CLINICAL NEWS
Written in Blood
ATG in Cord Blood Transplantation: Is Timing Everything? Rethinking
Genetic Profiles
in Acute Myeloid
Leukemia: It’s
The practice of using antithymocyte
globulin (ATG) to overcome the
risks of graft rejection in patients
who require allogeneic hematopoietic stem cell transplantation with
umbilical cord blood but lack a suitable HLA-matched donor is unwarranted, and may even be detrimental
to recovery, according to a recent
study published in Blood.
Unrelated cord blood transplantation (UCBT) is an alternative source of stem cells for these
patients, but cord blood contains
significantly fewer CD34+ cells and
mature lymphocytes than other
sources of stem cells, which can lead
to delayed post-transplant immune
reconstitution and an increased risk
of graft failure.
“The use of ATG, incorporated
within the conditioning regimen
prior to UCBT is still controversial, especially for adults receiving
a reduced-intensity conditioning,
single-unit allogeneic cord blood
eloproliferative neoplasm (MDS/
MPN; 19%). Forty-four percent
of patients who were transplanted
had advanced disease, all patients
received UCBT grafts with at least
four out of six HLA compatibilities, and the median number of
infused total nucleated cells was
3.5 x 107/kg.
The 82 patients in the ATG
group were older compared with
the 579 patients in the non-ATG
group (54 years vs. 52 years,
respectively; p=0.068), patients
in the ATG group presented with
a higher proportion of MDS/
MPN (31% vs. 17%; p=0.009),
and patients in the ATG group
had more advanced disease
(p=0.063).
With a median follow-up of 36
months (range, 2-99 months), the
cumulative incidence of 60-day
neutrophil engraftment (defined as
neutrophil recovery, excluding patients with autologous recovery) was
Hazard Ratios for Outcomes After UCBT According to the
Use of ATG
TABLE 3.
ATG in Conditioning
No
Yes
95% CI (p Value)
3-year overall survival
1.0
1.69
1.19-2.41 (p=0.003)
3-year non-relapse mortality
1.0
1.68
1.16-2.43 (p=0.0009)
Acute III-IV graft-versus-host disease
1.0
0.31
0.17-0.55 (p<0.0001)
transplant,” the authors, led by
Laurent Pascal, MD, from Hôpital
Saint Vincent de Paul, GHICL, Hematologie in Lille, France, wrote.
Dr. Pascal and colleagues
conducted a multicenter, retrospective study to examine the impact of
ATG on the outcomes of patients
undergoing single- or double-unit
UCBT following a reduced-intensity
conditioning.
A total of 661 adult patients
from 79 European Society for
Blood and Marrow Transplantation
centers were included: 226 patients
underwent single-unit UCBT, while
435 underwent double-unit UCBT.
The reduced-intensity conditioning
regimen consisted of cyclophosphamide (50 mg/kg), fludarabine
(200 mg/m2), and a single fraction
of total body irradiation (200 cGy in
86%, 400 cGy in 12%, and 600 cGy
in 2% of patients).
The median age of study participants was 54 years and diagnoses
included acute leukemias (51%),
lymphoproliferative diseases (30%),
and myelodysplastic syndrome/my-
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ASH Clinical News
83 percent, with no significant difference according to ATG use (84%
for non-ATG and 82% for ATG;
p=0.17). Graft failure occurred in
103 patients (15.6%), including 88
patients in the non-ATG cohort
and 15 in the ATG group. Of those
patients, 30 were alive at a median
of 33 months post-transplantation.
Dr. Pascal and authors concluded,
“in adults undergoing UCBT
following a reduced-intensity conditioning regimen for hematological
malignancies, this study shows that
adding rabbit ATG to the conditioning leads to less satisfactory
outcomes.” In multivariate analyses,
the use of ATG was associated
with a significantly decreased risk
of acute graft-versus-host disease
(GVHD), but also a significantly
higher risk of non-relapse mortality
and a decrease in overall survival
(TABLE 3).
In terms of mortality, 24 percent
of patients (n=20/82) in the ATG
group died of relapse or progression, compared with 27 percent of
patients (n=158/579) in the non-
ATG group (p=.58). Deaths in the
ATG group were more likely due to
infection (28% vs. 13%; p=0.0013)
and post-transplant lymphoproliferative disorders (6% vs. 0.5%;
p=0.001), compared with the nonATG group.
Although the absence of ATG in
the conditioning regimen was associated with higher rates of GVHD,
there was no clear improvement
on survival when ATG was used,
the authors noted. “This could be
explained by an overlapping impact
of several complex variables on the
final outcome,” they wrote. “Indeed,
the higher non-relapse mortality
observed in the ATG group might
outweigh the lower inciden 6R