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1
HEMATOPOETIC STEM CELL TRANSPLANT
NAME
COURSE
2
HEMATOPOETIC STEM CELL TRANSPLANTATION (HCT)
Introduction
Hematopoietic stem cell transplantation (HSCT) is a generic name covering a variety of
techniques. Its clinical application include treating deficiency of immune cells, providing
solution for failure in bone marrow, controlling hematological neoplasm, or conditions for
example thalassaemia (Lennard and Jackson, 2000). The technique has helped in
improving bone marrow performance for patients undergoing chemotherapy and
treatment of some solid tumors that include neuroblastoma or breast cancer. Other
clinical applications are in research on diseases that are difficult to treat, addressing
autoimmune diseases for example systematic sclerosis, and tumors such as multiple
myeloma, leukemias, or lymphomas. The technique of cure is rapidly increasing in
application due to its numerous clinical advantages as well as the potential to cure the
most debilitating cancers (Emedicine.medscape.com, 2014).
Types or sources of donors in HSCT are autologous, syngeneic, or allogeneic donors.
Autologous donor of grafts for HSCT is the recipient whose peripheral blood or bone
marrow is used for transplant. The advantage with autologous HSCT is trhat it has no
contraindication. Syngeneic donor is usually identical to the recipient geneticall for
example twin to the recipient and poses least challenges in transplantation, Allogeneic
donors who provide grafts that comprises of the use of peripheral blood, bone marrow,
or blood from umbilical cord are either relatives to the recipient or volunteers not related
to the patient. However, they should be not only healthy but also have matching HLA
type because the technique is limited by donor-recipient histocompatibility (Riddell and
3
Appelbaum, 2007). Peripheral blood, bone marrow, fetal liver and umbilical cord blood,
which is mostly helpful in children due to the fact that it has fewer cells useful for adult
patients, have been the most widely used sources of grafts in HSCT. HSCT has its
disadvantages such as graft rejection due to mismatch in HLA, GvHT disease, infection,
and infertility as complications in spite of its numerous useful clinical applications
(Merckmanuals.com, 2014). The aim of this critical review on HSCT is to explore various
therapies for Graft versus Host Transplantation (GvHT) disease available in the health
facilities or still under development.
Methods
In this study peer reviewed articles were sourced and reviewed both systematically and
critically to provide the necessary information. The papers reviewed were sourced from
electronic databases such as EBSCOhost, MEDLINE, CINAHL, EMBASE, and
SCOPUS. Literature search included papers published from 2000 to recent years with
emphasis being on the most recent publications. The most recent published articles on
hematopoietic stem cell transplantation were preferred because they can provide up to
date information and stronger evidence because the field of HSCT is rapidly developing
due to research as well as changes executed. References retrieved were listed and
relevant studies checked manually. They were then subjected to quality check with the
use of Downs and Black tool and only good studies of moderate and high quality were
included for review (Downs and Black, 1998).
The search terms were in English language and they included hematopoietic stem cells;
Transplantation complications; Graft versus host disease; transplantation therapy; graft
4
rejection; and HLA mismatch. Process of data extraction involves search outcome being
exported to Mendeley which is a free manager for reference. Abstracts were screened
for each title selected to retrieve full text article which were about HSCT. The findings
were critically reviewed or synthesized on the role of HLA in rejection and mismatch of
transplant, GvHT disease, treatment strategies, infection and infertility. Infection
associated with pre and post transplantation. The information extracted was tabulated in
a summary providing full reference, aim of the article, population sample or study
numbers, and period of study, results, and comment on quality.
Inclusion and exclusion criteria were specific on selecting articles that could critically
review the topic of study about HSCT and GvHT disease. The studies were not limited
in terms of area they were conducted, but should have been about HSCT, published
from 2000 to most recent, published or translated in English language. Any articles not
specific to HSCT, titles or abstract not related to topic of study, and expert opinions,
chapters of books, or letters were excluded from the review. The criteria involved vetting
each article for good quality which is a justification of the process because it provides
authentic, reliable, most current and valid information for critical review of HSCT and its
complications.
