Leucocytes Benign Disorders Nada Mohamed Ahmed, MD, MT (ASCP)i.
Acute leukemia Mohammed Al-matrafi. Leukemia Malignancy of leucocytes precursors Appearance of...
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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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85%
15%
Ac Leukemia
Chronic Leukemia
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85%
15%
ALL
AML
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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 < 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
> 100,000 bad prognosis
Anemia Neutropenia
Blast cells Thrombocytopenia
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Normal blood film
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L1L2
L3
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:
Diagnosis• Bone marrow (BM) Morphology: >25% blast cells in
marrow (normal <5%)
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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
{ >50 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• Patient’s 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 phase:2-4 weeks
{For prevention of relapse}• Maintenance phase:{2-5 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: <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
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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 <1year,female ,white
races ,WBC > 100,000, mediatinal mass, CNS involL1 type , Rapid response to induction therapy
• Relapse site• BMT indication