According to this longitudinal study, which includes pretransplant data, data from in-hospital transplantation, and posttransplant data, (1) psychosocial vulnerability of these BMT recipients was greatest during hospitalization before the transplant, (2) perceived personal control may be a potential indicator of vulnerability to secondary psychosocial morbidity, and (3) the demonstrated significance of psychosocial well-being before BMT indicates the importance of obtaining prospective data for both research and clinical purposes.
Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and B M from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 X I O 5 mononuclear cells. lmmunostained tumor cells were detected in 9.8% (1 3/133) PBSC specimens from 9/48 (1 8.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < ,005). IGH-DOSE chemotherapy followed by autologousH marrow infusion appears to be an effective treatment for some patients with locally advanced or metastatic breast cancer.I4 However, using sensitive immunocytochemical techniques, tumor cells can be observed in histologically normal bone marrow (BM) in 20% to 45% of patients with operable disease and in 20% to 70% of patients with metastatic breast cancer.'-* As a result, many patients who have multiple bone or BM metastases have not been considered eligible for autologous BM transplantation (BMT).Recently, peripheral blood stem collections (PBSC) have been used as an alternative to BM for hematopoietic support in patients with breast cancer or hematologic malignancies who have BM Several studies examining patients with neuroblastoma and lymphoma"-I3 suggest that PBSC collections are less likely to contain tumor cells than BM and thus may provide a less contaminated source of hematopoietic stem cell support after high-dose chemotherapy.The incidence and quantity of tumor cell contamination of PBSC collections in breast cancer patients has not been widely inve~tigated.'~,'' We prospectively examined the incidence of tumor cell contamination in paired samples of PBSC and BM collections from 48 advanced-stage breast cancer patients using a highly sensitive immunocytochemical technique. To determine whether these tumor cells were capable of clonogenic growth in vitro, tumor cell-specific clonogenic assays were performed on 58 BM or PBSC collections. MATERIALS AND METHODS Patient population andparticipating centers.Patients with histologically documented locally advanced or metastatic adenocarcinoma of the breast who were enrolled on high-dose chemotherapy programs at the participating treating institutions were eligible for this study. This protocol was approved by the Institutional Review Board for Human Investigation and each patient gave written in-The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/1 O5 mononuclear cells (range 0.33 to 2.0/105) compared with 22.9/105 mononuclear cells in BM (range 1 to 3,000/105, P < .0001). In culture experiments, clonogenic tumor colonies grew in 21 /26 immunocytochemically po...
Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.
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