Blood, 1 December 2001, Vol. 98, No. 12, pp. 3177-3177
In search of the ideal allogeneic inoculum
For more than 30 years, physicians have transplanted
allogeneic hematopoietic cells (HCs) harvested from the bone marrow
cavity without any specific HC stimulation. During the past
decade, blood HCs collected by apheresis after stimulation with
granulocyte-colony stimulating factor (G-CSF) of
the donor have been explored as an alternative source and it was
demonstrated in a phase III trial that G-CSF-mobilized blood HCs are
the preferred inoculum, compared with marrow HCs that had been
harvested from "steady state" donors, at least for patients in
advanced stages of their hematologic malignancy (Bensinger et al.
N Engl J Med. 2001;344:175-181).
Last year, intriguing phase II data were reported from 3 independent
groups (Couban et al, Biol Blood Marrow Transpl. 2000;6:422-427; Isola
et al, Biol Blood Marrow Transpl. 2000;6:428-433; Serody et al, Biol
Blood Marrow Transpl. 2000;6:434-440) indicating that G-CSF-treated
donors provide marrow HCs that lead to rapid engraftment and a
relatively low rate of graft-versus-host disease (GVHD). Here, Morton
and colleagues (page 3186) report phase III trial results showing that
G-CSF-mobilized HCs derived from marrow or blood have virtually
equivalent engraftment kinetics for granulocytes and platelets but that
marrow HCs are associated with significantly less steroid refractory
acute GVHD and a lower incidence of chronic GVHD. One would like to see
this important observation confirmed in a uniform patient population
conditioned with a single preparatory regimen.
Existing preclinical data could explain the interesting
observation described by Morton and colleagues. These studies in murine models indicate that bone marrow T cells induce less GVHD than equivalent amounts of blood T cells (189:1073-1081; Lan et al, Blood.
2001;97:3458-3465; Zeng et al, Blood. In press). Likewise, human T
cells from marrow or blood not only differ quantitatively but also may
have vastly different qualitative features and functions. In the days
of microarray assays, such differences should soon become evident.
Progress toward optimizing the allogeneic graft continues to be made.
Ultimately, ex vivo manipulation of allogeneic HCs, regardless of the
source, will provide the patient with the best result: a graft that
leads to rapid and durable engraftment with preserved
graft-versus-tumor effects and without GVHD.
Karl G. Blume
Stanford
University
