SUSTAINED LONG-TERM HEMATOPOIESIS AFTER MYELOABLATIVE THERAPY WITH PERIPHERAL-BLOOD PROGENITOR-CELL SUPPORT

A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 h ad non-Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eight y-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cy totoxic chemotherapy alone, while 99 patients received cytokines eithe r during steady-state hematopoiesis or post-chemotherapy. Sixty patien ts were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irra diation at a total dose of 14.4 Gy. The duration of severe pancytopeni a posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with ra pid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconst itution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 pati ents were autografted with a median of 1.75 x 10(4) CFU-GM per kilogra m resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow exami nations in 50 patients performed at a median follow-up time of 10 mont hs (range, 1 to 85 months) posttransplantation. A comparison with norm al volunteers showed a 3.2-fold smaller proportion of bone marrow CD34 + cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU-GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted wit h relatively low numbers of progenitor cells. This suggests that eithe r the pretransplant regimens were not myeloablative, allowing autochth onous recovery, or that a small number of cells capable of perpetual s elf-renewal were included in the autograft products. (C) 1995 by The A merican Society of Hematology.