GROWTH FACTORS AS THERAPEUTIC TOOLS

G.S. Schaison

Saint Louis Hospital, Paris, France

Recently, a panel of European haematologists, oncologists and neonatologists developed scientific guidelines for the use of colony stimulating factors (CSF) based on published literature and the clinical experience of these specialists (Eur J Pediatr 1998;157:955-966). Well established indications for use comprise intervention in patients with life threatening infection (proven Pseudomonas, fungal infection, multiorgan failure), adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitors cells for autologous BMT, patients with acquired aplastic anaemia on antilymphocyte globulin and cyclosporin regimen when nn allogenic donor is available, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies (high risk leukemia, B cell non Hodgkin lymphoma, stage IV neuroblastoma). The more intensive/sustained chemotherapy the more myelosuppression and fever and neutropenia are dose limiting factors. In our own study we have shown that CSF can increase chemotherapy dose intensity (CDI) in high risk childhood acute lymphoblastic leukemias. Its effects depend on the chemotherapy regimen given prior to CSF administration. The higher dose intensity was observed using a combination of high dose cytarabine-etoposid-dexamethasone for intensification but higher CDI did not improve disease control. CSF'S should not be given concomitantly with chemotherapy. CSF'S do not seem to promote tumoural growth. Their use are recommended in febrile sepsis poorly responding to antibiotics. CSF'S can used as second prophylaxis to prevent neutropenia in patients with history of severe neutropenia, as support therapy in case of poor marrow function following BMT and for deteriorating marrow function subsequent to successful transplantation. CSF'S appear to be benefical post ABMT in reducing morbidity. CSF'S can be recommended in neonatal sepsis and presumed sepsis in small preterm babies and for life threatening infection in any neonate. CSF'S are available for IV or SC administration. The recommended dose id 5 µg/kg per day or 150 µg/m2. For mobilization of peripheral blood stem cells GCSF can be administred alone at a dose of 10 µg/kg for 4-5 days. In Kostman syndrome, dosage should start at 5 µg/kg but if no response is observed incremental increase in dosage of 5 µg/kg per day should follow until a response is recorded.

Treatment is generally well tolerated and GCSF appears better tolerated than GM-CSF but GM-CSF is much more well tolerate in childhood than in adulthood. Economically, CSF'S have not been shown to induce excessive costs for a given patient. In some randomized study administration of CSF can lead to a reduction in the duration of antibiotic usage and hospital stay.

In conclusion, general adults guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasm, specific indications, neonatal use or congenital disorders) must be taken into account.