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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 >or=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 >or=65-years-old. In univariate analysis, age >or=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.

We sought to identify risk factors associated with the time to febrile neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who were receiving treatment with CHOP chemotherapy. Data were collected from 12 community and academic oncology practices participating in the Oncology Practice Pattern Study between 1991 and 1999. We reviewed the medical records of 577 intermediate-grade NHL patients who received initial CHOP chemotherapy and evaluated risk factors associated with time to first febrile neutropenic event. A febrile neutropenic event was defined as a body temperature of > 100.6 degrees F and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile neutropenic events. The risk of febrile neutropenia was significantly associated with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony-stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events occurred by day 14 of cycle 1 in one-half of patients experiencing febrile neutropenia. In multivariate analysis, the risk of febrile neutropenia remained significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32), renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54, 95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00), > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of patients at greatest risk of febrile neutropenia and, therefore, candidates for the selective prophylactic use of the hematopoietic growth factors.

Background: Severe neutropenia, a common consequence of chemotherapy, may result in infectious complications and hospitalizations. Preventive treatment with colony-stimulating factors is limited because of the inability to predict which patients will develop neutropenic complications. To the authors' knowledge, the current study is the first large prospective validation of a risk model in patients with early-stage breast carcinoma., Methods: Patients with Stage I-III breast carcinoma who were receiving adjuvant chemotherapy (n=624) were assigned to risk groups based on first-cycle absolute neutrophil count (ANC) nadirs of <0.5 x 10(9)/L. Filgrastim (a recombinant human granulocyte-colony-stimulating factor) was administered from Cycle 2 onward to high-risk patients. Dose intensity and rates of neutropenic complications, including febrile neutropenia and hospitalization resulting from it, were calculated for each group and compared. High-risk patients were matched by chemotherapy regimen, stage of disease, age, and baseline ANC to historic-control patients and outcomes were compared within the matched pairs., Results: Both risk groups were found to have a similar proportion of patients receiving >85% of the dose intensity (95.8% vs. 94.4%). The rate of febrile neutropenia and hospitalization in the low-risk group (n=264) was 2.6% (95% confidence interval [95% CI], 0.7-4.5%) and 0.8 (95% CI, -0.3-1.9%), respectively. The high-risk group was 2.6 times more likely to receive a full dose of chemotherapy, but no higher risk of neutropenic complications was reported compared with the matched controls., Conclusions: The risk-related prophylactic administration of filgrastim facilitated the delivery of planned chemotherapy to the high-risk group of patients. However, further research is needed to confirm the results obtained in the current study in a randomized trial, if feasible, and in other chemotherapy and disease settings., (Copyright 2003 American Cancer Society.)

Background: Filgrastim prophylaxis lessens the occurrence of febrile neutropenia in patients with non-Hodgkin.s lymphoma (NHL) treated with chemotherapy, but differences in days of therapy and mode (primary or secondary) of prophylaxis may affect clinical outcomes., Objective: To describe the patterns of use of filgrastim prophylaxis, especially days of therapy and mode, and the possible associated incidence of febrile neutropenia in patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy., Methods: Using medical records from the Oncology Practice Pattern Study in patients treated between 1991 and 1999 at 12 sites in the United States, we studied patients with intermediate-grade NHL treated with first-line CHOP chemotherapy and prophylactic filgrastim. The number of days of prophylactic filgrastim use, mode of prophylaxis, and incidence of febrile neutropenia were evaluated. The cycles were stratified into 2 groups based on days of filgrastim prophylaxis (<7 days [Group 1] and > or = 7 days [Group 2])., Results: One hundred seventy patients were treated with 652 cycles of CHOP chemotherapy with filgrastim prophylaxis. The mean days of filgrastim prophylaxis was 9.5 days (95% confidence interval [CI], 9.3-9.7 days) across all cycles, 4.7 days (95% CI, 4.5-5.0 days) across Group 1 cycles (n=73), and 10.1 days (95% CI, 9.9-10.3 days) across Group 2 cycles (n=579). Thirty-seven percent of patients were treated with primary prophylaxis; 94% of these patients. cycles were Group 2 cycles. The incidence of febrile neutropenia was 3.6% and 7.7% across cycles in patients receiving primary versus secondary prophylaxis, respectively. In patients treated with secondary prophylaxis, the incidence was 16.7% and 6.1% in Group 1 and Group 2 cycles, respectively. Multiple logistic regression modeling indicated that a lower risk of febrile neutropenia was associated with primary prophylaxis (mainly Group 2) (odds ratio [OR] 0.3; 95% CI, 0.1-0.6) and secondary prophylaxis in Group 2 (OR 0.4; 95% CI, 0.2-0.8), and lower body surface area was associated with a greater risk of febrile neutropenia (OR 1.8; 95% CI, 1.1-3.0)., Conclusion: Primary prophylaxis with filgrastim (mainly Group 2) and secondary prophylaxis in Group 2 (mean 10.1 days) may be associated with a lower incidence of febrile neutropenia than secondary prophylaxis in Group 1.

