EARLY LYMPHOPENIA AFTER CYTOTOXIC CHEMOTHERAPY AS A RISK FACTOR FOR FEBRILE NEUTROPENIA

Purpose: Febrile grade four (ie, less than or equal to 500/mu L) neutr openia (FN) is a frequent life-threatening complication of cancer chem otherapy. Although its incidence correlates to the dose of chemotherap y, FN may occur after almost any cytotoxic regimen. At present, there is no predictive method to identify patients who will experience FN. P atients and Methods: Univariate and multivariate analyses of risk fact ors for FN were performed on a retrospective cohort of 112 consecutive patients treated with various chemotherapy regimens. Two independent risk factors were identified by the logistic regression and used to cr eate a risk model for FN. The validity of the model was tested in thre e distinct groups of patients: two prospective groups of patients trea ted in two institutions (Centre Leon Berard [CLB] and Institut G. Rous sy [IGR]) and the group of patients with intermediate- or high-grade n on-Hodgkin's lymphoma (NHL) treated with the doxorubicin, cyclophospha mide, vindesine, bleomycin, and prednisone (ACVBP) regimen between 198 8 and 1992 at CLB. Results: Within the retrospective group, 23 of 47 ( 49%) patients with lymphocyte counts less than or equal to 700/mu L at day 5 after chemotherapy experienced FN compared with seven of 65 (11 %) of other patients (P=.00002). The type of chemotherapy (high dose v others) was also significantly correlated to FN (48% v 11%, P=.0003). Age, performance status, the number of previous chemotherapy cycles, o r polymorphonuclear leukocyte (PMN) counts, were not significantly cor related to the incidence of FN in univariate analyses. Two independent risk factors were identified in the logistic regression: day 5 lympho cyte counts (beta = 1.97 +/- 0.53) and the type of chemotherapy regime n (beta = 1.91 +/- 0.53). The calculated probability to experience FN in patients with none, one, and both of these risk factors was 4.3%, 2 4.0%, and 68.8%, respectively. The validity of this model was tested i n the three groups of patients used as validation samples. The observe d incidences of FN in the above defined risk subgroups were 3%, 19%, a nd 67%, respectively, within the CLB prospective series and 6%, 19%, a nd 75% within the IGR prospective series. In the ACVBP group, the inci dence of FN was 33% and 72%, respectively, in patients from the interm ediate- and high risk groups. In the two prospective groups and in the ACVBP series, the observed numbers of FN in the different risk groups did not differ significantly from those calculated by the model (P=.8 9, P=.86, and P=.72 for these three groups, respectively). Conclusion: Day 5 lymphocyte counts less than or equal to 700/mu L and the type o f chemotherapy regimen enable oncologists to define subgroups of patie nts treated with chemotherapy as those with a high intermediate, and l ow risk of FN. These criteria could be used to select subjects in whom prophylactic measures for FN, in particular hemotopoietic growth fact ors, should be proposed. (C) 1996 by American Society of Clinical Onco logy.