Section 2: Pediatric Cancers - Leukemia

Front 1

Define Leukemia

Back 1

A malignant disorder of blood & blood-forming organs (bone marrow, lymph nodes, & spleen)

Front 2

What is the pathophysiology of Leukemia?

Back 2

Immature cells (blasts) accumulate in the marrow spaces, peripheral vasculature & organs; blocking normal cell proliferation due to lack of space & nutrients.

Front 3

ALL stands for ______? - differentiation & proliferation of lymphoid cell lineage.

Back 3

Acute lymphoblastic, lymphocytic, lymphoid, precursor B, & precursor T leukemia.

Front 4

AML stands for ________? - differentiation & proliferation of myeloid/erythroid or megakaryocytic cell lines

Back 4

Acute myelogenous, non-lymphoblastic, myeloid, or myeloblastic leukemia.

Front 5

CML stands for ________? - an abnormality in proliferation of myeloid cells.

Back 5

Chronic myeloid leukemia

Front 6

How is leukemia classified today?

Back 6

By WHO - Using morphology, immunophenotyping, molecular genetic, and cytogenetic factors.

Front 7

How WAS leukemia classified previously?

Back 7

By French-American-British Cooperative Group (FAB) - based primarily on a morphologic & biochemical system. (M0 - M7 for AML; L1 - L3 for ALL)

Front 8

What % of childhood cancers account for each major classification?

Back 8

ALL, 75-80% childhood leukemia
AML, 15-20% childhood leukemia
CML, less than 5% childhood leukemia

Front 9

What is morphology based on?

Back 9

descriptive appearances of the blood & bone marrow cells under light microscope. (can see myeloid vs lymphoid)

Front 10

T or F: As cells mature in the bone marrow the expression of antigens change

Back 10

True

Front 11

What has been developed to help confirm the differentiation between ALL and AML?

Back 11

monoclonal antibodies that react with lineage-specific & stage-specific lymphoid & myeloid activation & differentiation antigens

Front 12

How are monoclonal antibodies identified?

Back 12

A classification number with the prefix "CD".

Front 13

What is the most common antigen identified with ALL & a good prognosis?

Back 13

CD10 - it is positive in 80% of ALL patients.

Front 14

T or F: One can differentiate between lymphoid or myeloid leukemia by exposing the cells to certain chemicals

Back 14

True - biochemical markers

Front 15

T or F: 90% of patients with ALL have a cytogenetic abnormality

Back 15

True

Front 16

What is the term used when an abnormality exists in the number of chromosomes?

Back 16

"ploidy" - can be 'di', 'tri', 'hyper', 'hypo', or 'pseudo'.

Front 17

What is the term used when an abnormality exists in the structure of chromosomes?

Back 17

"translocations" or "deletions"

Front 18

What other techniques are used to identify these cytogenetic abnormalities other than conventional chromosome analysis?

Back 18

RT-PCR = Reverse transcript polymerase chain reaction
FISH = Fluorescence in situ hybridization

Front 19

Abnormalities associated with the number of chromosomes is associated with what?

Back 19

Prognosis (Hyper = good; Hypo & pseudo = poor)

Front 20

T or F: Trisomes 4 and 10 are associated with low risk of treatment failure

Back 20

True

Front 21

Common translocations are associated with what in regards to ALL & AML?

Back 21

They hold prognostic significance

Front 22

What common translocations are associated with ALL?

Back 22

1. TEL-AML1 (20-30%) - favorable outcome; most common
2. BCR-ABL (Ph+) - can be ALL or CML
3. MLL (common to infant ALL) - poor prognosis

Front 23

What percentage of ALL is Ph+ (BCR-ABL protein expressed)?

Back 23

2-3% & responds poorly to conventional chemotherapy

Front 24

When does the TEL-AML1 abnormality occur?

Back 24

TEL gene on chromosome 12p13 fuses with AML1 gene on chromosome 21q22

Front 25

What chromosome is the MLL translocation t(4;11)?

Back 25

On chromosome 11q23

Front 26

What chromosome is the BCR-ABL protein characterized by?

Back 26

t(9;22) = BCR-ABL; on (q34;q11) translocation.

