Stem Cell Disorders Flashcards
1
Q
Aplastic Anemia
Overview
A
- A relatively uncommon disease
- Due to injury/destruction of the pluripotent stem cell
- Affects all subsequent cell populations ⇒ pancytopenia
2
Q
Aplastic Anemia
Etiologies
A
- 50% of cases have no identifiable cause
-
Congenital
- Fanconi’s anemia
-
Immune
- Ab that ⊗ hematopoiesis
-
Drugs/Toxins
- Predictable dose-related → idiosyncratic (unpredictable)
- Usu. improves w/ withdrawal of the agent
- Ex: chemotherapy, immunosuppressant drugs, XRT acute exposure – industrial accident benzene, gold, NSAIDS, neuroleptics
-
Chloramphenicol ⇒ both reversible dose-related and idiosyncratic rxns
- Idiosyncratic rxn is irreversible and fatal
- Occurs in 1 in 50K people who take the drug
-
Viral
- Hepatitis ⇒ usu. hep C; EBV
- Thymoma
- Pregnancy
3
Q
Fanconi’s Anemia
A
AR trait
Associated with:
- Hypoplasia or other abnormalities of the kidneys
- Hyperpigmentation of the skin
- Hypoplastic or absent thumbs and radii
- High risk of developing acute leukemia
4
Q
Aplastic Anemia
Clinical Manifestations
A
- Weakness, fatigue, high output failure
- Infection
- Bleeding
5
Q
Aplastic Anemia
Diagnosis
A
- Ultimately rests in the bone marrow interpretation
- Must distinguish from hypoplastic myelodysplasia
- Peripheral blood – pancytopenia
- Bone marrow –aplasia; replaced w/ fat
6
Q
Aplastic Anemia
Treatment
A
- Supportive care
- Transfusions
- Abx
- Immunosuppressant agents
- ATG; cyclosporine
- 50% of pts respond
- Bone marrow transplant
7
Q
Pure Red Cell Aplasia
A
- Selective failure of the red cell precursors
- Other cellular elements are normal
- Associated w/ Parvo B19 infection
8
Q
Myelophthisic Anemia
A
-
Infiltration of the bone marrow by tumor, fibrosis, granuloma
- Most common malignancies ⇒ breast, prostate, lung, thyroid
-
Thrombopoiesis is impaired but usu. not neutrophil production
- Often see a left shift
- Severe normochromic, normocytic anemia w/ teardrop cells and nucleated red blood cells
- Bone marrow biopsy is diagnostic
- Treat the underlying disorder
9
Q
Myelodysplastic Syndromes (MDS)
Overview
A
- Clonal disorder in which the exact mechanism remains undefined
- Ineffective hematopoiesis ⇒ peripheral cytopenias and hypercellular marrow
- Chromosomal abnormalities seen in 50-60% of cases
- Complex cytogenetics
- Associated w/ rapid progression to acute leukemia
10
Q
Myelodysplastic Syndromes (MDS)
Secondary Causes
A
-
Alkylating agents:
- Cytoxan
- Mustine
- Nitrosureas
- Procarbazine
- Melphalan
- Benzene
- Insecticides
- Pesticides
- Typically occur 2-3 years after exposure
- If d/t chemotherapy, can be up to 5-7 years
11
Q
Myelodysplastic Syndromes (MDS)
Clinical Manifestations
A
- Anemia: Pallor
-
Thrombocytopenia: Bleeding
- 60% of pts have thrombocytopenia
-
Leukopenia: Fever, infection
- 60% of pts neutropenic and cannot mount an inflammatory response to infection
- Qualitative abnormality in neutrophils
- 10% of pts present initially w/ infection
- Cause of death in 21% of pts
12
Q
Myelodysplastic Syndromes (MDS)
Pathology
A
-
Peripheral Blood ⇒ Macrocytic anemia (↑MCV)
- Multinucleated primitive RBCs
- Abnormal neutrophils
- Hypolobulated PMNs ⇒ Pelger-Huet anomaly
- Agranular PMNs
- Abnormally large platelets
-
Bone Marrow ⇒ Hypercellular
- ↑ Cells in intermediate stages of maturation: ringed sideroblasts, micromegakaryocytes, multinucleated normoblasts
- ↑ Iron stores
13
Q
Myelodysplastic Syndromes (MDS)
FAB Classification
A
- Refractory Anemia (RA) ⇒ < 5% blasts in marrow
