Abstract 649

TRM is among the major challenges for the success of HCT. Over the past two decades advances in the prevention and treatment of the major sources of TRM; regimen related toxicity, graft-versus-host disease (GVHD) and infections, have been made. To estimate the combined effect of these advances over time, we assessed changes in the incidence of TRM from 1985 through 2004 in 5,972 patients younger than 50 years, who received bone marrow (BM) or peripheral blood (PB) HCT with myeloablative conditioning for AML in first (CR1) or second (CR2) complete remission reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The incidence of TRM was determined for four consecutive five-year periods for HLA-matched sibling donors (MRD) and the later three for unrelated donor (URD) separately by donor type and disease status at transplant. Cox proportional hazard regression models of TRM and overall survival outcomes were constructed with time periods as the main effect. Adjustments for patient and disease characteristics including age, performance score, coexistent diseases and cytogenetics were made in all multivariate models. Subgroup analyses were performed to account for the influence of major changes in transplant characteristics over time, i.e. GVHD prophylaxis, graft source and HLA matching. We observed a steady drop in the risk of TRM over time among patients in CR1 and CR2 receiving MRD transplants, which was associated with a significant reduction in risk of death (table below). Among URD recipients, TRM also improved with lower RR in 2000-2004 compared to earlier periods. No improvements in long term OS was observed in URD CR1 group. For patients in CR2, the RR for overall mortality was 0.74 (0.6-0.9, p=0.03) for 2000-2004 compared to 1990-1994. Subgroup analyses restricted to recipients of BM grafts, cyclosporine/methotrexate for all transplants and partially HLA-matched grafts for URD resulted in similar trends, suggesting that improvements in TRM were not solely related to utilization of PB, newer GVHD prophylaxis or better HLA matching. In conclusion, our results demonstrate lower risk for TRM over time in patients receiving HCT from MRD and URD for AML in CR1 and CR2. These reductions in risk of TRM have been accompanied by reduced risk of overall mortality in most groups of patients studied.

Table 1:

Multivariate analyses of TRM and OS after MRD HCT adjusted for differences in patient and disease characteristics over time.

CR1
PeriodNTRM RR (95% CI)POverall Mortality RR (95% CI)P
1985-1989 1111 1.0 – 1.0 – 
1990-1994 1265 0.8 (0.7-0.1) <0.01 0.9 (0.8-1.1) 0.15 
1995-1999 871 0.7 (0.6-0.8) <0.01 0.8 (0.7-0.9) <0.01 
2000-2004 457 0.5 (0.4-0.7) <0.01 0.7 (0.6-0.9) <0.01 
CR1
PeriodNTRM RR (95% CI)POverall Mortality RR (95% CI)P
1985-1989 1111 1.0 – 1.0 – 
1990-1994 1265 0.8 (0.7-0.1) <0.01 0.9 (0.8-1.1) 0.15 
1995-1999 871 0.7 (0.6-0.8) <0.01 0.8 (0.7-0.9) <0.01 
2000-2004 457 0.5 (0.4-0.7) <0.01 0.7 (0.6-0.9) <0.01 
CR2
PeriodNTRM RR (95% CI)POverall Mortality RR (95% CI)P
1985-1989 202 1.0 – 1.0 – 
1990-1994 228 0.8 (0.6-1.1) 0.14 0.9 (0.7-1.1) 0.28 
1995-1999 199 0.6 (0.4-0.8) <0.01 0.9 (0.7-1.2) 0.44 
2000-2004 121 0.3 (0.2-0.5) <0.01 0.6 (0.4-0-9) <0.01 
CR2
PeriodNTRM RR (95% CI)POverall Mortality RR (95% CI)P
1985-1989 202 1.0 – 1.0 – 
1990-1994 228 0.8 (0.6-1.1) 0.14 0.9 (0.7-1.1) 0.28 
1995-1999 199 0.6 (0.4-0.8) <0.01 0.9 (0.7-1.2) 0.44 
2000-2004 121 0.3 (0.2-0.5) <0.01 0.6 (0.4-0-9) <0.01 
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Disclosures:

No relevant conflicts of interest to declare.

Topics:
hematopoietic stem cell transplantation, risk reduction, transplantation, graft-versus-host disease, human leukocyte antigens, tissue transplants, complete remission, cyclosporine, infections, methotrexate

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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