Rationale for development and refinement of search criteria is to enable selection of
literature with good quality. The author ensured that justification is regarded, information
used is up to date and exploration is rationalized objectively in this study through tight
screening with the criteria before checking the qualities of the studies with the use of
5
Downs and Black tool. This tool was selected for its reliability in identifying good quality
peer reviewed articles for providing evidence in a critical review. In the selection, the
author screened each article to conform that all titles as well as abstracts of the papers
included agreed to the exclusion and inclusion criteria. Retrieved articles were then
screened for reliability and validity before reading through to see possibility of extracting
data
The process yielded 20 peer reviewed articles focusing on HSCT, GvHT disease, and
complications associated with transplantation. The articles were read, information
analyzed, and tabulated in summary. Tabulated summaries were critically reviewed to
provide information on the aspects of the role of HLA in rejection and mismatch of
transplant, main complication of HSCT such as GvHT disease which can be acute or
chronic as well as its causes. The review analyzed some of the treatment strategies for
GvHT disease in addition to exploring complications such as infection and infertility.
Tabulated Summary
Reference Aim of the
paper
Populati
on
Measurem
ent of
exposure
Time span
Result Comme
nt
1. Hwang, J,
& Linker, C,
(2010).
Voriconazol
e is safe
and
effective as
prophylaxis
for early
and late
fungal
infections
Assessing
effectiveness
of
voriconazole
as prophylaxis
against fungal
infections in
allogeneic
HSCT
N=72 2 days
before
transplant
and >120
days post
transplant
14%
suffered
toxicity, 2
patients got
fungal
infection in
<120 days
post
transplant,
no infection
after 120
days,
Good
6
following
allogeneic
hematopoie
tic stem cell
transplantat
ion.
Transplant
Infectious
Disease,
12(1), pp.
45-50.
vericonazole
prophylaxis
is effective.
2. Kinch et al.
(2007).
Posttransplant
lymphoproli
ferative
disease
and other
EpsteinBarr virus
diseases in
allogeneic
haematopoi
etic stem
cell
transplantat
ion after
introduction
of
monitoring
of viral load
by
polymerase
chain
reaction.
Scandinavi
an Journal
Of
Infectious
Diseases.
39(3), pp.
235-244
10p.
Investigating
the clinical
value of
monitoring
Epstein-Barr
virus following
allogeneic
HSCT
N=39 1 year 41% were
infected with
the virus,
monitoring
EBV predicts
infection or
EBV disease
post
transplant.
Good
3. Nigel et al.
(2000).
Evaluate the
results of stem
N=25, 49
years
3.4 years Transplant
related
Good
7
Allogeneic
Haemopoie
tic Stem
Cell
Transplanta
tion for
Multiple
Myeloma or
Plasma Cell
Leukaemia
Using
Fractionate
d Total
Body
Radiation
and Highdose
Melphalan
Conditionin
g.
ActaOncol.
39(7),
pp.837-841.
cell
transplantation
for multiple
myeloma with
high dose
melphalan and
fractionated
total body
irradiation as
conditioning
regimen
median
age.
mortality of
30%, most
from viral
infection, 17
out of 25
achieved
remission,
18 patients
still alive.
4. Blennow et
al. (2014).
Incidence,
risk factors,
and
outcome of
bloodstrea
m infections
during the
preengraftment
phase in
521
allogeneic
hematopoie
tic stem cell
transplantat
ions.
Transplant
Infectious
Disease.
16(1), pp.
106-114.
Investigate
risk factors,
incidence,
microbiology
findings and
outcome of
bloodstream
infection (BSI)
post transplant
and preengraftment
period.
N=521 7 years 21%
incidence
recorded,
3.3%
mortality due
to BSI, 21%
crude
mortality at
120 days
post
transplant.
Other risk
factors were
antibiotic
resistance
and
prophylaxis
with
quinolones.
Good
8
5. Yoo et al.
(2004).
Infectious
complicatio
ns and
outcomes
after
allogeneic
hematopoie
tic stem cell
transplantat
ion in
Korea.
Bone
Marrow
Transplanta
tion, 34(6),
pp. 497-
504.
