Leukemia, Lymphoma, & Multiple Myeloma

Question 1

Abnormally low neutrophils is called:

Answer 1

Neutropenia

Question 2

Reduction in mature blood cells is called:

Answer 2

Cytopenia

Question 3

Pancytopenia is a deficiency of:

Answer 3

All three cellular components (RBCs, WBCs, Platelets)

Question 4

Normal WBC count

Answer 4

4,400-11,000/mcL

Question 5

< 4.5K WBC

Answer 5

Leukopenia

Question 6

WBC >10K

Answer 6

LEUKOCYTOSIS

Question 7

_________ is cancer of the body’s blood forming tissues

Answer 7

Leukemia

Effects Bone Marrow and Lymphatic System

High numbers of WBCs
• Immature cells
•Fast growth

Types:
• Acute Myeloid Leukemia (AML)
• Chronic Myeloid Leukemia (CML)
• Acute lymphoblastic Leukemia (ALL)
• Chronic lymphocytic Leukemia (CLL)

Question 8

Most common acute leukemia in adults is:

Answer 8

Acute Myeloid Leukemia (AML)

Relatively rate even though most common leukemia

Median age ~65 years
Incidence increases with:
• Age
• M:F ratio ~5:3
• Caucasians

Question 9

Acute Myeloid Leukemia is characterized by an accumulation of ________________.

Answer 9

Leukemia blasts

Peripheral blood is ALWAYS abnormal —> biopsy

Reduced production of normal cells (neutrophils, erythrocytes, platelets)

Question 10

AML Associations

Answer 10

Environmental Factors:
***Chemical exposure, radiation, tobacco, chemotherapy

Genetic abnormalities:
Trisomy 21, Fanconi’s anemia, Familial RUNX1 mutations

Malignant hematologists diseases
***Myelodysplastic syndrome (MDS), Myeloproliferative disorders

Question 11

Clinical presentation of AML

Answer 11

ANEMIA:
• shortness of breath
• dyspnea on exertion
• weakness/fatigue

NEUTROPENIA:
• Infection and fever related to infection

THROMBOCYTOPENIA:
• Bleeding (conjunctival hemorrhages, gingival bleeding, epistaxis, petechiae, menorrhagia, ecchymosis)

OPHTHALMIC CHANGES
• Hemorrhages or white plaques

Question 12

AML Diagnostic tests

Answer 12

***Bone marrow aspiration and biopsy

Blasts form ≥20% of cellularity
<20% blasts in BM with cytogenetic abnormalities

CBC with diff —> cytopenia and blasts ≥ 20%

AUER RODS on peripheral smear

Elevated Creatinine and LFTs and altered electrolytes

Elevated Uric Acid and Lactate Dehydrogenase (LDH) (both from high cell turnover)

Question 13

Absolute Neutrophil Count (ANC)

Answer 13

Normal = 2500-7500 (calculated as WBC x % neutrophils)

Neutrophilia (>10K) could be reactive (stress, trauma), proliferation (cancer), demargination (stress, infection), from meds (corticosteroids), from poison

Neutropenia could be from chemo, radiation, blood CA, overwhelming infection or meds (PCN)

If ANC is abnormal, RECHECK

Question 14

What are AUER RODS?

Answer 14

Clumps of azurophilic granule material
Form elongated needles in leukemia blasts
**Pathognomonic of myeoblasts —> AML

Question 15

AML treatment

Answer 15

Induction = chemotherapy (heavy), with goal to eradicate most leukemic cells

Consolidation = stem cell transplant, with goal to destroy remaining leukemic cells

Maintenance = lower dose chemo, supportive measures

Targeted therapies for certain mutations

Question 16

AML prognosis

Answer 16

Favorable if:
• < 60 years old
• Good performance status
• No comorbities (ie DM, CAD)
• No Hx of exposures to cytotoxic agents or radiation 

Unfavorable if:
• Age > 60
• Hx of exposure
• Hx of myelodysplasia

Question 17

Myelodysplastic Syndrome (MDS)

Answer 17

Cytopenia (low # blood cells)
Ineffective hematopoiesis
May be asymptomatic 
More common in those >60 (increased incidence in men, smokers, benzene exposure)
May progress to AML

Can be treatment related (chemotherapy, radiation therapy)
• Peak incidence 4-6 years after treatment

Question 18

MDS Treatment

Answer 18

Hematopoietic growth factors help blood cells grow/mature

Immunomodulatory agents can alter or regulate immune function

Hypomethylating agents inhibit DNA methylation

Immunosuppressive therapy

Goals to Tx: Minimize cytopenias, maintain quality of life, delay onset of AML transformation

