Hematopoietic Recovery and Overall Survival after HLA-Matched Sibling Transplants for Older Patients with Severe Aplastic Anemia (SAA).

Abstract

Long-term survival after HLA-matched sibling transplants for SAA is 80–90% in patients <20 years at transplantation. Survival in older patients is lower. Herein, we report risk factors affecting hematopoietic recovery and long-term survival in older patients with SAA after HLA-matched sibling transplants. All transplantations occurred in 1991–2004. Before analysis of risk factors affecting survival we determined the ages at which survival rates differed significantly. Significant differences in survival rates were observed in the following age groups: <20 years (n=818), 20–40 years (n=618) and >40 years (n=127). Beyond 40 years, we were unable to find an age effect despite 44% of patients in this group being ≥50 years. Patients older than 40 years were more likely to have received >50 red blood cell transfusions, immunosuppressive therapy (65% vs. 50% in patients <40 years), have poor performance scores at transplantation, a longer waiting period to transplant (40% received transplants beyond 6 months from diagnosis compared to < 25% in the other groups) and more likely to receive peripheral blood grafts. Neutrophil recovery rates (day-28) did not differ in the three groups; 83%, 88% and 86% in patients aged <20 years, 20–40 years and >40 years, respectively. Recovery was more likely with peripheral blood transplants (odds ratio [OR] 1.96, p=0.022). Neutrophil recovery was lower with cyclophosphamide alone (OR 0.50, p=0.002) and fludarabine-containing conditioning regimens (OR 0.44, p=0.033). In contrast, age at transplantation was associated with platelet recovery (day- 100). Recovery was lowest in patients >40 years (89%) compared to 94% in patients <20 years (p<0.001) and 94% in patients 20–40 years (p=0.004). Platelet recovery was higher in patients with performance scores 90–100, OR 2.22, p<0.001, independent of age. As expected acute and chronic graft-versus-host disease (GVHD) risks were higher in those ≥20 years. We did not observe differences in acute (RR 1.42, p=0.089) and chronic GVHD (RR 1.21, p=0.354) risks between patients aged 20–40 years and >40 years. As shown in the Table below mortality risks increased with age. The 5-year probabilities of overall survival after adjusting for performance score, preparatory regimen, interval from diagnosis to transplantation, donor-recipient sex match and cytomegalovirus serostatus, factors affecting overall survival, were 81%, 72% and 53% in patients aged <20 years, 20–40 years and >40 years, respectively (p<0.001). Independent of age, mortality rates were higher in patients with poor performance score (RR 1.92, p<0.001), recipients of transplant preparatory regimens other than cyclophosphamide with or without anti-thymocyte globulin (RR 1.52, p=0.004), >6 months from diagnosis to transplantation (RR 1.50, p=0.001) and female recipients receiving grafts from male donors (RR 1.57, p=0.001). Mortality rates were lower when both donor and recipient were CMV sero-negative (RR 0.53, p<0.001). In conclusion, survival after transplantation in patients >40 years was significantly lower compared to younger patients. Longer interval from diagnosis to transplantation, higher numbers of pretransplant red blood cell transfusions and poor performance scores at transplantation may explain the inferior outcomes in patients >40 years. Use of peripheral blood grafts did not affect overall survival (p=0.169). The data suggest there is a need to improve survival in older patients; early referral for transplantation and improved supportive care may improve outcomes.OutcomeRelative RiskP-valueOverall mortality20–40 years vs. <20 years1.63<0.001>40 years vs. <20 years3.25<0.001>40 years vs. 20–40 years2.00<0.001