MDS_and_MPNS Flashcards
MDS
Neoplastic clonal population from STEM CELLS → take over marrow → failure to make normal cells in 1/m lineages → ineffective hematopoiesis → AML risk
MPNs
Neoplastic clonal population from NORMAL cells → take over marrow (Hypercellular marrow) → make too many normal cells in 1/m lineages → splenomegaly and/or hepatomegaly →
can escalate to marrow fibrosis → BM failure → MDS or AML
Is MDS or MPNs due to persistant cytopenias in 1/m lineages?
MDS
Marrow findings of MDS
- Dysplasia: - dyserythropoiesis - dysgranulopoiesis - dysmegakaryopoiesis
- ringed sideroblasts
- bi-lobed PMNs : pseudo-pelger huet cells
4. small megakaryocytes
Types of MDS
- Primary/idiopathic
2. Secondary/ Therapy related
Types of MPNs
- Chronic Myelogenous leukemias (CML)
- Polycythemia Vera
- Primary Myelofibrosis (PMF)
- Essential Thrombocytopenia (ET)
Onset of Primary vs Secondary MDS primary: insidious
secondary: 2-8 yr latency
primary: insidious
secondary: 2-8 yr latency
Cytogenic abnormality of primary/idiopathic MDS
- Monosomy 5 or 7
- del 7q or 5q
- trisomy 8
MDS vs MPNs Pt population target
MDS: >50, median: 70
MPNs: 40-60yrs
Neoplastic causes of secondary (T-MDS)
whole/partial del ch 5 or 7
in conjunction w/ use of alkylating agents and ionizing radiation
Non-neoplastic causes of secondary (T-MDS)
- chemo drugs
2. Vit Def.
3. Viral infection
4. toxin/heavy metals
Low grade MDS
Myeloblasts 20% blasts)
High grade MDS
Myeloblasts >5 but >2% of peripheral blood cells
CML of MPNs have >20% blasts
Types of low grade MDS and prognosis
- Refractory Cytopenia with Unilineage Dysplasia (RC-UD) - good prognosis
- Refractory Cytopenia with Multilineage Dysplasia (RC-MD) - worse prognosis
Types of high grade MDS and prognosis
- Refractory Anemia with Excess Blasts-1 (RAEB-1)
- dismal prognosis
2. Refractory Anemia with Excess Blasts-2 (RAEB-2) - very dismal prognosis
Chromosomal abnormalities of: CML
BCR-ABL t(9;22) p(210)
Chromosomal abnormalities of:
Polycythemia Vera Jak2
- V617 point mutation
Jak2
- V617 point mutation
Chromosomal abnormalities of: Primary myelofibrosis (PMF)
Jak2 in 50%
or CALR or MPL ???
Chromosomal abnormalities of: Essential thromocytopenia (ET)
Jak2 in 50%
or CALR or MPL ???
Prognosis of:
- Polycythemia Vera
- Primary Myelofibrosis (PMF)
- Essential Thrombocytopenia (ET)
Polycythemia Vera
- Good (10-20 yrs)
Primary Myelofibrosis (PMF) - poor (~5 yrs)
Essential Thrombocytopenia (ET)
- Good (10-15 YRS)
Stages/phases of: CML
Initial phase (accelerated phase) Blast phase
Stages/phases of: PV
Polycythemic stage Spent phase
Stages/phases of: PMF
Prefibrotic stage Fibrotic stage
Observations in CML:
- Initial phase
- Blast phase
Initial phase:
(Hypercellular bone marrow):
- ↑neutrophils (neutrophilia)
- ↑ basophils
- ↑platelets
- Small megakaryocytes (w round, non lobulated nuclei)
Blast phase: - > 20% blasts in marrow/blood
Can progress to AML
Observations in PV:
- Polycythemic stage
- Spent phase
Polycythemic stage - ↑ cell count (hypercellularity)
Spent phase - ↓ cell count - marrow fibrosis - trilineage hyperplasia (erythrocytosis, neutrophilia, thrombocytosis) - Large macrophages
Observations in PMF:
- Prefibrotic stage
- Fibrotic stage
Prefibrotic stage (hypercellular marrow) - ↑neutrophils (neutrophilia) (no ↑ basophils) - ↑platelets - Large megakaryocytes (bizarre)
Fibrotic stage - reticulin fibrosis of marrow - dacrocytes - extramedullary hematopoiesis - leukoerythroblastosis
histo findings in ET
- normocellular
- Thrombocytosis
- Large megakaryocytes (bizzare)
- ↑platelets
Symptoms of CML
- Splenomegaly
- Fatigue
- Anemia
- Weight loss
- Night Sweats
Symptoms of PV
- Hepato/splenomegaly - Headaches - dizziness - Visual problems - Paresthesia - Plethora (redness) - Itching
Symptoms of ET
- No splenomegaly - Usually asymptomatic (Usu diagnosed from - ↑platelets) - transient ischemic attack
Which of the MPNs is at risk for thrombosis? Of which arteries? how do you treat it?
Polycythemia Vera - Portal - Mesenteric - Splenic
–> treat w/ serial phlebotomy