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ACUTELYMPHOBLASTICLEUKEMIA
LEUKEMIA
• Leukemia are the neoplastic proliferation of
hemopoietic cells.
• Acute leukemias are defined as neoplsam
• AML...
• Commonest form of malignancy in childhood.
• Peak incidence at 4 – 5 yrs of age.
• Acute onset with short history of dur...
• HEREDITARY
• ACQUIRED
• Ionizing radiations
• Therapeutic radiations
• Nuclear fallout
• Diagnostic Xrays
• Chemical age...
• Activation of a proto-oncogene to an oncogene when it
is translocated to a transcriptionally active site
• Formation of ...
SYMPTOMS
• FEVER
• FATIGUE
• BONE /JOINTS PAIN
• WEIGHT LOSS
• PURPURA AND BLEEDING MANIFESTATION
• LYMPHADENOPATHY
• HEPA...
FAB CLASSIFICATION
• Based on morphology and cytochemistry.
•
stain AML ALL
MPO + -
SBB + -
NSE + IN M4, M5 AND M7 -
PAS F...
FAB CLASSIFICATION
 ALL L1
 ALL L2
 ALL L3
 In childhood – L1 is the most common type
 In adults – L2 is the most com...
FAB classification
Morphology L1 L2 L3
1 Size of blast Small Large
heterogeneous
Large
homogenous
2 Cytoplasm Scanty Moder...
CRITICISM OF FAB CLASSIFICATION
1- It dose not include
• Immunophenotyping
• Cytogentics
• Molecular characteristics
2- im...
WHO CLASSIFIACTION OF ALL (2008)
1-B lymphoblastic leukemia/lymphoma nos
2- B lymphoblastic leukemia/lymphoma with recurre...
IMMUNOLOGICAL CLLASIFICATION
• 1- B ALL
• PRO B ALL
• EARLY PRE B ALL
• PRE B ALL
• MATURE B ALL
• 2- T ALL
• 3- MIXED LIN...
IMMUNOLOGICAL CLLASIFICATION
SUBTYPE HLA DR TdT CD 10 cIg smIg
Pro B ALL +_ + - - -
COMMON ALL + + + - -
Pre BALL + - - + ...
T ALL
• PAS negative acid phosphatase positive
• CNS involvement and mediastenal mass
• CD3 ,2 and 7 positive
Scoring system for biphenotypic leukemia
points B lineage T lineage Myeloid
2.0 CD 79a
CD 22.
CD 3 MPO
1.0 CD 10 CD 1 CD 1...
Uncommon variants of ALL
• Small cell variant- blast cells are small and
may be mistaken for lymphocytes.
• Hand mirror va...
Hand mirror variants
• Peripheral Blood smear
• Bone marrow aspiration smear
• Cytochemistry
• Immunophenotyping
• Cytogenetic analysis
• Molec...
PERIPHERAL BLOOD EXAMINATION
• Total leucocyte count raised , normal or low.
• Normocytic normochromic anaemia.
• Thromboc...
• Subleukemic leukemia-Total leukocyte count
is normal or low , but blast are seen in the
peripheral blood.
• Aleukemic le...
BONE MARROW EXAMINATION
• Hypercellular
• Normal hematopoietic elements diminished
ALL L1
Size – small.
Cytoplasm scanty basophilic.
N/C Ratio – high.
Nuclear membrane – regular.
Nucleoli – invisible or in...
BONE MARROW SMEAR
BLAST
ALL L2
 Size of blast – large & heterogenous
 Cytoplasm – moderate
 N/C Ratio – lower
 Cytoplasmic vacuoles – variable...
BONE MARROW SMEAR
ALL L3
 Size of blast – large & homogenous
 Cytoplasm – moderate & intensely basophilic
 N/C Ratio – lower
 Cytoplasmi...
BONE MARROW SMEAR
LYMPHOBLAST WITH CYTOPLASMIC VACUOLES &
NUCLEOLI
STARRY SKY PATTERN
PAS STAIN
LYMPHOBLAST WITH BLOCK & COARSE GRANULAR STAINING
STAINS
METHYL GREEN PYRONINE OIL RED
O(VACUOLES)
• Diagnosis and classification.
• Assessment of prognosis.
• Monitoring of minimum residual disease.
IMMUNOPHENOTYPING
• Establishment of lineage-DNA analysis.
• Identification of translocation.
• Detection of relapse.
• Detection of minimum...
OTHER INVESTIGATIONS
• Lumbar puncture.
• Testicular biopsy.
• X-Ray chest.
DIFFERENTIAL DIAGNOSIS
• Leukemic phase of Non Hodgkins Lymphoma
• Reactive lymphocytosis due to infections
• Metastatic t...
ALL Vs AML
ALL AML
Age Mainly children Mainly adults
Lymphadenopathy Usually present Usually absent
Hepatosplenomegaly +ve...
MorphologyLymphoblast Myeloblast
Nuclear chromatin Coarse Fine
Nucleoli 1-2 3-5
N:C ratio High High
Auer rod -ve +ve
Accom...
AML ALL
PROGNOSTIC FACTORS
Factor Good prognosis Bad prognosis
Race White Black
Age 2-8 yrs <1yr.,adult, >10 yrs
Sex Female Male
M...
Minimal residual disease detection
– ALL – B cell
– Cd20/cd10/cd19/cd45
– Cd9/cd34/cd19/cd45
– Cd58/cd10/cd38/cd19
– Cd20/...
• MODERATOR— Prof. Dr. C. V. KULKARNI
• SPEAKER- DR. NARMADA PRASAD TIWARI
• AML
• CD34/CD33/HLA-DR/CD45
• CD34/CD117/CD33/CD45
• CD115/CD117/CD33/CD34
• HLA-DR/CD117/CD33/CD34
• CLL
• CD20/CD79a/C...
Factors Predisposing to Childhood
Leukemia
• GENETIC CONDITIONS
Down syndrome
• Fanconi syndrome
• Bloom syndrome
• Diamon...
• ENVIRONMENTAL FACTORS
• Ionizing radiation
• Drugs
• Alkylating agents
• Nitrosourea
• Epipodophyllotoxin
• Benzene expo...
Acute lymphoblastic leukemia dr narmada
Acute lymphoblastic leukemia dr narmada
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Acute lymphoblastic leukemia dr narmada

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Acute lymphoblastic leukemia dr narmada

  1. 1. ACUTELYMPHOBLASTICLEUKEMIA
  2. 2. LEUKEMIA • Leukemia are the neoplastic proliferation of hemopoietic cells. • Acute leukemias are defined as neoplsam • AML - more than 20 % blast • ALL- more than 25% blast.
  3. 3. • Commonest form of malignancy in childhood. • Peak incidence at 4 – 5 yrs of age. • Acute onset with short history of duration. • 85% are B cell , 15% are T cell. ACUTE LYMPHOBLASTIC LEUKEMIA
  4. 4. • HEREDITARY • ACQUIRED • Ionizing radiations • Therapeutic radiations • Nuclear fallout • Diagnostic Xrays • Chemical agents • Viruses PREDISPOSING FACTORS
  5. 5. • Activation of a proto-oncogene to an oncogene when it is translocated to a transcriptionally active site • Formation of a chimeric transcription factor • Formation of a fusion protein with enhanced tyrosine kinase activity • Activation of FTL3 receptor • Inactivation of tumour suppressor gene pathway MECHANISM OF LEUKAEMOGENESIS
  6. 6. SYMPTOMS • FEVER • FATIGUE • BONE /JOINTS PAIN • WEIGHT LOSS • PURPURA AND BLEEDING MANIFESTATION • LYMPHADENOPATHY • HEPATOSPLENOMEGALY • STERNAL TENDERNESS • MEDIASTENAL MASS
  7. 7. FAB CLASSIFICATION • Based on morphology and cytochemistry. • stain AML ALL MPO + - SBB + - NSE + IN M4, M5 AND M7 - PAS FINE + IN M6 , M7 + , BLOCK ACID PHOSPHATASE - +, T ALL
  8. 8. FAB CLASSIFICATION  ALL L1  ALL L2  ALL L3  In childhood – L1 is the most common type  In adults – L2 is the most common type
  9. 9. FAB classification Morphology L1 L2 L3 1 Size of blast Small Large heterogeneous Large homogenous 2 Cytoplasm Scanty Moderate Moderate, intensely basophilic 3 N/C Ratio High Lower Lower 4 Cytoplasmic vacuoles +/- +/- Prominent 5 Nuclear membrane Regular Irregular with clef ting Regular 6 Nucleoli Invisible / indistinct Prominent 1-2 Prominent 1-2
  10. 10. CRITICISM OF FAB CLASSIFICATION 1- It dose not include • Immunophenotyping • Cytogentics • Molecular characteristics 2- immunological subtype of ALL 3-biphenotypic leukemia 4- Limited relevance to therapeutic or prognostic implications.