Question 19

Tumor Lysis Syndrome

Answer 19

ONCOLOGIC EMERGENCY! Associated with high mortality

Massive tumor cell lysis —> release of cell contents (Potassium, phosphate, nucleic acids)

Causes:
• Initiation of cytotoxic therapy (usually within 12-24 hours of start of chemo) - possible at at treatment but esp. at first
• Spontaneously with some tumor types (high proliferation rate, large tumor burden, high sensitivity to cytotoxic therapy)

Question 20

The four blood manifestations of tumor lysis syndrome:

Answer 20

Hyperkalemia (inc. potassium)
Hyperphosphatemia (inc. phosphate)
Hypocalcemia (dec. calcium)
Hyperuricemia (inc uric acid)

Question 21

Tumor Lysis Syndrome may result in …

Answer 21

Renal failure —> hemodialysis
ECG changes (arrhythmia)
Seizure
Tetany

Question 22

Treatment of Tumor Lysis Syndrome

Answer 22

PREVENTION!
Fluids, dieresis
Frequent monitoring during therapy (Creatinine, Potassium, Phosphorus, Uric Acid, Calcium)
Meds to lower Uric Acid
Monitor cardiac function
Seizure precautions
Treat hyperkalemia and hyperphosphatemia
Preserve renal function (dialysis)

Question 23

Chronic Myeloid Leukemia

Answer 23

AKA Chronic Myelogenous Leukemia

Uncontrolled production of mature and maturing granulocytes (neutophils and some basophils, eosinophils)

Abnormal gene called BCR-ABL1 fusion gene resulting from the translocation of chromosomes 9 & 22 (Philadelphia Chromosome)

15-20% of leukemia’s in adults (rare)

Slight male predominance

Median age at presentation ~50 years

Risk factor: Ionizing radiation

Question 24

CML signs and symptoms

Answer 24

20-50% are asymptomatic (first suspected on routine blood tests - WBC > 100K, Platelets >600K)

Fatigue (34%)
Malaise (3%)
Abdominal fullness (15%)
*Splenomegaly (48-76%)
Bleeding episodes (21%)
Pain over lower sternum (expanding bone marrow)
B symptoms
• Fever
• Weight loss 20%
• Drenching night sweats 15%

Question 25

The three phases of CML are:

Answer 25

Chronic • 85% of pats diagnosed here (often asymptomatic) • LEUKOCYTOSIS WBC >100K • <10% blood or BM blast cells • Chance for remission is high if to started in this phase Accelerated • 10-19% blood or BM cells are blasts • Progressively impaired neutrophil diff • Leukocyte counts more difficult to control • Sx - Anemia, fatigue, malaise, flu-like Sx Blast Crisis • Resembles acute leukemia • 20% or more of blood or BM cells are blasts • Sx - fatigue, fever, extramedullary blasts, splenomegaly

Question 26

Diagnosis of CML

Answer 26

Confirmed by identification of Philadelphia chromosome and/or BCR-ABL

Question 27

Treatment for CML depends on _________

Answer 27

Stage at Dx Tyrosine Kinase Inhibitors - reduces cell communication and reproduction Monoclonal Antibodies - Flag CA cells, trigger cell membrane destruction, block cell growth, prevent blood vessel growth, block immune system inhibitors, deliver chemo/radiation Allogenic Stem Cell Transplant (possible cure) Prognosis depends on phase as presentation (chronic phases = years of control, accelerated/blastic = poor prognosis), response to TKI tx, and age>65

Question 28

Complications for CML

Answer 28

Tumor lysis syndrome HYPERLEUKOCYTOSIS - WBC >100K • Medical emergency • Decreased tissue perfusion, may require leukapheresis Hyperviscosity syndrome - spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, neuro symptoms, headache, vertigo, seizures, coma • Treat with leukapheresis (blood filter) or plasma exchange

Question 29

The most common cancer in children and teens?

Answer 29

Acute Lymphoblastic Leukemia (ALL) About 30% of all childhood CA Peak incidence at 2-5 years of age M>F Caucasians + Hispanics > African Americans Cure rate more favorable in children

Question 30

Clinical features of ALL

Answer 30

* Fever * Fatigue * Pallor * Hepatosplenomegaly (64/61%) * Lymphadenopathy (50%) Other Sx: Lethargy, petechiae/ecchymosis, bone pain Thymic mass (superior vena cava syndrome, superior mediastinal syndrome) Testicular mass (rare, painless, unilateral) Children: Limp, arthralgia, bleeding Elderly: Anemia-associated dyspnea, angina, dizziness

