Most common type of leukemia in children - Children \> adults - Males \> females - Whites \> blacks 85% B cell; 15% T cell

- Don't know; idiopathic - In utero events (1, 2, vs. 10,000 hits) - Environmental exposure/drug-toxin metabolizing genes - Blasts vs. the immune system (stochastic?) - "Genetics"

_Nonmalignant conditions:_ - Juvenile rheumatoid arthritis - infectious mononucleosis - ITP - Pertussis and Parapertussis - Aplastic anemia - Other viral illnesses

8/14- ALL Flashcards by Kathryn Kudlaty

What is the stem cell problem in the following conditions:

Aplastic anemia:
Myeloproliferative Syndromes:
Myelodysplasia:
Acute Leukemia:

- Aplastic anemia: stems are gone

- Myeloproliferative Syndromes: SCs lead to progenitros with increased proliferation, normal maturation

- Myelodysplasia: SCs support ineffective hematopoiesis (seems to mature, but ineffective; low counts but cellular marrow)

- Acute Leukemia: SCs proliferate but do not mature

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What does this show?

Blasts (probably lymphoid)

Not as distinct nucleoli as myeloblast
Little cytoplasm

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Thyroid mass suggests what?

Lymphoma

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TdT(+) is a marker of what?

Very young cells

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What is CD34(+) a marker of?

Stem cells (very young)

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What is t(11;19) associated with?

Prevalent in childhood and infant ALL
Associated with CNS involvement and a poor prognosis

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What is the genetic alteration common in childhood/infant ALL and associated with CNS involvement/poor prognosis?

t(11;19)

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What are some characteristics of ALL?

Acute Lymphocytic Leukemia (ALL):

Bone marrow > 30% lymphoblasts
May present as mediastinal or LN only: lymphoblastic lymphoma
Acquired somatic mutations in a single lymphoid progenitor cell
The blast shares many features of normal lymphoid progenitors– “arrested development”

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Clinical presentations of ALL?

Fatigue
Malaise
Arthralgias, arthritis
Lymphadenopathy
Hepatosplenomegaly
Fever, Infection
Bleeding

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What is this?

Acute Lymphoblastic Leukemia

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Epidemiology of ALL?

Most common type of leukemia in children

Children > adults
Males > females
Whites > blacks

85% B cell; 15% T cell

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T/F: Pts with ALL commonly present in a characteristic way? How?

False; there is variable presentation

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What are the variable presentations of ALL?

Completely asymptomatic: 1-2% (CBC may be wnl or very closely to nl)
Significant HSM in 2/3
Clinically significant adenopathy in 1/2
Fever in 60% (life threatening sepsis at Dx is rare but not impossible)
Bone pain in 1/4
Some bleeding manifestation (petechiae, purpura) in 1/2

Variable prodromal period:

Vague hx of not feeling well for days-weeks (THIS IS AN ACUTE PROCESS)
Occassionally several months (BEWARE PRE-TREATMENT, e.g .steroids)

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What causes ALL?

Don’t know; idiopathic
In utero events (1, 2, vs. 10,000 “hits”)
Environmental exposure/drug-toxin metabolizing genes
Blasts vs. the immune system (stochastic?)
“Genetics”

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ALL is associated with what other conditions?

- Down

- Unstable genes: ataxia telangiectasia, Bloom, Fanconi

- Wiskott Aldrich, congenital Hypogammaglobulinemia

- In utero: high risk for twin if one twin has ALL

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DDx of ALL?

Nonmalignant conditions:

Juvenile rheumatoid arthritis
infectious mononucleosis
ITP
Pertussis and Parapertussis
Aplastic anemia
Other viral illnesses

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When should a pediatrician consider Dx of ALL?

Combo of:

Unexplained adenopathy or marked HSM
Bone pain
Bleeding symptoms/pallor

Meets the threshold of obtaining a CBC:

2+ more cell lines “down” or WBC up and one other line down

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Incidence of acute lymphoid leukemia by age?

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More in KIDS

Peak at 4 yo
75% of childhood leukemia
Most common pediatric cancer

What is this?

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Lymphoblasts in CSF from ALL patient

What is a big difference between ALL and AML?

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ALL commonly includes CNS involvement

Like meningitis, with headache and CN palsies

What is the typical presentation of T cell ALL?

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Young boy with a mediastinal mass

If there is no bone marrow involvement, we call this “lymphoblastic lymphoma” (can be B or T cell disease)
If you wait long enough, you will have bone marrow and peripheral blood involvement
Same treatment as ALL, just lymphoblastic lymphoma is the lymph node version

Types/characteristics of ALL in terms of cell types involved and presentation?

