Clinical News
Literature Scan
While this exclusion pattern has
been seen in other types of nonDS leukemia, the current pairing
of RAS and JAK2 mutations is
the most “clear-cut” evidence of
the relationship in DS leukemia
so far, co-author Dean Nizetic,
MD, PhD, from Queen Mary
University in London and the Lee
Kong Chian School of Medicine
in Singapore, told ASH Clinical
News. “In fact, fueled by our
observation on DS-ALL, we reanalyzed recently published data
on [DS-acute megakaryoblastic
leukemia] and found that a
complete mutual exclusion pattern
is followed in that disease, too.”
Children with DS-ALL have
worse survival outcomes and do
not tolerate chemotherapy well,
so there is a need for better, more
targeted therapeutic regimens in
this patient population, the authors
explained. In light of the current
findings, standard chemotherapy
regimens for DS-ALL could be
improved by patient stratification
based on profiling these mutations,
Dr. Nikolaev and co-authors
concluded. More specifically,
clinicians may consider adding
KRAS inhibitors and/or chromatin
modifier enzyme inhibitors to DSALL therapeutic strategies.
Commenting on the study’s
findings, Edward Allan R. Sison,
MD, from the Texas Children’s
Cancer and Hematology Centers
in Houston, Texas, pointed
out that various JAK2 and
RAS inhibitors are currently in
development and may prove
efficacious in JAK2- or RASmutated DS-ALL. “From a drug
development perspective, these
inhibitors would first be tested in
patients with relapsed disease,” he
added. “While targeted therapies
are generally better tolerated
than traditional cytotoxic
chemotherapy, it is unlikely that
JAK and/or RAS inhibitors would
be used as a single agent, and
would likely be used combined
with salvage chemotherapy in a
child who relapsed.”
Dr. Sison also noted that
the type of next-generation
sequencing employed in this
study may not be available at all
institutions, but the technology
will prove valuable as a way to
“prospectively identify genetic
alterations that may portend a
poor prognosis” in these patients.
Good, But Not Optimal — HSCT
Match Possible for Most Patients
For patients with certain blood cancers or other
diseases, hematopoietic stem cell transplants
(HSCT) are a potentially life-saving therapy. While
the majority of patients are able to find a suitable,
unrelated donor, the likelihood of finding a match
varies quite dramatically based on a patient’s race
and ethnicity. In a recent New England Journal of
Medicine article, researchers from the National
Marrow Donor Program (NMDP) tried to measure
the odds of finding a suitable donor in the NMDPoperated Be the Match® Registry.
Led by Loren Gragert, BS, BA, at the NMDP,
the researchers reported that Caucasians had the
greatest likelihood (75%) of finding an optimal
HLA-matched adult donor, while African
Americans had less than a 20 percent chance. The
likelihood of an ideal match (8/8 allele level match,
or matching at a high resolution for HLA-A, -B,
-C, and -DRB1) for other ethnic/racial groups fell
in between: 41 percent for Chinese patients, 33
percent for South Asians, 37 percent for Mexicans,
and 52 percent for Native Americans (Figure).
Across the board, a drop to a 7/8 match
requirement increased the likelihood of finding a
donor, and the authors pointed out that “patients
belonging to groups with high levels of genetic
admixture, such as Hispanic groups, are more likely
to have donors identified from outside their group.”
Age also played a major role in finding an
ideal, 6/6 cord blood match: A patient of white
European descent under 20 years of age had a 38
percent probability of finding an ideal cord blood
match, but that probability dropped to 16 percent
when the patient was older than 20. For AfricanAmerican patients, the corresponding, age-based
chances were 6 percent and 2 percent. This
age-based relationship was likely due to the fact
that “most units have sufficient cells to provide
an adequate cell dose for patients who weigh
less than 50 kg [110 lbs],” the authors explained.
Going for a lower match, though, such as 4/6,
meant that almost all younger patients would have
a cord blood match with adequate cell dose.
“For both graft sources, the racial and ethnic
group of the patient strongly influences the
likelihood of having a suitable graft identified,”
Mr. Gragert told ASH Clinical News. “The results
suggest that almost all patients likely to benefit
from HSCT will have a donor. However, many will
not have an optimal adult donor — that is, a donor
who is m