03 Myeloid Leukemias and Reactive Disorders Flashcards
Benign WBC disorders
Leukemoid reaction Leukoerythroblastic reaction Neutrophilia Neutropenia Eosinophilia Basophilia
Leukoerythroblastic RXN
Immature BM cells in peripheral blood
Infiltration of BM- Mets, BM fibrosis
Stress- Sepsis or GF stress
i.e. Myeloblasts and nucleated RBCS
Neutrophilia
Neutrohils >7k
- Infection
- Sterile inflam and necrosis (MI)
- Drugs- ie. lithium, steroids, catecholamines
Increased production or decreased margination
Leukemoid Rxn
50-80 or 90K Leukocytes
Neutrophils, lymphocytes, or eosinophils
Causes:
- Perforating appendicitis(neut)
- Bordatella (lymphocytes) - Whooping cough
- Cutaneous larval migrans- Eosinophilia
Neutropenia
<1.5k Neuts
- chemo
- aplastic anemia
- immune destruction (SLE)
- Septic shock
Decreased production or increased margination/destruction
Eosinophilia
> .7k eosin
- Asthma/allergy
- parasitic
- addisons/hypercortisol
- Hodgkins lymphoma
Increased recruitment or production via leukotriene stimulation
Basophilia
> .2K
- CML
- CKD
MPNs
CML
Polycythema Vera
PMF (primary myelofibrosis)
Essential Thrombocythemia
Polycythema Vera
JAK mutation
Increased RBC mass, Leukocytosis, thrombocytosis
Decreased EPO
BM fibrosis and hypercellularity in late disease
Splenomegaly, thrombosis, gout, histamine
PMF
Primary myelofibrosis TEARDROP RBCs Leukoerythroblastic rxn - Immature cess in peripheral blood Jak/MPL mutation BM fibrosis and Megakaryocyte atypia
- Splenomegaly with portal HTN,
- Splenic infarct and reactive left pleural effusion
10 years in prefribrotic then 3-7 in fibrotic stages 5-30% get AML *BM failure *Throbosis *Portal HTN *HF
CML t(9:22)
40-60 YO
Hepatosplenomegaly with weakness, weight loss, anorexia
WBC increased (100K): Mature Myeloid cells present with left shift
BM- Granulocytic hyperplasia
t(9:22) BCR-ABL fusion “philadelphia chromosome”
Chronic phase-3 years, accelerated 1 yr, then AML or ALL
Constitutive TK activity - treat with TKi - DASATINIB, IMATINIB (gleevec)
Myelodysplastic syndromes
Blasts <20% in BM and PB Monosomy 5, 7 Trisomy 8 Leukoerythroblastic rxns and syplasia hypercellular dysplasia Hypolobulated, hypogranular, Ring sideroblasts (rings or granules around RBC nuclei) - can be MDS drugs or alcohol
MDS Clinical
50-80 yo.
Weakness, infections, bleeding, or assymptomatic
9-29 month survival
30% progression to AML
Treatment:
Supportive
Hypomethylating agents - Decitabine, Azacitidine
SCT
Essential Thrombocythemia
Jak2 mutation
>450K atypical platelets
Hypercellular BM with abnormal megakayocytes
Giant hypogranular platelets
Bleeding, splenomegalu
12-15 year survival- treat with alkylating agents
0 AML
- course of weeks to months
- Adults age 60
- 25% long term survival (poor prognosis overall)
- large uniform blasts (>20% in BM or PB)
- fine chromatin with many nucleoli
- Cytoplams with granules
- Auer rods!!!
- myelodysplasia
Test with MPE or NSE enzyme assay (blue granules and bright red cytoplasm respectively)
AML clinical presentation
*Cytopenia- weakness, fatigue, petechiae, infections Sometimes: Orgaonmegaly lymphadenopathy extramedullary infiltration rare coagulopathy
AML with good prognosis
t(8:21)
Inv(16)
T(15:17)
AML t(15:17)
Acute promyelocytic leukemia
hypergranular progmyelocytes with auer rods FAGGOT CELLS
Leukopenia with DIC
Treat with ATRA (screwed up RA signaling)
FAVORABLE PROGNOSIS
AML with T(8:21)
Granulocytic AML with a few auer rods
FAVORABLE PROGNOSIS
AML Inv(16)
Granulocytic and monocytic AML
Extramedullary involvemen
FAVORABLE PROGNOSIS
AML 11q23
MLL
monocytic hyperleukocytosis
INTERMEDIATE TO POOR PROGNOSIS
AML with MDS changes
Monosomy 5, 7
POOR PROGNOSIS
ALL
Common in children(75% of childhood cancers) though 50% are adults
M>F
*small blasts
*High N/C
*Absent or scant nucleoli
85%b cell ALLs t(12;21), t(9;22)BCR/ABL (philadelphia chromosome has bad prog)
15% T ALL- adolescent males with mediastinal masses. Worse prognosis
Langerhans cell histocytosis
CD1a langerin positive
*Tennis racket BIRBECK GRANULLES
BRAF MUTATIONS
Hemophagocytic lymphohistocytosis
Primary: defects in perforin gene
Secondary: EBV and Lymphoma associated
*Hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis
FEVER