Allogeneic Hematopoietic Stem-Cell Transplantation for Patients 50 Years or Older With Myelodysplastic Syndromes or Secondary Acute Myeloid Leukemia

The optimum intensity of conditioning therapy in patients aged 40-60 years with AML and myelodysplastic syndrome (MDS) undergoing allogeneic haematopoietic cell transplantation (alloHCT) remains uncertain. We compared outcomes of reduced intensity conditioning (RIC) and conventional intensity conditioning (CIC) in 101consecutive patients (CIC, 62; RIC, 39) with AML and MDS aged 40-60 years undergoing alloHCT from 2002 to 2008 at our centre. The median age, unrelated transplants and co-morbidity index were higher in the RIC group. Median OS and EFS were 31.0 months (95% confidence interval (CI): 12.8-59.3) and 20.7 months (95% CI: 11.0-30.4), respectively, with no significant difference between the two cohorts. The 3-year treatmentrelated mortality (TRM) and relapse were 28% (95% CI: 21-39) and 25% (95% CI: 17-36), respectively, with no significant difference between the two cohorts. No difference in OS, EFS, TRM or relapse was observed between the two cohorts in the multivariate model. Only disease risk was significantly associated with OS (Hazard ratio (HR): 1.85, CI: 1.01-3.45), EFS (HR: 1.73, 95% CI: 1.00-3.10) and cumulative relapse (HR: 3.24, 95% CI: 1.08-10.12). Disease biology rather than intensity of conditioning regimen seems to determine outcomes of alloHCT in patients aged 40-60 years with AML/MDS.

Section: Discussionsupporting

confidence: 81%

Impact of intensity of conditioning therapy in patients aged 40–60 years with AML/myelodysplastic syndrome undergoing allogeneic transplantation

Khabori

Elemary

et al. 2010

“…20 Another study of the EBMT group including 1333 patients between 50 and 74 years again shows that older age had no significant influence on the outcome. 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.…”

Section: Discussionmentioning

confidence: 99%

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

Federmann

Faul

Meisner

et al. 2015

Reduced intensity conditioning regimens lead to an increasing use of allogeneic hematopoietic cell transplantation (HCT) in elderly patients. We retrospectively analyzed 151 patients aged ⩾ 60 receiving allogeneic HCT 2000-2012 at our center. Median age was 66 years. Kaplan-Meier estimated 3-year OS was 42% with a median follow-up of 38 months. Cumulative incidences of progression and non-relapse mortality after 3 years were 38 and 24%. OS was better in the group of patients 465 years with a Kaplan-Meier estimated OS of 50% vs 34%, P = 0.060. We observed a significant influence of donor age (o 50 years: 53% vs 450 years: 30%, P = 0.017) and gender match (matched: 57% vs mismatched: 32%, P = 0.007) on outcome. The use of a matched related donor was inferior compared with a matched or mismatched unrelated donor (19% vs 47%, P = 0.015). On multivariate analysis there was an increased hazard ratio for a non-gender-matched HLA-matched-related donor (hazard ratio 3.23, 95% confidence interval 1.55-6.74, P = 0.002). Age had no significant impact on OS (P = 0.414). In conclusion, the data suggest that older age alone has no negative impact on the outcome of allogeneic HCT. Transplant decision should be tailored to disease risk and patient performance status rather than age.

“…6,12 The selection of conditioning regimen (myeloablative, reduced intensity or nonmyeloablative) on the basis of age cutoffs alone is, however, not thought to be optimal when predicting NRM and survival. 13,14 Other factors, such as disease status and co-morbidities, may also affect NRM and survival and hence may need to be taken into account. 13 A number of risk-assessment scores have been utilized to predict NRM and outcomes of HCT.…”

Section: Introductionmentioning

confidence: 99%

Role of HCT-comorbidity index, age and disease status at transplantation in predicting survival and non-relapse mortality in patients with myelodysplasia and leukemia undergoing reduced-intensity-conditioning hemopoeitic progenitor cell transplantation

Bokhari

Watson

Nagra

et al. 2011

Reduced-intensity-conditioning (RIC) regimens have allowed older patients to have allogeneic hemopoietic progenitor cell transplantation (HCT). This retrospective study was done to assess the impact of the HCTcomorbidity index (HCT-CI) in addition to other pretransplant factors on the outcome of RIC transplants. In all 121 such patients were transplanted between 2002 and 2008 at two centers using fludarabine, melphalan and alumtuzumab conditioning. The OS and non-relapse mortality (NRM) were 56% and 30% at 2 years, respectively. The NRM of patients with HCT-CI X3 was not significantly different from the NRM of those with HCT-CI 0-2 (P value 0.24). Age and disease status at transplantation were significant factors affecting OS (P value 0.07 and 0.008, respectively), with no impact on NRM (P value 0.14 and 0.24, respectively). Although HCT-CI on its own did not independently predict NRM or survival, taken together with age and disease status at transplantation, it can be utilized to further delineate RIC allograft recipients into groups with different outcomes. Patients with none or one of these three adverse factors (ageX60 years, leukemia in second CR or PR/high-risk myelodysplasia (MDS) and HCT-CIX3) had a 2-year NRM and survival of 18% and 80%, respectively, which was significantly better than those of patients with two or more of these adverse factors with 2-year NRM and survival of 46% (P value 0.03) and 40% (P value 0.02), respectively. None of the patients with all three adverse factors (ageX60 years, leukemia in second CR or PR/ high-risk MDS and HCT-CIX3) had survived for 2 years (median survival 12 months). This information can be used to guide patient selection for RIC transplants and to appropriately counsel patients of the risks and benefits of this treatment.