Abstract
The purpose of this study was to determine the feasibility and efficacy of nonmyeloablative allogeneic stem cell transplantation in patients with hematologic malignancies and metastatic renal cell carcinoma (RCC). Thirty patients with various pathologies (AML/MDS, n=9; CML, n=5; lymphoid malignancy, n=6; Multiple Myeloma, n=7; RCC, n=3) received a fludarabine (F)-based nonmyeloablative regimen (F+Busulphan, n=5; F+TBI, n=18; F+Cyclophosphamide, n=3; others, n=4), followed by unmanipulated peripheral stem cells from HLA-identical sibling donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and mycophenolate mofetil. Median age was 43 years (range, 17–62), median time from diagnosis to transplant was 1.6 years (range, 0.4–9.1). Patients underwent a median of 2 prior chemotherapy regimens (range, 0–7). Prior stem cell transplantation failed in seven patients (23%) (autologous, n=6; ablative allogeneic, n=1). Disease phase prior to transplant was complete or partial remission in 16 patients (CR, n=12; PR, n=4) and active disease in 14 patients (Primary refractory, n=1; Relapse, n=10; Untreated, n=3). Recipients were male and donors were female in 15 transplants (50%). The median numbers of mononuclear and CD34+ cells infused were 8.8 x 108/kg (range, 4–26 x 108/kg) and 9.7 x 106/kg (5.2–32.5 x 106/kg) respectively. Neutrophil engraftment achieved after a median of 9 days (range, 6–12) and platelet engraftment occurred after a median of 11 days (range, 9–19). In twelve (40%) patients, absolute netrophil count did not fall below 500/mm3 and 14 patients (47%) required no platelet transfusions. The patients received a median of 2 donor lymphocyte infusions (range, 0–8). Nine patients (30%) had acute GVHD (Grade II-IV, n=5, 17%) and 12 patients (40%) had chronic GVHD (limited, n=4; extensive, n=8, 27%). Three patients (10%) died of nonrelapse treatment-related complications within 100 days post-transplant (Pneumonia, n=2; Bronchoalveolar hemorrhage, n=1). Two patients had graft failure at day 100 post-transplant. Twenty two patients (73.4%) are currently alive with a median follow-up of 6 months. Primary causes of deaths (n=8, 26.6%) are as follows; GVHD (n=3), pneumonia (n=2), bronchoalveolar hemorrhage (n=1), and relapse (n=2). Among 22 evaluable patients, response was obtained in 18 patients (82%) (CR, n=14; PR, n=2; stable disease, n=2) and 4 patients relapsed. Our data suggest that nonmyeloablative allogeneic transplantation is a safe and effective treatment strategy in hematological malignancies.
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