11/02/09

Pediatrics Wards Presentation

TTUHSC SOM

ALL
Acute Lymphoblastic Leukemia
Acute Lymphoblastic Lymphoma

Path:
Precursor B cells (sometimes T cells; lymphoblasts); hyperploidy (>50 chromosomes),
t(12;21) w CBF α and ETV6, t(9;22), t(4;11)

Etiology:
2500 new cases dgx/yr. <15yo, peak at 4yo (teens if T cell). Whites>>Nonwhites. M>F.
2.1% of Downs pts have ALL.

Protective Factors: Stat!Ref

Daycare attendance, early common infx, longer breast feeding, HiB vaccine, residence in
remote rural counties.

SSx:
Abrupt onset (eg <weeks), fatigue, fever due to low mature leukocytes, bleeding,
petechiae, ecchymoses, epistaxis, gum bleeding, bone pain, lymphadenopathy,
hepato/splenomegaly, HA, vomiting, nerve palsies due to meningeal spread;
Pancytopenia ssx eg bleeding, easy bruising

Dgx:
Anemia, neutropenia, thrombocytopenia; Microscopy=condensed chromatin,
inconspicuous nuclei, scant agranular cytoplasm; normal tissue infiltrated w
lypmhoblasts.

Immunophenotyping:
B-lineage ALL: CD 19, 20, 22, 79a and/or surface or cytoplasmic immunoglobulin
T-lineage ALL: CD2, surface or cytoplasmic CD3, CD4, CD5, CD7, and/or CD8

Staining:
TdT staining to differentiate bw L1-L2 and L3 (Burkitt Lymphoma; TdT neg). CXR to
eval x presence of mediastinal lymphadenopathy/exclude infx

Tx:
Cyclophosphamide 1200mg/m2 iv on day 1
Daunorubicin 45mg/ m2 iv x 3-4days
Prednisone 60mg/ m2 PO x 7-21 days
Vincristine 1.4mg/ m2 IV w a Max 2mg, weekly x 2-4 doses
L-Asparaginase 6000IU/ m2 sc 2x weekly x 4-7 doses (3-4 weeks)

Prognosis:
With aggressive tx 90% reach remission, 2/3rds can be considered "cured". Favorable if
low WBC count, 2-10yo, B phenotype, hyperploidy, t(12;21); No tx; Poor prognosis if
<2yo cuz of choromosome 11 involvement, teen/adult presentation, t(9;22)

DDx:
AML
Biphenotypic Leukemia
Mantle Cell Lymph\oma (blastic variant)
Gamma Delta T cell hepatosplenic lymphoma
Plasma Cell Leukemia
Other CA

Considerations:
Pts may be at risk for Minimal Residual Dss
Multidrug resistance is possible and must be evaluated for. MDR related proteine 1, p-
glycoprotein, lung resistance protein and breast cancer resistance protein are some
examples. 10% exhibit MDR.
Allogenic transplantation shows benefit in some studies, but not in others.
History and Physical Examination Elements for ALL
Category Element Notes
There is a 4-fold higher risk of leukemia in patients
with siblings who have leukemia than in the
Siblings with
History general population. In identical twins, the other
leukemia
twin has an increased chance of being diagnosed
with ALL within 1 year (17)
History Genetic disorders Down syndrome (2% of ALL cases in children) (18)
History Maternal age Risk is higher in children of mothers aged >35 (18)
History Paternal age Risk is higher in children of fathers age >35 (19; 20)
Risk is higher in children of mothers with history of
History History of fetal loss
fetal loss (19; 20)
Increased weight at Risk is higher in patients with higher birth weight
History
birth (19; 20)
History Exposures Ask about exposure to radiation, chemotherapy
History Habits Ask about smoking
Risk is higher in children of higher socioeconomic
History Socioeconomic status
status (20)
History Malaise and fatigue May be due to anemia
History Dyspnea May be due to profound anemia or pneumonia
May be due to thrombocytopenia and/or rarely
History Easy bruising
disseminated intravascular coagulopathy
May be due to leukemic cell infiltration or growth in
History Bone pain
the bone marrow
History Headache May be due to CNS leukemia or anemia
Look for neurologic deficits, including blurred
Other neurologic vision or cranial nerve dysfunction manifested by
History
symptoms numbness or hyperesthesia, e.g., numb-chin
syndrome (21; 22)
History Infections Look for pneumonia and other infections
Physical exam Fever Usually due to infection
Skin exam for pallor,
ecchymoses, Pallor may be due to anemia and ecchymoses,
Physical exam
petechiae, petechiae; hemorrhage due to thrombocytopenia
hemorrhage
Eye exam for
Physical exam Rare (23)
leukemic hypopyon
Lymph node exam for
Physical exam Frequency ~30% (17; 18; 19; 20)
lymphadenopathy
Abdominal exam for
Physical exam Frequency ~30% (17; 18; 19; 20)
hepatosplenomegaly
Physical exam Genital exam for Rare (17; 18; 19; 20)
 testicular
enlargement
<10%, usually asymptomatic (17; 18; 19; 20).
Neurologic exam for Examples include blurred vision or cranial nerve
Physical exam
CNS involvement dysfunction manifested by numbness or
hyperesthesia
ALL = acute lymphoblastic leukemia; CNS = central nervous system.

