Hematopoietic stem cells and discorders Flashcards
Polycythemia Vera
Sx
Pruritus after a warm shower
Erythromelalgia
TIA
DVT/PE
Polycythemia Vera
Physical exam
Splenomegaly
Plethora
Polycythemia Vera
Labs
Low EPO Basophilia (smear) Leukocytosis Thrombocytosis JAK2 positive High Vitam in B12 levels Hyperuricemia
DDx with PV Mediated by hypoxemia COPD/OSA Congenital heart disease Intrapumonary shutting Elevated altitude RAS
Thrombosis
TIA
Erythromelalgia unlikely
Pruritus unlikely
Mediated by hypoxemia
Physicals
Plethora
No splenomegaly
Mediated by hypoxemia
Labs
High EPO
No basophilia
No leukocytosis
JAK2 negative
mediated by ectopic or excessive EPO
Renal cell carcinoma
Hepatocellular carcinoma
Uterine fibroids
Mediated by ectopic or excessive EPO
Sx:
Thrombosis possible
TIA unlikely
Erythromelagia unikely
Pruritus unlikely
Mediated by ectopic or excessive EPO
Physicals
Plethora
No HSM
Mediated by ectopic or excessive EPO
Labs
High EPO Microscopic hematuria No basophilia Leukocytosis possible JAK 2 negative
Unusual causes similar to PV
High oxygen affinity hemoglobin
Unusual causes
High oxygen affinity hemoglobin
Sx:
Thrombosis
TIA
Erythromelagia unlikely
Pruritus unlikely
Unusual causes
High oxygen affinity hemoglobin
Physicals
Plethora
No HSM
Unusual causes
High oxygen affinity hemoglobin
Labs:
High EPO
No basophilia
No Leukocytosis
JAK2 negative
PV
What are the 3 phases
- Latent phase
- Proliferative phase
- Spent phase (mimics PMF)
PV
Treatment
When to start?
At the time of diagnosis
PV
Treatment
ASA + phlebotomy if age < 60 yo w/o prior VTE or arterial thrombosis
Hydroxyurea + phlebotomy if age>60 or w/ prior VTE or arterial thrombosis
PV
Treatment goal
Hct <45%
PV
Prognosis
10% evolve into 2nd AML
20% spent phase: bone marrow fibrosis
ET
Dx:
Plt>600 at least 1 month apart
Exclude 2nd causes (iron deficiency and inflammation/infection)
ET
Rx:
when to treat
Can be observed
ET
Sx:
Digital ischemia, erythromelalgia, TIA, visual disturbances, VTE or bleeding
ET
Low risk population
Age<60;
No prior VTE;
WBC<11
ET
Rx: for high risk patients
Hydroxyurea
Plateletpheresis if plt>1000
ET
JAK 2 mutation
Only 50% of patients
Primary Myelofibrosis (PMF) Causes
One of the MPN;
Clonal myeloid disorder–>abnormal proliferating megakaryocytes–>excess fibroblast growth factor–>marrow fibrosis and extramedullary hematopoiesis
PMF
Rx:
When to start
Can be observed;
Rx for symptomatic splenomegaly, worsening cytopenias, and constitutional symptoms.
PMF
Rx:
Splenectomy (perilous);
JAK2 inhibitor: roxolitinib;
HSCT: applied in younger patients, treatment is palliative
Eosinophilia and hypereosinophilic syndrome
Dx
Eosinophilia>1.5x10 9
Eosinophilia and hypereosinophilic syndrome
Causes
Molecular activation of platelet-derived growth factor receptor (PDGFR) alpha or beta or without a known stimulanting factor
Eosinophilia and hypereosinophilic syndrome
Rx:
Glucocorticoids;
Imatinib better in steroid-refractory primary hypereosinophilic syndrome
Myelodysplastic syndrome
Bone marrow character:
Hypercellular
Myelodysplastic syndrome
Dx and prognosis
Bone marrow biopsy and aspiration with cytogenetic studies
Myelodysplastic syndrome
Rx goals:
- Relieve transfusion dependence
2. Prevent transformation to AML
Myelodysplastic syndrome
Rx
Low-risk patient
Does not require treatment at all or infrequent transfusions
Myelodysplastic syndrome
Risk stratification
IPSS-R score: Bone marrow blasts (%); Cytogenetics; Hgb; Plt count; ANC.
