CLINICAL NEWS
of transplant recipients (and inherent selection bias of
those who undergo transplantation) makes it difficult
to evaluate HCT benefit among this patient group.
“With all the limitations, our observation points
to the fact that patients with very poor response to in-
duction treatment may be transplanted and rescued,”
the authors concluded. “Major treatment-type modifi-
cations are thus to be considered only in children who
do not achieve [first complete remission] by the end
of induction.”
“The authors are to be congratulated for such an
ambitious undertaking,” Patrick Brown, MD, told
ASH Clinical News when asked for comment on the
study. He added that “the creation of the infrastruc-
ture to support [future trials] is perhaps the greatest
consequence of this important study.” Read more from
Dr. Brown in “Perspectives” at the end of this article.
The study is limited by its retrospective design
and that the findings need to be tested further in a
prospective, multinational study. Some subgroups
included small patient populations, which is another
limitation of the study.
The corresponding authors report no financial
conflicts. ●
REFERENCE
Hrusak O, De Haas V, Stancikova J, et al. International cooperative study identifies
treatment strategy in childhood ambiguous lineage leukemia. Blood. 2018 May 2. [Epub
ahead of print]
PERSPECTIVES
Immunogenicity
The development of factor VIII inhibitors with the use of ADVATE was evaluated in
clinical trials with pediatric PTPs (<6 years of age with ≥50 factor VIII exposures)
and PTPs (≥10 years of age with ≥150 factor VIII exposures). Of 276 subjects who
were treated with ADVATE for at least 10 exposure days or on study for a minimum
of 120 days, 1 adult developed a low-titer inhibitor (2 BU in the Bethesda assay)
after 26 exposure days. Eight weeks later, the inhibitor was no longer detectable,
and in vivo recovery was normal at 1 and 3 hours after infusion of another
marketed recombinant factor VIII concentrate. This event results in a factor VIII
inhibitor frequency in PTPs of 0.4% (95% CI of 0.01 and 2% for the risk of any
factor VIII inhibitor development). No factor VIII inhibitors were detected in the
53 treated pediatric PTPs. USE IN SPECIFIC POPULATIONS
In clinical trials that enrolled previously untreated subjects (defined as having had
up to 3 exposures to a factor VIII product at the time of enrollment),
16 (29.1%) of 55 subjects who received ADVATE developed inhibitors to factor VIII.
Seven subjects developed high titer (>5 BU) and nine subjects developed low-titer
inhibitors. Inhibitors were detected at a median of
13 exposure days (min-max: 6−26 exposure days) to the product. Pediatric Use
Pharmacokinetic studies in children have demonstrated higher clearance, a shorter
half-life and lower recovery of factor VIII compared to adults. This may be explained
by differences in body composition and should be taken into account when dosing or
following factor VIII levels in the pediatric population. Because clearance (based on
per kg body weight) has been demonstrated to be higher in the pediatric population,
dose adjustment or more frequent dosing based on per kg body weight may be
needed in this population. In the ADVATE routine prophylaxis clinical trial, 3 children
aged 7 to <12 and 4 adolescents aged 12 to <16 were included in the per-protoc