Acute leukemia

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Acute leukemia

• Mohammed Al-matrafi

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Leukemia

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

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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

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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

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Etiology

• Unknown
• Genetic predisposition
• Viral infection
• Cong. immune deficiency
• Ionizing radiation
• Certain toxic chemicals

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• At risk patients

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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

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•   Clinical presentation of ALL

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Clinical presentation of ALL

• SYMPTOMS
• Usually lt 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

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  Clinical Presentation of ALL

• SIGNS
• Pallor
• Hepatomegaly
• Spleenomegaly
• Lymphadenopathy
• Petechie
• Bony tenderness

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• Diagnosis

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Diagnosis

• Peripheral blood
• CBC Normal, increased,
  decreased
• gt 100,000 bad
  prognosis
• Anemia
• Neutropenia
• Blast cells
• Thrombocytopenia
•  
•  

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Normal blood film
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L1
L2
L3
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    Diagnosis

• Bone marrow (BM)
• Morphology
•      gt25 blast cells in
  marrow
• (normal lt5)
•  

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Other investigations

• Uric acid high
• LDH high

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Bone marrow aspirate

• Morphological classification
• Cytochemical analysis
• Immune phenotyping
• Cytogenetic
• Molecular studies

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Morphology

• FAB classification
• depending on size,cytoplasm,nucleus
• L1
• L2
• L3
• L1 commonest and has good prognosis

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Immune phenotype

• T cell leukemia
• B cell leukemia
• Non T cell non B cell leukemia

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Cytogenetic studies

• Higher ploidy
• gt50 chromosomes good prognosis
• Diploidy or hyperdiploidy
• 47-50 chromosomes Intermediate prognosis
• Haploid cell
• worst prognosis

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Differential diagnosis

• Non malignant conditions like
• Juvenile Rheumatoid Arthritis / other connective
  disorders
• Infectious Mononucleosis
• Aplastic Anemia
• Idiopathic Thrombocytopenic Purpura ITP

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Treatment of ALL

• BASED ON
• Lineage (B or T)
•  Cytogenetic abnormalities
• Patients age and other risk factors
• White blood cell count (WBC)

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Supportive measures

• Hydration
• Treatment of infection
• Correction of electrolyte disturbances
• Blood product transfusion
• Psychological support
• Treatment of tumor lysis syndrome

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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
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Treatment

• Induction phase 4 weeks 3-4 drugs
• vincristine, prednisilone, L-asparaginase etc
• CNS prophylaxis
• Intrathecal methotrexate
• Cranial irradiation
• Consolidation phase2-4 weeks
• For prevention of relapse
• Maintenance phase2-5 years

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Sanctuaries areas

• Relatively impermeable to the medications
• Sites of relapse
• 2 sites
• CNS
• Testis

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Prognostic factors contd.

• Morphology, histochemistry, cytogenetic
• L1 good prognosis
• Response to induction therapy
• Rapid- good prognosis
• Slow- poor prognosis
• B cell leukemia worst prognosis

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Prognostic factors

• Demographic
• Age lt2year,gt10year poor prognosis
• Race Black poor prognosis
• Sex Male poor prognosis
• Leukemic burden
• WBC gt50,000 poor prognosis
• Mediastinal LN poor prognosis
• CNS involvement. at diagnosis poor prognosis

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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

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Bone marrow transplant

• Very high risk cases
• Following relapse

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Bone marrow transplantBlood stem cell transplant

• Autologous
• Allogeinic

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• 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.

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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

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• 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 lt1year,female ,white
  races ,WBC gt 100,000, mediatinal mass, CNS invol
• L1 type , Rapid response to induction therapy
• Relapse site
• BMT indication