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Minimal GVHD following in-vitro Tcell–depleted allogeneic stem cell transplantation with reduced-intensity conditioning allowing subsequent infusions of donor lymphocytes in patients with hematological malignancies and solid tumors

2003; Elsevier BV; Volume: 31; Issue: 10 Linguagem: Inglês

10.1016/s0301-472x(03)00200-5

1873-2399

Renée M. Y. Barge, Susanne Osanto, W.A.F.Erik Marijt, C.W.J. Starrenburg, Willem E. Fibbe, J.W.R. Nortier, JH Falkenburg, Roel Willemze,

Immune Cell Function and Interaction

Allogeneic stem cell transplantation (alloSCT) following reduced-intensity conditioning offers a relatively nontoxic regimen while preserving rapid and sustained engraftment. Acute and chronic graft-vs-host disease (GVHD) is, however, a significant cause of severe morbidity. To reduce the incidence of GVHD, we treated a group of high-risk patients with a reduced-intensity conditioning regimen followed by in vitro T-cell-depleted alloSCT using Campath 1-H incubation.Eighteen patients were treated with fludarabine (6 x 30 mg/m(2)), busulphan (2 x 3.2 mg/kg), and ATG (4 x 10 mg/kg) followed by the infusion of high-dose T-cell-depleted peripheral stem cells from sibling donors. No posttransplant GVHD prophylaxis was administered. At 6 months after alloSCT, low-dose donor lymphocyte infusion (DLI) was administered.All patients had sustained engraftment of donor cells with a median of 95% donor cells at 3 months after alloSCT. Minimal acute and no chronic GVHD was observed after alloSCT. A high incidence of cytomegalovirus (CMV) reactivation but no CMV disease was observed. Eleven patients received DLI at a median of 6.5 months after alloSCT. Acute GVHD grade II-III developed in 6 patients. All patients showed improvement of donor chimerism after DLI. With a median follow-up of 211 days, 11 patients are alive. Particular in patients with chronic lymphocytic leukemia and acute myeloid leukemia, a significant graft-vs-tumor effect was observed.In vitro T-cell-depleted alloSCT following reduced-intensity conditioning leads to durable donor engraftment without GVHD. The high levels of donor chimerism allow the subsequent use of cellular immunotherapy to treat residual disease.