Wake All

Front 1

Precursor B ALL
Favorable Prognostic Factors

Back 1

Ages: 1-10
WBC Count: <50,000
CNS disease: Absent
HypERdiploidy (>50)
Cytogenetics: t(12;21)
Response to treatment: Rapid

Front 2

Precursor B ALL
Unfavorable Prognostic Factors

Back 2

Ages: <1, >=10
WBC Count: >=50,000
CNS disease: Present
HypOdiploidy (<44)
Cytogenetics: t(4;11); t(9;22)
Response to treatment: Slow

Front 3

Controversial poor prognostic factors in ALL

Back 3

- Black and Hispanic Ethnicity
- Obesity

Front 4

Late effects of ALL therapy

Back 4

1. Neurocognitive delay (CNS therapy)
2. Endocrinopathies (CNS therapy and steroids)
3. Gonadal failure/sterility (alkylating agents)
4. Cardiac dysfunction (antharcyclines)
5. Musculoskeletal disease (steroids)
6. Second malignancies (chemotherapy and radiation therapy)

Front 5

Relapsed ALL

Back 5

- Longer first remissions are better than shorter first remissions
- In general, prognosis for relapsed ALL is 30-50%
- if long first remission - chemotherapy alone
- if short first remission - stem cell transplant
- CNS, testicles (“sanctuaries”) are relatively common sites of extramedullary relapse

Front 6

ALL - risk assessment

Back 6

- Best done by combining the following data for each patient:
- presenting clinical features (age, WBC count)
- blast cell immunophenotype (T-cell vs. B-cell) and genotype (cytogenetics, other DNA tests)
- early responsiveness to treatment
- Patients are currently classified as low, standard, high, or very high risk

Front 7

Pediatric ALL - Prognosis (percentages)

Back 7

- is generally GOOD, with ~80% overall event-free survival
- Unlike adult ALL, where prognosis is relatively poor - only 30-50% of adults are cured

Front 8

Why is genetic variability important in ALL treatment?

Back 8

Host
- Drug metabolism (affects efficacy and toxicity)
Leukemia cells
- Intracellular drug levels

Front 9

ALL - CNS treatment

Back 9

- Intrathecal chemotherapy (delivered by lumbar puncture (LP)) – start on first day of therapy and continue throughout treatment duration (18-20 LPs over ~3 years)
- radiation therapy (e.g. CNS positive at diagnosis or relapse, T-ALL)
- Only 5-10% patients currently get CNS radiation
- Can it be omitted for all patients?
- high dose IV methotrexate - penetrates CNS

Front 10

Newer drugs for ALL treatment

Back 10

- imatinib (bcr-abl specific)
- nelarabine (T cell specific)
- rituximab (CD-20 specific)
- clofarabine

Front 11

Commonly used drugs for ALL

Back 11

Steroids (prednisone, dexamethasone)
Vincristine
Asparaginase
Doxorubicin/daunorubicin (antharcyclines)
Methotrexate
Mercaptopurine
Cytarabine
Cyclophosphamide

Front 12

ALL Treatment Chemotherapy Regime

Back 12

1. Remission induction (~1 month)
2. Intensification (consolidation) (~6 months)
3. CNS treatment (throughout all phases)
4. Continuation (“maintenance”) (2-3 years)

Front 13

ALL emergencies

Back 13

Sepsis (infection)
- Bleeding (from thrombocytopenia)
- Tumor lysis syndrome
- Hyperleukocytosis (very high WBC count)
- Tracheal compression/SVC syndrome

Front 14

Precursor T cell (T cell) ALL

Back 14

associated with:
- Males > Females
- older age (5-12 years)
- high WBC count
- bulky adenopathy, mediastinal mass, hepatosplenomegaly
- CNS disease

Front 15

Classification of ALL

Back 15

- Acute lymphoblastic leukemia (L1/L2 morphology)
- Precursor B cell (B-lineage, pre-B, early pre-B)
- Precursor T cell (T cell)
- Acute lymphoblastic leukemia, B-cell (L3 morphology) (mature B-cell, Burkitt cell leukemia)
- Acute leukemia, biphenotypic

Front 16

ALL – molecular genetics

Back 16

- Fluorescent in situ hybridization (FISH) and Polymerase chain reaction (PCR) allow detection of DNA abnormalities that may not be detectable by cytogenetics
- Global gene expression profiling

Front 17

cIg

Back 17

cytoplasmic Immunoglobulin

Front 18

ALL - Diagnosis/classification

Back 18

Morphology (L1, L2, L3 – based on FAB criteria)
cytochemical stains (ALL vs. AML)
immunophenotyping - monoclonal antibodies reacting with cell surface antigens (ALL vs. AML, T vs. B lineage)

Front 19

Diagnosis of ALL

Back 19

- >25% lymphoblasts in bone marrow
- lumbar puncture also required for evaluation of CNS disease

Front 20

Differential diagnosis of ALL

Back 20

- Infection (especially EBV, other viruses)
- Immune thrombocytopenic purpura (ITP)
- juvenile rheumatoid arthritis
- aplastic anemia
- other malignancies (e.g. neuroblastoma)

Front 21

ALL Blood Laboratory Finding

Back 21

- leukocytosis or leukopenia (high or low white blood cell count, respectively); may see “blasts” on the blood smear
- anemia (low hemoglobin/hematocrit)
- thrombocytopenia (low platelets)
- may see chemical abnormalities consistent with “tumor lysis” (increased uric acid, phosphorus, potassium, creatinine)

Front 22

Clinical Manifestations of ALL

Back 22

- fatigue
- pallor
- bruising, bleeding
- fever
- lymphadenopathy
- hepatosplenomegaly
- mediastinal mass
- pain (musculoskeletal)

Front 23

ALL Epidemiology

Back 23

- < 5% cases associated with ionizing radiation (pre- and post-natal) or a genetic syndrome such as Down syndrome, neurofibromatosis, Shwachman syndrome, Bloom syndrome, Ataxia telangectasia, Klinefelter syndrome
- Evidence exists suggesting some cases have prenatal origins

Front 24

What is the peak incidenc of ALL?

Back 24

2-5 years of age

Front 25

ALL is more common in blacks or whites?

Back 25

whites

Front 26

ALL is more common in males or females?

Back 26

males

Front 27

ALL - Epidemiology

Back 27

- ALL is the most common childhood malignancy
- In the U.S., ~3,000 children per year are diagnosed with leukemia; ~80% of these are ALL