Assessing the
infection
complication
outcome in
patients
following
HSCT
N=242 2 years Bacterial,
fungal, and
viral
infections
occurred
most
respectively.
3%
tuberculosis,
1 case of
measles,
6.5% and
pneumocysti
s carinii
pneumonia.
43%
mortality
cumulative
and 59.6%
from
infection.
Infection and
mortality
was higher
in allogenic
recipients
from
unrelated
donors.
Good
6. Gotoh et al.
(2014).
Human
herpesvirus
6
reactivation
on the 30th
day after
allogeneic
hematopoie
tic stem cell
transplantat
ion can
predict
grade 2-4
acute graftversus-host
Determining
the
relationship
between
transplantation
related
complication
and viral
reactivation.
N=49, 37
men and
12
women.
100 days
from 30th
day
assessment
after
transplant,
for 6 years
Viral
reactivation
was tested
positive for
CMV-44.9%,
EBV 22.4%,
HHV6-
53.1%, and
HHV7-
18.3%,
HHV6
correlated
with GvHT
disease
grade 2-4,
therefore
can be used
Good
9
disease.
Transplant
Infectious
Disease.
16(3), pp.
440-449.
as a
predictive
marker.
7. Frère et al.
(2006).
Infections
after
allogeneic
hematopoie
tic stem cell
transplantat
ion with a
nonmyeloa
blative
conditioning
regimen.
Bone
Marrow
Transplanta
tion. 37(4),
pp. 411-
418.
Analyzing risk
factors and
incidents of
infection in
patients
undergoing
nonmyeloablat
ive
conditioning
transplant
N=62 >1 year 70%
infection
incident rate,
donor who is
not a sibling,
being male,
early
disease,
older age,
and
corticosteroi
d use are
risk factors
Good
8. Olkinuora
et al.
(2010).
Multiple
viral
infections
posthematopoie
tic stem cell
transplantat
ion are
linked to
the
appearance
of chronic
GVHD
among
pediatric
recipients
of
allogeneic
Evaluating
viral infection
impact on the
recovery of
pediatric
recipients
posttransplant in
regard to
immunereconstitution.
N=124 6 years Prophylaxis
failure of
40%, 89%
viral
infection
rate, impacts
include
secondary
graft failure
and chronic
GvHT
disease due
to
immunologic
al
derangemen
t.
Good
10
grafts.
Pediatric
Transplanta
tion. 14(2),
pp. 242-
248.
9. Siegler et
al. (2005).
Activated
natural
killer cells
from
patients
with acute
myeloid
leukemia
are
cytotoxic
against
autologous
leukemic
blasts in
NOD/SCID
mice.
Leukemia
(08876924)
. 19(12),
pp. 2215-
2222.
Studying the
role of natural
killer cells in
acute myeloid
leukemia
patients during
diagnosis
N=27 12 weeks Natural killer
cells derived
in acute
myeloid
leukemia are
functional,
autologous
acute
myeloid
leukemia
natural killer
cells
decrease
acute
myeloid
leukemia
load by 8-
77%, and
immunother
apy with IL-2
can be
beneficial in
autologous
transplant.
Good
10. Ludajic et
al. (2008).
Impact of
HLA-DPB1
allelic and
single
amino acid
mismatches
on HSCT.
British
Journal Of
Hematology
. 142(3),
pp. 436-
443.
Investigating
the role of
HLA-DPB1 in
HSCT
outcomes
regarding
allele
matching
N=161 8-132
months
Mismatch of
HLA
increases
incidents of
GvHT
disease.
Good
11. Bertinetto Determining N=77 3 years There is a Good
11
et al.
(2006).
Role of
non-HLA
genetic
polymorphi
sms in
graftversus-host
disease
after
haematopoi
etic stem
cell
transplantat
ion.
Internationa
l Journal Of
Immunogen
etics. 33(5),
pp. 375-
384.
genetic
polymorphism
and
correlation to
GvHT disease
using
genotype of
cytokines or
mHA.
positive
correlation
between low
risk of GvHT
disease and
haplotypes
of IL-10,
absence of
IL-1allele
increases
disease risk,
and they can
be used to
identify high
risk patients
prior to
transplant.