- Refractory Anemia w/ Ringed Sideroblasts (RARS) ⇒ 15% sideroblasts in iron stains of the marrow
- Refractory Anemia w/ Excessive Blasts (RAEB) ⇒ Blasts of 5% to < 20%
- Refractory Anemia w/ Excessive Blasts in Transformation (RAEB-T) ⇒ > 20% blasts (now defined as acute leukemia)
14
Q
Chronic Myelomonocytic Leukemia (CMML)
A
- Peripheral monocytosis > 1,000/ul accompanied by other lineage cytopenia
- Peripheral blasts < 5%
- Dysplastic ∆ in the marrow
- Often see pleural/pericardial effusions from 3rd spacing of fluids
- ± Hepatosplenomegaly
- Some feel that it belongs to the myeloproliferative disorders
15
Q
Myelodysplastic Syndromes (MDS)
Chromosomal Abnormalities
A
Most common:
- Trisomy 8, 5q
- Monosomy 7
- Complex (> 3)
16
Q
Myelodysplastic Syndromes (MDS)
Treatment
A
- Supportive Care
- Aggressive Chemotherapy ⇒ anti-leukemia drugs
- Experimental ⇒ monoclonal Ab, Arsenic
- Hypomethylating agents ⇒ help ∆ of marrow and ⊕ nl hematopoiesis
- Bone Marrow Transplant
17
Q
Myeloproliferative Neoplasms
(MPN)
A
- Neoplasms of the multipotent stem cell
- Diseases share features and overlap
- Often have cytogenetic abnormalities ⇒ can progress to acute leukemia
- Except CML, diseases run a chronic course over many years
-
4 main types are:
- Polycythemia Vera
- Essential thrombocytosis
-
Agnogenic Myeloid Metaplasia
(also known as Primary Myelofibrosis) - Chronic Myelogenous Leukemia (CML)
18
Q
Polycythemia Vera
A
- Clonal disorder involving the hematopoietic stem cell
- Leads to autonomous proliferation of erythroid, myeloid, and megakaryocytic cell lines w/ red cells predominating
- Males > females
- Occurs in middle life
- Average age @ dx is 60-65 years
- Must be distinguished from secondary polycythemia
25
Q
Essential Thrombocytosis
Overview
A
- Clonal disorder of the hematpoietic stem cell
-
Leads to autonomous proliferation of all cell lines w/ platelets predominating
- Platelet count can be as high as 3 to 4 million
- An overproduction of platelets in the absence of stimulus
- Must rule out reactive thrombocytosis which can be caused by:
- Inflammation, Bleeding, Iron deficiency, Hemolysis, Malignancy, Post-splenectomy
- Usu. occurs in age > 60 years
33
Q
Agnogenic Myeloid Metaplasia
“Primary Myelofibrosis”
Pathology
A
-
Peripheral Blood:
- Anemia w/ pancytopenia
- Tear drop cells
- Abnormal large platelets
- Presence of precursor WBCs and nucleated RBCs
-
Bone Marrow:
- “Dry tap” ⇒ difficult to aspirate
- ↑ megakaryocytes
- > ⅓ myelofibrosis w/ ↑ reticulin + collagen
- Extramedullary hematopoiesis ⇒ spleen, kidneys, liver, lungs, adrenal glands
38
Q
Chronic Myelogenous Leukemia (CML)
Chromosomal Abnormalities
A
-
The Philadelphia Chromosome
- Translocation b/t chromosomes 9 and 22
- c-abl oncogene from chromosome 9 → bcr breakpoint on chromosome 22
- Aberrant bcr/abl transcript ⇒ tyrosine kinase gene product w/ enhanced activity
- ⊕ Cell division much greater than normal c-abl gene product
- ⊗ Apoptosis
- Unregulated myeloproliferation
-
JAK2
- Located on short arm of chromosome 9
- Mutations ⇒ constitutive tyrosine kinase phosphorylation activity ⇒ hypersensitivity to cytokines
- Most abundant in RBCs and myeloid cells
- Dysregulated TK activity ⇒ possible tx approaches such as in CML
39
Q
Chronic Myelogenous Leukemia (CML)
Pathology
A
-
Peripheral Blood:
- ↑ in granulocytes w/ presence of immature or intermediate stage cells of myeloid series
- ± ↑ Basophils
- ↑ Platelets
- ↓ (zero) in LAP score
-
Bone Marrow:
- Hypercellular w/ ↑ in myeloid elements
