Bone Marrow Failure Flashcards
What is unilineage bone marrow failure
one cytopenia: anemia (RBC) OR neutropenia (WBC) OR thrombocytopenia (platelets)
What is multilineage bone marrow failure
multiple cytopenias: anemia (RBC) AND neutropenia (WBC) AND thrombocytopenia (platelets) AKA pancytopenia
define pancytopenia
all three cell lines (RBCs, WBCs, and platelets) are decreased
What are RBCs, WBC, and platelets made from
hematopoietic stem cells in the bone marrow
Define hematopoiesis
process of making blood cells
Define erythropoiesis
making erythrocytes
Define myelopoiesis
making neutrophils
Define thrombopoiesis
making platelets
Define bone marrow failure (BMF)
refers to peripheral blood cytopenias resulting from decreased or absent blood cell production in the bone marrow
Is bone marrow failure (BMF) acquired or inherited (genetics)
both VERY important to distinguish between the two
Classifications of bone marrow failure (BMF)
severe: bone marrow with less than or equal to 25% cellularity AND meets at lest two criteria of cytopenias (ANC less than 500, platelets less than 20K, or ARC less than 40K) moderate mild
ANC ARC
absolute neutrophil count absolute retic count
Clinical manifestations of bone marrow failure (BMF)
as per their cytopenias ie) symptomatic anemia or bleeding or…etc)
Diagnosis of bone marrow failure (BMF)
examination of bone marrow so do a bone marrow biopsy unexplained inc or dec in blood cell counts unexplained inc or dec in abnormal cells
Difference between BMF and Aplastic Anemia (AA)
see picture
Diff Dx for hematopoietic stem cell (HSC) injury
aplastic anemia or bone marrow failure: idiopathic immune mediated due to drugs, toxin, viruses inherited BMF syndorme (fanconi anemia or dyskeratosis congenita)
Acquired AA/BMF
idiopathic (80% of acquired AA/BMF) post-hepatitis drugs toxins infection
Congenital AA/BMF
Falconi Anemia Dyskeratosis Congenita Diamond Blackfan Anemia
Clinical presentation of AA/BMF
sign and symptoms of: anemia (fatigue, pallor) thrombocytopenia (bruising, bleeding) leukopenia/neutropenia (fever, signs/symptoms of severe infection)
Diagnostic tests
CBC with diff bone marrow aspirate and biopsy
Other diagnostic tests for acquired AA/BMF
viral studies (parvovirus B19) liver panel vit B12 ANA profile (antinuclear antibody: screens for Lupus) PNH (paroxysmal nocturnal hemoglobinuria) by flow cytometry
Other diagnostic tests for congenital AA/BMF
elevated Hgb F elevated MCV chromosome breakage analysis* telomere length testing* genetic panel
Treatment for AA/BMF
depends on underlying etiology
pathophysiology of acquired idiopathic AA
not sure, but maybe immune mediated destruction of hematopoietic stem cells (HSC)
diagnostic test for acquired idiopathic AA
no confirmatory test rule out genetic/congential causes
is acquired idiopathic AA life threatening
yes, requires urgent evaluations and care as patients are at high risk for serious bacterial infection
treatment of acquired idiopathic AA
Best/1st choice: hematopoietic stem cell (HSC) transplant 2nd choice: immunosuppressive therapy (combo of antithymocyte globulin (ATG) and cyclosporine (CSA): unclear why works but they are lymphocytotoxic so they may decrease immune mediated destruction of HSC) (about 1/3 relapse) also: supportive care with blood transfusions util definitive therapy
treatment of acquired post-hepatits AA
similar to acquired idiopathic AA
treatment of acquired AA due to infection
similar to acquired idiopathic AA
treatment of acquired AA due to drugs
remove offending agent
treatment of acquired AA due to toxins
remove offending agent
another name for congenital/inherited/genetic AA
inherited bone marrow failure syndrome (IBMFS)
the three IBMFS
Falcon Anemia Dyskeratosis Congentia Diamond Blackfan Anemai
why is it important to rule out IBMFS before looking at acquired AA causes for patients with AA prior to initiation of therapy (another way to ask this question: why is it important to distinguish if AA is acquired or congenital
