Granulocyte colony-stimulating factor ameliorates toxicity of intensification chemotherapy for acute lymphoblastic leukemia

Background. intensification chemotherapy improves the prognosis for childre n with acute lymphoblastic leukemia (ALL), but results in considerable morb idity, primarily due to myelosuppression with resultant neutropenia. Recomb inant granulocyte colony-stimulating factor (G-CSF) shortens neutropenia fo llowing intensive chemotherapy, but potential benefits in the therapy of AL L remain inadequately explored. Accordingly, a randomized, crossover study was undertaken to clarify this issue. Procedure. Seventeen children with ac ute lymphoblastic leukemia or T-cell non-Hodgkin lymphoma and treated on st andard protocols were randomized to receive C-CSF following either the firs t or second intensification blocks of chemotherapy. G-CSF was administered as a single daily subcutaneous injection of 5 mcg/kg from day 9 following t he start of intensification therapy, and continued until the neutrophil cou nt exceeded 0.5 x 10(9)/l for 3 days. Study endpoints were days of neutrope nia (neutrophils <1 x 10(9)/l) and severe neutropenia (neutrophils <0.5 x 1 0(9)/l), days in hospital, days of fever, and days on antibiotics. Results. There were significant reductions in the duration of neutropenia (95% conf idence 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 in terval 0.9-6.3 days, P = 0.01) for children receiving G-CSF. Overall, the d uration of neutropenia was longer following the second block (95% confidenc e interval 2.2-6.4 days, P = 0.0003) bur this difference was abolished by C -CSF, and children receiving G-CSF after the second intensification were mo re likely to restart maintenance chemotherapy on schedule (P = 0.05). Concl usions, G-CSF reduces the hematological toxicity of intensification chemoth erapy and may allow improved compliance with treatment scheduling. Med. Ped iatr. Oncol. 32:331-335, 1999. (C) 1999 Wiley-Liss, Inc.