Laboratory and Other Studies for ALL Test Notes

CBC
Leukocyte count ≥30 × 109/L occurs in approximately 25%-63% of patients with ALL (13;
14; 15) and indicates a trend toward a worse outcome (13).
Platelet count ≥50 × 109/L occurs in approximately 50% of patients with ALL. There is a
trend toward shorter survival with lower platelet count (13).
Hemoglobin <10 g/dL occurs in approximately 69% of patients with ALL (13)

Serum bilirubin
Hyperbilirubinemia is associated with worse outcome (13)

Lactic dehydrogenase
Elevated in 40%-59% of patients with ALL (13; 15)

Chemical survey
Electrolytes including uric acid, phosphorus, and renal function

LFTs
Evaluate the ability to administer chemotherapy

Coagulation studies
PT, APTT, fibrinogen, FDP, and D-dimer to exclude DIC

Blood type
For transfusion

HLA A, B, and DR
For transplantation candidates

Urinalysis
To confirm dehydration, uric acid nephropathy, DIC, infection

Blood cultures
Needed in febrile patients to evaluate for infection

Chest x-ray
Needed to evaluate for infection

Head MRI/CT
If neurologic symptoms are present. Required in patients with neurologic findings

Lumbar puncture
Required in patents with neurologic findings pending results of head MRI/CT

Peripheral blood smear

To examine cellular elements and to look for lymphoblasts of specific morphologic
subtype

Bone marrow examination

To examine morphology of leukocyte precursors, looking for lymphoblasts of specific
morphologic subtype

Cytochemistry
Peroxidase negative (25) and nonspecific staining for Sudan black B (27; 28; 29) and
terminal deoxynucleotidyl transferase (30; 31; 32)

Immunophenotyping
B-lineage ALL: CD19, CD20, CD22, CD79a and/or surface/cytoplasmic immunoglobulin
and T-lineage ALL: CD2, surface/cytoplasmic CD3, CD4, CD5, CD7, and/or CD8 (33)

Cytogenetic analysis
Specimens are processed directly or following a short-term (24-72 hours) culture. The
chromosomes are labeled with G-banding and a minimum of 20 metaphases is analyzed
(43)

Molecular testing
PCR with patient-specific junctional regions of rearranged immunoglobulin for B-lineage
disease or T-cell receptor genes for T-lineage disease (43)
ALL = acute lymphoblastic leukemia; APTT = activated partial thromboplastin time; CBC = complete blood
count; CT = computed tomography; DIC = disseminated intravascular coagulation; FDP = fibrinogen
degradation product; HLA = human leukocyte antigen; LFTs = liver function tests; MRI = magnetic
resonance imaging; PCR = polymerase chain reaction; PT = prothrombin time.

Comparison of the FAB and WHO Classifications for ALL

FAB Classifications
≥30% blasts
L1/L2 (morphology subgroups)
WHO Classifications*
≥20% blastsa
Precursor B- or T-cell ALL (cytogenetic
subgroups)
t(9;22)(q34;q11) BCR/ABL
t(v;11q23) MLL rearranged
t(1;19)(q23;p13) E2A/PBX1
t(12;21)(p12;q22) ETV/CBF-α
(TEL/AML1)
 L3 Burkitt-cell leukemia

* In the WHO classification, ALL and lymphoblastic lymphoma are regarded as a single entity with different
clinical presentation.
a
A disease with <20% blasts is defined as lymphoblastic lymphoma.
ALL = acute lymphoblastic leukemia; BCR = breakpoint cluster region; FAB = French-American-British
classification; WHO = World Health Organization.

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