Transplantation of enriched and purged peripheral blood progenitor cells from a single apheresis product in patients with non-Hodgkin's lymphoma

High-dose chemotherapy with or without radiotherapy followed by autologous transplantation of hematopoietic progenitor cells is an effective treatment for patients with high-risk or relapsed non- Hodgkin's lymphoma. Chemotherapy and/or hematopoietic growth factors have been used to mobilize progenitor cells in the peripheral blood for transplantation. However, the mobilized blood cell products have been found to be frequently contaminated with tumor cells, and techniques have not been developed to purge tumor cells from these products. In addition, the minimum number of hematopoietic progenitor cells required for engraftment has not yet been fully elucidated. We treated 21 patients with a single infusion of cyclophosphamide (4 g/m2) followed by daily administration of granulocyte colony-stimulating factor (G- CSF). After recovery of the white blood cell count, a single 3-hour apheresis collection was performed. The apheresis product was then applied to a discontinuous Percoll gradient. The low-density fractions resulting from this separation procedure were enriched for CD34+ progenitor cells (total cell yield, 19.5%; CD34+ cell recovery, 81.2%). These enriched cellular products were treated with a panel of anti-B cell or anti-T cell monoclonal antibodies and complement in an effort to remove residual tumor cells. After treatment of the patient with myeloablative therapies, the enriched and purged cells were reinfused. Hematologic recovery was rapid, with median neutrophil engraftment in 10 days [absolute neutrophil count (ANC), greater than 0.5 x 10(9)/L] and 11 days (ANC, greater than 1.0 x 10(9)/L). Median platelet transfusion independence required 13 days. The rapidity of multilineage engraftment correlated with the number of CD34+ cells per kilogram that were infused. Patients who received more than 2 x 10(6) CD34+ cells per kilogram had rapid hematologic engraftment, whereas those patients transplanted with less than 2 x 10(6) CD34+ cells per kilogram had slower platelet recovery. Modeling studies using a lymphoma cell line with a t(14; 18) chromosomal translocation demonstrated the successful removal of tumor cells assayed using the polymerase chain reaction (PCR) after the processing and purging. Four of the 21 patients had PCR- detectable lymphoma cells in the bone marrow and peripheral blood; however, the enriched and purged blood products reinfused in all four did not contain detectable tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Antigenic heterogeneity of human mononuclear phagocytes: immunohistologic analysis using monoclonal antibodies

Eight monoclonal antibodies to cell surface antigens of human monocytes were evaluated as immunologic markers for recognition of macrophages in sections of normal and diseased tissues, using immunoperoxidase and enzyme histochemical techniques. Monoclonal antibodies assessed were PHM2, PHM3, FMC17, FMC32, FMC33, FMC34, OKM1, and 63D3. Sites studied were human bone marrow, blood, lymph node, spleen, thymus, liver, kidney, lung, and peritoneal lavages, rejecting renal allografts containing inflammatory macrophages, and granulomata showing epithelioid and multinucleate giant cell formation. All antibodies bound to at least some tissue macrophages and, except for FMC32 and FMC33 antibodies, which were identically distributed, each antibody had a distinctive tissue distribution. Some antigens were shared by other bone-marrow-derived cells (megakaryocytes and cortical thymocytes), endothelium, epithelium, and dendritic cells. Antigenic differences were also detected between mononuclear phagocytes present at different sites, different stages of differentiation, and likely different states of activation. These studies provide evidence of major antigenic differences between various populations of human mononuclear phagocytes. They therefore indicate the need for careful evaluation of experiments involving the recognition of macrophages in tissue sections and smears based solely on the use of antimonocyte monoclonal antibodies.     

盐酸塞利洛尔合成工艺改进

目的:合成盐酸塞利洛尔,并进行工艺改进。方法:革除溴化反应,对醚化反应进行了优化。结果:使合成路线缩短一步,醚化收率比文献值提高20％以上。结论:该路线较适合于工业化生产。