Human Granulocyte Colony-Stimulating Factor after Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia
Ching-Hon Pui, M.D., James M. Boyett, Ph.D., Walter T. Hughes, M.D., Gaston K. Rivera, M.D., Michael L. Hancock, M.S., John T. Sandlund, M.D., Timothy Synold, Pharm.D., Mary V. Relling, Pharm.D., Raul C. Ribeiro, M.D., William M. Crist, M.D., and William E. Evans, Pharm.D.
Background Recombinant human granulocyte colony-stimulatingfactor (G-CSF, or filgrastim) hastens the recovery from neutropeniaafter intensive chemotherapy, but its role in the managementof childhood leukemia is unclear.
Methods We randomly assigned 164 patients with acute lymphoblasticleukemia (age range, 2 months to 17 years) to receive placeboor G-CSF (10 µg per kilogram of body weight per day subcutaneously),beginning one day after the completion of remission-inductiontherapy and continuing until the neutrophil count was greaterthan or equal to 1000 per cubic millimeter for two days. Theclinical and laboratory effects of this therapy were documentedfor 21 days. The area under the plasma G-CSF concentration–timecurve was measured on days 1 and 7 in both groups.
Results Responses to the growth factor could be assessed in148 patients (73 in the G-CSF group and 75 in the placebo group).G-CSF treatment did not significantly lower the rate of hospitalizationfor febrile neutropenia (58 percent in the G-CSF group vs. 68percent in the placebo group; relative risk, 0.85; 95 percentconfidence interval, 0.59 to 1.16), increase the likelihoodof event-free survival at three years (83 percent in both groups),or decrease the number of severe infections (five in the G-CSFgroup vs. six in the placebo group). Patients treated with G-CSFhad shorter median hospital stays (6 days vs. 10 days, P = 0.011)and fewer documented infections (12 vs. 27, P = 0.009). Themedian total costs of supportive care were similar in the G-CSFand placebo groups ($8,768 and $8,616, respectively). Amongpatients who did not have febrile neutropenia during the firstweek of G-CSF or placebo injections, higher systemic exposureto the growth factor on day 7 was significantly related to alower probability of subsequent hospitalization (P = 0.049).
Conclusions G-CSF treatment had some clinical benefit in childrenwho received induction chemotherapy for acute lymphoblasticleukemia, but it did not reduce the rate of hospitalizationfor febrile neutropenia, prolong survival, or reduce the costof supportive care.
Source Information
From St. Jude Children's Research Hospital (C.-H.P., J.M.B., W.T.H., G.K.R., M.L.H., J.T.S., T.S., M.V.R., R.C.R., W.M.C., W.E.E.) and the University of Tennessee, Memphis, Colleges of Medicine (C.-H.P., J.M.B., W.T.H., G.K.R., J.T.S., R.C.R., W.M.C., W.E.E.) and Pharmacy (M.V.R., W.E.E.) — all in Memphis.
Address reprint requests to Dr. Pui at St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-0318.
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