Childhood Leukaemia Aengus S. O’Marcaigh, M.D., F.R.C.P.I., F.A.A.P. Department of Paediatric Haematology &Oncology Our Lady’s Hospital for Sick Children.

Childhood LeukaemiaChildhood Leukaemia

Aengus S. O’Marcaigh, M.D., F.R.C.P.I., F.A.A.P.Department of Paediatric Haematology &Oncology

Our Lady’s Hospital for Sick ChildrenCrumlin, Dublin 12.

Acute Acute LeukaemiaLeukaemia

ALL AML

80% 15%

2 - 6 yo 0 - 15 yo

2 - 3 yr, mild Rx 6mo, aggressive Rx

80% cure 65% cure

Acute leukaemia - Acute leukaemia - diagnosisdiagnosis

1. Clinical

2. Blood tests

3. Bone marrow tests

Diagnosis - ClinicalDiagnosis - Clinical

History - Fatigue, bruising, bleeding(symptoms) - Bone pain, limping

Examination - Pallor(signs) - Bruising

- Fever / infection

- Organomegaly- Lymphadenopathy- Mediastinal mass

Diagnosis - ClinicalDiagnosis - Clinical

Examination

- Pallor- Bruising- Fever

- Organomegaly- Lymphadenopathy- Mediastinal mass

Diagnosis - ClinicalDiagnosis - Clinical

Examination

- Pallor- Bruising- Fever

- Organomegaly- Lymphadenopathy- Mediastinal mass

Diagnosis - ClinicalDiagnosis - Clinical

Examination

- Pallor- Bruising- Fever

- Organomegaly- Lymphadenopathy- Mediastinal mass

Diagnosis - ClinicalDiagnosis - Clinical

Examination

- Pallor- Bruising- Fever

- Organomegaly- Lymphadenopathy- Mediastinal mass

Diagnosis - ClinicalDiagnosis - Clinical

Examination

- Pallor- Bruising- Fever

- Organomegaly- Lymphadenopathy- Mediastinal mass

Acute leukaemia - Acute leukaemia - diagnosisdiagnosis

FBC - Leucocytosis ? WBC 1.0 - 1000 x 109/LNeutropaenia ANC 0.5 x 109/L Anaemia Hb 7.8 g/dLThrombocytopaenia Plt 40 x 109/L

Chemistry Incerased Uric acidIncreased LDH

B Marrow MorphologyCytochemistryImmunophenotypingGenetics

Diagnosis - Bone marrowDiagnosis - Bone marrow

Bone marrow diagnosis

- Morphology

- Cytochemistry

- Immunophenotyping

- Cytogenetics

Diagnosis - Bone marrowDiagnosis - Bone marrow

Bone marrow diagnosis

- Morphology

- Cytochemistry

- Immunophenotyping

- Cytogenetics

Normal bone marrow

Diagnosis - Bone marrowDiagnosis - Bone marrow

Bone marrow diagnosis

- Morphology

- Cytochemistry

- Immunophenotyping

- Cytogenetics

Acute Leukaemia

Diagnosis - CytogeneticsDiagnosis - Cytogenetics

Translocation

t (1;22)

Infant M7 AML

Very poor prognosis

Initial managementInitial management

1. Pancytopaenia ?

2. Sepsis / infection

3. Mediastinal mass

4. Tumour lysis syndrome

TransfusionCMV-neg, irradiated

Initial managementInitial management

1. Pancytopaenia

2. Sepsis / infection

3. Mediastinal mass

4. Tumour lysis syndrome ?

Uric acid / LDHRenal functionHydrationUrate oxidase

TreatmentTreatment

ALL 2003

Regimen A - Standard risk 60%Regimen B - Intermediate risk 30%Regimen C - High risk 10%

Risk assignment 1. Age2. WBC3. Cytogenetics4. Response to treatment

Treatment - MRC ALL 2003Treatment - MRC ALL 2003

1. Age (years)

< 1 to Interfant protocol

1 - 10 to Regimen A

> 10 to Regimen B

Treatment - MRC ALL 2003Treatment - MRC ALL 2003

2. WBC (x 109/L)

< 50 to Regimen A

>50 to Regimen B

Treatment - MRC ALL 2003Treatment - MRC ALL 2003

3. Cytogenetics

Hypodiploidy to Regimen C

t(9:22) to Regimen C

iAMP 21 to Regimen C

Treatment - MRC ALL 2003Treatment - MRC ALL 2003

4. Response to therapy

- Day 8 bone marrow >25% blasts - B to C Day 15 bone marrow >25% blasts - A to C

- Day 28 MRD (minimal residual disease)