Severe neutropenia in cycle one of CHOP is a marker of early death among intermediate and high grade lymphoma (IHL) patients

Abstract

6717 Background: Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy is effective therapy for IHL. However, it may produce severe neutropenia in cycle 1 (C1SN), which can lead to dose modifications and early termination of therapy. We recently developed a predictive model for C1SN, using clinical information routinely obtained before chemotherapy initiation (ASH 2003). In the current study, we assessed the relationship between C1SN and 6-month survival. Methods: Medical records of IHL (Working Formulation D-H) patients (pts) treated at a single institution between 1981 and 2002 were retrospectively reviewed. 187 pts treated with CHOP who did not receive preemptive growth factor in cycle 1 were selected. SN was defined as absolute neutrophil count ≤250/mm3 or febrile neutropenia. Early death was defined as death within 6 months of chemotherapy initiation. Stepwise logistic regression analysis was used to select risk factors significantly associated with early death. Results: 55 pts (29.4%) experienced C1SN. 15 pts (8.0%) had early death, of which 11 (73.3%) had C1SN. Causes of death were lymphoma (7), sepsis (4), chemotherapy toxicity (3), and other (1). C1SN increased the observed risk of early death in pts with good and poor performance status (PS) 8.9-fold and 7.5-fold, respectively (p=0.89). Risk factors associated with early death in univariate analysis included C1SN, poor PS, decreased serum albumin and elevated LDH. In multivariate analysis, C1SN (OR 8.3; 95% CI 2.4–28.5) and poor PS (OR 5.3; 95% CI 1.6–17.4) showed significant association with early death (c-statistic 0.81). For pts with C1SN the predicted probability of early death was 0.46 and 0.14 in pts with poor and good PS, respectively. For pts without C1SN the predicted probability of early death was 0.09 and 0.02 in pts with poor and good PS, respectively. Conclusions: SN in cycle 1 of CHOP chemotherapy may serve as an early warning sign for increased risk of premature death. Pts with C1SN appear to have significantly greater risk of early death regardless of baseline PS. The biological significance of this observation needs to be explored. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc. Amegn, Inc. Amgen, Inc.