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Lymphoblasts in bone marrow and blood

FAB L1, L2

Lymphoblastic lymphoma

Mediastinal or lymph node T-cell blasts
Rare Patients have a B-cell phenotype

FAB L3 leukemia

Burkitt’s lymphoma

Molecular markers of B cell development

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Molecular makers of T cell development

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Which antigen markers do we care about the most? - pre-B: - pre-T: - Myeloid: - "Stem cell":

**pre-B:** - CD10 - CD19 - CD20 - CD22 **pre-T:** - CD3 - CD5 - CD7 **Myeloid:** - CD13 - CD14 - CD15 - CD33 **"Stem cell":** - CD34 - TDT

What are current classification methods of ALL?

- FAB classification on Wright Stain (L1-3) - Other morphological and special stain criteria (PAS stain) - Immunophenotype - Cytogenetics (ploidy/DI;standard G-banding, FISH, RT-PCR) - Molecular/Experimental: cDNA microarray

What is the breakdown of immunophenotypes in ALL?

**B-cell** precursor ALL: 85% **T-cell** precursor ALL :13-15% **B-cell** ALL: 1-2% \*Cytogenically, adults are not just big children

What are some chromosomal findings with poor prognostic significance in ALL?

_Poor:_ **- t(4;11):** AFP and MLL/ALL-1/HTRX **- t(1;19):** E2Aa and PBX1 **- t(9;22):** Bcr/ABL (Philadelphia chrom) - Euploidy - Hypoploidy - Extreme hyperdiploidy (i.e. tetraploidy)

What are some chromosomal findings with good prognostic significance in ALL?

_Good:_ - t(12;21): TEL and AML1 (RT-PCR or FISH) - Trisomy 4 and 10 (17 but not 5) - Hyperdiploidy

What are some good clinical prognostic factors in ALL?

- female sex - age 3-8 - low WBC - Pre-B phenotype - C10 (CALLA +) - low LDH - hyperdiploid cytogenetics

What are some poor clinical prognostic factors in ALL?

- male sex - age above 8 - high WBC - L3, T-cell - CNS presentation - high LDH - Ph chromosome

What are some accepted principles of therapy in ALL?

One drug is NEVER enough - Duration of therapy should be \> 18 months (130 weeks on POG protocols, COG 2.5 years for girls and 3.5 years for boys) - Sanctuary sites need special consideration—primarily CNS - Intensity is scaled to risk, but variation in intensity is important

Emerging principles of therapy in ALL?

Early Response and Degree of that response may be the most important prognostic indicator - Minimal Residual Disease (MRD) is probably important - Relapse is the worst prognostic sign and salvage rate will depend on timing of the relapse and the intensity of the initial therapy

Active Agents to use (chemo) for ALL?

- Vincristine - Pred/Dexamethasone - L-Asp (Ecoli, Erwinia,Peg) - Daunomycin (all anthra) - Cytoxan (other alkylators) - Ara C - 6 mercaptopurine (6MP), MTX

Common Approaches to ALL Therapy?

(Don't need to know details) - CNS as a sanctuary is a worry - Bone marrow transplant used in first remission for high risk disease or in 2nd remission

What is BiTE? CAR?

**Bispecific T cell engager** - Targets malignant T cells?? **Chimeric Antigen Receptor (CAR)** involved in harnessing your T cells - Anti B19 CAR T used in ALL with 70-90% response rates - Often durable but at least allow segue to transplant _Complications:_ - Cytokine release syndrome - Encephalopathy - B cell depletion

What does this show?

Burkitt cells in the blood and marrow - Characteristic appearance in peripheral blood with medium sized cells with open nuclei and nucleoli visible; cytoplasm is very blue with vacuoles - Can be a leukemia-- L3 in FAB classification

Important genetics in Burkitt lymphoma?

t(2;8) t(8;14) t(8;22)

What is Burkitt lymphoma?

- African variety: jaw tumor, strongly linked to Epstein-Barr Virus infection (50% BL due to EBV in US) - May present as abdominal mass - Most rapidly growing human tumor - Treated with multidrug regimen similar to pediatric leukemia/lymphoma regimens

What is shown here?

Jaw tumor characteristic in presentation of Burkitt lymphoma (African variety)

What is this?

Burkitt lymphoma (Starry Night cells)

What is Tumor Lysis Syndrome? When does it occur?

Occurs in **ALL L3** and **Burkitt's Lymphoma** - High grade lymphomas - AML less often _Massive tumor death results in:_ - High LDH - Increased Uric Acid - Increased Phosphate - Hypocalcemia - Renal Failure (urate nephropathy, CaPO4 crystals) - Hyperkalemia

How can Tumor Lysis Syndrome be prevented?

- Hydration - Allopurinal - Alkalinization - Recombinant uricase

8/14- ALL Flashcards

(43 cards)