroblastoma. No further treatment was given. The residual primary tumor regressed spontaneously. Four years after diagnosis, both twins are healthy and normally developed. Pediatr Blood Cancer 2007;48:358–360.

Over 15 years of ELTEC: A report of the international BFM study group

Early and late toxicities of antineoplastic treatment are becoming more important as the paradigm shifts from ‘‘Survival to Cure’’ and the prevalence of cancer survivors rises [1]. For more than 15 years now, the Early and Late Toxicity Educational Committee (ELTEC) of the International BFM Study Group (I-BFM-SG) has been investigating adverse effects of antineoplastic treatment and disseminating good clinical practice guidelines [2]. We herein summarize the proceedings of the last ELTEC meeting, held on February 2–3 in Erlangen, Germany. The meeting focused on the results of the ongoing educational and research projects of ELTEC (Table I). Early and late effects of chemotherapy on central nervous system (CNS) function form a focus, as these can pose important clinical problems [3]. Ongoing studies of the Italian Association of Pediatric Hematology and Oncology (AIEOP) on WHO Grade 3–4 adverse CNS-events during antileukemic treatment have made it clear that large international studies are necessary for the examination of rare toxicities such as methotrexate-induced CNS-events. Thus, a retrospective (Chairs: M. Jankovic, A. Möricke) and a prospective study (Chairs: J.D. Beck, R. Haupt) will be planned within the ALLAIEOP/BFM studies for further investigation. This twofold approach was chosen since large prospective studies, like the Late Effects Surveillance System [4–8], have proven very useful for the study of toxicities of antineoplastic therapy as it is possible to react to reported pathologies, directly improving individual patient care. Also for this reason, a remote data-entry system has been developed at the Gaslini Children’s Hospital to build up a prospective followup network in Italy. Another focus was infectious complications. In addition to acute infections [9], the long-term evolution (>10 years) of hepatitis C virus infection acquired during antineoplastic treatment is being studied; as in oncologic patients other factors, for example, immunosuppression, may further complicate the clinical course [10,11]. Furthermore, the previously described educational booklet for hematologists/oncologists [2] has been expanded with new flow-charts to assist decision-making for adverse events. This meeting underscored the necessity for further research and education on early and late toxicities after cancer treatment. The direction for the future can only be that of intensified international collaboration. Another crucial aim is the education of former patients and provision made for adequate counseling to meet information needs. Ultimately, the goal is to advance from the survivors to truly cured patients who can lead lives to their full potential. ACKNOWLEDGMENT

Erkennen, Vermeiden und Behandeln von Spätfolgen

ZusammenfassungViele der ehemaligen Krebspatienten sind mit einer guten physischen und psychischen Leistungsfähigkeit in unsere Gesellschaft integriert, können ihre beruflichen Fähigkeiten entwickeln und Familien gründen. Die multimodale Behandlung kann aber nicht nur Akuttoxizitäten, sondern auch Spätschäden auslösen, die nach Abschluss der aktiven onkologischen Behandlung weiterbestehen oder sich erst entwickeln [2–5].