IBMFS will not respond to immunosuppressive therapy (have exposed them to drugs that could have nasty side effects and have delayed definitive Dx) other family members may be affected (this is important info if matched related bone marrow transplant is planned)
Common phenotypes of IBMFS
poor growth endocrinopathies anatomical abnormalities of the limbs/digits (i.e. thumbs) anatomical abnormalities of genitourinary tract anatomical abnormalities of heart
Persons with IBMFS are predisposed to develop what
leukemia or other cancers
diagnosis of IBMFS
genetic testing
treatment of IBMFS
HSC transplant is curative but not always indicated for IBMFS
define falconi anemia (FA)
mostly autosomal recessive disorder characterized by PROGRESSIVE BMF leading to pancytopenia (often starts with isolated thrombocytopenia and/or macrocytosis)
common congenital abnormalities of falconi anemia (FA)
abnormal skin pigment (cafe au lait spot), short stature, skeletal abnormalities (microophthalmia: small eyes), upper limb abnormalities (thumbs), and reproductive organ abnormalities (25% may have no anatomical abnormalities)
when are hematologic abnormalities noticed in Falconi Anemia (FA)
median age 7
diagnostic test for Fanconi Anemia (FA)
chromosome breakage: increased chromosome breakage when exposed to DNA cross linking agents
treatment of Fanconi Anemia (FA)
HSC transplant supportive blood transfusions until HSCT
prognosis of Fanconi Anemia (FA)
800-1000x higher risk of developing cancer inc risk of myelodysplastic syndrome (MDS) and progression to acute myeloid leukemia (AML) requires continued monitoring for development of endocrinopathies, cancer surveillance, and anatomic abnormalities
characteristics of Dyskeratosis Congenita
BMF (may present early on with mild cytopenia, most often thrombocytopenia) high incidence of cancer lung and liver fibrosis
what are those with Dyskeratosis Congenita at risk for
MDS leukemia head/neck cancer
what percent of those with Dyskeratosis Congentia develop BMF by age 30
90%
Clinical presentation of Dyskeratosis Congentia
leukoplakia (oral) hypo/hyper-pigmentation (reticulate) nail dystrophy can show all together as classic mucocutaneous triad
Common family Hx of Dyskeratosis Congentia
MDS early graying of hair nail abnormalities lung fibrosis
Pathogenesis of Dyskeratosis Congenita
mutations in genes encoding for factors implicated in telomere function
diagnostic test for Dyskeratosis Congenita
test for telomere length (will be very short for age)
define Diamond Blackfan Anemia (DBA)
genetically and clinically heterogeneous due to mutations in the ribosomal subunit, bone marrow will have paucity of erythroid precursors but normal myeloid precursors and megakaryocytic
Presentation of Diamond Blackfan Anemia (DBA)
isolated macroytic anemia within first year of life, generally rest of CBC looks normal
characteristics of Diamond Blackfan Anemia (DBA)
skeletal abnormalities (thumb) renal issues craniofacial or cardiac abnormalities short stature
diagnosis of Diamond Blackfan Anemia
RBC have inc activity of adenosine deaminase (eADA)
what are patients with Diamond Blackfan Anemia at risk for
malignancies
treatment of Diamond Blackfan Anemia
supportive care with RBC transfusions anemia may respond to steroid therapy HSC transplant if indicated
what is the only curative option for congenital/inherited BMF
HSC transplant
what are your options to treat acquired BMF
HSC transplant immune suppressive therapy
HLA matching best source
MRD (matched related donor) usually sibling
other sources for HLA matching
MUD (matched unrelated donor) haploidentical (50% match of related donor so usually parent: not the best outcomes: in emergency situations)
complications of HSC transplant
graft rejection (original disease returns because recipients immune system attacked and killed donated stem cells) graft vs host disease (when donor stem cells attack the recipients native tissues) above increased with mismatching between donor and recipient
complications of HSC transplant if use autologous source (from donor)
no complications except that there is a risk of same disease returning
