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Acute leukemia. Mohammed Al-matrafi . Leukemia. Malignancy of leucocytes precursors Appearance of abnormal cells in BM, peripheral blood, infiltration in LN, Liver spleen etc. Childhood Leukemia. Types: Based on clinical presentation Acute leukemia 95% Chronic leukemia 5%

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Acute leukemia

Acute leukemia

Mohammed Al-matrafi


Leukemia
Leukemia

  • Malignancy of leucocytes precursors

  • Appearance of abnormal cells in BM, peripheral blood, infiltration in LN, Liver spleen etc.


Childhood leukemia
Childhood Leukemia

Types:

Based on clinical presentation

  • Acute leukemia 95%

  • Chronic leukemia 5%

    Based on type of predominant leukemic cells

  • Acute leukemia:

       Acute lymphoblastic leukemia- 85%

      Acute myeloid leukemia- 15%


Childhood leukemia1
Childhood leukemia

Prevalence:

  • Most common malignancy in children

  • 30% of all pediatric malignancies

  • Average incidence 4/100,000 children

  • Peak age:

    ALL : 4 years

    AML: Same from birth –10 years


Etiology
Etiology

Unknown:

Genetic predisposition

Viral infection

Cong. immune deficiency

Ionizing radiation

Certain toxic chemicals



Genetics
Genetics

  • At risk:

    Trisomy 21 {15 times}

    Fanconi aplastic anemia

    Ataxia telengectasia

    Siblings of patient with ALL {2-3 times}

    Identical twins{ concordance of ALL}



Clinical presentation of all
Clinical presentation ofALL

  • SYMPTOMS:

    Usually < 4 weeks history at diagnosis

    Fatigue/malaise

    Fever/infection

    Extremity, joint or bone pain

    Bleeding manifestations

    CNS symptoms (Increased ICP)

    Weight loss

    Others: DIC, Chloroma {AML}


Clinical presentation of all1
Clinical Presentation of ALL

  • SIGNS:

    Pallor

    Hepatomegaly

    Spleenomegaly

    Lymphadenopathy

    Petechie

    Bony tenderness



Diagnosis
Diagnosis

  • Peripheral blood :

    CBC : Normal, increased, decreased

    > 100,000 bad prognosis

    Anemia

    Neutropenia

    Blast cells

    Thrombocytopenia



L1

L2

L3


Diagnosis1
:Diagnosis

  • Bone marrow (BM)

    Morphology:

    >25% blast cells in marrow

    (normal <5%)


Other investigations
Other investigations

  • Uric acid high

  • LDH high


Bone marrow aspirate
Bone marrow aspirate

  • Morphological classification:

  • Cytochemical analysis:

  • Immune phenotyping:

  • Cytogenetic:

  • Molecular studies:


Morphology
Morphology

  • FAB classification:

    { depending on size,cytoplasm,nucleus}

    L1

    L2

    L3

    L1: commonest and has good prognosis


Immune phenotype
Immune phenotype

  • T cell leukemia

  • B cell leukemia

  • Non T cell non B cell leukemia


Cytogenetic studies
Cytogenetic studies

  • Higher ploidy

    { >50 chromosomes}: good prognosis

  • Diploidy or hyperdiploidy:

    { 47-50 chromosomes} Intermediate prognosis

  • Haploid cell:

    worst prognosis


Differential diagnosis
Differential diagnosis

Non malignant conditions like:

  • Juvenile Rheumatoid Arthritis / other connective disorders

  • Infectious Mononucleosis

  • Aplastic Anemia

  • Idiopathic Thrombocytopenic Purpura {ITP}


Treatment of all
Treatment of ALL

BASED ON:

  • Lineage (B or T)

  • Cytogenetic abnormalities

  • Patient’s age and other risk factors

  • White blood cell count (WBC)


Supportive measures
Supportive measures

  • Hydration

  • Treatment of infection

  • Correction of electrolyte disturbances

  • Blood product transfusion

  • Psychological support

  • Treatment of tumor lysis syndrome


Treatment of all1
Treatment of ALL

REQUIRES:

  • Intensive systemic multi agent chemotherapy

  • Repetitive intrathecal chemotherapy

  • Cranial irradiation when necessary in older children

  • Bone marrow transplant in special circumstances

  • Treatment continued for  3 years


Treatment
Treatment

  • Induction phase: 4 weeks {3-4 drugs}

    vincristine, prednisilone, L-asparaginase etc

  • CNS prophylaxis:

    Intrathecal methotrexate

    Cranial irradiation

  • Consolidation phase:2-4 weeks

    {For prevention of relapse}

  • Maintenance phase:{2-5 years}


Sanctuaries areas
Sanctuaries areas

  • Relatively impermeable to the medications:

  • Sites of relapse:

    2 sites:

    CNS

    Testis


Prognostic factors contd
Prognostic factors {contd.}

  • Morphology, histochemistry, cytogenetic

    L1; good prognosis

  • Response to induction therapy

    Rapid- good prognosis

    Slow- poor prognosis

  • B cell leukemia: worst prognosis


Prognostic factors
Prognostic factors

  • Demographic

    Age: <2year,>10year poor prognosis

    Race: Black poor prognosis

    Sex: Male poor prognosis

  • Leukemic burden

    WBC: >50,000 poor prognosis

    Mediastinal LN: poor prognosis

    CNS involvement. at diagnosis: poor prognosis


Outcome
Outcome

  • Relapse sites:

    Bone marrow

    CNS

    Testis in males

  • Disease free for 5 years after diagnosis:

    overall 60-70%, in standard risk group 80%

  • Relapse: Allogenic bone marrow transplant


Bone marrow transplant
Bone marrow transplant

  • Very high risk cases

  • Following relapse


Bone marrow transplant blood stem cell transplant
Bone marrow transplantBlood stem cell transplant

  • Autologous

  • Allogeinic


In a blood stem cell transplant, the patient is first given a pre-transplant treatment of chemotherapy and/or radiation therapy to destroy the patient's leukemia cells and immune system.

Blood stem cells are then put into the patient's blood to restore the patient's immune system and blood production.


Acute myelogenous leukemia
Acute myelogenous leukemia a pre-transplant treatment of chemotherapy and/or radiation therapy to destroy the patient's leukemia cells and immune system.

  • FAB classification:

    M1,M2,M3,M4,M5,M6,M7

    M3 { promyelocytic} may present with DIC

  • Disease free survival with

    chemotherapy 30 %

    BMT 50-60 %


Questions a pre-transplant treatment of chemotherapy and/or radiation therapy to destroy the patient's leukemia cells and immune system.

  • Commonest childhood malignancy

  • Types of Ac leukemia

  • Peak age

  • Etiology

  • At risk Patients

  • Symptoms

  • Signs

  • Diagnosis: PBS and bone marrow changes

  • D/D

  • Sanctuary areas

  • Prognostic factors: eg: age <1year,female ,white races ,WBC > 100,000, mediatinal mass, CNS invol

    L1 type , Rapid response to induction therapy

  • Relapse site

  • BMT indication


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