Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia

Abstract

Between January 1988 and March 1993, 48 patients received T-cell- depleted marrow grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML). The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48 patients greater than 40 years of age. Twenty-seven patients were transplanted in chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients received a standardized preparative regimen of cyclophosphamide, high-dose cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow grafts were depleted of mature T cells with the alpha beta T- cell receptor antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either serology or high- resolution oligonucleotide genotyping. Nine of 28 were mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48) of patients. The actuarial probability of developing grades II to IV and grades III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and 8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the incidence of grades II to IV acute GVHD between patients receiving matched (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18% (95% CI 4 to 41) for patients transplanted in either the accelerated or blast crisis phase (advanced disease). One cytogenetic relapse has occurred among patients transplanted in the chronic phase. The probability of disease- free survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced disease. No difference in disease-free survival was observed between patients receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can achieve durable engraftment with a low incidence of severe GVHD and apparent preservation of graft-versus-leukemia reactivity. These data also suggest that T-cell depletion may allow patients who might otherwise experience unacceptable toxicity from GVHD-related complications caused by older age or increased HLA disparity to benefit from unrelated marrow grafts.

T-cell receptor αβ+ and CD19+ cell–depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency

“…We suspect that apart from the conditioning, residual TCRgd cells and other immune cells contribute to robust engraftment and a very low rate of graft failure. It has been shown that infusion of activated gd T cells can promote engraftment 35,36 without causing GvHD, even in the MHC-mismatched situation. 37 Patients going into transplantation with active viral infections had the worst outcomes in our cohort, as shown previously in patients with SCID undergoing HSCT in which infants (>3.5 months of age) with infection had a poor survival in comparison with those with resolved infections or those without prior infection (50% vs 82% vs 90%).…”

Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment

“…However, graft-versus-host disease (GVHD) and the toxicity of ablative conditioning have limited the widespread clinical application of this approach (3,4). T cell depletion (TCD) of BM prevents GVHD, but is associated with significantly impaired engraftment (5)(6)(7). We were the first to identify a CD8 ϩ /TCR Ϫ BM population that facilitates hematopoietic stem cell (HSC) engraftment across MHC barriers without causing GVHD (8)(9)(10).…”

Cytomegalovirus seropositivity adversely influences outcome after T‐depleted unrelated donor transplant in patients with chronic myeloid leukaemia: the case for tailored graft‐versus‐host disease prophylaxis

“…However, the role of MUD transplants for CML is still limited by the fact that the incidence of acute and chronic graft‐versus‐host disease (GVHD) is greater than after an HLA‐identical sibling transplant (Enright et al , 1996; Hansen et al , 1998). Depletion of T cells from the donor marrow can reduce the incidence of acute and chronic GVHD (Mackinnon et al , 1990; Drobyski et al , 1994; Spencer et al , 1995a), but is associated with delayed immune reconstitution and an increased risk of relapse and graft failure (Goldman et al , 1988; Martin et al , 1988; Marks et al , 1993; Ochs et al , 1995). Consequently, it has been unclear what role, if any, T‐cell depletion (TCD) strategies should play in the prevention of GVHD after MUD transplantation.…”