Changes of granulopoiesis during and after adjuvant chemotherapy of breast cancer.

Adjuvant chemotherapy allows a study of the effects of cytotoxic drugs on natural human haematopoiesis. We describe serial studies of granulopoiesis performed during and after intermittent adjuvant chemotherapy for breast cancer (adriamycin plus cyclophosphamide, given for six courses at monthly intervals). After drug administration, a sequential wave of depletion and regeneration through successive granulopoietic compartments was observed. With repeated chemotherapy, moderate neutropenia developed, and the blood CFU-C pool size became progressively reduced. After the sixth chemotherapeutic course, granulopoietic regeneration was delayed. Following discontinuation of chemotherapy, a long-lasting (greater than 200 d) reduction of the blood CFU-C pool size, together with neutropenia and reduction of marrow segmented neutrophils, was observed, suggesting a defect of granulopoiesis with persistent granulopoietic hypoplasia. In patients with expected long survival, residual bone marrow damage should be added to the list of potential late side effects of cytotoxic drug therapy.