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Featured research from recent issues of Blood
PAPER SPOTLIGHT
Double-Unit Cord Blood Transplantation
Not Superior to Single-Unit in Reducing
Risk of Transplant Failure in Children
and Young Adults
The strategy of using two
unrelated cord blood (UCB)
units is no better than
the standard single-unit
approach in preventing
hematopoietic cell transplantation (HCT)-related
mortality or engraftment
failure, according to a
report published in Blood.
For patients who need
to undergo HCT but lack a
human leukocyte antigen
(HLA)-identical donor, use
of UCB units has been
proposed as an alternative
hematopoietic cell source.
However, UCB units contain
a limited number of these
cells, which may lead to
poorer post-HCT outcome.
Doubling UCB units was
thought to increase cell
dose, Gérard Michel, MD,
from La Timone Hospital
in Marseille, France, and
co-authors of the report
explained.
Dr. Michel and authors
enrolled 151 patients
(children and you ng adults
≤35 years) from 22 French
transplant centers in a
prospective, multi-center,
randomized trial comparing the single- and doubleUCB strategies. Patients
had acute leukemia in
remission or myelodysplastic syndromes (MDS;
with <20% bone marrow blasts): 74 received
single-UCB transplant, and
77 received double-UCB
transplant. All underwent
a myeloablative conditioning regimen.
Patients were included
in the study if they:
26
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• required unrelated HCT
• did not have an acceptable unrelated donor,
according to the transplant center, based on
HLA compatibility and
donor availability
• had at least two UCB
units that were a 4-6
HLA match to the
patient
Patients were excluded
if they had a history of
allogeneic HCT (alloHCT)
or a poor health status
that precluded the use of
a myeloablative conditioning regimen. This regimen
included:
• Busulfan (administered
from days 9-5 prior to
transplant and dosed
depending on patient
weight), clophosphamide (50 mg/kg/day
on days 5-2 prior to
transplant), and antithymocyte globulin (2.5
mg/kg/day from days
3-1 prior to transplant)
• Fludarabine (25 mg/
m2/day from days 9-7
prior to transplant,
total body irradiation
(from days 6-4 prior
to transplant), and
clophosphamide (60
mg/kg/day on days 3-2
prior to transplant)
The study’s primary
endpoint was cumulative
incidence of transplant
strategy failure, which was
defined as the first of the
following four events to
occur: transplant-related
mortality (TRM), autologous recovery (defined as
hematopoietic recovery
with >80% blood recipient
chimerism), second alloHCT, or infusion of an
autologous hematopoietic
cell rescue for engraftment failure. Secondary
endpoints included hematologic recovery, relapse
risk, incidence and grading
of acute and chronic
graft-versus-host disease
(GVHD), immune recovery,
TRM, disease-free survival,
and overall survival (OS).
The majority of the
patients were <18 years
(79.5%); 59.6 percent had
acute lymphocytic leukemia, and the remaining
40.4 percent had acute
myeloid leukemia or MDS.
The mean interval from
randomization to trans-
plantation was 39.3 days,
and the mean follow-up
from UCB transplant was
798 days.
Fourteen patients (six
in the single-unit group
and eight in the doubleunit group) relapsed and
could not receive transplant. Of the remaining 137
transplanted patients in
both groups, none crossed
over to the other treatment group.
In the intent-to-treat
analysis, the cumulative
incidence of transplant
failure (in which patients
who relapsed before their
planned graft could not be
transplanted due to refractory disease) was 14.9
percent in the single-unit
group and 23.4 percent
in the double-unit group
(p=0.21). In the per-protocol analysis, which included
only patients who received
a transplant, the cumula-
tive incidence was 7.3
percent in the single-unit
group versus 14.5 percent
in the double-unit group
(p=0.20).
Of the five patients
who experienced transplantation strategy failure
after single-unit UCB
transplant, the first classifying event was TRM
(n=3), followed by autologous recovery (n=1), and
secondary transplant for
engraftment failure (n=1).
This was similar in the 10
patients in the double-unit
UCB transplant group who
experienced a transplant
strategy failure: eight
patients experienced TRM,
one had autologous recovery (n=1), and one underwent second transplant for
engraftment failure.
The median times to
neutrophil recovery (24.8
days after single-UCB
unit and 23.5 days after
Outcomes of Single- Versus Double-Unit UCB
Transplant
TABLE 1.
Single-unit UCB
n=68
Double-unit UCB
n=69
p value
2-year CI of relapse
23.5%
17.4%
0.31
Day 100 acute GVHD
Grade ≥2
Grade ≥3
41.2%
25%
44.9%
18.8%
0.76
0.40
2-year chronic GVHD
Overall
Extensive only
50%
14.7%
52.6%
31.9%
0.70
0.02
2-year transplant-related
mortality
5.9%
11.6%
0.25
2-year disease-free survival
67.6%
68.1%
0.74
2-year OS
68.8%
74.8%
0.56
UCB = unrelated cord blood; CI = cumulative incidence; GVHD = graft-versus-host disease;
OS = overall survival
July 2016