Nonmyeloablative stem cell transplantation using Fludarabine-based conditioning regimen (Preliminary results)

초록

The use of non-myeloablative stem cell transplantation (NST) has been on increase for the aim of reducing treatment related mortality (TRM) while preserving the graft versus malignancy effect. We report our experience in 14 patients (median age 43, male to female 7:7) who had chemorefractory malignancies, i.e., acute myeloid leukemia (AML) in 4, acute lymphoid leukemia (ALL) in 2, non-Hodgkin's lymphoma (NHL) in 2, multiple myeloma (MM) in 1, myelodysplastic syndrome in 1, renal cell carcinoma in 2, non-small cell lung cancer in 1 and breast cancer in 1. Eligibility required contraindication to conventional allograft (prior allogeneic bone marrow transplant in 3, autologous bone marrow transplant in 2, old age in 3, major organ dysfunction in 2, and refractory solid cancer in 4). The patients with AML received fludarabine 30mg/m2/day and cytarabine 2g/m2/day for 5 consecutive days. The others were conditioned with fludarabine 30mg/m2/day and cyclophosphamide 60mg/kg/day for 5 and 2 consecutive days respectively. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporin A alone. Peripheral blood stem cells from HLA-identical sibling donors mobilized with G-CSF were given on days 0 and 1. The median number of CD34+ cells/kg infused was 3.3 (range 1.2-13.3). All patients achieved ANC over 500/uL on median day of 11 (range 8-17). Donor/recipient chimerism was determined monthly using VNTR and/or FISH analysis. Donor lymphocytes were given in case of persistent mixed chimerism and/or progression of malignancy. Major disease response was observed in 9 (64%), including 3/4 AML, 2/2 ALL (one Ph+ patient achieved and maintained molecular remission up to day 340+), 2/2 NHL, 1/1 MM, 0/1 MDS, 1/1 breast cancer, 0/1 NSCLC and 0/2 renal cell carcinoma. Relapse was observed in 3/9. Toxicity was mild aside from acute GVHD (50%). Until now, 4 died (3 of disease progression, 1 of acute GVHD) with a TRM of 7%. These preliminary results show that NST is well-tolerated with