12. Brand et al.
(2013). On
the role of
HLA
antibodies
in
hematopoie
tic stem cell
transplantat
ion. Tissue
Antigens.
81(1), pp.
1-11.
Review on the
role of HLA
antibodies in
graft failure of
HSCT with
mismatched
HLA
irrespective of
patient
condition or
type of graft.
37
papers
reviewed
Varied
periods for
each study
reviewed
Donor
specific HLA
antibodies
increases
graft failure
by 2-10
folds,
reducing
HLA
antibodies or
preventing
reactions
leading to
graft failure,
and negative
posttransplantati
on outcome,
and antibody
assessment
has to be
made
forefront in
treatment.
Good
12
13. BorgmannStaudt et al.
(2012).
Fertility
after
allogeneic
haematopoi
etic stem
cell
transplantat
ion in
childhood
and
adolescenc
e. Bone
Marrow
Transplanta
tion. 47(2),
pp. 271-
276.
Determining
the proportion
of patients
who
developed
infertility
following
HSCT and
associated
risk factors.
N=344
pediatrics
,
206
males
and 138
females
5 years Fertility
impairment
was in 83%
females and
69% males.
Risk factors
included TBI
and BU
based
regimens.
Good
14. Masetti et
al. (2015).
Impact of
Inflammator
y Cytokine
Gene
Polymorphi
sms on
Developing
Acute
Graftversus-Host
Disease in
Children
Undergoing
Allogeneic
Hematopoi
etic Stem
Cell
Transplanta
tion.
Journal Of
Immunolog
y Research.
2015, pp. 1-
5.
Testing
polymorphism
s to establish
single
nucleotide
polymorphism
s associated
with GvHT
disease.
N=117
children
15 years There is a
significant
association
between
SNPs and
GvHT
disease
grade II-IV,
donor IL-10,
FAS, and
TLR4, and
recipient IL18 SNP
increased
risk of GvHT
disease.
Good
13
15. Chen et al
(2015).
Efficacy of
Mesenchy
mal Stem
Cell
Therapy for
SteroidRefractory
Acute
GraftVersusHost
Disease
following
Allogeneic
Hematopoi
etic Stem
Cell
Transplanta
tion: A
Systematic
Review and
MetaAnalysis.
Plos ONE.
10(9), pp.
1-17.
Determining
factors
affecting
prognostic
efficacy of
MSCs in
treating GvHT
disease
refractory to
steroid
therapy.
N=301 in
total for
metaanalysis
of studies
Varied
period per
study
Prognosis
depends on
age, lower
GvHT
disease
grade, skin
involvement,
and infusion
numbers.
Complete
response in
136, partial
69, overall
response in
205 patients.
Good
16. Oguz, G,
Akin, S, &
Durna,
(2014).
Symptoms
After
Hospital
Discharge
Following
Hematopoi
etic Stem
Cell
Transplanta
tion. Indian
Journal Of
Palliative
Care. 20(1),
pp. 41-49
Assessing
symptoms and
the need to
manage them
after HSCT in
patients.
N=66 1 year Psychologic
al symptoms
were higher
than
physical
symptoms;
worse
symptoms
were sexual
inactivity or
loss of
interest,
diarrhea,
and
insomnia.
98.5% of
patients
received
Good
14
9p. symptoms’
education at
discharge,
symptoms
managemen
t is vital post
discharge.
17. Guimarães
et al.
(2014).
Autologous
hematopoie
tic stem cell
transplantat
ion in
systemic
sclerosis:
nursing
actions.
Revista
Eletronica
De
Enfermage
m. 16(1),
pp. 77-83
7p.
Identifying
complications
and nursing
actions
following
HSCT during
the use of
regimen for
conditioning
N=27 4 years 96.2%
mucous
membrane
and skin
lesions,
Raynaud’s
phenomeno
n in 81.4%,
and 100%
water
retention.
Actions
included
furosemide
administratio
n, control of
fluid intake,
monitoring,
examination
s, controlling
weight and
venous
pressure.
Good
18. Rodgers et
al. (2014).
