Transcript BONE MARROW FAILURE SYNDROMES

Maj Gen (R) Masood Anwar
Bone marrow failure syndromes
can be defined as a group of
diseases in which occurs failure
on the part of bone marrow to
produce mature and functional
blood cells in required quantities.
In peripheral blood it will manifest
as pancytopenia, bicytopenia or
some times monocytopenia.
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Suppression of normal bone marrow
maturation (ineffective haemopoiesis)
Destruction or suppression of stem cells
and/or microenvironment
Replacement of normal bone marrow with
abnormal tissue or cells
Destruction of bone marrow with disease
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Most common cause is ineffective
haemopoiesis because of Vitamin B12 and/or
Folate deficiency – 29%
Aplastic anaemia – 22-27%
All other causes for remaining <50%
Aplastic
Anaemia
is
defined
as
pancytopenia in the peripheral blood
with hypoplastic bone marrow and no
evidence
of
any
primary
disease
infiltrating, replacing or suppressing
active haematopoiesis.
APLASTIC ANAEMIA
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Abnormalities of Stem cell
Abnormalities of Stroma
Abnormalities of cytokines
◦ Failure of stem cells to grow in normal culture
◦ Failure of normal stem cells to grow in patient
stromal cell culture
◦ High CSF releaser levels
◦ Decreased response of stem cells to CSF and EPO
EXTRINSIC AGENT
INTRINSIC DEFECT
SILENT IMMUNE
MILD TO
MODERATE
AUTOREACTIVITY
ACUTE DESTRUCTION

Direct Injury (Secondary or Acquired)
◦ Drugs (Iatrogenic), radiation, viruses
◦ Drug toxicity is through intermediate
metabolites
◦ Bind covalently to marrow cell proteins and
DNA leading to DNA damage and apoptosis
◦ Radiation causes direct damage to DNA
◦ Viruses intercalate with DNA

Immune Mediated (idiopathic)
◦ Improvement in
allogeneic BMT
pancytopenia
after
failed
 Immunosuppressive
conditioning
(ALG
or
Cyclophosphamide) intended to allow engraftment
of donor marrow might have promoted the function
of host marrow*
 BMT
of
an
identical
immunosuppression
twin
also
requires

Immune Mediated (idiopathic)
◦ Improvement in
allogeneic BMT
pancytopenia
after
failed
 Immunosuppressive
conditioning
(ALG
or
Cyclophosphamide) intended to allow engraftment
of donor marrow might have promoted the function
of host marrow*
 BMT
of
an
identical
immunosuppression
twin
also
requires

Immune Mediated (idiopathic)
◦ Trials of IST (Immunosuppressive Therapy)
◦ Most successful regimens have been multi-drug
combinations
◦ Effectiveness of such trials strongly suggest immune
mediated cause of the disease
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Congenital
Acquired
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Skeletal
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Skin
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Genitiurinary tract
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Short stature
Microcephaly
Radial anamolies
Hip and spine anamolies
◦ Hyperpigmentation
◦ Hypopigmentation
◦ Renal tract anamolies
◦ Hypogonadism
Craniofacial
Gastrointestinal
Cardiac
No associated abnormalities
SHORT
STATURE
RADIAL ABNORMALITIES
RENAL
ANAMOLIES
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
Primary Idiopathic
Secondry
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PNH
Radiation
Chemicals
Viruses
Drugs
 Regularly causing – cytotoxic
 Probably causing – chloramphenicol
 Rarely causing – Quinine etc
◦ Stroma and growth factors
 Low Hb/Hct, TLC and platelet count defined for
the age and sex together with hypocellular
marrow
 Conveniently divided into three groups for
therapeutic decisions
 Non Severe Aplastic Anaemia (NSAA)
 Severe Aplastic Anaemia (SAA)
 Very Severe Aplastic Anaemia (VSAA)
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Presenting complaints – anaemia, infection,
bleeding
History – family, personal, occupational, drugs
Physical examination – liver, spleen, lymph nodes
Blood counts
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Hb <10 g/dl
Neutrophil count <1.0 X 10^9/l
Platelet count <100 X 10^9/l
Reticulocyte count (corrected) <1%
MCV ~100 fl
Bone marrow
◦ Aspirate
◦ Biopsy