ALLOGENEIC PERIPHERAL-BLOOD PROGENITOR-CELL TRANSPLANTATION IN A MURINE MODEL - EVIDENCE FOR AN IMPROVED GRAFT-VERSUS-LEUKEMIA EFFECT

Peripheral blood progenitor cells (PBPCs) are increasingly being used to replace bone marrow cells (BMCs) as a source of hematopoietic stem cells also in the field of allogeneic transplantation. Whereas it is w ell known that PBPC grafts and BM differ significantly in progenitor c ell content and lymphocyte dose, the clinical consequences of these di fferences with respect. to engraftment, graft-versus-host disease (GVH D), and the graft-versus-leukemia (GVL) effect are more difficult to a ssess. We present a murine model that allows us to evaluate engraftmen t, GVHD, and GVL effect of allogeneic PBPC transplantation (PBPCT). Ba lb/c mice (H-2d) served as recipients, Donors were major histocompatib ility complex-matched DBA/2 mice or syngeneic Balb/c mice, respectivel y. Experiments with increasing numbers of BMCs or Filgastrim-mobilized PBPCs showed that the number of progenitor cells in the graft was cor related with the probability to engraft, irrespective of the graft typ e. With identically high cell numbers transferred (1 x 10(9) nucleated cells/kg body weight [BW]), the mortality rates due to GVHD (25%) wer e about the same after allogeneic BM transplantation (BMT) and allogen eic PBPCT, although PBPC grafts contained four times more CD3(+) T cel ls as compared with BM grafts (6.2 x 10(8) v 1.4 x 10(8)/kg BW). For i nvestigation of GVL activity, Balb/c recipients were injected with. sy ngeneic cells of the B-lymphocytic leukemia cell line A20 2 days befor e transplantation, After total body irradiation to a dose of 7.5 Gy, 1 x 10(9)/kg BW Balb/c PBPCs, DBA BMCs, or DBA PBPCs were infused. The relapse rates observed were 80% after syngeneic PBPCT (n = 22), 60% af ter allogeneic BMT (n = 23), and 34% after allogeneic PBPCT (n = 26) ( allogeneic BMT v PBPCT, P = .032). We conclude that transplantation of allogeneic PBPCs instead of BM may enhance the GVL effect without an increase of GVHD. (C) 1997 by The American Society of Hematology.