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Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE STn-KLH cancer vaccine.

The purpose of this study was to evaluate the toxicity and potential efficacy of administering the THERATOPE STn-KLH cancer vaccine to ovarian and breast cancer patients after an autologous stem cell transplant. Forty patients (11 high-risk stage II/III breast cancer, 22 stage IV breast cancer, and seven stage III/IV ovarian cancer patients) were treated with high-dose chemotherapy followed by autologous/syngeneic stem cell rescue and vaccination with THERATOPE STn-KLH (Sialyl-Tn-KLH with Detox-B Stable Emulsion). Each patient was scheduled to receive a total of five vaccinations beginning on days 30-151 after stem cell infusion. The vaccine was well tolerated. Induration and erythema at the site of injection were the most common side-effects. When one compares the outcome of patients vaccinated with 66 breast and ovarian cancer patients who were not, following risk-adjustment analysis, vaccinated patients appeared more likely to survive (P = 0.07) and less likely to relapse (P = 0. 10). Vaccinated patients with the greatest specific lytic activity against STn+OVCAR tumor cells relative to nonspecific killing of Daudi cells tended to remain in remission longer than patients who displayed less specific immune activity (P = 0.057). We conclude that the THERATOPE STn-KLH cancer vaccine is well tolerated in breast and ovarian cancer patients after autologous transplant and, while not statistically significant, the trends in data support the concept that THERATOPE vaccine may decrease the risk for relapse and death and thus warrants further study. Bone Marrow Transplantation (2000) 25, 1233-1241.

Adult↗

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques.

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 BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.

Adult↗

[High-dose chemotherapy with autologous bone marrow transplantation or peripheral blood stem cell transplantation--testicular cancer].

Through advances in chemotherapy with the appearance of the drug cisplatin, testicular cancer treatment has improved dramatically. Consequently, testicular cancer has become one of the group of tumors that can be completely cured. Even in advanced testicular cancer, a curative rate of approximately 70% is obtainable from first-line chemotherapy, commonly by BEP combination. The problem, however, is treatment of the remaining 30% of the patients who fail to respond to first-line chemotherapy or who relapse shortly after first-line chemotherapy. Supportive therapy strengthens the chemotherapy of testicular cancer, for example, high-dose chemotherapy with carboplatin and etoposide with autologus bone marrow rescue, either by autologus bone marrow transplantation or peripheral blood stem cell transplantation, which can cure 15% to 20% of patients whose disease has progressed during prior chemotherapy combined with cisplatin. Though more cases of relapse were observed with high-dose chemotherapy compared to first-line chemotherapy, and the long-term prognosis is unknown, we should evaluate the usefulness of high-dose chemotherapy as an initial treatment for testicular cancer patients with poor prognoses.

Antineoplastic Combined Chemotherapy Protocols↗

Neural stem cells as novel cancer therapeutic vehicles.

The startling resemblance of many of the behaviours of brain tumours to the intrinsic properties of the neural stem/progenitor cell has triggered a recent dual interest in arming stem cells to track and help eradicate tumours and in viewing stem cell biology as somehow integral to the emergence and/or propagation of the neoplasm itself. These aspects are reviewed and discussed here.

Brain Neoplasms↗

Much ado about not...enough data: high-dose chemotherapy with autologous stem cell rescue for breast cancer.

High-dose chemotherapy with autologous bone marrow or stem cell rescue (HDC/ASCR) has been proposed as a promising treatment strategy for breast cancer. Despite the frequency with which this procedure is performed, the role of HDC/ASCR in the treatment of breast cancer remains undefined. The purpose of this review is to examine the rationale for the procedure, the research progress to date, and the limitations of available data. A literature search of Medline from January 1966 through May 1997, CancerLit from January 1983 through May 1997, and Current Contents through May 1997 identified more than 600 English language papers or abstracts on this topic. Our review focuses on the preclinical and clinical data that explore the concept of chemotherapy dose intensity and the role of dose intensity in treating breast cancer. HDC/ASCR is based on the hypothesis that high-dose chemotherapy will overcome drug resistance, eradicate metastatic disease, and increase the proportion of women with breast cancer who are "cured." To date, results from only one phase 3 trial of HDC/ASCR compared with more conventional therapy have been published. Phase 2 and some phase 3 data on HDC/ASCR in the treatment of high-risk primary breast cancer and metastatic breast cancer are discussed. However, the results are inconclusive. The completion of national and international randomized trials is urgently needed to establish definitively the role of HDC/ASCR in the treatment of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[A guide for the timing of peripheral blood stem cell harvest in patients with lung cancer].

