High-dose consolidation with CPA/cDDP/BCNU and ABMS after standard-dose CAF results in a decreased frequency of relapse in patients with high-risk primary breast cancer compared with historical series at the median follow-up of 2.5 years. Evaluation in a prospective, randomized trial is warranted and currently underway.
A significant percentage of women with primary breast cancer have micrometastatic disease in the bone marrow. Bone marrow involvement may be an adverse prognostic factor, and more aggressive therapy may be indicated for these patients. There are a number of different techniques and antibodies used to detect tumor cells in the bone marrow. We used the same panels of four antibreast cancer antibodies and compared three immunodetection techniques: two-color immunofluorescence, immunohistochemical staining, and fluorescence-activated cell sorting with cytologic examination of the sorted cells. The two-color immunofluorescence technique was superior and consistently detected one tumor cell contaminating one million normal bone marrow cells and had no reactivity with normal bone marrow.
The use of hematopoietic support for patients receiving high-dose chemotherapy has increased over the past 10 years. Various quality controls are performed on the hematopoietic cells, including microbiologic cultures. There is considerable expense associated with the serial cultures performed at different times during the collection, processing, and use of the cells. We reviewed all the microbiologic cultures performed on bone marrow harvests and leukaphereses over a 17 month period. Of the 227 bone marrow harvests, 16 cultures were positive, but only 3 (1.3%) were repeat positives with the same organism after processing or at the time of reinfusion. Of the 560 leukaphereses, 4 (0.7%) were cultured positive at the time of collection and reinfusion. Two patients were bacteremic with gram-negative bacilli at the time of leukaphereses despite being asymptomatic, and these were the only two products that had to be collected again. No patient suffered an adverse clinical result after receiving culture-positive cells. Bone marrow and peripheral blood progenitor cells can be safely collected, and a culture after processing is adequate to ensure the safety of the product.
Immunization with ex vivo-generated, tumor antigen-loaded dendritic cells (DC) has been proposed as a strategy for reducing relapses following high-dose chemotherapy, but the ideal time and method for obtaining DC progenitors are unknown. We determined the percentage yield, phenotype, and function of DC generated over 7 days in GM-CSF and IL-4-supplemented, serum-free medium from PBMC obtained from breast cancer and lymphoma patients at the time of their initial presentation for transplant, cytokine or chemotherapy plus cytokine-mobilized leukapheresis, and following granulocyte recovery from high-dose chemotherapy. The median yield of large dendritic-like cells as a percentage of the starting number of PBMC was similar for all the mobilization strategies (11.6%-13.8%) studied and at all time points (9.9%-12.7%), except the yield was lower from the pretherapy, unmobilized peripheral blood (6.3%). The phenotype of the generated cells was similar for the various mobilization procedures, and there were no differences in allostimulatory function of the DC from any of the groups. We conclude that functional DC may be generated equally well from mobilized PBPC and PBPC obtained after high-dose chemotherapy.
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