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Summary:We investigated whether a T cell-reduced allogeneic stem cell transplant (SCT) with minimal conditioning and subsequent donor lymphocyte infusions (DLI) could reduce the incidence and severity of GVHD while retaining stable engraftment. Five patients with hematological malignancies (three MM, one CLL, one ChediakHigashi syndrome) were conditioned with TBI (200 cGy). One patient additionally received fludarabine (120 mg/m 2 ). CsA and mofetyl-mycophenolate (MMF) were administered to prevent GVHD. All patients were grafted with Ͼ3 ؋ 10 6 /kg highly purified CD34 + cells together with 2 ؋ 10 6 /kg CD3 + cells (three patients) or 1 ؋ 10 5 /kg CD3 + cells (two patients). Quick hematopoietic recovery and initial mixed donor chimerism was observed. Treatment-related toxicity was minimal in all but one patient who died of treatment-refractory GVHD on day 112. The four other patients only achieved partial donor T cell chimerism. BM and PBMC donor chimerism was lost between day 40 and 209 despite DLI. Three patients are alive with disease and one is in CR. We conclude that T cell-reduced SCT using 200 cGy as the conditioning regimen does not result in stable hematopoietic engraftment. Predominant donor T cell chimerism is not a prerequisite for initial allogeneic hematopoietic proliferation. However for sustained long-term engraftment it is of major importance. Bone Marrow Transplantation (2001) 28, 157-161. Keywords: non-myeloablative; fludarabine; T cell depletion; multiple myeloma; allogeneic stem cell transplantation; chimerism analysisIn conventional allogeneic SCT, myeloablative conditioning therapy serves the purpose of eradicating the underlying disease and ensuring engraftment of donor hematopoiesis. Treatment-related toxicity and GVHD remain the major post-transplantation complications resulting in high morbidity and mortality. Allogeneic SCT with reduced intensity conditioning regimens are increasingly used in order to decrease the procedure-related complications in patients not eligible for standard SCT because of age, comorbidities or prior excessive therapies. 1,2 Storb and colleagues [3][4][5] showed in a canine model that stable engraftment can be reached with minimal myelosuppressive conditioning regimens and minimal treatment-related toxicities. In addition, they provided evidence that a state of mixed donor-recipient chimerism is connected with a reduced incidence of GVHD. 5,6 However, an ongoing clinical trial revealed a 36% acute GVHD rate in this setting in spite of intensive prophylactic immunosuppression. 1 One way to circumvent the problems of GVHD is T cell depletion of the donor stem cell product. However, these allografts are more likely to be rejected and the graft-versus-leukemia potential is reduced. 7-9 DLI subsequent to establishment of donor chimerism represents one possibility to immunologically eradicate the underlying disease. We report on the results of a pilot trial which combines the 200 cGy conditioning with transplantation of T cell-reduced grafts followed by prophylactic ...