Harvest of peripheral blood stem cells (PBSC) was performed 57 times in 17 lung cancer patients after standard-dose chemotherapy (cisplatin, etoposide) supplemented with granulocyte-colony stimulating factor (G-CSF). In every case, more than 1.5 x 10(6)/kg CD 34+ cells were collected by 2-5 apheresis. Statistical significance was noted between peripheral leukocyte counts (WBC) and collected CD 34+ cell counts (p = 0.0298), between peripheral platelet counts and collected CD 34+ cell counts (p = 0.0009), and between the peripheral immature granulocyte ratio and collected CD 34+ cell counts (p < 0.0001). Because of the remarkable relationship between collected CD 34+ cell counts and peripheral WBC counts, peripheral platelet counts and the peripheral immature granulocyte ratio, these parameters were useful for determining the correct timing of PBSC harvest.

Adult↗

Mobilization of dendritic cells from patients with breast cancer into peripheral blood stem cell leukapheresis samples using Flt-3-Ligand and G-CSF or GM-CSF.

Treatment with myeloablative chemotherapy and autologous peripheral blood stem cell (PBSC) transplantation followed by vaccination with autologous dendritic cells (DCs) treated with tumor antigens is a promising therapeutic strategy for several types of cancer. Obtaining sufficient numbers of both PBSCs and DCs is central to this approach. Previously, it has been shown that administration of Flt-3-Ligand (FL) combined with either G-CSF or GM-CSF mobilizes large numbers of PBSCs in patients with cancer. In the current study, we sought to determine whether these same cytokines could simultaneously mobilize DCs into the PBSC leukapheresis collection. DCs were analysed in PBSC leukapheresis samples obtained from five patients with high-risk breast cancer who received G-CSF alone as priming prior to leukapheresis, four patients who received FL+G-CSF and five patients who received FL+GM-CSF. DCs were defined as cells with a lin(dim/-) HLA-DR+ CD11c+ phenotype. The proportions of DCs in the FL+G-CSF and FL+GM-CSF samples were significantly higher than in pre-mobilization peripheral blood and G-CSF leukapheresis samples. The mean yield of DCs/kg in the FL+GM-CSF samples was also significantly higher than the mean yield of DCs in the G-CSF samples. The FL+G-CSF and FL+GM-CSF mobilized DCs were immature by morphologic and phenotypic criteria but stimulated allogeneic T-cells at levels similar to DCs generated in culture from PBMCs. Overnight culture?of the immature DCs obtained from patients receiving either FL+G-CSF or FL+GM-CSF in TNF-alpha?resulted in the generation of mature DCs. In summary, administration of FL in combination with GM-CSF and G-CSF to patients with breast cancer can mobilize large numbers of immature DCs into PBSC leukapheresis collections.

Antibodies, Monoclonal↗

Bayesian optimal design in population models for haematologic data.

We introduce a population model to design optimal apheresis schedules to collect blood stem cells from cancer patients. Blood stem cells are collected prior to the patient undergoing high-dose chemoradiotherapy and are returned after this treatment to enable reconstitution of the white blood cell components. Maximizing the number of cells collected in as few apheresis as possible is desirable. We use a longitudinal data model with random effects to describe profiles of individual patients. A hierarchical prior model introduces common mean profiles for patients undergoing different treatments. We find the optimal apheresis schedule for a new patient by minimizing an expected loss over the posterior predictive distribution of the patient's predicted CD34 profile. We implement estimation of the model and solution of the optimal design problem by a simulation approach, which allows us to accommodate arbitrary shapes for the profiles and realistic loss functions that include relative penalties for the number of scheduled stem cell collections and for collecting fewer than a specified target quantity of total collected stem cells.

Antigens, CD34↗