Chronic Leukemias

Question 1

Criteria to initiate treatment for CLL

Answer 1

• Disease-related symptoms
• Development of cytopenias (hemoglobin less than 10 g/dl or platelet counts less than 100,000/uL)
• Massive spleen (>6cm below rib) and/or adenopathy (>10cm)
• Autoimmune cytopenias poorly responsive to standard therapies
• Symptomatic or functional extranodal involvement
• Lymphocyte doubling time (although this in isolation is not necessarily an indication to treat)

Question 2

Subtypes of BCR-ABL1

Answer 2

Question 3

MPN with the closest to normal morphology

Answer 3

Essential thrombocythemia

Marrow may be very minimally perturbed!

Question 4

ET-associated mutations

Answer 4

90% have one of JAK2, CALR, and MPL.

10% have a more general myeloid mutation like TET2 or DNMT3A.

Question 5

Answer 5

Essential thrombocythemia with staghorn megakaryocytes

Question 6

What do you do if the JAK2 comes back negative in suspected PV?

Answer 6

1. Try a more sensitive assay! The VAF may be very low.
2. If still negative, you must demonstrate a subnormal EPO level to make the diagnosis

Question 7

Answer 7

Polycythemia vera

“Panmyelosis” with an increase in all myeloid lineages, not just erythroids

Megas are more clustered, more hyperchromatic, “bulbous,” and with less prominent nuclear lobation

Question 8

Answer 8

Primary myelofibrosis

Very aggressive clustering of megakaryocytes and bulbous, “cloud-like”, hyperchromatic nuclei.

Dilated bone marrow sinuses and increased reticulin, sometimes with intrasinusoidal hematopoiesis.

Question 9

Answer 9

Early primary myelofibrosis

Hypercellular marrow with bulbous and hyperchromatic megakaryocytes of varying size with clustering.

Increased M:E ratio.

Elevated platelets are also usually present!

Question 10

Key differences between early PMF and ET in a patient who presents with chronic thrombocytosis

Answer 10

ET: Normocellular marrow, giant megakaryocytes with staghorn nuclei.

Early PMF: Hypercellular marrow, bulbous megekaryocytes with nuclear hyperchromasia and prominent clustering.

Question 11

Chronic neutrophilic leukemia

Answer 11

• Leukocytosis with >25 x 10^9 neutrophils / L
• No dysplasia of neutrophils (normal, mature morphology)
• Less than 5% immature myeloids in the blood
• No significant basophilia or eosinophilia
• Splenomegaly often present

Caused by mutations in CSF3R (present in 85% of cases). If CSF3R mutation is defected, the ICC abs neutrophil requirement drops to 13 x 10^9.

Must be negative for BCR::ABL1.

Question 12

Progression in ET/PV/PMF

Answer 12

Note: In the ICC, we also define 10-19% blasts as “accelerated phase”

Question 13

Paraneoplastic eosinophilias

Question 14

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

Answer 14

Notably, all involve pluripotent stem cells that retain the capacity to differentiate into myeloid and lymphoid neoplasms. Important to subclassify because they respond to TKIs.

Question 15

Chronic eosinophilic leukemia / idiopathic hypereosinophilic syndrome

Answer 15

Persistent eosinophilia >1,500 with associated bone marrow eosinophilia

Exclusion of CML, secondary causes, paraneoplastic causes, and MLN with specific tyrosine kinase rearrangement.

In this case, call HES when there is no evidence of clonality, but organ damage is present. Call CEL when there is evidence of clonality. In the ICC, increased PB (>2%) or BM (>5%) blasts is also sufficient to prove clonality, but must be less than 20% (otherwise it becomes AML).