Heme malignancy

Question 1

Define the following terms:

Lymphoma

Leukemia

Multiple myeloma

Answer 1

Lymphoma: mass lesion of lymphocytes (comes from lymphoid tissue and NOT bone marrow)

Leukemia: excess leukocytes in the blood (lymphoid/myeloid derived; blood AND bone marrow disorder)

Multiple myeloma: plasma cell mass lesion

Question 2

What are some etiologies of WBC neoplasms?

Answer 2

Chromosomal translocations and oncogenes

Inherited genetic factors: Down’s, NF-type I

Viruses: HTLV-1, EBV, HHV8

Environmental agents

Iatrogenic factors

Question 3

Viruses that can causes WBC neoplasms include:

Answer 3

HTLV-1

EBV

HHV-8

Question 4

Acute myeloid leukemia tends to involve the ___ or ___ (which cell types?)

Answer 4

Acute myeloid leukemia tends to involve the hematopoietic stem cell or common myeloid progenitor

Question 5

___ is an antigen expressed by most leukocytes (aka leukocyte common antigen)

Answer 5

CD45

Question 6

CD19 and CD20 are __ (early/late/both) antigens expressed by B cells

Answer 6

CD19 and CD20 are early + late antigens expressed by B cells

Question 7

What antigen is a late B cell antigen? Which antigen is expressed by plasma cells?

Answer 7

CD38 - late B cell antigen

CD138 - plasma cell antigen

Question 8

CD2, CD5, CD7 are all __ T cell markers

Answer 8

CD2, CD5, CD7 are all early + late T cell markers

Question 9

CD3, CD4 and CD8 are expressed by which cells?

Answer 9

CD3, CD4 and CD8 are late T cell antigens

Question 10

___ is expressed on hematopoietic stem cells and persists through the common myeloid and lymphoid stages before disappearing

___ is expressed on the common lymphoid progenitor then disappears when the cells differentiate

Answer 10

CD34 is expressed on hematopoietic stem cells and persists through the common myeloid and lymphoid stages before disappearing

TdT is a expressed on the common lymphoid progenitor then disappears when the cells differentiate

**note that CD10 is B cell specific and CD1a is T cell specific**

Question 11

What is the criteria for AML diagnosis?

Answer 11

At least 20% blasts in marrow or blood

**

Acute myeloid leukemia affects the blast and promyelocyte stages

*need to do iliac crest bone marrow biopsy if AML suspected but not sure*

Question 12

How would a pt with AML present?

Answer 12

AML presentation is typically non specific:

Fatigue, weakness, shortness of breath (low red blood cells)

Fever and/or Infections (low neutrophils)

Bleeding/bruising (low platelets)

(aml can also be discovered incidentally)

**symptoms progress pretty quickly - weeks to months**

Question 13

There are 2 broad categories of AML, namely ___

Answer 13

There are 2 broad categories of AML, namely de novo AML and secondary AML (which occurs secondary to a pre-existing condition e.g. aplastic anemia)

Question 14

De novo AML can further be split into 2 categories. Name them.

Answer 14

AML with genetic aberrations and just AML or AML not otherwise specified

Question 15

Secondary AML can be split into ___ related or ___ related

Answer 15

Secondary AML can be split into myelodysplasia-related or therapy-related

Question 16

Fill in the blanks

Answer 16

AML with t(8; 21) + inv(16) (ass’d w/ eosinophilia in bone marrow or blood) : core binding factor leukemia

T(15;17) is pathognomonic for acute pro-myelocytic leukemia; treated differently from all the other AML types

T(11q23): typically arises following dna damage from topoisomerase inhibitors (e.g. anthracyclines)

NPM: nucleoplasmin, can be mutated and may or may not be a more favorable risk disease

Question 17

What are the treatment options for AML?