Symptom
Prevalence
and
Physiologic
Biomarkers
Among
Adolescent
s Using a
Mobile
Phone
Intervention
Following
Hematopoi
etic Stem
Examining
reports on
symptoms or
complications
following
HSCT during
recovery
period.
N=16 60 days Symptoms
steadily
reduced with
time post
discharge,
distress due
to symptoms
remained
stable,
weight and
BMI reduced
significantly,
the most
occurring
symptoms
were less
Good
15
Cell
Transplanta
tion.
Oncology
Nursing
Forum.
41(3), pp.
229-236 8p.
distressing
and nursing
intervention
was vital for
patients’
recovery.
19. Vokurka at
el. (2014).
The
availability
of HEPAfiltered
rooms and
the
incidence of
pneumonia
in patients
after
haematopoi
etic stem
cell
transplantat
ion (
HSCT):
results from
a
prospective
,
multicentre,
eastern
European
study.
Journal Of
Clinical
Nursing,
23(11/12),
pp. 1648-
1652 5p.
Establishing
the impact of
high efficiency
of HEPA and
non-HEPA
filtered rooms
on mortality
and infections
such as
pneumonia
following
HSCT.
N=689 100 days The
incidence of
pneumonia
infection is
lower in
autologous
than
allogenic
HSCT,
HEPA
filtration
showed a
slightly
better
outcome
compared to
non-HEPA
filtered
rooms, and
the
difference
was
significant in
allogenic
group,
infection was
high in
patients
receiving
corticosteroi
ds.
Good
20. Curro’, D,
Vuolo, L,
Gualandi,
F,
Bacigalupo,
A,
Assessing the
outcome of
patients of low
intensity
lymphoablative
N=7 60 months Low intensity
conditioning
regimen
before
autologous
HSCT is
Good
16
Roccataglia
ta, L,
Capello, E,
Uccelli, A,
Saccardi,
R, Sormani,
M, &
Mancardi,
G, (2015).
Low
intensity
lymphoablative
regimen
followed by
autologous
hematopoie
tic stem cell
transplantat
ion in
severe
forms of
multiple
sclerosis: A
MRI-based
clinical
study.
Multiple
Sclerosis
Journal,
21(11), pp.
1423-1430.
regimen preautologous
HSCT using
clinical data
and MRI.
neffective in
controlling
relapse and
MRI
evidenced
inflammation
but not in
aggressive
disease.
After 5 years
2 patients
were stable,
1 improved,
and 4 mild
disease
progression.
1 patient
relapsed.
Critical Discussion
Role of HLA in rejection and mismatched of transplant has been studied in details
although the mechanism has not been understood conclusively. However, it is important
to note that HLA compatibility is the hallmark of graft rejection and GvHT. The assertion
was confirmed by Ludajic et al. (2008) who investigated the role of HLA-DPB1 in HSCT
outcomes regarding allele matching and found that mismatch of HLA increases
17
incidents of GvHT disease. Bertinetto et al. (2006) further studied the field by determining
genetic polymorphism and correlation to GvHT disease using genotype of cytokines or
mHA. The study demonstrated that there is a positive correlation between low risk of
GvHT disease and haplotypes of IL-10, absence of IL-1 allele increases disease risk,
and they can be used to identify high risk patients prior to transplant. The outcome can
be improved with low intensity lympho-ablative regimen prior to transplantation. This is
supported by Curro et al. (2015) who assessed the outcome of patients of low intensity
lympho-ablative regimen pre-autologous HSCT using clinical data and MRI. The study
showed that low intensity conditioning regimen before autologous HSCT is effective in
controlling relapse and MRI evidenced inflammation but not in aggressive disease.
