Blood, 15 March 2003, Vol. 101, No. 6, pp. 2077-2077
UCB allogeneic transplantation for hemoglobinopathies
-thalassemia and sickle cell disease reduce lifespan and
quality of life for children and young adults, and the only cure for
these disorders is allogeneic stem cell transplantation. The decision-making processes in recommending allogeneic transplantation for patients with thalassemia and sickle cell disease differ, due to
the clinical heterogeneity of sickle cell disease, and transplantation
is recommended only in patients with severe disease, particularly
sickle-related neurologic problems. The potential risk of disabling
chronic graft-versus-host disease (GVHD) raises concerns on the part of
pediatric hematologists in the wide application of allogeneic
transplantation for patients with hemoglobinopathies. Currently, the
event-free survival rate after allogeneic HLA-matched sibling
transplantation for thalassemia and sickle cell disease ranges from
82% to 86%. Nevertheless, short-term and long-term transplantation-related complications remain, particularly in older patients with lifelong complications of sickle cell disease. Novel conditioning regimens that minimize transplantation-associated toxicity have been developed. Moreover, alternative stem cell sources
are currently being explored to increase the availability and efficacy
of allogeneic transplantation for patients with -thalassemia and
sickle cell disease.
Although allogeneic stem cell transplantation can cure patients with
hematologic disorders, limiting factors such as lack of suitable donors
and GVHD toxicity have led to the exploration of umbilical cord
blood (UCB) as an alternative source of hematopoietic stem cells. In
this issue, Locatelli and members of the Eurocord Transplant Group
(page 2137) report their retrospective analyses of 44 children with
either thalassemia (n = 33) or sickle cell disease (n = 11) treated
with fully ablative conditioning and allogeneic-related cord blood
transplantation. No patient died, and the 2-year event-free and overall
survival rates in these children are 79% and 90%,
respectively. Further observations outlined in this issue parallel
those reported on other series, which indicate that use of related cord
blood has been associated with a very low incidence of acute and
chronic GVHD. Locatelli et al observed grade II acute GVHD to occur
in only 4 of 38 evaluable children (Kaplan-Meier estimate,
11%), with 2 of these children having received HLA disparate grafts,
and only 2 of 36 children developed limited chronic GVHD (Kaplan-Meier
estimate, 6%). The majority of these patients received cyclosporine
alone as prophylaxis. This low incidence of GVHD compares favorably
with the 15%-25% incidence of grade II-IV acute GVHD and the
25%-30% incidence of chronic GVHD observed in children receiving
HLA-matched sibling allogeneic bone marrow grafts.
-thalassemia and sickle cell disease are among the most common
genetic disorders, affecting several million children and young adults
worldwide. Proposed gene therapy-based strategies for these patients
require complex, regulated, lineage-specific expression of the
-globin gene at relatively high levels. Although the recent
discovery of the -globin locus control region (LCR) has renewed
interest in gene therapy, difficulties in attaining high-titer vectors,
along with a tendency toward rearrangement when segments of the LCR are
incorporated into retroviral vectors, have impeded further
progress. As outlined by Locatelli and colleagues' study, the
use of UCB makes possible a better chance of cure and lower rates of
GVHD. Reed et al (Blood. 2003;101:351-357) recently reported on their
successful banking initiative of sibling donor UCB for children with
hematologic disorders, despite the challenges associated with
remote-site collections. Further studies are indicated to determine the
impact of HLA disparity on related-donor UCB transplantation outcomes.
Mary J. Laughlin
Case Western Reserve
University
