Hämatopoetische Wachstumsfaktoren in der Infektionsprävention bei Kindern mit hämatologisch-onkologischen Erkrankungen

Zusammenfassung.

Mit dem Einsatz von gentechnologisch hergestellten hämatopoetischen Wachstumsfaktoren wie G-CSF (granulocyte colony stimulating factor) oder GM-CSF (granulocyte-macrophage colony stimulating factor) versprach man sich einen großen Fortschritt in der Supportivtherapie krebskranker Patienten. Beide Wachstumsfaktoren stimulieren Proliferation und Reifung der myeloischen Vorläuferzellen und verringern so Ausmaß und Dauer der Neutropenie. Allerdings können durch hämatopoetische Wachstumsfaktoren infektiöse Komplikationen nicht verhindert werden. Basierend auf den Ergebnissen zahlreicher Studien wurden in den letzten Jahren Leitlinien für den rationalen Einsatz der teuren Wachstumsfaktoren erstellt [2] [3] [78] [92]. Um das Risiko schwerer infektiöser Komplikationen 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 und Patienten mit metastasiertem Neuroblastom von der Gabe der Wachstumsfaktoren, während dies für Patienten mit soliden Tumoren, wie z. B. für Patienten mit Rhabdomyosarkom oder Ewing-Sarkom, noch unklar ist. Die Mobilisierung peripherer Stammzellen stellt ein neues und viel versprechendes Einsatzgebiet der hämatopoetischen Wachstumsfaktoren dar. Allerdings müssen zukünftige Studien noch 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.

The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce, but not eliminate infectious complications associated with therapy-induced 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 multitude of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors [2] [3] [78] [92]. To prevent serious infection, the use of G- or GM-CSF is recommended in a subset of pediatric cancer patients shortly after receiving chemotherapy or a marrow transplant. Children with intensive chemotherapy (e.g., children with high risk ALL, NHL or metastatic neuroblastoma) seem to benefit from hematopoietic growth factors whereas it is not clear that this applies to children undergoing therapy for solid tumors such as rhabdomyosarkoma or Ewing's sarcoma. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells. Future studies in pediatric cancer 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, depending upon underlying malignancy and therapy given. 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.

Schlüsselwörter

Hämatopoetische Wachstumsfaktoren - G-CSF - GM-CSF - Infektionsprävention - Kinder - Malignom

Key words

Hematopoietic growth factors - G-CSF - GM-CSF - prevention of infection - children - malignancy

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