Main complication of HSCT is GvHT disease which can be acute or chronic. It is caused
by derangements in immune system, infections, HLA mismatch, and reaction between
graft and the host. It is indispensable to address these associated causal factors for
successful HSCT because it is an important therapeutic strategy against hematological
neoplasm. This is confirmed by Siegler et al. (2005) who studied the role of natural killer
cells in acute myeloid leukemia patients during diagnosis and found that Natural killer
cells derived in acute myeloid leukemia are functional, autologous acute myeloid
leukenis natural killer cells decrease acute myeloid leukemia load by 8-77%, and
immunotherapy with IL-2 can be beneficial in autologous transplant. Single nucleotide
polymorphism is also associated with GvHT disease. Masetti et al. (2015) tested
polymorphisms to establish single nucleotide polymorphisms associated with GvHT
disease and found that there is a significant association between SNPs and GvHT
18
disease grade II-IV, donor IL-10, FAS, and TLR4, and recipient IL-18 SNP which
increase risk of GvHT disease.
Management of GvHT is important for improved outcome of transplantation. The
strategies include immune-modulation with steroids or mesenchymal stem cell therapy.
Chen et al. (2015) determined factors affecting prognostic efficacy of MSCs in treating
GvHT disease refractory to steroid therapy and found that MSCs therapy is effective but
prognosis depends on age, lower GvHT disease grade, skin involvement, and infusion
numbers. Patients should be followed up pre and post transplantation for psychological
support and management of physical symptoms because GvHT disease affects
patients. Oguz, Akin, and Durna (2014) assessed symptoms and the need to manage
them after HSCT in patients and found that psychological symptoms were higher than
physical symptoms; worse symptoms were sexual inactivity or loss of interest, diarrhea,
and insomnia. The symptoms affected the patients negatively despite that most patients
received symptoms’ education at discharge; therefore, symptoms management is vital
post discharge. Nursing actions is one of the most applicable strategies for symptoms
management. Guimarães et al. (2014) attempted to identify complications and nursing
actions following HSCT during the use of regimen for conditioning. The study found that
patients suffered from mucous membrane and skin lesions, Raynaud’s phenomenon in
and water retention. Patients benefited from nursing actions which included furosemide
administration, control of fluid intake, monitoring, examinations, controlling weight and
venous pressure.
19
The importance of following up patients to address post-transplantation symptoms as a
therapeutic strategy to manage HSCT complications is fundamental in improving
outcome. Rodgers et al. (2014) further studied the strategy by examining reports on
symptoms or complications following HSCT during recovery period and found that
symptoms steadily reduced with time post discharge, distress due to symptoms
remained stable, weight and BMI reduced significantly, and the most occurring
symptoms were less distressing and nursing intervention was vital for patients’
recovery. These symptoms and infections post transplantation can be reduced by air
conditioning. The assertion is supported by Vokurka et al. (2014) who attempted to
establish the impact of high efficiency of HEPA and non-HEPA filtered rooms on
mortality and infections such as pneumonia following HSCT. The study found that the
incidence of pneumonia infection is lower in autologous than allogenic HSCT, HEPA
filtration showed a slightly better outcome compared to non-HEPA filtered rooms, and
the difference was significant in allogenic group. It was also noted that infection was
high in patients receiving corticosteroids for immune modulation.
Other treatment strategies to improve transplantation outcome involve providing
conditioning regimen. Nigel et al. (2000) evaluated the results of stem cell transplantation
for multiple myeloma with high dose melphalan and fractionated total body irradiation as
conditioning regimen. The strategy reduced transplant related mortality, most from viral
infection, and most patients achieved remission. It is important to adopt infection control
strategies especially from allogeneic recipients because assessment has shown that
infections are the main complication with adverse effects that include graft rejection,
20
worsening of GvHT disease, and mortality post transplantation. Yoo et al. (2004)
assesed the infection complication outcome in patients following HSCT and confirmed
that Bacterial, fungal, and viral infections occurred most respectively. It was
demonstrated that infection and mortality was higher in allogeneic recipients from
unrelated donors, especially due to infection. The assertion is supported by Gotoh et al.
(2014) who determined the relationship between transplantation related complication and
viral reactivation and found that viral reactivation tested positive in recipients posttransplantation. The reactivation is correlated with GvHT disease grade 2-4, therefore
can be used as a predictive marker, as well as providing evidence that GvHT disease is
responsible for infections post-transplantation.
