Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Abstract

PURPOSE Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). PATIENTS AND METHODS We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). RESULTS Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and > or = 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. CONCLUSION With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

“…This study also identified poor risk cytogenetics, being in second versus in first CR, and conditioning with low-dose TBI-based RIC as being associated with worse LFS or OS, confirming previous reports. 18,31,32 Finally, our study demonstrated higher mortality in patients above 56 years of age at transplantation in comparison with younger patients, in contrast to what has been observed in a recent report from the CIBMTR analyzing data from 545 patients with AML given RIC allo-SCT, 18 perhaps because analyses were not adjusted for comorbidities at transplantation (more likely to be more frequent in older patients) in current study.…”

“…5,6 Allo-SCT following reduced-intensity conditioning (RIC) is being increasingly used as treatment for patients with AML who are too old or too frail to tolerate high-dose conditioning regimens. [7][8][9][10][11][12][13][14][15][16][17][18][19] The goal of RIC allo-SCT is to harness the GVL effect, 7 while minimizing toxicities and the risk of GVHD. However, this is a delicate balance as a number of prior studies have shown a lower risk of relapse in AML patients who experienced chronic GVHD after RIC allo-SCT compared with those patients who did not, [10][11][12]20,21 while some other studies failed to find such an association.…”

Influence of age on outcome after allogeneic hematopoietic cell transplantation: a single center study in patients aged ⩾60

“…21 Data of the CIBMTR in 1080 patients older than 40 years demonstrated in multivariate analysis that chronological age did not influence NRM, relapse or rate of GVHD, and therefore lead to the conclusion that age alone should not be a contraindication for allogeneic HCT. 22 In a recent published study of Brunner et al 13 describing patients over the age of 70 years, a 2-year-OS of 39% was found with a median follow-up of 21 months of patients alive. In our study the subgroup of patients ⩾ 66 years had a comparable outcome with a 3-year-OS of 50% with a high proportion of patients ⩾ 70 years of age (n = 28).…”

Survival benefits with transplantation in secondary AML evolving from myelodysplastic syndrome with hypomethylating treatment failure

“…In line with our observation, recent data have shown that older age alone should not be considered a contraindication to SCT in medically fit patients. 22,23 Alternative donors for SCT such as a haploidentical familial member can be a feasible option if a HLA-compatible donor is unavailable, as most patients with sAML/MDS-HTF die within 6 months without allo-SCT and the median CR duration after CTx was within 3.6 months. 9 The 1-year OS of 60.0% in our cohort suggested the feasibility of alternative donor SCT as an alternative option for these high-risk patients.…”