Curative therapy:
Gene Therapy:
The
hemoglobinopathies are ideal candidates for gene therapy in that the tissues to
be treated can be removed, treated, and re-infused with relative ease.
The obstacles to success of this therapeutic approach and the availability of
this therapy for humans include the need for improved efficiency of gene
delivery, regulated and sustained expression of introduced genes, and insertion
of the gene into non-oncogenic sites (Sadelain et al., 2005).
BM Transplantation:
The
decision to perform allogeneic bone marrow transplantation is generally
considered appropriate only for those patients who have a fully HLA-matched
donor (at most, 30-40% of all patients) (Rund and Rachmilewitz, 2000).
Outcomes after transplantation are greatly influenced by the presence of
hepatomegaly, portal fibrosis and ineffective chelating therapy before
transplantation. Children without any of these risk factors have rates of
survival and event free survival exceeding 90% three years after
transplantation (those identified as class 1). By contrast, in those with all
three risk factors, (class 3 patients) the rates are approximately 60%. In
patients with either hepatomegaly or portal fibrosis (class 2), the event free
survival rate is approximately 80% (Weatherall, 1999).
One of the major reasons for failure of BMT in
thalassemia may be the unpredictable kinetics of busulfan used in most
preparative regimens. Hyper-absorption of the drug is associated with hepatic
veno-occlusive disease, while hypo-absorption with recurrent thalassemia (Goussetis
et al., 2000).
Umbilical Cord Blood Stem
Cell Transplantation:
Stem
cell transplantation is currently the only curative therapy. Use of stem cells
from cord blood makes possible earlier transplant with better chance of cure,
although the engraftment is slower compared to bone marrow transplantation (Issaragrisil,
2002).
Intrauterine Bone Marrow
Transplantation:
A
small number of centers have begun to perform intrauterine bone marrow
transplantation, with either fetal liver or bone marrow derived stem cells, as
the source of hematopoietic stem cells (Flake et al., 1998).
At
present, sustained, successful intrauterine transplantations have been
reportedly performed only for congenital immunodeficiency syndromes. Such
procedures have not yet been performed successfully for thalassemia (Hayward
et al., 1998).
Figure
(3): Management of
thalassemia and treatment related complications (Rund and
Rachmilewitz, 2005).
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