Transplantation of allogeneic CD34+selected cells followed by early T-cell add-backs:: favorable results in acute and chronic myeloid leukemia

Background The aim of this study was to investigate preservation of anti-leukemic activity and protection from opportunistic infections after transplantation of allogeneic CD34(+) cells in patients with hematologic malignancies and bad prognosis. Methods Thirty-three patients [median age 42 years, range 23-55 years, diagnosis AML/myelodysplastic syndrome (MDS) 14, ALL nine, CML seven and multiple myeloma ( MM) three] received myeloablative conditioning followed by infusion of selected CD34(+) cells from matched unrelated donors (31) or HLA-identical siblings ( two). Early donor lymphocyte infusions (DLI; 0.5 and 1.0 x 10(6) CD3(+) cells/kg) were given while patients were on immunosuppressive therapy. Results Ninety-seven per cent of patients engrafted and 24 of 29 patients surviving more than 30 days received at least one pre-emptive DLI. Three patients (10%) developed acute (a) GvHD (two grade I-II, one grade III-IV) spontaneously, and 16 patients (67%) developed aGvHD after DLI (12 grade I-II, four grade III-IV). Eight of 24 evaluable patients developed chronic (c) GvHD (33%, six limited, two extensive). After a median follow-up of 590 days (range 138-1610 days) 18 patients were alive (55%), 16 in complete remission (CR), one in hematologic and one in molecular relapse. Seven patients died after relapse (21%) and eight died from transplantation-related causes (24%). Patients with myeloid malignancies had a significantly better survival than patients with ALL or MM (74% +/- 10 vs. 30% +/- 13, PB < 0.05). Discussion Early pre-emptive low-dose DLI following transplantation of selected CD34(+) cells from unrelated donors after myeloablative conditioning is feasible and effective without undue toxicity, especially in patients with myeloid malignancies.