Number of Older Patients Receiving AlloHCT Increased Over the Past Decade

Historically, older adults have not been considered optimal candidates for hematopoietic cell transplantation (HCT) because of concerns about transplant-related toxicity and mortality. Over the past 13 years, however, the rate of transplantation among older adults (≥70 years) in the United States (U.S.) increased steadily, likely because of lower-intensity conditioning regimens and more accurate human leukocyte antigen (HLA)-typing, according to results of an observational study published in Blood.

The findings “suggest that select older patients achieve a substantial …survival benefit after HCT,” wrote Lori Muffly, MD, MS, from the Division of Blood and Marrow Transplantation at the Stanford University Medical Center, and co-authors.

The authors analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry for 1,106 allogeneic HCT (alloHCT) recipients ≥70 years of age who had a hematologic malignancy and underwent first alloHCT in the U.S. between 2000 and 2013. Patients were excluded if they had a syngeneic donor transplant.

The absolute number of transplants increased from five in 2000 to 283 in 2013, with the proportion of alloHCT recipients ≥70 years old increasing from 0.1 percent to 3.85 percent in that time frame. The median age at HCT was 72 years (range = 70-84 years), and most transplants occurred in patients with acute myeloid leukemia (AML; n=599; 54%).

“The majority of growth was … due to increasing numbers of patients with early or intermediate risk AML or myelodysplastic syndromes (MDS),” the authors wrote, also noting that “greater [use] of HCT for MDS beginning after 2010 coincides with the decision in the U.S. to cover this disease indication … through the Centers for Medicare and Medicaid Services Coverage with Evidence Development.”

The use of unrelated donor grafts increased from 51 percent to 70 percent during the study period, “driven mostly by greater use of matched unrelated donors,” the authors wrote. When the researchers separated the data into two cohorts (2000-2007 and 2008-2013), they found that the number of centers performing transplants in these older adults also increased, from 65 by 2007 to 93 by 2013.

Two-year overall survival (the primary endpoint) significantly improved from 26 percent in 2000 to 2007 to 39 percent in 2008 to 2013 (p<0.001). Two-year progression-free survival similarly improved from 22 percent to 32 percent (p=0.003).

However, rates of two-year transplant-related mortality (TRM; defined as death in the absence of disease relapse or progression) and graft-versus-host disease remained unchanged over the observation period. “To reduce TRM, we must consider both improvements in patient selection, as well as further refining the transplant process to allow for less toxicity and morbidity in older adults,” the authors wrote. (See TABLE for all post-HCT outcomes).

To identify prognostic factors associated with inferior survival, the researchers conducted a subset analysis in the 2008 to 2013 cohort, finding that the following factors predicted worse outcomes:

  • high comorbidity (defined as HCT-Comorbidity Index ≥3): hazard ratio (HR) = 1.27; 95% CI 1.07-1.51; p=0.006
  • receipt of cord blood for donor source relative to HLA matched sibling donor: HR=1.97; 95% CI 1.37-2.82; p=0.0002
  • use of myeloablative conditioning regimen: HR=1.61; 95% CI 1.25-2.08; p=0.0002

Myeloablative conditioning was also associated with higher mortality in the subset of 416 patients with early or intermediate AML/MDS or chemosensitive non-Hodgkin lymphoma transplanted between 2008 and 2013, compared with reduced-intensity conditioning (HR=1.60; 95% CI 1.13-2.28; p=0.009). Female recipients appeared to have a higher mortality rate, compared with male recipients (HR=1.30; 95% CI 1.03-1.65; p=0.029).

Age, disease status, disease, and functional impairment did not significantly influence survival.

The authors also hypothesized that physician and patient willingness to consider transplant has changed over the years and may have affected these outcomes, but they noted this is difficult to measure.

The study is limited by its retrospective design and the potential for information to be missing from the CIBMTR registry. Prospective studies are required to effectively compare outcomes between HCT and non-HCT regimens in this older patient population.

The authors report no conflicts.


Reference

Muffly L, Pasquini MC, Martens M, et al. Increasing use of allogeneic hematopoietic cell transplantation in patients age 70 years and older in the United States. Blood. 2017 July 3. [Epub ahead of print]

TABLE. Post-Transplant Outcomes in Patients ≥70 Years Old
  Total Cohort 2000-2007 2008-2013 p Value*
Acute GVHD (grade II-IV)
n 427 105 322 0.63
100 days 32 (95% CI 28-37) 31 (95% CI 23-41) 33 (95% CI 28-38) 0.82
Acute GVHD (grade III-IV)
n 427 105 322 0.05
100 days 13 (95% CI 10-17) 18 (95% CI 11-26) 12 (95% CI 9-16) 0.13
Chronic GVHD
n 1,025 161 864 0.94
1 year 32 (95% CI 30-35) 32 (95% CI 25-40) 32(95% CI 29-36) 0.97
2 years 37 (95% CI 34-40) 35 (95% CI 28-43) 38 (95% CI 35-41) 0.55
TRM
n 1,086 192 894 0.77
1 year 25 (95% CI 23-28) 26 (95% CI 20-33) 25 (95% CI 22-28) 0.73
2 years 33 (95% CI 30-36) 35 (95% CI 28-42) 33 (95% CI 29-36) 0.54
Relapse/progression
n 1,086 192 894 0.04
1 year 32 (95% CI 30-35) 38 (95% CI 31-45) 31 (95% CI 28-34) 0.09
2 years 37 (95% CI 34-40) 43 (95% CI 36-50) 35 (95% CI 32-38) 0.04
PFS
n 1,086 192 894 0.001
1 year 42 (95% CI 39-45) 36 (95% CI 29-43) 44 (95% CI 40-47) 0.04
2 years 30 (95% CI 27-33) 22 (95% CI 16-28) 32 (95% CI 29-36) 0.003
OS
n 1,106 207 899 <0.001
1 year 50 (95% CI 47-53) 42 (95% CI 35-49) 52 (95% CI 49-56) 0.007
2 years 36 (95% CI 33-39) 26 (95% CI 21-33) 39 (95% CI 35-42) <0.001
*Significance between 2000-2007 and 2008-2013 cohorts.

GVHD = graft-versus-host disease; TRM = transplant-related mortality; PFS = progression-free survival; OS = overall survival

 

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