Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by preemptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n = 5) or metastatic renal cell carcinoma (n = 1), and with an HLA-identical (n = 4) or alternative (n = 2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n = 4), 2 Gy TBI and fludarabine (RCC patient, n = 1) or cyclophosphamide and fludarabine ( patient who had previously received 12 Gy TBI, n = 1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade greater than or equal to2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.