CLINICAL NEWS
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 Univer-
sity Medical Center, and co-authors.
The authors analyzed data from the Center for International Blood
and Marrow Transplant Research (CIBMTR) registry for 1,106 alloge-
neic 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 increas-
ing 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 oc-
curred 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 syn-
dromes (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 Medi-
care 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
TABLE. Post-Transplant
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.
“[The findings] suggest that
select older patients achieve
a substantial ... survival
benefit after HCT.”
—LORI MUFFLY, MD, MS
Two-year overall survival (the primary endpoint) significantly im-
proved 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 pe-
riod. “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:
Outcomes in Patients ≥70 Years Old
Total Cohort
2000-2007 2008-2013 p Value*
427 105 322 0.63
32 (95% CI 28-37) 31 (95% CI 23-41) 33 (95% CI 28-38) 0.82
Acute GVHD (grade II-IV)
n
100 days
Acute GVHD (grade III-IV)
n
100 days
427 105 322 0.05
13 (95% CI 10-17) 18 (95% CI 11-26) 12 (95% CI 9-16) 0.13
1,025 161 864 0.94
Chronic GVHD
n
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
1,086 192 894 0.77
TRM
n
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
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
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
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
Relapse/progression
n
PFS
n
OS
n
*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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• 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%