Biol Blood Marrow Transplant 26 (2020) e303 e304

Biology of Blood and

Marrow Transplantation
journal homepage: www.bbmt.org

Improving Hematopoietic Stem Cell Transplant in the Elderly: Can We

Finally Start to Impact Nonrelapse Mortality?
Thomas G. Knight*
Levine Cancer Institute, Atrium Health, Charlotte, North Carolina

Article history: led to the Composite Health Assessment Model for Older
Received 8 October 2020
Adults study, which is a large prospective observational multi-
Accepted 11 October 2020
center study being performed by the Blood and Marrow Trans-
plant Clinical Trials Network. The goal of the study is to
combine the different efficacious tools to create a new com-
The role of allogeneic hematopoietic cell transplant (HCT)
posite health risk model that will hopefully allow standardiza-
in the treatment of older patients with hematologic malignan-
tion of pre-HCT risk assessment and serve as the definitive
cies has rapidly evolved over the past 2 decades. Historically,
work on the subject.
older patients were not offered HCT despite being both dispro-
In this issue of BBMT, Bhargava et al. [10] examine this
portionally affected by hematologic malignancies and having a
important issue from a different perspective by focusing on the
higher propensity for higher risk/more aggressive disease. In
transplant process itself and, more specifically, the impact that
fact, it was estimated as recently as 2011 that only 6% of
the use of potentially inappropriate medications (PIMs) has on
patients with acute myelogenous leukemia (AML) older than
morbidity and mortality in older HCT recipients. This is novel
60 years in the United States underwent stem cell transplanta-
and groundbreaking work and builds upon well-established
tion [1]. However, the development of reduced-intensity con-
geriatric care principles by utilization of the American Geriatric
ditioning and nonmyeloablative regimens in combination
Society’s Beers criteria. First developed by Mark Beers, MD, and
with improved infectious and graft-versus-host disease man-
colleagues in 1991, these criteria have been maintained and
agement has transformed the field, allowing increased utiliza-
continued to be updated by the American Geriatric Society
tion of this potentially curative therapy [2-4]. In the latest data
using a comprehensive, systematic review and grading of the
from the Center for International Blood and Marrow Trans-
evidence on drug-related problems and adverse drug events in
plant Research (CIBMTR), 39% of all allogeneic HCT recipients
older adults [11]. Despite these well-established guidelines,
were 60 years and older, with 9% being older than 70 years [5].
inappropriate prescribing of medications remains prevalent
This rapid expansion has also led to an urgent need for evalua-
with an estimated 7.3 billion doses of potentially inappropriate
tion of best practices.
medications being dispensed in the United States in 2018 [12].
Of particular concern is the high rate of morbidity and non-
As standard practices for allogeneic HCT were initially designed
relapse mortality (NRM) observed in older adults undergoing
with a younger patient population, the authors hypothesized
allogeneic HCT. Despite the lower intensity of conditioning
that PIM use would be similar in older (65 years) and younger
therapies and the improvements in care noted above, rates of
(40 to 64 years) patients as these practices were followed, with
NRM in older patients have barely budged, with recent
higher rates of grade 3 or 4 Common Terminology Criteria for
CIBMTR data showing a 2-year NRM rate of 33% to 34% over
Adverse Events in the older group.
the past decade in patients 70 years and older [6]. Increasing
Unfortunately, this hypothesis proved accurate with their
recognition of this issue has resulted in a growing consensus
results. On multivariate analysis, the prevalence of PIM use did
on the need for intervention. The first work in this area has pri-
not differ by age. Interestingly, there was variation among
marily consisted of improving pretransplant assessment to
medication classes as older recipients were more likely to
better characterize risk evaluation. Multiple approaches have
have higher use of Gastrointestinal (GI) & Genitourinary (GU)
been undertaken in this space utilizing physician-based
medications, with similar use of anticholinergics and central
assessments, transplant-specific scales, and geriatric-based
nervous system medications and lower use of narcotics and
tools with evidence of efficacy [7-9]. This approach has now
benzodiazepines. This likely reflects the growing awareness by
the general medical community on the importance of delir-
Financial disclosure: See Acknowledgments on page e304. ium-decreasing actions, including limiting narcotic and benzo-
E-mail address: Thomas.Knight@atriumhealth.org diazepine use in the elderly. However, these results are also in
* Correspondence and reprint requests: Thomas G. Knight, MD, Levine Can- keeping with general prescribing trends where there is a
cer Institute, 1021 Morehead Medical Drive, LCI Building 2, Suite 60100, Char-
much greater lag in practice behavior when using other PIMs
lotte, NC 28204.

https://doi.org/10.1016/j.bbmt.2020.10.013
1083-8791/© 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
e304 T.G. Knight / Biol Blood Marrow Transplant 26 (2020) e303 e304
that may be equally as harmful [13]. This practice pattern is
also likely more prevalent in protocol-driven services such as
HCT, where there is less discretion on medications used and
depend on constant updating of practice guidelines.
More distressingly, use of PIMs among older recipients, par-
ticularly narcotics, was associated with higher odds of grade 3 to
4 toxicities, a lower likelihood of discharge to home, and higher
rate of mortality. It is always difficult to attribute causality with
medication usage, especially in a high-acuity environment with
as many variables as the peri-HCT time period. However, these
are disturbing results, especially in the context of the persistently
high NRM rates seen in the older population, and will need fur-
ther investigation with larger cooperative trials.
Overall, this work by Bhargava et al. [10] is thought provok-
ing and, in combination with other ongoing studies, will hope-
fully lead to a reimagining and improvement of our current
practices in older patients receiving allogeneic HCT. If risk
assessment prior to transplant and geriatric safety/medication
protocols in the peri- and post-transplant period can be
improved, it is reasonable to think that we can finally start to
improve NRM. This may not only improve results in the cur-
rent population, but this risk reduction can also allow expan-
sion of this potentially curative treatment and greatly improve
outcomes for older patients with hematologic diseases.
ACKNOWLEDGMENTS
Financial disclosure: The author has nothing to disclose.
Conflict of interest statement: There are no conflicts of inter-
est to report.
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