HSCT technique has faced a challenge of GvHT disease and the use of corticosteroid
was adopted but it is associated with increased infection rate. Frère et al. (2006) analyzed
the risk factors and incidents of infection in patients undergoing nonmyeloablative
conditioning transplant. The outcome showed that corticosteroid use increased infection
incident rate with other risk factors including donor who is not a sibling, being male,
early disease, and older age. Such risk factors have negative impacts for example
secondary graft failure and chronic GvHT disease. This is supported by Olkinuora et al.
(2010) who evaluated viral infection impact on the recovery of pediatric recipients posttransplant in regard to immune-reconstitution, and found that impacts of prophylaxis
failure against viral infection include secondary graft failure and chronic GvHT disease
duse to immunological derangement.
21
Infection associated with pre and post transplantation includes mainly viral, bacterial,
and fungal infections. According to Hwang and Linker (2010), antifungal drugs such as
vericonazole have been used as prophylaxis for pre-and post allogeneic HSCT fungal
infections. It was demonstrated that although such drugs have adverse effects such as
toxicity, they reduced incidence of fungal infections and the prophylaxis is effective. It is
important to monitor patients against infections following allogeneic especially for viral
diseases such as Epstein – Barr virus. Evidence in a study by Kinch et al. (2007)
demonstrated that monitoring of patients is useful in predicting as well as managing infections
post-transplantation.
It is important to address risk factors for infection because patients are susceptible to
infections due to immunosuppressant interventions aimed at reducing occurrence of
GvHT disease. A study by Blennow et al. (2014) investigated risk factors, incidence,
microbiology findings and outcome of bloodstream infection (BSI) post transplant and
pre-engraftment period. The study found that antibiotic resistance and inappropriate
prophylaxis with antimicrobials were responsible for increased incidence of infection,
mortality from blood stream infection, and crude mortality post transplantation.
Infertility is one of the main complications as a consequence of HSCT that is important
to understand in order to either treat or prevent especially in pediatric population.
Borgmann-Staudt et al. (2012) studied infertility as a complication of HSCT by determining the
proportion of patients who developed infertility following HSCT and associated risk
factors. The study found that fertility impairment was in 83% female and 69% male
22
patients during post-HSCT. The risk factors included TBI and BU based regimens as
the main cause of infertility.
Conclusion
The aim of this critical review on HSCT was to explore HSCT principles, various
therapies for GvHT disease available in the health facilities or still under development.
The study used systematic critical review to provide evidence that could be used to
achieve the aim of the research study. Findings of the study demonstrated that HLA
incompatibility and mismatch is responsible for failures and most complications in
HSCT. Autologous and syngeneic donors have least complications as compared to
allogeneic donors due to the high propensity of HLA incompatibility in allogeneic donors
to the recipient. Main complications identified as a consequence of HSCT include GvHT
disease, immune-suppression partly due to immune-modulation with drugs such as
corticosteroids, infections, infertility, and other non specific symptoms such as water
retention, diarrhea, and mucosal membrane or skin lesions. Therapeutic measures
include ensuring HLA compatibility, immune modulation and boosting with
mesenchymal stem cells, pharmacological and lympho-ablative conditioning regimen to
minimize GvHT disease. Infection control can be achieved with prophylaxis and
antimicrobial treatment, air conditioning with HEPA to reduce respiratory diseases in
cases of reducing infections. Infertility can be controlled by avoiding TBI and BU based
regimens. Non-specific symptoms can be managed through follow up, psychological
counseling, and nursing actions such as furosemide administration, control of fluid
intake, monitoring, examinations, controlling weight and venous pressure. The gaps
23
identified include inadequate research to explore HLA incompatibility which is
fundamental in preventing or treating GvHT disease, inefficient immune-modulation
strategy that does not result in suppression of immune system, and lack of conditioning
regimen that can be used in pediatrics without resulting in infertility. The advancement
in the field of HSCT and the HLA compatibility mechanisms are puzzling, however,
further research is necessary in improving the applications of HSCT in clinical practice.
The dilemma is in achieving immune-modulation to prevent GvHT disease without
causing immune-suppression. This critical review with contribute in improving HSCT,
guiding researchers to dwell in the gaps identified, and it will benefit patients who need
HSCT.
24
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