Summary:initially reported by Stiff et al 1 in 1983. Makino et al 2 modified this method and evaluated its clinical use for peripheral blood stem cell transplantation (PBSCT) in 1991. A simplified method for cryopreservation at −80؇C of peripheral blood stem cells (PBSC) has been increasThey reported that rates of CFU-GM remained at more than 70% during 18 months of cryopreservation and that rapid ingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl and sustained trilineage engraftment was obtained in 10 patients who received marrow-ablative chemotherapy and starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has sevautotransplantation of PBSC cryopreserved by this method. While this simplified method has several advantages eral advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is such as being a quick and inexpensive procedure and less clumping of the thawed cells compared with the convenknown about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitional method using rate-controlled freezing with 10% DMSO and storage in liquid nitrogen, 2 little is known about tors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplithe influence of long-term cryopreservation for years and of the thawing process on frozen-thawed hematopoietic fied method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure stem cells. In order to assess the clinical efficacy of this simplified for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37؇C. In our study, we found method, we investigated effects of long-term cryopreservation (1-5 years), exposure of frozen-thawed cells to that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; DMSO, and slow thawing at room temperature on hematopoietic activity of PBSC when they were cryopreserved by they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after this method. rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between Materials and methods thawing at 37؇C and 20؇C. These observations indicate that PBSC cryopreserved for at least 5 years by the simPreparation of peripheral blood mononuclear cells plified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic Peripheral blood mononuclear cells (PBMNC) were collected by apheresis from patients with hematologic maligactivity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when nancies in remission during hematologic recovery from consolidation chemotherapy with or without G-CSF. Aph-PBSC are thawed gradually at room temperature.
Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age p75 years, and adequate organ function were eligible. Both docetaxel and cisplatin were given on days 1, 8, 29, and 36. Doses of docetaxel/cisplatin (mg m À2 ) in the phase I study portion were escalated as follows: 20/30, 25/30, 30/30, 30/35, 30/40, 35/40, 40/40, and 45/40. Beginning on day 1 of chemotherapy, thoracic radiotherapy was given at a total dose of 60 Gy with 2 Gy per fraction over 6 weeks. In the phase I portion, the maximum tolerated doses (MTD) among 33 patients were docetaxel 45 mg m À2 and cisplatin 40 mg m À2 . The major doselimiting toxicity (DLT) was radiation oesophagitis. The recommended doses (RDs) for the phase II study were docetaxel 40 mg m À2and cisplatin 40 mg m À2 . A total of 42 patients were entered in the phase II portion. Common toxicities were leukopenia, granulocytopenia, anaemia, and radiation oesophagitis, with frequencies of grade X3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66 -91%). The median survival time was 23.4 þ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.
BACKGROUNDParathyroid hormone‐related protein (PTH‐rP) is a major cause of tumor‐induced hypercalcemia (TIH) and frequently is found to be elevated in serum of patients with TIH. In the current study, the authors examined the usefulness of PTH‐rP measurement at the time of first presentation in the follow‐up of lung carcinoma patients with TIH.METHODSThe authors retrospectively studied 23 of 1149 lung carcinoma patients who were found to have TIH at the time of first presentation for the correlation between serum PTH‐rP and the development of bone metastases and survival compared with lung carcinoma patients without TIH who were matched by gender, age, Eastern Cooperative Oncology Group performance status, histological type of tumor, and stage of the disease.RESULTSTwenty‐three lung carcinoma patients with TIH demonstrated significantly increased serum levels of PTH‐rP (mean ± standard error [SE], 84.1 ± 16.5 pmol/L) compared with control patients without TIH (mean ± SE, 36.2 ± 2.0 pmol/L) at the time of first presentation, (P < 0.001). In these hypercalcemic patients, patients whose serum PTH‐rP was > 150 pmol/L (n = 16) were found to have a significantly increased rate of bone metastases (71.4% vs. 12.5%; P = 0.01) and decreased survival (median survival of 1.4 months vs. 5.4 months; P < 0.015) compared with patients whose serum PTH‐rP was < 150 pmol/L (n = 7).CONCULUSIONSThe data from the current study suggest that serum PTH‐rP as determined at the time of first presentation is a useful indicator of not only hypercalcemia but also bone metastasis and eventual survival in patients with lung carcinoma. Cancer 2002;95:1706–13. © 2002 American Cancer Society.DOI 10.1002/cncr.10828
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