Acute Lymphoblastic Leukemia (ALL)

Question 1

most common types of leukemia in children

Answer 1

1. ALL (acute lymphoblastic leukemia) ~80%
2. AML (acute myeloid leukemia) ~15%
3. CML (chronic myeloid leukemia) ~4%

Question 2

acute vs. chronic leukemias

Answer 2

*acute: predominance of immature WBC precursors; these cells proliferate and LACK DIFFERENTIATION

*chronic: proliferation of relatively mature (differentiated) WBCs; often indolent; much more commonly seen in adults than children

Question 3

ALL (acute lymphoblastic leukemia) - epidemiology

Answer 3

*ALL is the single most common childhood malignancy, accounting for 25% of all childhood cancers
*hispanics > whites > blacks
*males > females

Question 4

clinical manifestations of ALL (acute lymphoblastic leukemia)

Answer 4

*fatigue
*pallor
*bruising, bleeding
*fever
*lymphadenopathy
*hepatosplenomegaly
*MEDIASTINAL MASS (T-ALL)
*pain (musculoskeletal)

Question 5

lab findings of ALL (acute lymphoblastic leukemia)

Answer 5

*WBC count may be normal, high (leukocytosis) or low (leukopenia); may see blasts on the blood smear
*anemia (low Hb/Hct)
*thrombocytopenia (low platelets)
*may see chemical abnormalities consistent with “tumor lysis” (increased uric acid, phosphorous, potassium, creatinine)

Question 6

differential dx for ALL (acute lymphoblastic leukemia)

Answer 6

*infection (EBV or other viruses)
*immune thrombocytopenic purpura (ITP)
*juvenile idiopathic arthritis
*aplastic anemia
*other malignancies (lymphoma, neuroblastoma)

Question 7

diagnosis for ALL (acute lymphoblastic leukemia)

Answer 7

*bone marrow aspirate: 20% or more of lymphoblasts in bone marrow = acute leukemia
*4-19% may be myelodysplasia
*lumbar puncture also required for evaluation of CNS disease (looking for blasts in CSF)

Question 8

classification of ALL (acute lymphoblastic leukemia)

Answer 8

*marrow is usually hypercellular (lots of blasts, few normal cells)
*microscopy: assess morphology of cells
*immunophenotyping (flow cytometry) - monoclonal antibodies reacting with cell surface antigens [helps distinguish ALL vs. AML, T vs. B lineage]
*genetic testing of leukemia cells (cytogenetics, FISH, PCR)

Question 9

good prognostic factors for ALL (acute lymphoblastic leukemia)

Answer 9

*age 1-10 years
*highest pre-treatment WBC count on a CBC < 50,000
*somatic findings associated with a favorable prognosis:
-hyperdiploidy (>50 chromosomes per leukemia cell)
-t(12;21) translocation
-trisomies of chromosomes 4, 10, and 17

Question 10

bad prognostic factors for ALL (acute lymphoblastic leukemia)

Answer 10

*age < 1 year or 10+ years
*highest pre-treatment WBC counts on a CBC > 50,000
*somatic findings associated with an unfavorable prognosis:
-hypodiploidy (<44 chromosomes per leukemia cell)
-KMT2A gene rearrangement
-t(9;22) translocation (Philadelphia chromosome)

Question 11

T lymphoblastic leukemia / T cell ALL - common findings

Answer 11

*males > females
*older age than B-ALL (5-12 years, but may be older or younger)
*high WBC count
*bulky adenopathy, MEDIASTINAL MASS, hepatosplenomegaly
*CNS disease

Question 12

emergencies associated with ALL (acute lymphoblastic leukemia)

Answer 12

*sepsis (infection)
*bleeding (from thrombocytopenia)
*tumor lysis syndrome (elevated uric acid, potassium, phosphorus, creatinine)
*hyperleukocytosis (very high WBC count)
*tracheal compression/superior vena cava (SVC) syndrome

Question 13

basic principles for treatment of ALL (acute lymphoblastic leukemia)

Answer 13

*multi-agent chemotherapy is key:
*4 major phases of therapy:
1. induction (1 month)
2. consolidation (2-6 months)
3. delayed intensification (2 months)
4. maintenance (~2 years)

note: CNS treatment is delivered throughout ALL phases:
a. intrathecal chemo (methotrexate most common)
b. radiation therapy (in select cases)

Question 14

commonly used drugs to treat ALL (acute lymphoblastic leukemia)

Answer 14

*steroids (prednisone, dexamethasone)
*vincristine
*asparaginase
*doxorubicin/daunorbuicin
*methotrexate
*mercaptopruine
*cytarabine
*cyclophosphamide

Question 15

hematopoietic cell transplant for ALL (acute lymphoblastic leukemia)

Answer 15

*reserved for very high risk patients in first remission, selected patients with relapsed ALL
*potential donors:
-matched sibling
-matched unrelated donor
-umbilical cord blood
-haploidentical donor (parent or sibling)

Question 16

minimal residual disease (MRD) in ALL (acute lymphoblastic leukemia)

Answer 16

*early response to therapy (typically measured in bone marrow at day 29 of induction) is the SINGLE MOST POWERFUL PROGNOSTIC FACTOR in ALL in children (the lower the MRD level, the better)

Question 17

short term toxicities of ALL (acute lymphoblastic leukemia) therapy

Answer 17

*INFECTION (most life-threatening)
*myelosuppression
*bleeding/bruising
*alopecia (hair loss)
*nausea/vomiting
*fatigue

Question 18

long term toxicities of ALL (acute lymphoblastic leukemia) therapy

Answer 18

*neurocognitive delay (due to CNS therapy)
*endocrinopathies (short stature, obesity, etc due to CNS therapy & steroids)
*gonadal failure/sterility

Question 19

prognosis for newly diagnosed pediatric ALL (acute lymphoblastic leukemia)

Answer 19

~90% (really good prognosis for kids)

Question 20

lymphoblasts in ALL

Answer 20

*> 20% lymphoblasts in bone marrow is diagnostic of ALL
*lymphoblasts:
1. TdT+ (a marker of immaturity)
2. markers of either B-cell lineage (CD19, CD20, etc) or T-cell lineage (CD4, CD5, CD8, etc)