Hematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells.

Abstract

A study of CD34+ cell selection and transplantation was carried out with particular emphasis on characteristics of short- and long-term hematopoietic recovery. Peripheral blood stem and progenitor cells (PBPCs) were collected from 32 patients, and 17 CD34+ cell-selection procedures were carried out in 15 of the 32. One patient in whom two procedures failed to provide 1 x 10(6) CD34+ cells per kg was excluded from further analysis. After conditioning, patients received CD34+ cells (n = 10, CD34 group) or unmanipulated (n = 17, PBPC group) PBPCs containing equivalent amounts of CD34+ cells or progenitors. The yield of CD34+ cells was 53 percent (18-100) with a purity of 63 percent (49-82). The CD34+ fraction contained 66 percent of colony-forming units--granulocyte-macrophage (CFU-GM) and 58 percent of CFU of mixed lineages, but only 33 percent of burst-forming units-erythroid (BFU-E) (p < 0.05). Early recovery of neutrophils and reticulocytes was identical in the two groups, although a slight delay in platelet recovery may be seen with CD34+ cell selection. Late hematopoietic reconstitution, up to 1.5 years after transplant, was also similar. The two groups were thus combined for analyses of dose effects. A dose of 40 x 10(4) CFU-GM per kg ensured recovery of neutrophils to a level of 1 x 10(9) per L within 11 days, 15 x 10(4) CFU of mixed lineages per kg was associated with platelet independence within 11 days, and 100 x 10(4) BFU-E per kg predicted red cell independence within 13 days. However, a continuous effect of cell dose well beyond these thresholds was apparent, at least for neutrophil recovery. CD34+ cell selection, despite lower efficiency in collecting BFU-E, provides a suitable graft with hematopoietic capacity comparable to that of unmanipulated PBPCs. In both groups, all patients will eventually show hematopoietic recovery of all three lineages with 1 x 10(6) CD34+ cells per kg or 5 x 10(4) CFU-GM per kg, but a dose of 5 x 10(6) CD34+ cells or 40 x 10(4) CFU-GM per kg is critical to ensure rapid recovery.