Lymphopenia associated with adjuvant anthracycline/taxane regimens

Abstract

Background: We observed 2 cases of Pneumocystis carinii pneumonia (PCP) occurring in HIV-negative patients during treatment with dose-dense chemotherapy with doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T). These represent the first case reports of PCP occurring during dose-dense chemotherapy for breast cancer. Because lymphocyte depletion is thought to predispose patients to PCP, we explored whether the shortened intervals between cycles during dose-dense chemotherapy might place patients at risk for lymphocyte depletion and thereby a potentially increased risk of opportunistic infection. Patients and Methods: Three cohorts of patients were analyzed. Cohort 1 involved 135 patients receiving dose-dense AC → T on a phase II study. Cohort 2 included 64 patients who received treatment with dose-dense AC → albumin-bound paclitaxel on a phase II clinical trial. Cohort 3 consisted of 59 patients who received AC → T given every 3 weeks who were identified from the Clinical Research Information System database at Dana-Farber Cancer Institute. For cohorts 1 and 3, the electronic medical record was reviewed to determine absolute lymphocyte counts (ALCs) and absolute neutrophil counts (ANCs) for day 1 of each of the 8 cycles of treatment. For cohort 2, data was prospectively collected and entered into an electronic database. The lowest ALC obtained by each patient on day 1 of any cycle was termed the nadir. Results: Patients experienced grade 3 (ALC < 500 cells/mm3) or grade 4 (ALC < 200 cells/mm3) lymphopenia in all 3 cohorts: 63% with dose-dense AC → T, 23.4% in dosedense AC → albumin-bound paclitaxel, and 69% with dose-dense AC → T every 3 weeks. Patients experienced their lowest median ALC count at cycle 5 of treatment in all 3 cohorts, with a median nadir of 400 cells/mm3 in cohort 1,690 cells/mm3 in cohort 2, and 400 cells/mm3 in cohort 3. Conclusion: The majority of patients receiving AC → T every 2 or 3 weeks experience grade 3/4 lymphopenia. Median lymphocyte counts appear to be lowest around cycle 5, the point at which we observed 2 cases of PCP. Lymphocyte counts appear to be reaching a low enough level to place patients at risk for opportunistic infection during treatment with dosedense AC → T and with AC → T given every 3 weeks.