High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer

PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.     

Tumor immunology

Malignant tumors express antigens that may stimulate and serve as targets for antitumor immunity. Virally induced tumors usually contain integrated proviral genomes in theircellulargenomes and often express viral genome-encoded proteins that may stimulate specific host immune responses. Antigens unique to individual tumors that stimulate specific rejection of transplanted tumors have been demonstrated only in experimental animals. Other tumor antigens that potentially can stimulate immune responses are shared by different tumors. These include products of mutated or rearranged oncogenes or tumor-suppressor genes. Tumors may also overexpress tissue differentiation antigens or embryonic antigens, which also have the potential to be recognized by the immune system. The recent identification of tumor antigens recognized by cytotoxic T cells opens up new possibilities for constructing chemically defined antigens for specific immunotherapy. Treatment of malignant tumors in humans by immunologic approaches, although theoretically attractive, has not yet succeeded on a large scale. Important progress in immunotherapy of cancer is emerging with several different treatment modalities.     

Effect of the attractive potential of the walls on the flow of a rarefied gas in a long thin plane channel

We consider the flow of a rarefied gas in the presence of attractive surface forces. It is shown that when the channel thickness is close to the range of the surface forces the gas flow is described by an equation which differs from the formula for free-molecular flow.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 58, No. 5, pp. 799-804, May, 1990.