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Chemotherapy used to treat lymphoma can cause severe neutropenia. Risk models have identified factors that predict neutropenia across all chemotherapy cycles. We used clinical information obtained during pretreatment evaluation to develop a predictive model for severe neutropenia in the first cycle of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This case series study included lymphoma patients receiving CHOP chemotherapy with or without rituximab who did not receive pre-emptive hematopoietic growth factor. Risk factors for neutropenia were identified from previously published models and included age ≥65 years, hypoalbuminemia, renal/cardiovascular disease, anemia, abnormal bone marrow and increased lactate dehydrogenase (LDH). A composite score equal to the number of pretreatment risk factors was used to predict severe neutropenia in cycle 1. Fifty-three percent of patients (47 of 89) had severe neutropenia, with 70% of first episodes occurring during cycle 1. Eighty-two percent of first-cycle, severe neutropenia events occurred in patients ≥65-years-old. In univariate analysis, age ≥65 years and increased baseline LDH were significantly associated with increased risk for severe neutropenia in cycle 1. In logistic regression modeling, the probability of severe neutropenia in cycle 1 increased as the number of pretreatment risk factors increased, with a one-unit increase in risk score resulting in a 2.3-fold increase in severe neutropenia. The study results suggest that data obtained before initiating CHOP-based chemotherapy can be used to identify those patients who are at risk for severe neutropenia in cycle 1. If validated, our model could be used to identify patients who would benefit from early use of growth factors. [ABSTRACT FROM AUTHOR]