Chronic Leukemias - DSA

Question 1

Hairy Cell Leukemia - pathobiology

Answer 1

B lymphocyte - heavy and light chain Ig rearrangements

BRAF V600E activating mutation

Express: CD19, CD20, CD11C, CD103**, FMC17, CD22

Does not express: CD21, CD5, CD10, CD23

Kappa and lambda light chain phenotype

Express CD25 (TAC), low affinity IL2 receptor (high levels in sera)

Monocytopenia

B and T lymphocytes decreased - CD4/CD8 ratio inverted

Skin test reactivity and Ab-dependent cellular cytotoxicity impaired

Humoral immunity preserved, normal Ig levels

Marrow failure - inhibitory factors - TNF by leukemic infiltrate

Pancytopenia - more marked than anticipated by degree of leukemic infiltration

Question 2

Hairy Cell Leukemia - Clinical manifestations

Answer 2

Pancytopenia, splenomegaly

fatigue, fever, wt loss, infection secondary to granulocytopenia or monocytopenia

Lymphocytosis uncommon, lymphadenopathy rare

Anemia - 85%
Leukopenia, thrombocytopenia 60-75%

Cytopenias - marrow failure or hypersplenism

Repeated infections, rarely systemic vasculitis resembling polyarteritis nods

Predilection to develop TB, atypical mycobacterial infections, fungal infections

Severe monocytopenia characteristic

Question 3

Hairy Cell Leukemia - diagnosis

Answer 3

Cytoplasmic projections, pale blue cytoplasm, loos chromatin structure, 1-2 indistinct nucleoli

Marrow aspiration - inadequate d/t increased reticulum, collagen, fibrin deposits - need bx.
-interstitial or patchy involvement - fried-egg appearance

Strong acid phosphatase (isoenzyme 5) cytochemical reaction - resistant to tartaric acid (TRAP)

Peroxidase -, lysozyme activity absent

Splenomegaly, cytopenia, nonaspirable marrow in middle-aged man - high index of suspicion

Question 4

Hairy Cell Leukemia - ddx

Answer 4

Splenomegaly and minimal lymphadenopathy: NHL, CLL

Splenomegaly, pancytopenia w/ few atypical cells: myelodysplastic syndrome, chronic myeloproliferative neoplasm

Splenomegaly and cytopenia: SLE, autoimmune dz, b-cell and t-cell prolymphocytic leukemias, infiltrative splenomegaly, TB
-dx made on hx, PE, blood/marrow exam

HCL varient: high WBC counts, TRAP -, prominent nucleoli, Ab against CD25; doesn’t respond to agents effective against typical HCL

Question 5

Hairy Cell Leukemia - Treatment

Answer 5

First line: cladribine - 2-Chlorodeoxyadenosine: continuous IV for 7 days or daily short IV for 5 days
-80% remission after single course; retreat relapse for 2nd remission

partial response to purine analogues poor prognostic factor

Remission: add rituximab

Deoxycoformycin - weekly or every 2 weeks for up to 6 mo - 70-80% remission; toxicity - N/V, infection, renal/liver dysfxn, conjunctivitis, photosensitivity - mild

Human leukocyte interferon (HuIFN) or r-IFN-a: rapidly improves granulocyte, platelet, hemoglobin levels w/in 1-3 mo; reduces spleen size, decreases marrow infiltration; complete remission uncommon
-when d/c - relapse within 1-2 years

Rituximab: monoclonal anti-CD20 Ab - 8 weekly infusions

Refractory:
LMB2 - Fc portion of anti-TAC Ab linked to Pseudomonas exotoxin

Moxetumomab - Pseudomonas exotoxin liked to anti-CD22 Ab

BRAF inhibitor - vemurafenib

Splenectomy for splenic infarcts or massive splenomegaly

Prognosis: 85-90% tx w/ cladribine or pentostatin alive at 10 yrs