Hämatopoetische Wachstumsfaktoren in der Prophylaxe und Therapie infektiöser Komplikationen bei Kindern mit Neutropenie

Zusammenfassung.

Der Einsatz von gentechnologisch hergestellten hämatopoetischen Wachstumsfaktoren wie G-CSF (granulocyte colony stimulating factor) oder GM-CSF (granulocyte-macrophage colony stimulating factor) versprach einen großen Fortschritt in der Supportivtherapie von Patienten mit angeborener oder erworbener Neutropenie. Basierend auf den Ergebnissen zahlreicher Studien wurden in den letzten Jahren Leitlinien für den rationalen Einsatz der teuren Wachstumsfaktoren erstellt [3] [4] [152] [174]. Um das Risiko schwerer infektiöser Komplikationen bei krebskranken Patienten zu verringern, wird der Einsatz von G-CSF oder GM-CSF bei einer Untergruppe von Patienten kurz nach Gabe der zytotoxischen Therapie oder nach Knochenmark- oder Stammzelltransplantation empfohlen. So profitieren Kinder mit sehr intensiver Chemotherapie, wie z. B. Hochrisikopatienten mit ALL oder NHL von der Gabe der Wachstumsfaktoren, während dies für Patienten mit soliden Tumoren noch unklar ist. Die Mobilisierung peripherer Stammzellen zur autologen oder allogenen Transplantation stellt ein neues und viel versprechendes Einsatzgebiet der hämatopoetischen Wachstumsfaktoren dar. Während Studien zum Einsatz der hämatopoetischen Wachstumsfaktoren bei Kindern mit myelodysplastischem Syndrom weitgehend fehlen, sollen Kinder mit schwerer aplastischer Anämie frühzeitig G-CSF erhalten. Ebenfalls ist die Gabe von G-CSF bei Kindern mit schwerer chronischer Neutropenie indiziert, wobei die Kinder jedoch engmaschig auf zytologtische Auffälligkeiten untersucht werden müssen. Bisher konnte keine größere Studie einen klinischen Nutzen der hämatopoetischen Wachstumsfaktoren bei Früh- und Neugeborenen zeigen, so dass hier der routinemäßige Einsatz der Wachstumsfaktoren nicht empfohlen wird. Zukünftige Studien müssen zahlreiche offene Fragen klären. So fehlen Daten, welche Untergruppen von Patienten wirklich von der Gabe der Wachstumsfaktoren profitieren, das heißt, bei welchen Patienten G-CSF oder GM-CSF die Inzidenz von Infektionen oder die Dauer von intravenösen Antibiotikagaben verringert, die Krankenhauszeit verkürzt oder zu einer Verbesserung der Überlebensrate führt. Zudem müssen weitere Studien für die einzelnen Patientengruppen die optimale Dosis und die geeignete Dauer der Wachstumsfaktorgabe herausfinden. Dabei muss für jede Indikationsstellung der teuren Wachstumsfaktoren der klinische und der ökonomische Nutzen mit der Einsparung der Gesamttherapiekosten kritisch gegeneinander abgewogen werden.

Hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures to reduce infectious complications associated with congenital or acquired neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the corpus of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors [3] [4] [152] [174]. To prevent serious infection, the use of G-CSF or GM-CSF is recommended in a subset of pediatric cancer patients shortly after having received chemotherapy or a form of a marrow transplant. Children with highly intensive chemotherapy (e.g., children with high risk ALL or NHL) seem to benefit from hematopoietic growth factors whereas this is still unclear for children undergoing therapy for solid tumors. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells for autologous or allogeneic transplantation. In pediatric patients with hematological diseases, there are only few data on the use of hematopoietic growth factors in children with myelodysplastic syndrome. Experts recommend the early administration of G-CSF in children with very severe aplastic anemia. The use of G-CSF is also recommended in children with severe chronic neutropenia, but these patients have to be monitored regularly for cytogenetic abnormalities. No larger study has shown a clinical benefit of hematopoietic growth factor in preterm or term infants. Future studies in pediatric patients are clearly warranted to address several issues. Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support. In this regard, efforts must be directed at better defining the endpoints and in particular assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups of patients. In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients.

Hämatopoetische Wachstumsfaktoren - G-CSF - GM-CSF - Kinder - Infektion - Neutropenie

Hematopoietic growth factor - G-CSF - GM-CSF - children - infectious complication - neutropenia

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