Granulocyte colony-stimulating factor ameliorates toxicity of intensification chemotherapy for acute lymphoblastic leukemia.
BACKGROUND
Intensification chemotherapy improves the prognosis for children with acute lymphoblastic leukemia (ALL), but results in considerable morbidity, primarily due to myelosuppression with resultant neutropenia. Recombinant granulocyte colony-stimulating factor (G-CSF) shortens neutropenia following intensive chemotherapy, but potential benefits in the therapy of ALL remain inadequately explored. Accordingly, a randomized, crossover study was undertaken to clarify this issue.


METHODS
Seventeen children with acute lymphoblastic leukemia or T-cell non-Hodgkin lymphoma and treated on standard protocols were randomized to receive G-CSF following either the first or second intensification blocks of chemotherapy. G-CSF was administered as a single daily subcutaneous injection of 5 mcg/kg from day 9 following the start of intensification therapy, and continued until the neutrophil count exceeded 0.5 x 10(9)/l for 3 days. Study endpoints were days of neutropenia (neutrophils < 1 x 10(9)/l) and severe neutropenia (neutrophils < 0.5 x 10(9)/l), days in hospital, days of fever, and days on antibiotics.


RESULTS
There were significant reductions in the duration of neutropenia (95% confidence interval 3.8-8 days, P = 0.0001), severe neutropenia (95% confidence interval 1.8-7.4 days, P = 0.002), and days in hospital (95% confidence interval 0.9-6.3 days, P = 0.01) for children receiving G-CSF. Overall, the duration of neutropenia was longer following the second block (95% confidence interval 2.2-6.4 days, P = 0.0003), but this difference was abolished by G-CSF, and children, receiving G-CSF after the second intensification were more likely to restart maintenance chemotherapy on schedule (P = 0.05).


CONCLUSIONS
G-CSF reduces the hematological toxicity of intensification chemotherapy and may allow improved compliance with treatment scheduling.
Clarke
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V
Department of Paediatric Oncology and Haematology, Llandough Hospital, London, United Kingdom.
Dunstan
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FD
Webb
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DK
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control / Q000628:therapy*; D010349:Patient Compliance; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor