1. Acute leukemia
Mohammed Al-matrafi

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

5. 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%

6. 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

7. Etiology Unknown: Genetic predisposition Viral infection
Cong. immune deficiency
Ionizing radiation
Certain toxic chemicals

8. At risk patients

13. 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}

14.   Clinical presentation of ALL

15. 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}

16. Clinical Presentation of ALL
SIGNS:
Pallor
Hepatomegaly
Spleenomegaly
Lymphadenopathy
Petechie
Bony tenderness

18. Diagnosis

19. Diagnosis Peripheral blood : CBC : Normal, increased, decreased
> 100,000 bad prognosis
Anemia
Neutropenia
Blast cells
Thrombocytopenia

20. Normal blood film

21. L1 L2 L3

22. : Diagnosis Bone marrow (BM) Morphology: >25% blast cells in marrow
(normal <5%)

23. Other investigations
Uric acid high
LDH high

24. Bone marrow aspirate Morphological classification:
Cytochemical analysis:
Immune phenotyping:
Cytogenetic:
Molecular studies:

25. Morphology FAB classification: { depending on size,cytoplasm,nucleus}
L1: commonest and has good prognosis

26. Immune phenotype T cell leukemia B cell leukemia
Non T cell non B cell leukemia

27. Cytogenetic studies Higher ploidy
{ >50 chromosomes}: good prognosis
Diploidy or hyperdiploidy:
{ chromosomes} Intermediate prognosis
Haploid cell:
worst prognosis

28. Differential diagnosis
Non malignant conditions like:
Juvenile Rheumatoid Arthritis / other connective disorders
Infectious Mononucleosis
Aplastic Anemia
Idiopathic Thrombocytopenic Purpura {ITP}

29. Treatment of ALL BASED ON: Lineage (B or T) Cytogenetic abnormalities
Patient’s age and other risk factors
White blood cell count (WBC)

30. Supportive measures Hydration Treatment of infection
Correction of electrolyte disturbances
Blood product transfusion
Psychological support
Treatment of tumor lysis syndrome

31. 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

32. 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}

33. Sanctuaries areas Relatively impermeable to the medications:
Sites of relapse:
2 sites:
CNS
Testis

34. Prognostic factors {contd.}
Morphology, histochemistry, cytogenetic
L1; good prognosis
Response to induction therapy
Rapid- good prognosis
Slow- poor prognosis
B cell leukemia: worst prognosis

35. 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

36. 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

37. Bone marrow transplant
Very high risk cases
Following relapse

38. Bone marrow transplant Blood stem cell transplant
Autologous
Allogeinic

39. 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.

40. 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 %

41. 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 invol
L1 type , Rapid response to induction therapy
Relapse site
BMT indication