Acute Leukemia

Question 1

define ALL

Answer 1

acute lymphoid leukemia
uncontrolled proliferation of immature lymphoid cells like B and T cells

Question 2

define AML

Answer 2

acute myeloid leukemia
uncontrolled proliferation of immature myeloid cells like neutrophils, basophils, eosinophils etc.

Question 3

ALL is more common in ________
AML is more common in _________

Answer 3

children
adults

Question 4

RF for ALL and AML include

Answer 4

genetic conditions: trisomy 21 and Li-Fraumeni syndrome

environmental factors: exposure to ionizing radiation, benzenes, prev exposure to chemo

ALL specific: Human T-lymphotropic virus 1 (HTLV1)
AML specific: myelofibrosis or myeloproliferative disorders like PV and aplastic anemia

Question 5

common genetic variants in ALL vs AML

Answer 5

ALL
- may have the t(9;22) Philadelphia chromosome (BCR::ABL fusion gene)

AML
- may have a t(15;17) which results in the formation of Auer rods
- TP53

Question 6

general pathophys for dev of ALL and AML

Answer 6

1. Accumulation of mutations in myeloid or lymphoid progenitor cells
2. Clonal expansion of neoplastic undifferentiated myeloid/lymphoid progenitor cells (blasts)
3. ↑ blasts in bone marrow → ↓ progenitors of other cell lines (RBCs and Plts) → ineffective erythropoiesis and BM failure

Question 7

what is the timeline like for developing and presenting with s/s of AML and ALL?

Answer 7

weeks to months

Question 8

what common s/s do AML and ALL share

Answer 8

anemia s/s
thrombocytopenia s/s
hepatomegaly and splenomegaly
BM expansion - bone pain
constitutional s/s

*constitutional s/s are less common/evident in peds

Question 9

what unique s/s are present in AML and ALL

Answer 9

ALL
- LAD
- potential mediastinal mass if they have T cell based
- CNS s/s

AML
- leukemia cutis
- DIC bc neoplastic cells may secrete ↑ coagulation promoting cytokines into circulation
- Gingival hyperplasia

Question 10

general workup for suspected acute leukemia

Answer 10

diagnostic: PBS and BM aspiration and biopsy
- >20% blasts
- ALL: lymphoblasts
- AML: myeloblasts +/- Auer rods

metastatic w/u
- imaging: XR, CT CAP
- ALL: LP for CSF analysis – looking for presence of blasts

Genetics: immunophenotyping, flow cytometry and cytogenetic testing to help inform tx options

bloodwork
- cbc
- lytes and extended lytes
- cr, urea
- LFT
- PT/INR and aPTT
- LDH

Question 11

Induction, consolidation and maintenance therapy for ALL + other tx

Answer 11

induction: MT inhibitor + antitumour abx + corticosteroid
consolidation: step down lowering of chemo doses
maintenance: low dose chemo (2Y for adults; 2-3Y for children)

add intrathecal mxt for prophylactic prevention of CNS ALL involvement

consider allogenous stem cell transplant if non responsive or recurrent ca

Question 12

Induction, consolidation and maintenance therapy for AML + other tx

Answer 12

induction: antimetabolite + antitumour abx
consolidation: step down lowering of chemo doses
maintenance: low dose chemo (2Y for adults; 2-3Y for children)

add all-trans retinoic acid (ATRA) if auer rods present

consider allogenous stem cell transplant if non responsive or recurrent ca

Question 13

what onc emergency are we worried about with high dose induction therapy?

Answer 13

tumour lysis syndrome: increase in uric acid, potassium, and phosphate and a decrease in Ca