Question 31

Lab findings for ALL

Answer 31

Lymphoblasts on peripheral blood smear Cytopenias (neutropenia, anemia, thrombocytopenia) Elevated LDH Dx: • BM biopsy

Question 32

Bone marrow biopsy findings for ALL

Answer 32

Morphology (shape) Immunophenotype (proteins expressed by cells) • 70-80% B precursor • 15-17% T precursor Cytogenics (chromosomal abnormalities)

Question 33

Different types of ALL

Answer 33

Precursor B-cell ALL • 70-80% of all childhood cases • 80% express CD10 • Favorable prognosis ``` T-cell ALL • Standard relapse risk • Male predominance • Medistinal Mass • Intramedullary disease ``` ``` Mature B-cell ALL • Also called Burkitt cell leukemia/lymphoma • Male predominance • Bulky extramedullary disease • Often presents with CNS symptoms ```

Question 34

ALL treatment

Answer 34

Chemotherapy Induction • Goal to reduce tumor burden by 99% • Restore normal hematopoiesis • Mortality 5% Consolidation Maintenance Children have 98% rate of complete response

Question 35

ALL Prognosis

Answer 35

``` Good —> 5-year survival >85% if: • Age at Dx <35 • Favorable cytogenetic • Absence of CNS disease at Dx • B-cell v T-cell phenotype ``` Poor for all others

Question 36

Chronic lymphocytic leukemia (CLL) is characterized by progressive _____________________________________.

Answer 36

Accumulation of functionally incompetent B-cell lymphocytes Most prevalent leukemia in western countries 35% of leukemia in US - adults only Median age at dx is 70 M:F is 2:1, caucasians most affected

Question 37

Clinical Features of CLL

Answer 37

Bone Marrow failure —> anemia, thrombocytopenia, neutropenia Organomegaly - most common finding at Dx (LAD 50-90%, Spleen 25-55%, Liver 15-25%) Skin is the most common non-lymphoid organ affected (Leukemia cutis)

Question 38

CLL Indolent Stage

Answer 38

Most patients are asymptomatic Lymphocytosis on blood work B symptoms • Unintentional weight loss ≥10% in 6 months • Fevers >100.5 for at least 2 weeks with no infections • Drenching night sweats • Extreme fatigue

Question 39

Advanced Stage CLL

Answer 39

``` Rapidly progressive/terminal phase May follow indolent phase Lasts 1-2 years Anemia B symptoms Atypical infections Death secondary to infection, bleeding, cachexia ```

Question 40

CLL Diagnostic Tests

Answer 40

``` CBC w Diff • Absolute B lymphocytes ≥5000µL • Mature appearing, small lymphocytes Flow cytomegalovirus of peripheral blood • Clonality of B lymphocytes Bone Marrow Aspirate and biopsy • Increased cellularity • Lymphocytes > 30% Lymph node biopsy • Infiltrate-mostly mature appearing, small lymphocytes ```

Question 41

CLL Prognosis

Answer 41

Based on Staging (Rai and Binet systems) • Asymptomatic early stage, median survival >10 years • Advanced stage or progressive disease, 18 mon to 3 years survival rate without treatment Lymphocyte doubling time • <12 months = significantly shorter survival rate

Question 42

CLL Treatment

Answer 42

Asymptomatic early stage • Observation - not all pt require Tx • Localized radiation therapy Chemotherapy Immunotherapy • Rituximab (CD20) and other monoclonal antibodies, used in combo with chemo Radiation Splenectomy

Question 43

Lymphoma is defined as cancer that begins in ______________

Answer 43

The lymphocytes Lymphocytes located in lymph nodes, spleen, thymus, bone marrow, tonsils, adenoids Main types = Hodgkin and Non-Hodgkin

Question 44

Risk factors for Hodgkin Lymphoma

Answer 44

``` Socioeconomic status Hx of mono caused by EBV Immunosuppressive Autoimmune disorders Family Hx ```

Question 45

Characteristics of Hodgkin Lymphoma

Answer 45

Enlargement of lymph nodes, spleen, liver REED-STERNBERG CELLS - Multinucleated B Cell • Aka “Popcorn cells”

Question 46

Virus found in the Hx for 40-50% of Hodgkin Lymphoma cases

Answer 46

Epstein Barr Virus

Question 47

Key Clinical Features of HL

Answer 47

Painless LAD - cervical most common presentation Mediastinal mass (incidental finding on CXR) Severe pain response after alcohol Systemic symptoms (B symptoms) • Fever > 100.4 • Night sweats • Weight loss Fatigue Pruritus without rash

Question 48

What are the B symptoms?