Front 27

T or F: AML is a highly molecular heterogeneous disease with many chromosome abnormaltities

Back 27

True - so many changes; therefore has been difficult to assign prognostic significance

Front 28

What are some common translocations associated in AML?

Back 28

1. PML/RARA
2. AML1-ETO
3. Inv (16)

Front 29

What chromosome abnormalities are seen in M3 AML (acute promyelocytic leukemia)?

Back 29

PML/RARA, t(15;17), (q22;q12)
= best prognosis of all AML subgroups

Front 30

What is the most common abnormality seen in AML, and carries an average-to-good prognosis?

Back 30

AML1-ETO, t(8;21)
- 8-13% of all AML diagnoses

Front 31

What is the single-best predictor of a favorable outcome in AML?

Back 31

presence of trisomy 21 (Down syndrome)

Front 32

Unfavorable prognostic chromosome abnormalities in 'B-cell ALL', and 'AML'

Back 32

B-cell ALL = hypodiploidy, t(4;11)
AML = t(4;11)

Front 33

What are the presenting S/S of ALL?

Back 33

1. Anemia = malaise, fatigue, pallor
2. Thrombocytopenia = bleeding
3. Neutropenia = fever
4. Hepatosplenomegaly
5. CNS dz (<10%) = Incr'd ICP, HA, vomiting, visual disturbance
6. Bone pain (23% present)
7. Lymphadenopathy

Front 34

What are the presenting S/S of AML?

Back 34

1. Lymphadenopathy
2. Fever
3. Pallor
4. Anorexia, weight loss
5. Weakness, fatigue
6. Sore throat, recurrent infections
7. GI s/s= n/v, abd pain
8. Gingival hypertrophy
9. Chloromas

Front 35

What is peak age of onset for ALL?

Back 35

2 to 6 years old

Front 36

What ethnicity is more greatly affected with ALL?

Back 36

Caucasian and Hispanics

Front 37

What gender is more greatly affected with ALL?

Back 37

Males >females
Males (Tcell disease)

Front 38

T or F: There is a higher incidence of ALL in Western and industrialized nations

Back 38

True

Front 39

T or F: ALL accounts for 40% of all childhood cancers

Back 39

True (75-80% new leukemia cases/yr)

Front 40

What environmental exposures have been associated with the development of ALL?

Back 40

exposure to ionizing radiation

Front 41

What genetic factors are associated with ALL?

Back 41

1. Trisomy 21 (Down syndrome) - twenty times greater risk
2. Fanconi & Diamond-Blackfan anemia
3. Older maternal age at birth
4. Maternal history of fetal loss
5. Ataxia telangiectasia, Klienfelter, Shwachman and Bloom syndromes.
6. Sibiling with ALL
7. Monozygotic twins <7yrs old = 25% chance of ALL once one twin does

Front 42

What percentage of childhood leukemia does AML account for?

Back 42

15% of all childhood leukemia cases in US

Front 43

When is the peak incidence for diagnosis of AML?

Back 43

Neonatal period; with slight incr'd frequency during adolescence

Front 44

What ethnicity is AML more commonly diagnosed?

Back 44

Hispanic (also with APML), with higher incidence in African Americans than Caucasians.

Front 45

What genetic factors are associated with AML?

Back 45

1. Trisomy 21 (greatest occurrence <3years old)
2. Fanconi, aplastic, & Diamond-Blackfan anemias; Bloom syndrome
3. Neurofibromatosis
4. Myelodysplastic syndrome (Monosomy 7)
5. Sibling with AML
6. Twin <6yrs old has 20-25% chance of AML once one twin does

Front 46

What environmental exposures are associated with Leukemia?

Back 46

1. Certain drugs/chemicals (alkylating agents, epipodophyllotoxins, nitro-soureas, benzenes, herbicides, pesticides)
2. Ionizing radiation
3. Prenatal maternal cigarette smoke exposure
4. Prenatal maternal alcohol use
5. Advanced maternal age
6. Petroleum product exposure

Front 47

What are favorable prognostic factors for AML?

Back 47

1. Age >2 years
2. WBC <50,000
3. Female
4. No extramedullary disease
5. Presence of t(8;21), inv(16), or normal chromosomes
6. Down syndrome

Front 48

What tests are done for diagnosis of leukemia?

