Correspondence

Granulocyte Colony-Stimulating Factor in Afebrile Patients with Neutropenia

N Engl J Med 1997; 337:1319-1320October 30, 1997

Article

To the Editor:

Hartmann et al. (June 19 issue)1 apparently assumed that a neutrophil count of zero per cubic millimeter has the same implications as a count of 499 per cubic millimeter, an assumption we all know is not correct. Failing to stratify according to the degree of neutropenia at the time of randomization fails to acknowledge this point. Furthermore, we are not told how many patients who were potentially eligible for this study refused to undergo randomization or how many were rejected for the study by their physicians because of extremely severe neutropenia. Since ethical considerations can skew the population of patients enrolled in randomized studies in favor of less seriously ill patients, it is possible that this study did not include a large proportion of patients with neutrophil counts below 100 per cubic millimeter. Even if it did, we are not told how many of them were treated in each group. Finally, there was no attempt to analyze whether granulocyte colony-stimulating factor (G-CSF) was of any advantage in patients with extremely severe neutropenia.

Fernando Cabanillas, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

1 References

1. 1

   Hartmann LC, Tschetter LK, Habermann TM, et al. Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia. N Engl J Med 1997;336:1776-1780
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We compared G-CSF with placebo in a group of 138 afebrile patients with absolute neutrophil counts of 500 or less per cubic millimeter. Dr. Cabanillas questions the severity of the neutropenia in our study population. The distribution of absolute neutrophil counts among our patients at entry into the study was as follows: 19 percent had counts of 0 to 99 per cubic millimeter, 26 percent had counts of 100 to 199 per cubic millimeter, 15 percent had counts of 200 to 299 per cubic millimeter, 25 percent had counts of 300 to 399 per cubic millimeter, and 15 percent had counts of 400 to 500 per cubic millimeter. Among the patients in the lowest quintile (absolute neutrophil count, <100 per cubic millimeter), 15 received G-CSF and 11 received placebo (P = 0.5).

We are not aware of a randomized study of a colony-stimulating factor used therapeutically for post-chemotherapy neutropenia that has stratified for the absolute neutrophil count at base line, nor have subgroup analyses of these studies demonstrated an effect of the base-line count on the length of hospitalization.1 We did not perform or report subgroup analyses according to base-line absolute neutrophil counts, because our study was not designed to do so.

Dr. Cabanillas hypothesizes that physicians are less likely to enroll seriously affected patients in randomized trials. The degree of neutropenia in the majority of patients enrolled in our study does not support that hypothesis. Moreover, his premise assumes that G-CSF will positively affect clinical outcomes when used in the treatment of established neutropenia. Such efficacy has not been demonstrated in the randomized trials of the agent used therapeutically — namely, in studies of febrile neutropenia.1,2

Dr. Cabanillas would also like to know how many patients who were potentially eligible for the study refused to undergo randomization and how many were rejected for study entry by their physicians because of extremely severe neutropenia. Although we agree that such information would be ideal for every reported randomized, controlled trial, to place results in their proper context, such information is not routinely obtained for clinical trials and was not recorded in this study.

Lynn C. Hartmann, M.D.
Vera J. Suman, Ph.D.
Mayo Clinic, Rochester, MN 55905

for the North Central Cancer Treatment Group

2 References

1. 1

   American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 1994;12:2471-2508
   Web of Science | Medline

2. 2

   American Society of Clinical Oncology. Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based clinical practice guidelines. J Clin Oncol 1996;14:1957-1960
   Web of Science | Medline