The number of donor CD3+ cells is the most important factor for graft failure after allogeneic transplantation of CD34+ selected cells from peripheral blood from HLA-identical siblings

Abstract

This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factormobilized peripheral blood progenitor cells depleted of T cells by CD34 ؉ positive selection (allo-PBT/CD34 ؉ ) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14.9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34 ؉ and CD3 ؉ cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3 ؉ cells in the inoculum. Twentythree of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 ؋ 10 6 /kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 ؋ 10 6 /kg (actuarial probability 18% vs 1%, respectively; P ‫؍‬ .0001). The actuarial probability of graft failure progressively increased as the number of CD3 ؉ cells in the graft decreased, which was determined by grouping the number of CD3 ؉ cells in quartiles (log-rank P ‫؍‬ .03; log-rank for trend P ‫؍‬ .003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3 ؉ cells less than or equal to 0.2 ؋ 10 6 /kg (risk ratio ‫؍‬ 17; P < .0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio ‫؍‬ 4.8; P ‫؍‬ .001). From these results it appears that the number of CD3 ؉ cells in the inoculumwith a threshold of 0.2 ؋ 10 6 /kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34 ؉ from HLA-identical siblings. In addition, for patients with CML receiving 0.2 ؋ 10 6 /kg or less CD3 ؉ cells, total body irradiation might be better than busulphan-based regimens.

Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution

“…[23][24][25] Several studies have shown, however, that 'partial' TCD is associated with a lower risk of graft failure than 'total' TCD. 26,27 In our study, every patient received a T-cell dose of 40.1 Â 10 6 /kg in the graft, and this is in sharp contrast to data from other studies using totally TCD grafts which report graft failure rates of up to 15%. 28 In this regard, although the optimum number of T cells that should be left in the graft to allow reliable engraftment is presently unknown, our series supports the idea that the number of CD3 þ cells in the inoculum is the most critical factor relating to the development of graft failure after allo-PBT/ CD34 þ , as has been recently suggested.…”

“…28 In this regard, although the optimum number of T cells that should be left in the graft to allow reliable engraftment is presently unknown, our series supports the idea that the number of CD3 þ cells in the inoculum is the most critical factor relating to the development of graft failure after allo-PBT/ CD34 þ , as has been recently suggested. 27,29 Acute GVHD, grade I or II, was observed in two patients, but was limited to the skin. When compared with the data reported by other groups after standard allo-BMT, 19 no patient in our series developed grade III or IV acute GVHD.…”

Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH)

“…23 Recently, the number of CD3 þ cells in the graft has been considered of relevance in the outcome of allogeneic PBSC transplantation. 24 In fact, in our study, the number of CD3 þ cells grafted was a risk factor for cGvHD. However, no conclusions have been reached regarding this issue in several randomized studies due to the limited number of cGvHD cases.…”

Split chimerism after allogeneic bone marrow transplantation in Chediak–Higashi syndrome

“…On the contrary, immune tolerance was easily obtained after two episodes of GVHD, possibly because the underlying disease was CHS. It is also reported that the number of CD3-positive T cells transplanted is the most important factor for engraftment, 12 and it is now understood that Tcell depletion increases the risk of failure of engraftment. 13 However, the precise mechanisms of the development of split chimerism as well as the induction of immune tolerance remain to be elucidated.…”