Leukaemia
Oncology Dx
Summarised to supportive care in ALL, as well as AML
Leukaemia
Most common malignancy in childhood (31% or 4.5:100,000)
ALL:AML 10:1 in 1-15yo > 2:1 in infants and adolescents >15y
Adolescents and young adults do better on paediatric protocols than adult protocols
Cause marrow failure by displacing other cells
Associations:
GENETIC CONDITIONS
Presentation
Ix
Usually low Hb and Plt
WCC high but can be normal or low with film showing atypical lymphocytes
Bone marrow aspiration and biopsy,
cytogenetics
molecular studies
CSF for staging (i.e. identifying CNS disease) with first dose on intrathecal chemotherapy
Pharmacogenetic testing of the thiopurine S-methyltransferase gene
DDx
EBV
JIA
AML
neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and retinoblastoma that has invaded the marrow
ALL
First cancer to be curable!
Heterogenous group of malignancies, with varying genetic abnormalities
Twin has 70% chance if MChorionic and <1, drops to 2x background if Dx 5-7yo
Higher risk
Associations:
Prognostic factor
Age at onset (1-10 good)
Initial leukocyte count (<50 good)
Response to initial therapy
(infant or unfavourable chromosomes) worse than (older and >50) worse than (1-10 and <50)
Rx
Induction (aim to eradicate leukaemia from marrow > 98% acheive remission = <5% blasts and recovery of rest of marrow)
Relapse
AML
Summarised to supportive care in ALL, as well as AML
Leukaemia
- ALL (77%)
- B-Lymphoblastic (B-cell precursors) (85% of ALL)
- Pro-B (CD10-) (5%)
- Precursor-B (CD10+) (64%)
- Favourable: Trisomy 4,10, and 17, t(12;21), Hyperdiploidy
- Neither: (t(9;22)
- Unfavourable: t(4;11), t(9;22), Hypodiploidy
- Pre-B (16%)
- Mature-B (Burkitt) (FAB3) (4% of ALL)
- Neither: t(8;14)
- T-cell (12% of ALL)
- B-Lymphoblastic (B-cell precursors) (85% of ALL)
- AML (11%)
- M0-2: Acute myeloblastic leukaemia
- M2: t(8;21) favourable
- M3: Acute promyelocytic (APL)
- t(15;17): favourable
- t(11;17): unfavourable
- M4: Juvenile myelomonocytic leukemia or JMML (2%)
- Eo: inv(16), t(16;16) favourable
- 11q23 unfavourable
- M5: Acute monocytic leukemia
- 11q23 unfavourable
- M6: Erythroleukemia
- M7: Acute megakaryocytic leukemia
- Favourable: M1 - t(8;21), M3 - t(5;17), M4 - (inv(16)
- Unfavourable: del(7), infant 11q23
- M0-2: Acute myeloblastic leukaemia
- CML (3%)
- t(9;22)
- Mixed
Most common malignancy in childhood (31% or 4.5:100,000)
ALL:AML 10:1 in 1-15yo > 2:1 in infants and adolescents >15y
Adolescents and young adults do better on paediatric protocols than adult protocols
Cause marrow failure by displacing other cells
Associations:
GENETIC CONDITIONS
- Down syndrome
- Fanconi anemia
- Bloom syndrome
- Diamond-Blackfan anemia
- Schwachman-Diamond syndrome
- Kostmann syndrome
- Neurofibromatosis type 1
- Ataxia-telangiectasia
- Severe combined immune deficiency
- Paroxysmal nocturnal hemoglobinuria
- Li-Fraumeni syndrome
- Ionizing radiation
- Drugs
- Alkylating agents
- Nitrosourea
- Epipodophyllotoxin
- Benzene exposure
- Advanced maternal age
Presentation
- Anorexia, fatigue, malaise, irritability, intermittent, low-grade fever (disease or infection)
- URTI in preceding 2 months
- Proliferation in marrow
- High WC
- Low Hb (pallor, fatigue, exercise intolerance)
- Low Plt (bruising, or epistaxis)
- Bone or joint pain / swelling, waking from sleep (often on Hx but no bone pain on exam)
- Organ infiltration
- Lymphadenopathy
- Hepatosplenomegaly
- Mediastinal mass (T-cell) Thymus or nodes, (Wheeze
- CNS disease occasionally (if <1y or T-cell)
- cranial neuropathies, headache, ICP, seizures
- subcutaneous nodules or “blueberry muffin” lesions (especially in infants)
- chloromas or granulocytic sarcomas (M2 with t(8;21))
- disseminated intravascular coagulation (M3: promyelocytic)
- infiltration of the gingiva (M4/M5: myelomono/monocytic)
- myeloperoxidase stain differentiates ALL from AML
Ix
Usually low Hb and Plt
WCC high but can be normal or low with film showing atypical lymphocytes
- if pancytopenia ? aplastic anaemia ? myelofibrosis
- failure of a single cell line can be difficult to differentiate often needs BMA as well
Bone marrow aspiration and biopsy,
- >25% of cells a homogeneous population of lymphoblasts > ALL
- >20% of cells a homogeneous population of myeloid(-monocyte-megakaryocyte) blast
cytogenetics
molecular studies
CSF for staging (i.e. identifying CNS disease) with first dose on intrathecal chemotherapy
Pharmacogenetic testing of the thiopurine S-methyltransferase gene
- converts mercaptopurine or thioguanine (both prodrugs) into active chemotherapeutic agents
- Identifies rapid metabolizers (toxicity) or slow metabolizers (treatment failure) to adjust doses
DDx
EBV
JIA
AML
neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and retinoblastoma that has invaded the marrow
ALL
First cancer to be curable!
Heterogenous group of malignancies, with varying genetic abnormalities
Twin has 70% chance if MChorionic and <1, drops to 2x background if Dx 5-7yo
Higher risk
- Philadelphia translocation (t(9;22))
- <1y (usually Pro-B)
- >10y (usually mature B/T)
- CNS disease
Associations:
- Down syndrome
- Bloom syndrome
- ataxia-telangiectasia
- Fanconi anemia
- EBV (B-cell)
- Ionising Radiation
Prognostic factor
Age at onset (1-10 good)
Initial leukocyte count (<50 good)
Response to initial therapy
(infant or unfavourable chromosomes) worse than (older and >50) worse than (1-10 and <50)
Rx
Induction (aim to eradicate leukaemia from marrow > 98% acheive remission = <5% blasts and recovery of rest of marrow)
- vincristine weekly
- dexamethasone or prednisone
- asparaginase
- IT cytarabine and/or methotrexate
- HR add daunomycin
- Multiagent
- IT
- if HR > ?cranial irradiation
- daily mercaptopurine
- weekly methotrexate
- intermittent doses of vincristine
- corticosteroid
Relapse
- <10% get CNS
- 2% get testicular (usually T-cell ALL)
AML
- 5% die before inducing remission
- Intensive induction chemotherapy successful in achieving remission in 90%
- Those with favourable prognostic feature may have chemo alone unless relapse
- M3 with t(15,17) Rx all-trans-retinoic acid (tretinoin) combined with anthracyclines and cytarabine excellent
- For the rest matched sibling (bone marrow or stem cell) transplant during after remission improved survival from 50% with chemo alone to 70%
- Match unrelated donor have significant GVHD risk so only if relapse unless unfavourable prognostic features