Acute leukemia

Mohammed Al-matrafi

Leukemia

• Malignancy of leucocytes precursors

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

85%

15%

Ac Leukemia

Chronic Leukemia

85%

15%

ALL

AML

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 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

Unknown:

Genetic predisposition

Viral infection

Cong. immune deficiency

Ionizing radiation

Certain toxic chemicals

At risk patients

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 of ALL

• 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

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

  

Normal blood film

L1L2

L3

: 

   Diagnosis• Bone marrow (BM) Morphology:     >25% blast cells in

marrow (normal <5%) 

Other investigations

• Uric acid high

• LDH high

Bone marrow aspirate

• Morphological classification:

• Cytochemical analysis:

• Immune phenotyping:

• Cytogenetic:

• Molecular studies:

Morphology

• FAB classification:

{ depending on size,cytoplasm,nucleus}

L1

L2

L3

L1: commonest and has good prognosis

Immune phenotype

• T cell leukemia

• B cell leukemia

• Non T cell non B cell leukemia

Cytogenetic studies

• Higher ploidy

{ >50 chromosomes}: good prognosis

• Diploidy or hyperdiploidy:

{ 47-50 chromosomes} Intermediate prognosis

• Haploid cell:

worst prognosis

Differential diagnosis

Non malignant conditions like:

• Juvenile Rheumatoid Arthritis / other connective disorders

• Infectious Mononucleosis

• Aplastic Anemia

• Idiopathic Thrombocytopenic Purpura {ITP}

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

• Hydration

• Treatment of infection

• Correction of electrolyte disturbances

• Blood product transfusion

• Psychological support

• Treatment of tumor lysis syndrome

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• 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

• Relatively impermeable to the medications:

• Sites of relapse:

2 sites:

CNS

Testis

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

• 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• 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

• Very high risk cases

• Following relapse

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

• 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• 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 involL1 type , Rapid response to induction therapy

• Relapse site• BMT indication