Reduced mortality after allogeneic hematopoietic-cell transplantation

Ted A Gooley, Jason W Chien, Steven A Pergam, Sangeeta Hingorani, Mohamed L Sorror, Michael Boeckh, Paul J Martin, Brenda M Sandmaier, Kieren A Marr, Frederick R Appelbaum, Rainer Storb, George B McDonald, Ted A Gooley, Jason W Chien, Steven A Pergam, Sangeeta Hingorani, Mohamed L Sorror, Michael Boeckh, Paul J Martin, Brenda M Sandmaier, Kieren A Marr, Frederick R Appelbaum, Rainer Storb, George B McDonald

Abstract

Background: Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation.

Methods: We analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation.

Results: In the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs.

Conclusions: We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).

Figures

Figure 1
Figure 1
Probability of non-relapse mortality (NRM) by day 200 (upper panel) and overall survival (lower panel) during two time periods. Patients alive beyond seven years are censored at 7 years for graphical purposes only.
Figure 2
Figure 2
Display of daily total serum bilirubin (top panel) and serum creatinine (lower panel) values from day 0 to day 100 in mg/dL, during two eras. The lines represent fitted cubic spline curves of the observed data. Conversion to SI units: For total serum bilirubin, 1 mg/dL=17.1 μmol/L and for serum creatinine, 1 mg/dL=88.4 μmol/L.
Figure 3
Figure 3
Distribution of the overall grade of acute GVHD and the stage of liver and gastrointestinal GVHD in two eras.

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