Myeloproliferative Neoplasms (MPN) What does it include
CML PV ET Primary myelofibrosis Eosinophilia and hypereosinophilic syndromes
CML
Causes
Philadelphia chromosome;
Translocation of chromosome 9 and 22 t(9;22)
BCR-ABL gene
CML
Rx
When to treat
Treatment required at diagnosis
CML
Rx
What to treat
TKI: Imatinib, nilotinib, or dasatinib and ponatinib
CML
Rx
SE
TKI: prolong QT
CML
Rx
SE: dasatinib:
Pericardial and pleural effusion, pulmonary artery HTN
CML
Rx
SE: ponatinib
severe VTE
AML
Dx
20% or more myeloblasts in either peripheral blood or the marrow
AML
Prognosis
Genetic profile of the leukemic cells.
AML
Rx decisions
Confirm AML
Exclude leukemoid reaction, atypical monocytosis, and chronic leukemias: peripheral blood smear review, flow cytometry
AML
Rx decisions
AML vs ALL
Auer rod on blood smear suggests AML, confirmed with flow cytometry; different treatment paths
AML
Rx decisions
Exclude APL
1 Clinically suspected with DIC, classically with promyelocytes and prominent Auer rods, microgranular variant evaluated by flow cytometry (within 24 hours is ideal, but not possible at all institutions),
2 FISH for t(15; 17).
3 Administer ATRA if suspected; do not await confirmation.
AML
Rx decisions
AML not APL
Begin induction therapy with cytosine arabinoside and an anthracycline
AML
Rx decisions
ALL
Philadelphia chromosome positivity or negativity (determination within 24 hours is ideal, but not possible at all institutions) decides TKI therapy during induction; adolescents/young adults benefit from more intensive pediatric regimens
AML
Rx decisions
Later dexisions- Allogeneic HSC consolidation
Based on fitness of patient and risk of leukemia, predominantly determined by cytogenetic and molecular risk profile
AML
Rx decisions
Later dexisions- Chemotherapy consolidation
Lower risk leukemia, older or less fit patient
AML
Genetic risk profile cytogenetic category
Favorable
t (8;21)
inv (16)
t (15;17)
AML
Genetic risk profile cytogenetic category
Intermediate
Neither favorable nor high
AML
Genetic risk profile cytogenetic category
High risk
complex (>=5 abnormalities) -5 -7 del (5q) 3q abnormal
AML
Treatment
Non-APL
7 day course of cytarabine + 3 day course of anthracycline
AML
Treatment
Non-APL- if patient is age>70 or ill
less toxic hypomethylating agent
Azacitidine or decitabine
ALL
How to stage
CNS analysis with intrachecal chmo
ALL
Dx
25% lymphoblasts in the blood or bone marrow
ALL
Lymphoid blasts features
TdT positve;
MPO negative
ALL
Risk factors
MLLgene rearrangement Hypodiploidy Philadephia chromosome (treatment with TKI)
ALL
Treatment
Young adults
Intensive pediatric regimens: asparaginase
HIgh-risk: allogeneic HSCT
Hematopoietic growth factors
G-CSF
Stimulate neutrophil:
- autoimmune neutropenia
- hasten neutrophil recovery after cytotoxic chemotherapy
- HSC mobilization
Hematopoietic growth factors
EPO
Anemia of CKD in HD or predialysis 1. Iron, B12 and folic acid are repleted 2. TIBC>25%, serum ferritin >100ng/mL; 3. Goal 11g/dL Hasten recovery in chemotherapy-associated anemia
HSCT
Treatment-most helpful
AA
High-risk MDS
AML
HSCT
Risks
Opportunistic infection;
GVH disease: atact gut, liver and skin
HSCT
Treatment for GVHD
Steroids
HSCT
Primary cause of mortality after HSCT for malignant disease
Relapse of the original disease