Back 48

H&P, family hx, psychosocial assess, CXR, labs BMA/Bx, LP

Front 49

What labs are needed to identify increased risk for tumor lysis syndrome?

Back 49

chemistry panel (K+,Ca+,Phos, Mag, BUN, Cr)
LDH = estimate of tumor burden
Uric acid = high levels (and high Creatinine) are associated w/renal failure

Front 50

Why is it important to identify the risk group classification with ALL?

Back 50

It will dictate therapy
ALL - 75-80% are cured
AML - 45-50% are cured

Front 51

What are the principles of treatment for ALL?

Back 51

1. Use of CNS prophylaxis
2. Combo chemo to maintain remission
3. Monitor for tumor lysis syndrome
4. Understand prognostic features

Front 52

What are the 3 most important factors in understanding prognostic features at diagnosis for ALL?

Back 52

1. Age at diagnosis (age 2-10 = most favorable)
2. Initial leukocyte count (<50K = most favorable)
3. speed of response to treatment

Front 53

What is induction therapy in ALL? And what is the goal?

Back 53

Weekly Vincristine, corticosteroid, and asparaginase;
GOAL = eliminate blasts & obtain remission (= <5% blasts in marrow)

Front 54

Higher risk ALL patients also receive what during induction?

Back 54

Anthracycline (doxo or duano);
IT Cytarabine &/or methotrexate (MTX)

Front 55

What is the remission rate after induction in ALL?

Back 55

Induction produces a 98% remission rate after 4-5 weeks of treatment

Front 56

What is one of the major concerns during induction treatment for ALL?

Back 56

Tumor lysis syndrome

Front 57

What does consolidation therapy consist of for ALL?

Back 57

To ensure eradication of disease - aspariginase, high-dose or intermediate-dose MTX, Vincristine, Doxo, corticosteroid, Cytarabine, oral MTX, & mercaptopurine

Front 58

What is CNS prophylaxis?

Back 58

IT MTX or triple IT(MTX, cytarabine, & hydrocortisone);
used in induction, consolidation, & maintenance therapies

Front 59

Why is CNS prophylaxis given?

Back 59

It decreased the likelihood of CNS relapse to less than 5%.

Front 60

Who is given cranial irradiation in addition to CNS prophylaxis.

Back 60

Those at diagnosis with high-risk features: lymphoblasts in CSF, elevated CSF leukocyte count, physical sign of CNS leukemia, or T-cell disease (during consolidation)

Front 61

What does maintenance therapy consist of for ALL?

Back 61

2-3 years of mercaptopurine and MTX; intermittent doses of Vincristine & a corticosteroid; CNS prophy continues throughout

Front 62

What is the relapse rate for ALL?

Back 62

15-20% relapse ALL; if occurs during therapy = extremely poor prognosis
if occurs >12mo after completion of therapy = better chance of long-term survival

Front 63

What is treatment for relapsed ALL?

Back 63

Intensive chemotherapy - usually with drugs not used in previous therapy; consider allogeneic stem-cell transplant

Front 64

What percentage of patients have CNS relapse?

Back 64

10% of patient have CNS extramedullary relapse

Front 65

What is the treatment for Extramedullary relapse?

Back 65

Intrathecal therapy & craniospinal irradiation w/systemic chemo.

Front 66

What percentage of patients have testicular relapse?

Back 66

2-3% of patients have testicular extramedullary relapse

Front 67

What is treatment for testicular relapse?

Back 67

Testicular radiation and chemotherapy

Front 68

What percentage does a relapsed AML patient have of achieving second remission?

Back 68

25% if relapse while on chemotherapy
50% if relapse after completing chemo

Front 69

If relapse occurs in AML what other treatment should be considered whenever possible?

Back 69

Allogeneic bone marrow transplant; Autologous may be considered

Front 70

What 4 nursing goals should be prioritized in the diagnosis of leukemia?

Back 70

1. Pt. will have minimal complications related to leukemia dx.
2. Pt. will have minimal complications related to leukemia treatment.
3. Pt & family will informed re:diagnosis, disease, & treatment.
4. Pt. & family will cope adequately