Background: The nadir value of the absolute neutrophil count (ANC) in the first cycle of chemotherapy is an effective predictor of subsequent neutropenic events. This study was designed to validate an earlier published study based on a retrospective data analysis from a prospective randomized clinical trial., Methods: The original published model was applied to a trial of 143 patients to cross-validate the model. We also tested the specification of the model on our data by using a logistic regression model with several variables, including first-cycle nadir ANC, age, menopausal status, hormone-receptor status, previous radiotherapy, and first-cycle decrease in hemoglobin concentration. Patients received fluorouracil, doxorubicin, and cyclophosphamide every 21 or 28 days for six cycles without hematopoietic support from colony-stimulating factor., Results: In the cross-validation analysis, the original model successfully classified patients by risk of neutropenic events (C = 0.78). When the model specification was tested, first-cycle nadir ANC was the sole significant (P < 0.0001) predictor of neutropenic events and the model had a good predictive power (C = 0.78). The estimated relative risk of 4.8 did not differ from the risk cited in the original model (P = 0.91). A significantly higher percentage of our patients with a low first-cycle nadir ANC of 0.25 x 10(9)/liter or less experienced febrile neutropenia (30% versus 10%, P = 0.04) and received at least 85% of the planned dose intensity (55% versus 32%, P = 0.05)., Conclusions: The original risk model used to predict neutropenic events was validated by our study. This information can be used to target high-risk patients for prophylactic treatment with filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) in chemotherapy cycles 2 to 6.

Background: In intermediate-grade non-Hodgkin's lymphoma (NHL) patients, full-dose CHOP improves survival but increases myelosuppression, causing febrile neutropenia hospitalization (FNH) in 28% of patients 65 years of age or greater. Several risk factors for FNH are known, but their relationship to length of stay (LOS), an indicator of the total burden of FNH, is unclear., Methods: We conducted a study to identify factors associated with the incidence, recurrence, and duration of hospitalizations for FN and to describe the frequency of administration of colony-stimulating factor (CSF) as primary and secondary prophylaxis and its association with repeated hospitalization episodes., Results: Compared with patients who did not experience hospitalizations for FN, those who did were significantly older, had more comorbid conditions, were planned for standard dose intensity, and received CSF less often during the first 5 days of cycle 1 (early CSF). Overall, 73% of these hospitalizations occurred within the first 2 cycles of chemotherapy, with 56% occurring within the first cycle. Patients age > or = 65 years accounted for 66% of cycle 1 FNH. Patients receiving early CSF were less likely to experience repeated hospitalizations (0% vs 12%; P<.05). Multiple regression analysis of those hospitalized found a 3.9-day longer LOS for patients age > or = 65 years and a 5.13-day longer LOS for those not receiving early CSF., Conclusions: Older NHL patients have a higher risk of hospitalization for FN and longer LOS. The majority of hospitalization days occur in the first 2 cycles of chemotherapy. Early CSF use is associated with decreased risk of repeated hospitalizations and shorter total LOS. Secondary CSF use is also associated with reduced risk of repeated FNH.