In conclusion, AlloHCT has shown
success in eradicating the symptoms and complications related to SCA IN
PAEDIATRIC PATIENTS however more prospective
controlled trials comparing HSCT and standard of care are needed to determine
the long-term influence on QOL in adult patients (Yawn et al, 2014). However,
development of more therapies targeting GVHD is currently most critical in those
with the disorder.
Figure 4: Overall
survival in children with SCA who had an unrelated donor transplant facilitated
by NMDP/Be The Match.
Although substantial evidence exists supporting
the use of MSD HSCT, only 18% of SCA patients have a HLA MSD (Angelucci et al,
2014). Recent data from a matched unrelated donor (MUD) clinical trial of 29 children with
severe SCA showed 1- and 2-year EFS of 76% and 69%, and OS rates of 86% and 79%
after a median follow-up of 26 months. The incidence rate
of cGVHD was reported at 62%
with 38% extensive cGVHD and an associated mortality of seven deaths. In future, the focus of MURD transplantation for SCA should be to decrease
occurrence of GVHD prophylaxis. Additionally, an OS rate of 72% was documented for children
with a MUD and CB units at 5 years Figure 4.
the other hand, CB transplantation poses a risk of infection because of slower neutrophil engraftment as well as higher risks of graft failure and rejection. To counteract
this, a conditioning regimen with increased intensity is needed but this poses
it’s own risk of further toxicities such as organ damage etc.
Subsequently, Locatelli et al (2013) conducted
a study assessing outcomes of HSCT using either BM or CB to establish whether CB decreased
HSCT complications. With
a median follow-up of 70 months, 6- year OS was high at 97% whereas 6-year EFS rates
were 92% and 90%. Patients with SCA had excellent outcomes after HLA identical
sibling CBT with less GVHD and none had cGVHD.
An alternative source of HSCs to consider
in transplantation is Umbilical cord blood (CB) which in comparison to BMT provides
reduced incidence and
severity of GvHD as well as the ease and safety of hematopoietic collection (Pinto et al, 2008).
summary, NMC could be the preferred conditioning
regimen in adult patients usually excluded from BMT trials. Despite the promising survival outcomes, routine
application of this method is not possible for children because of the probable,
long-term toxicity of TBI.
In 2014, a phase 1-2 study carried out
by Hsieh et al (2014) determined the
possibility of decreasing the toxicity of HSCT via nonmyeloablative allogeneic BMT.
A single total body irradiation (TBI)
dose of alemtuzumab and oral sirolimus were given to 23 adults with
severe SCA. Data showed
improvement in mean Hb levels for females and males. Nine patients developed
long-term, stable donor engraftment. After a median follow up of 30 months, all
patients were alive with no acute or chronic GVHD (See figure 4).
A better outcome of transplantation
was experienced in children with HLA matched donors however MC is generally too
toxic for adult patients with SCA who have accumulated organ damage, therefore
causing a risk of morbidity and
mortality. Some of the toxicities
observed are infertility and gonadal failure and graft versus host disease
(GVHD) (an immunological reaction where the donor
cells reject recipient tissues).
Chronic GVHD (cGVHD) seems to be an important issue affecting
the quality of life of patients in most studies with high rates of >20%. Graft failure (GF) is another damaging complication defined as
>95% recipient CD3+ or CD34+ cells at any single time after engraftment. Panepinto et al (2007) reported
6/54 patients given
the bone marrow graft type developed aGVHD and 11 had cGVHD whereas 9 patients had GF with signs of sickle erythropoiesis.
Median Age (Years)
Panepinto et al (2007)
Bu-Cy, CsA, MTX
85% @ 5 years
Bernaudin et al (2010)
80% by age 18 in Africa (Piel
et al, 2013). SCA is a blood disorder caused by an inherited qualitative
mutation in the haemoglobin beta gene (HBB) resulting in the
Sickle haemoglobin (HbS). The ?rst curative treatment for SCA was
reported in 1984 after haematopoietic stem cell transplantation (HSCT) of a patient with both SCA and acute myeloid Leukemia. Significant
advances have been made since and many children have undergone the procedure.