Similar Outcome of Non-Myeloablative and Myeloablative Allogeneic Hematopoietic Cell Transplantation for Patients Greater Than Fifty Years of Age.

Abstract

Advanced age is a relative contraindication to myeloablative allogeneic transplantation due to the increased incidence of treatment related complications seen in older patients. Therefore, non-myeloablative stem cell transplantation (NST) is increasingly utilized in this population. The impact of the shift from myeloablative to NST upon relapse, transplant complications, and outcome has yet to be examined. We performed a retrospective analysis of 152 patients older than age 50 receiving either NST or myeloablative transplantation over a 5 years period. The decision to pursue non-myeloablative as opposed to myeloablative conditioning during this period was based on patient and physician preference. Seventy-one patients received non-myeloablative conditioning, fludarabine (30 mg/m2/day x 4) and intravenous busulfan (0.8 mg/kg/d x 4). Eighty-one patients received myeloablative conditioning, primarily cyclophosphamide and TBI. All patients received pharmacologic prophylaxis to prevent GVHD with the majority of patients receiving FK 506 and methotrexate in both groups (78% NST, 96% myeloablative) with the remainder receiving cyclosporine and prednisone. 93% of NST patients received mobilized PBSC, the median CD34+ cell count infused was 6.4 x 106 CD34+ cells/kg (range 1.0 to 31.0 x 106 CD34+ cells/kg). 80% of myeloablative patients received marrow. The median age was 58 (range 51–70) years for patients receiving NST and 54 (range 51–66) years for patients receiving myeloablative transplantation. Major disease groups included acute leukemia and MDS (51% NST, 41% myeloblative). Ten percent of non-myeloablative transplant patients were in CR1 or had early stage disease at transplantation compared with 40% of myeloablative transplant patients. Primary indications for NST were advanced age (56%) and prior myeloablative transplant (24%). The median follow-up is 18 months (range 6 to 34 months) for patients receiving non-myeloablative transplantation and 46 months (range 3 to 73 months) for patients receiving myeloablative transplantation. NST patients were more likely to have unrelated donors (58% vs. 36%, p=0.009), prior transplant (25% vs. 4%, p=<0.0001), and active disease at transplantation (85% vs. 59%, p=<0.001). Despite the adverse characteristics, overall survival was improved in the NST group at 1 (51% vs. 39%) and 2 (39% vs. 29%) years (p = 0.056). There was no difference in progression free survival (2 year, 27% vs. 25%, p =0.24). Incidence of 2–4 GVHD was similar, (28% vs. 27%). Non-relapse mortality was lower for NST patients (32% vs. 50%, p=0.01), but relapse was higher (46% vs. 30%, p=0.052). A subset analysis was performed assessing overall and progression free survival in patients with advanced leukemia (beyond CR1) and advanced MDS. This demonstrated marginally improved overall survival and progression free survival for patients receiving NST. Our experience suggests that, in patients over age 50, NST with fludarabine and low dose busulfan leads to an overall outcome at least as good as myeloablative therapy.