Answer 48

Weight loss Fever Night sweats

Question 49

Hodgkin Lymphoma diagnostics

Answer 49

Lymph node biopsy —> Reed Sternberg cells confirm Dx Staging involves CT/PET of neck, chest, abdomen, pelvis

Question 50

Treatment of Hodgkin Lymphoma

Answer 50

Combination chemotherapy curative in most cases (even end-stage) Often combined with radiation Tx (particularly in bulky disease or relapsed disease) Stem Cell Transport - secondary relapse or persistent progressive disease

Question 51

Prognosis for HL

Answer 51

Curable in >75% of patients Worse prognosis for those with: • Affected lymph nodes on both sides of the diaphragm • Bulky disease • Distant spread

Question 52

Other considerations for Hodgkin Lymphomas

Answer 52

``` Secondary malignancy or recurrence of HL CAD Pulmonary dysfunction Infertility Hypothyroidism DM Psychosocial issues ```

Question 53

Non-Hodgkin Lymphoma

Answer 53

Can be derived from B or T cells (90% are derived from B lymphocytes) Risk Factors: • Personal or familial Hx of lymphoma • Exposure to pesticides, hair dyes Associations: • Immunodeficiency *HIV) • Autoimmune disease (Lupus, RA, Sjogren’s, Hashimoto’s) • Inflammatory GI disease (Crohn’s, H pylori)

Question 54

Clinical Features of NonHodgkin Lymphoma

Answer 54

Painless, persistent LAD (diffuse or isolated) Mediastinal mass in 20% Extra lymphatic sites (GI, skin, bone, BM, abdominal fullness) B symptoms in intermediate/high grade

Question 55

Aggressive NonHod Lymphomas

Answer 55

1/3 curable with chemo Rapidly growing mass - mediastinal or GI B Symptoms Elevated LDH/uric acid

Question 56

Diagnostic studies for NHL

Answer 56

Biopsy for diagnosis/classification • lymph nodes 2cm or > give best Dx CT or PET/CT to learn areas of involvement and preferred biopsy site Bone marrow aspiration and biopsy ``` Other options • CSF LP • Pleural fluid • Peritoneal fluid • Splenectomy ```

Question 57

Lugano classification for lymphomas

Answer 57

I - one node or a group of adjacent nodes II - two or more nodal groups on the same side of diaphragm II bulky - II with bulky disease III - Nodes on both sides of diaphragm and with spleen involvement IV - additional noncontiguous extralymphatic involvement

Question 58

NHL treatment

Answer 58

Based on stage of disease and patients clinical status Indolent with 1-2 nodes = Radiation alone Agressive intermediate or high grade —> Chemo, immunotherapy, autologous stem cell transplant

Question 59

General characteristics of Multiple Myeloma

Answer 59

``` Malignancy of plasma cells, proliferating in BM • Extensive skeletal destruction • Osteolytic lesions • Osteopenia • Pathologically fractures ``` Can form tumors —> spinal compression Instead of making immunoglobulins, plasma cells secrete paraproteins • Paraproteins in blood —> hyperviscosity • Paraproteins in urine —> renal failure

Question 60

Protein electrophoresis

Answer 60

Performed on blood/urine to show paraproteins as varying narrow bands on the test strip Demonstrates which paraproteins is present Provides an early indication of malignant condition Multiple Myeloma —> “M spike”

Question 61

Clinical Presentation of Multiple Myeloma

Answer 61

``` Fatigue (32%) Back pain Neurological changes (weakness in 32%, paresthesia of LE, bladder/bowel incontinence) Bone pain (58%) esp low back, ribs Infections Renal Failure Bleeding Weight loss (24%) ```

Question 62

Hyperviscosity Syndrome

Answer 62

Spontaneous bleeding from mucous membranes Visual disturbances due to retinopathy Neurological symptoms (HA, vertigo, seizures, coma)

Question 63

Diagnostic studies for Multiple Myeloma

Answer 63

``` CRAB • Calcium > 10.5 • Renal Insufficiency (Cre >2) • Anemia (Hb <10) • Bone Lesions ``` ROULEAUX formation (RBC stacks) Hallmark: MONOCLONAL SPIKE on Protein electrophoresis (SPEP or UPEP) “M Spike” BENCE-JONES proteins in urine X-rays of axial skeleton —> lytic lesions, general osteoporiosis

Question 64

Treatment for Multiple Myeloma

Answer 64

Refer to hematology/oncology Combo chemotherapy Vertebroplasty or balloon kyphoplasty IV BISPHOSPHONATES prevent the loss of bone mass Autologous Hemopoeitic Cell Transplant (HCT)