References of "Heimfeld, S"
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See detailHigh doses of transplanted CD34(+) cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation
Baron, Frédéric ULg; Maris, M. B.; Storer, B. E. et al

in Leukemia (2005), 19(5), 822-828

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood ... [more ▼]

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) ( n = 116) or marrow ( n = 14) transplantation after nonmyeloablative conditioning with 90 mg/m(2) fludarabine and 2Gy TBI. The median number of CD34(+) cells transplanted was 6.5 x 10(6)/ kg. Higher numbers of grafted CD14(+) ( P = 0.0008), CD3(+) ( P = 0.0007), CD4(+) ( P = 0.001), CD8(+) ( P = 0.004), CD3 - CD56(+) ( P = 0.003), and CD34(+) ( P = 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14(+) ( P = 0.01) and CD34(+) ( P = 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8(+) ( P = 0.005) and CD34(+) ( P = 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34(+) cells were associated with higher levels of day 28 donor T-cell chimerism ( P = 0.01), rapid achievement of complete donor T-cell chimerism ( P = 0.02), and a trend for lower risk for graft rejection ( P = 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34(+) cells in unrelated grafts administered after nonmyeloablative conditioning. [less ▲]

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See detailAssessing donor chimerism level among CD3 T, CD4 T, CD8 T, and NK cells predicts subsequent graft rejection, GVHD, and relapse after allogeneic HCT with nonmyeloablative conditioning
Baron, Frédéric ULg; Storb, R.; Gooley, T. et al

in Biology of Blood & Marrow Transplantation (2005), 11(2), 11

We previously showed that low levels of day-14 CD3 T and NK (CD56) cells donor chimerism predicted graft rejection, whereas high levels of day-28 CD3 T-cell donor chimerism predicted acute graft-versus ... [more ▼]

We previously showed that low levels of day-14 CD3 T and NK (CD56) cells donor chimerism predicted graft rejection, whereas high levels of day-28 CD3 T-cell donor chimerism predicted acute graft-versus-host disease (GVHD) after HCT with nonmyeloablative conditioning. Here we investigate whether assessing chimerism levels among CD4 T cells and CD8 T cells, and also the absolute number of lymphocyte subsets of donor and host origins, would lend greater precision to our initial observations. We analyzed data from 157 patients receiving HCT after conditioning with 2 Gy TBI +/− fludarabine as treatment for AML (n= 22), ALL (n= 4), CML (n= 13), CLL (n= 19), MDS (n= 26), MM (n= 24), NHL (n= 30), HD (n= 14), RCC (n= 4), and WASP deficiency (n= 1). Postgrafting immunosuppression included MMF and CSP. A total of 97 patients received grafts from HLA-identical siblings, and 60 patients received grafts from HLA-matched unrelated donors. Lymphocyte subsets were isolated from peripheral blood by flow cytometry on days 14, 28, and 42. The proportion of cells of donor origin (chimerism levels) were assessed by VNTR-PCR and quantified by phosphor imaging. Eighteen patients (11%) had graft rejection. Day-14 donor chimerism levels< 50% among CD3 T (P =.0007), CD4 T (P =.03), and NK cells (P =.003) but not CD8 T cells predicted graft rejection. High absolute numbers of CD3 T (P =.002) and NK cells (P= .002) of host origin on day 14 were each associated with increased risks of graft rejection when treated as continuous linear variables. Grades 2, 3, and 4 acute GVHD were seen in 40%, 9%, and 5% of patients, respectively. High donor chimerism levels on day 14 among CD3 T (P= .02), CD4 T (P =.03), and CD8 T cells (P =.02) but not NK cells were each associated with increased risks of grades 2–4 acute GVHD. High absolute numbers of CD4 T (P =.04) and CD8 T cells (P =.04) of donor origin on days 14–42 were each associated with increased risks of grade 2–4 acute GVHD when treated as continuous linear variables, whereas high donor CD3 T (P= .002), CD8 T (P= .006), and NK cell (P= .002) chimerism levels from days 14–42 were associated with decreased risks of relapse. No statistically significant correlations between absolute numbers of donor cells and risks of relapse were found. These data suggest that assessing CD3, CD4, CD8, and NK cell donor chimerism levels and determining absolute numbers of CD3 and NK cells of host and donor origins are useful for predicting HCT outcomes after nonmyeloablative conditioning. [less ▲]

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