BACKGROUND: Persistent neutropenia associated with severe aplastic anemia (SAA) is an important risk factor for development of life-threatening infections. Earlier studies underscored the high mortality associated with invasive fungal infections (IFIs) in SAA. However, little is known about the current patterns of infections and the impact of advances in anti-infective therapy on survival in SAA. METHODS: We reviewed the records of 174 patients with SAA admitted to the Hematology Branch at NHLBI from 1989 to 2008 who were unresponsive to initial immunosuppressive therapy (IST) at 6 months. Three patient groups determined by IST protocol and time interval were compared: group 1 (43 patients; December 1989-October 1996), group 2 (51 patients; November 1996-October 2002), and group 3 (80 patients; November 2002-April 2008). Outcome variables included infections, patterns of resistance, survival, and infection-related mortality. RESULTS: During the past 2 decades, infection-related mortality decreased from 37% in group 1 to 11% in group 3 (P < .001), and the frequency of IFIs decreased from 49% in group 1 to 8% in group 3 (P < .001). Overall 5-year survival for all patients (n = 420) increased from 64% in group 1 to 79% in group 3 (P < .001). Among non-responders (n = 174), it increased from 23% in group 1 to 57% in group 3 (P < .001). In multivariate analysis, younger age, absolute neutrophil count > 200 cells/μL before IST, absence of IFIs, and use of voriconazole were independently predictive of survival. CONCLUSION: During the past 2 decades, there has been a significant decrease in IFIs, infection-related mortality, and overall mortality in patients with SAA unresponsive to initial IST.
BACKGROUND: Persistent neutropenia associated with severe aplastic anemia (SAA) is an important risk factor for development of life-threatening infections. Earlier studies underscored the high mortality associated with invasive fungal infections (IFIs) in SAA. However, little is known about the current patterns of infections and the impact of advances in anti-infective therapy on survival in SAA. METHODS: We reviewed the records of 174 patients with SAA admitted to the Hematology Branch at NHLBI from 1989 to 2008 who were unresponsive to initial immunosuppressive therapy (IST) at 6 months. Three patient groups determined by IST protocol and time interval were compared: group 1 (43 patients; December 1989-October 1996), group 2 (51 patients; November 1996-October 2002), and group 3 (80 patients; November 2002-April 2008). Outcome variables included infections, patterns of resistance, survival, and infection-related mortality. RESULTS: During the past 2 decades, infection-related mortality decreased from 37% in group 1 to 11% in group 3 (P < .001), and the frequency of IFIs decreased from 49% in group 1 to 8% in group 3 (P < .001). Overall 5-year survival for all patients (n = 420) increased from 64% in group 1 to 79% in group 3 (P < .001). Among non-responders (n = 174), it increased from 23% in group 1 to 57% in group 3 (P < .001). In multivariate analysis, younger age, absolute neutrophil count > 200 cells/μL before IST, absence of IFIs, and use of voriconazole were independently predictive of survival. CONCLUSION: During the past 2 decades, there has been a significant decrease in IFIs, infection-related mortality, and overall mortality in patients with SAA unresponsive to initial IST.
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