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Blood, 1 December 2001, Vol. 98, No. 12, pp. 3221-3227
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
CD34 cell dose in granulocyte colony-stimulating
factor-mobilized peripheral blood mononuclear cell grafts affects
engraftment kinetics and development of extensive chronic
graft-versus-host disease after human leukocyte antigen-identical
sibling transplantation
J. Maciej Zaucha,
Theodore Gooley,
William I. Bensinger,
Shelly Heimfeld,
Thomas R. Chauncey,
Renata Zaucha,
Paul J. Martin,
Mary E. D. Flowers,
Jan Storek,
George Georges,
Rainer Storb, and
Beverly Torok-Storb
From the Fred Hutchinson Cancer Research Center, the
University of Washington, and the Veterans Affairs Medical Center,
Seattle, WA.
A retrospective analysis of granulocyte colony-stimulating factor
(G-CSF)-mobilized peripheral blood mononuclear cell (G-PBMC) products
harvested from healthy donors indicates significant variability in both
the absolute number and relative proportion of CD34, CD3, and CD14
cells obtained. This report examined whether variations in the
cellular composition of G-PBMC products correlated with clinical
outcomes after myeloablative allogeneic transplantation. The
numbers of CD34, CD3, and CD14 cells infused into 181 human leukocyte
antigen (HLA)-identical sibling recipients were analyzed with respect
to tempo of engraftment, acute graft-versus-host-disease (GVHD),
clinical extensive chronic GVHD, overall survival, and disease relapse.
Neither acute GVHD, overall survival, nor disease relapse was
statistically significantly associated with CD34, CD3, or CD14 cell
doses or the CD14 to CD3 ratio. CD3 and CD14 cell doses and CD14 to CD3
ratios did not correlate with the tempo of neutrophil and platelet
engraftment. However, increasing CD34 cell numbers were significantly
associated with accelerated neutrophil (P = .03) and
platelet (P = .01) engraftment. Higher doses of CD34
cells (> 8.0 × 106/kg) were also associated with a
significantly increased hazard of clinical extensive chronic GVHD
(HR = 2.3, 95% confidence interval [CI] 1.4-3.7, P = .001), but neither CD3 nor CD14 doses were
statistically significantly associated with chronic GVHD. It was
concluded that CD34 cell dose in G-PBMC grafts appears to affect both
the engraftment kinetics and the development of clinical extensive
chronic GVHD in HLA-identical sibling recipients but without a
demonstrable impact on survival, relapse, and acute GVHD. Given the
morbidity associated with extensive chronic GVHD, efforts to further
accelerate engraftment in HLA-matched sibling transplants by increasing
CD34 cell number in G-PBMC products may be counterproductive.
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