  11. 11. WHO CLASSIFIACTION OF ALL (2008) 1-B lymphoblastic leukemia/lymphoma nos 2- B lymphoblastic leukemia/lymphoma with recurrent abnormalities • t( 9; 22) , BCR ABL1 • t( v; 11q23) MLL rearangement • t (12;21) ETV6-RUNX1 • With hypodiploidy • With hyperdiploidy • t (5;14) il3 –igh • t ( 1;19) E2A-PBX1 (tcf3-pbx1) 3-T lymphoblastic leukemia/lymphoma
  12. 12. IMMUNOLOGICAL CLLASIFICATION • 1- B ALL • PRO B ALL • EARLY PRE B ALL • PRE B ALL • MATURE B ALL • 2- T ALL • 3- MIXED LINEAGE ACUTE LEUKEMIA • 4-Undifferentiated acute leukemia
  13. 13. IMMUNOLOGICAL CLLASIFICATION SUBTYPE HLA DR TdT CD 10 cIg smIg Pro B ALL +_ + - - - COMMON ALL + + + - - Pre BALL + - - + - Mature B ALL - - - - +
  14. 14. T ALL • PAS negative acid phosphatase positive • CNS involvement and mediastenal mass • CD3 ,2 and 7 positive
  15. 15. Scoring system for biphenotypic leukemia points B lineage T lineage Myeloid 2.0 CD 79a CD 22. CD 3 MPO 1.0 CD 10 CD 1 CD 13 0.5 TdT TdT, CD 7 CD 11b CD 11c Score above 2 from two lineage is diagnostic of biphenotypic leukemia
  16. 16. Uncommon variants of ALL • Small cell variant- blast cells are small and may be mistaken for lymphocytes. • Hand mirror variants- a subtype with cytoplasmic protrusion . • ALL with eosinophilia • Granular cell ALL- The cells are large and demonstrate azurophilic granulaes .
  17. 17. Hand mirror variants
  18. 18. • Peripheral Blood smear • Bone marrow aspiration smear • Cytochemistry • Immunophenotyping • Cytogenetic analysis • Molecular genetic analysis DIAGNOSIS OF ACUTE LEUKEMIA
  19. 19. PERIPHERAL BLOOD EXAMINATION • Total leucocyte count raised , normal or low. • Normocytic normochromic anaemia. • Thrombocytopenia.
  20. 20. • Subleukemic leukemia-Total leukocyte count is normal or low , but blast are seen in the peripheral blood. • Aleukemic leukemia- Blast are not seen in the peripheral blood , but are demonstrable only in bone marrow.
  21. 21. BONE MARROW EXAMINATION • Hypercellular • Normal hematopoietic elements diminished
  22. 22. ALL L1 Size – small. Cytoplasm scanty basophilic. N/C Ratio – high. Nuclear membrane – regular. Nucleoli – invisible or indistinct.
