‫ قسم المختبرات الطبية‬/ ‫ كلية التقنيات الطبية‬/ ‫جامعة الكتاب‬
2020 / 6 / 10
‫جامعة الكتاب‬
‫كلية التقنيات الطبية‬
‫قسم المختبرات الطبية‬
aplastic anemia
‫ شعيب إبراهيم إسماعيل‬: ‫اعداد الطالب‬
)‫المرحلة الثالثة (تحميل‬
‫ برهان احمد‬.‫اشراف د‬
Introduction
Acquired aplastic anemia (AA) is a rare and life-threaten- ing
disorder, which can be satisfactorily treated in about 90 % of
cases. Survival has progressively ameliorated over the last
30 years thanks to improvement of immunosup- pressive
treatment and of Hematopoietic Stem Cell Trans- plantation
(HSCT). The improvement of supportive care also
contributed to ameliorate the outcome, especially for
patients who do not respond the upfront therapies.
However, correct diagnosis can be very mindful to exclude
possible underlying congenital diseases and thus proceed to
the choice of the right treatment.
In the following sections, we describe the disease’s char-
acteristics, the diagnostic approach and the available treat-
ment options.
Definition
AA is a rare disorder with an estimated incidence of around
1–2 cases per million per year, that is about three-fold
higher in East Asia . Most cases develop between 10 and 25
years of age and over 60 years. AA is defined as pancy-
topenia associated to a persistent hypocellular bone marrow
in the absence of major dysplastic signs and marrow fibro-
sis. The involvement of at least two lineages in peripheral
blood cells is required to confirm diagnosis. Values have to
lower than <10 gr/dl for hemoglobin, than 1.5 × 109/L for
neutrophils and than 50 × 109/L for platelets. The sever- ity
of AA is defined according the modified Camitta criteria .
Treatment
Standard treatment for patients who have a matched sib-
ling donor is HSCT that provides a cure in about 90 % of
patients. This treatment can be applied to patients aged
below 50 years although age limit can be increased to below
age 60 if the patient is medically fit. For those subjects aged
below 50–60 years who lack an identical donor in the
family, combined immunosuppression still represents a
rea- sonable front line option. In younger patients mainly
chil- dren and adolescents, Immunosuppressive Therapy
(IST) can still be a first line option essentially because the
high survival rate, which peaks to about 90 %, enables in
case of failure, good rescue treatment with second-line
HSCT. However in this age group front-line HSCT, if a
matched unrelated donor is rapidly made available, can be
a very effective alternative.
Hematopoietic stem cell transplantation
A recent survey from the EBMT showed an overall good
outcome of AA in adolescents (age 12–18 years). OS was
comparable in front-line MSD HSCT group (82 %) vs IST (86
%). But due to the high rate of relapse of IST, EFS was far
lower in this group (37 %) as compared to transplanted
patients (83 %; P < 0.000) [31]. Second line HSCT proven to
be a good rescue option (OS 78 %, EFS 71 %) for those who
failed first-line IS. Similar results were obtained in large
cohort of 562 children aged 0–12 years
The good outcome in children and adolescents and the
higher significant morbidity and mortality demonstrated in
older AA patients undergoing HSCT make the choice of first
line treatment different according to the patients’ age.
Currently, HSCT in children and young adults (<40 years)
who have a matched sibling donor, still remains the first-
choice treatment with the tendency to con- sider
transplantable from a matched sibling donor, also those
patients up to 50–60 years who are medically fit.
Summary
All patients with AA should be referred to appropriate
Centers with expertise in AA and marrow failure disorders
and offered an accurate diagnostic work-up and follow- up.
In this context, the possibility to identify congenital defects
and/or the appearance of abnormal evolutive clones by
NGS is becoming a challenging tool. For patients with
severe disease and who have a MSD, HSCT represents the
first choice treatment. IS should be administered as a first
options to patients lacking a sibling donor aged >50 years
or even older if medically fit. In younger patients, IST can
still be considered a first line option mainly because the
good rescue chances offered by HSCT performed after IST
failure. In this age group if an UD is made quickly avail-
able, front line transplant can be seriously considered.
Alternative donor transplants and/or different IS strategies
should also be offered to refractory patients as potential
chance of treatment. Future efforts should be
implemented to ameliorate both transplant conditioning
regimens/strate- gies and to investigate novel growth
factors committed to the improvement of stem cell
amplification.