Reduction of T cells in allogeneic stem cell grafts to a fixed low number might prevent GVHD and avoid typical problems of T cell depletion as graft failure, viral infections and disease relapse. To test this hypothesis we initiated a prospective study for patients aged over 45 years with hematological diseases and an HLA-identical or one antigen mismatched sibling. CD34+ cells were selected using the CliniMACS device (AmCell Corporation, Sunnyvale, USA) and CD3+ cells were added to yield a final dose of 2 x 105 CD3+ cells per kilogram body weight. So far 13 patients ( 1 ALL, 4 AML, 4 CML, 1 RA, 1 RAEB-T, 1 OMF, 1 NHL) with a median age of 52 years (range 47-58) have been transplanted after conditioning with TBI (12 Gy in 6 fractions) and cyclophosphamide (120 mg/kg). In four patients busulfan (16 mg/kg) was given instead of TBI. Ten patients received cyclosporine A (CSA) for GVHD prophylaxis. A median dose of 6.2 x 106 CD34+ cells per kg (range 4.1-10.0) were transplanted. All but two patients achieved a primary and sustained engraftment (neutrophils > 0.5 x 109/l on day 11 (range 10-12), platelets > 25 x 109/l on day 14 (range 9-20). One patient had a primary graft failure and a further patient showed a graft rejection on day 61. Both patients had been treated with busulfan. Eight of twelve evaluable patients developed acute GVHD (4 grade I, 3 grade II, 1 grade IV) and three of eight chronic GVHD (1 limited disease, 2 extensive disease). The patient with grade IV aGVHD and one patient with extensive disease cGVHD received no CSA prophylaxis. In ten instances patients or donors were CMV seropositive but no patient developed CMV disease. No EBV associated lymphoproliferative syndrome occurred. Seven patients died (2 relapse, 2 aspergillosis and GVHD, 2 lung failure, 1 primary graft failure). With a median follow up of 16 month (range 2-32) overall survival at 1 year was 34 Â± 15 %. We conclude that transplantion with a fixed number of 2 x 105 CD3+ cells per kilogram results in prompt and sustained engraftment in TBI treated patients and is not accompanied by a high incidence of viral infections but short course cyclosporine A prophylaxis is required to prevent acute GVHD.
Full conference title:
43rd American Society of Hematology (ASH) Annual Meeting
- ASH 43rd (2001)