  23. 23. BONE MARROW SMEAR BLAST
  24. 24. ALL L2  Size of blast – large & heterogenous  Cytoplasm – moderate  N/C Ratio – lower  Cytoplasmic vacuoles – variable  Nuclear membrane – irregular with clefting  Nucleoli – prominent ,1-2
  25. 25. BONE MARROW SMEAR
  26. 26. ALL L3  Size of blast – large & homogenous  Cytoplasm – moderate & intensely basophilic  N/C Ratio – lower  Cytoplasmic vacuoles – prominent  Nuclear membrane – regular  Nucleoli – prominent , 1-2
  27. 27. BONE MARROW SMEAR LYMPHOBLAST WITH CYTOPLASMIC VACUOLES & NUCLEOLI
  28. 28. STARRY SKY PATTERN
  29. 29. PAS STAIN LYMPHOBLAST WITH BLOCK & COARSE GRANULAR STAINING
  30. 30. STAINS METHYL GREEN PYRONINE OIL RED O(VACUOLES)
  31. 31. • Diagnosis and classification. • Assessment of prognosis. • Monitoring of minimum residual disease. IMMUNOPHENOTYPING
  32. 32. • Establishment of lineage-DNA analysis. • Identification of translocation. • Detection of relapse. • Detection of minimum residual disease. Molecular Genetics-
  33. 33. OTHER INVESTIGATIONS • Lumbar puncture. • Testicular biopsy. • X-Ray chest.
  34. 34. DIFFERENTIAL DIAGNOSIS • Leukemic phase of Non Hodgkins Lymphoma • Reactive lymphocytosis due to infections • Metastatic tumours in bone marrow • AML
  35. 35. ALL Vs AML ALL AML Age Mainly children Mainly adults Lymphadenopathy Usually present Usually absent Hepatosplenomegaly +ve mild +ve mild Gum hypertrophy -ve +ve in M4/M5 Skin infiltration -ve +ve in M4/M5 CNS involvement +ve in some +ve in some Granulocytic sarcoma -ve +ve in few cases Mediastinal mass +ve in T-ALL - Associated DIC -ve +ve in M3 Serum muramidase Normal In M4/M5 (monocytic type) Prognosis Good Bad
  36. 36. MorphologyLymphoblast Myeloblast Nuclear chromatin Coarse Fine Nucleoli 1-2 3-5 N:C ratio High High Auer rod -ve +ve Accompanying cells Lymphocytes Myeloid precursor Myelo peroxidase -ve +ve Sudan Black B -ve +ve PAS stain Block positivity -ve in blast
  37. 37. AML ALL
  38. 38. PROGNOSTIC FACTORS Factor Good prognosis Bad prognosis Race White Black Age 2-8 yrs <1yr.,adult, >10 yrs Sex Female Male Meningeal involvement - + Lymphadenopathy, liver, spleen - Massively enlarged Mediastinal mass - + TLC <20x109 /L >50 x109 /L Type of ALL L1 L2,L3 Cytogenetics Hyperdiploidy >50 chromosomes Pseudodiploidy, t (4;11),t (9;22), BCR-ABL fusion m RNA, MLL-AF4 fusion mRNA. Immuno-phenotype B-ALL,CD 10+, Early pre-B cell T-ALL in children
  39. 39. Minimal residual disease detection – ALL – B cell – Cd20/cd10/cd19/cd45 – Cd9/cd34/cd19/cd45 – Cd58/cd10/cd38/cd19 – Cd20/cd10/cd19/cd34 – ALL –T cell – TdT/CD5/CD3/CD7
  40. 40. • MODERATOR— Prof. Dr. C. V. KULKARNI • SPEAKER- DR. NARMADA PRASAD TIWARI
  41. 41. • AML • CD34/CD33/HLA-DR/CD45 • CD34/CD117/CD33/CD45 • CD115/CD117/CD33/CD34 • HLA-DR/CD117/CD33/CD34 • CLL • CD20/CD79a/CD19/CD5
  42. 42. Factors Predisposing to Childhood Leukemia • GENETIC CONDITIONS Down syndrome • Fanconi syndrome • Bloom syndrome • Diamond-Blackfan anemia • Schwachman syndrome • Klinefelter syndrome • Turner syndrome • Neurofibromatosis • Ataxia-telangiectasia • Severe combined immune deficiency • Paroxysmal nocturnal hemoglobinuria • Li-Fraumeni syndrome
  43. 43. • ENVIRONMENTAL FACTORS • Ionizing radiation • Drugs • Alkylating agents • Nitrosourea • Epipodophyllotoxin • Benzene exposure • Advanced maternal age

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