Answer 17

Rx for AML is typically chemotherapy +/- stem cell transplant

Question 18

The 2 types of drugs given to pts in induction chemotherapy for AML are ___ and ___

Answer 18

The 2 types of drugs given to pts in induction chemotherapy for AML are cytarabine and idarubicin/daunorubicin (anthracyclines)

**note that this regimen is very toxic and can cause tumor lysis syndrome, alopecia etc (all the bad side effects of chemo you can think of)**

(the goal of Rx is to have <5% blasts in the bone marrow + good blood counts)

Question 19

Pts who experience relapse/primary AML can undergo stem cell transplantation. Explain briefly how a stem cell transplant is done

Answer 19

Injection of GCSF into donor >> cells processed >> given to recipient (along with chemotherapy)

Question 20

There 4 main complications of transplantation. Name them.

Answer 20

Graft vs host disease

Hepatic Sinusoidal Obstruction/Veno-occlusive disease

Mucositis

Infections

Question 21

What treatment options are available to older/more frail pts that can’t tolerate induction chemo for AML?

Answer 21

These pts receive hypomethylating agents (5-Azacitidine) + (Decitabine)

(can also receive gemtuzumab - selectively targets CD33 on myeloid cells, or low dose cytarabine)

Question 22

Describe the mechanism of action of hypomethylating agents

Answer 22

In the normal setting, promoter regions that sit upstream of genes can be hypermethylated by DNMT3a (methyltransferase), which leads to gene silencing

Hypomethylating agents work by inhibiting DNMT3a, thereby blocking the methylation and subsequent silencing of genes

Question 23

Which form of AML results from the translocation of chromosomes 15 and 17?

Answer 23

t(15:17) >> Acute promyelocytic leukemia

**

The t(15:17) translocation leads to the fusion of retinoic acid receptor (RARa) and the PML tumor suppressor protein. The resulting fusion protein RARa/PML leads to acute pro-myelocytic leukemia

Question 24

Acute promyelocytic leukemia is characterized by what changes in the cells?

Answer 24

Large, often bilobed nuclei, azurophilic cytoplasmic granules and Auer rods (which are basically fused lysosomes)

Question 25

Pts with APL will typically present with ___ (low everything) and \_\_\_

Answer 25

Pts with APL will typically present with **panycytopenia** (all your blood cells are low) and DIC (which is what usually kills pts) \*\*need to initiate Rx early; labs look as follows: PT increased PTT increased Fibrinogen decreased Fibrin split products and D-dimers increased\*\*

Question 26

At the first suspicion of APL, pts should be given ___ because it can quickly mitigate the DIC. The treatment of APL includes ___ and \_\_\_

Answer 26

At the first suspicion of APL, pts should be given **all trans retinoic acid** because it can quickly mitigate the DIC. The treatment of APL includes **ATRA** and **arsenic trioxide**

Question 27

A **73 year old woman** with a **history of hypertension** presents to her primary care physician for **slowly worsening fatigue** over the last **several months**. CBC shows: WBC of **1100/μL** (normal, 4,500 - 11,000), Hemoglobin **7.8 g/dL** (normal 12.6-16) Hematocrit **24%** (normal, 37% - 50%) MCV **110 fL** (normal 80-100) Platelets **32,000/μL** (normal, 153,000-367,000). Peripheral smear shows the following: (see image) \*\*discuss the concerning findings\*\*

Answer 27

So the pts WBC, and platelet counts are all low so she's pancytopenic; has worsening fatigue over several months, MCV is elevated The neutrophils aren't quite bands. Its like the bands have split or something

Question 28

A 73 year old woman with a history of hypertension presents to her primary care physician for slowly worsening fatigue over the last several months. CBC shows: WBC of 1100/μL (normal, 4,500 - 11,000), Hemoglobin 7.8 g/dL (normal 12.6-16) Hematocrit 24% (normal, 37% - 50%) MCV 110 fL (normal 80-100) Platelets 32,000/μL (normal, 153,000-367,000). Peripheral smear shows the following: (see image) \*\* **What is the next best step in management?** A.Watchful waiting B.Prescribe iron for anemia C.Prescribe Vitamin B12/folate for anemia D.Perform bone marrow biopsy E.Treat with hypomethylating agent

Answer 28

Perform bone marrow biopsy