acute lymphoblastic leukemia dr narmada
DESCRIPTION
ALL SEMINARTRANSCRIPT
![Page 1: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/1.jpg)
ACUTE LYMPHOBLASTIC LEUKEMIA
![Page 2: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/2.jpg)
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.
![Page 3: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/3.jpg)
• 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
![Page 4: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/4.jpg)
• HEREDITARY
• ACQUIRED• Ionizing radiations• Therapeutic radiations• Nuclear fallout• Diagnostic Xrays• Chemical agents• Viruses
PREDISPOSING FACTORS
![Page 5: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/5.jpg)
• 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
![Page 6: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/6.jpg)
SYMPTOMS• FEVER • FATIGUE• BONE /JOINTS PAIN• WEIGHT LOSS• PURPURA AND BLEEDING MANIFESTATION• LYMPHADENOPATHY• HEPATOSPLENOMEGALY• STERNAL TENDERNESS• MEDIASTENAL MASS
![Page 7: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/7.jpg)
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
![Page 8: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/8.jpg)
FAB CLASSIFICATION
ALL L1 ALL L2 ALL L3
In childhood – L1 is the most common type In adults – L2 is the most common type
![Page 9: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/9.jpg)
FAB classificationMorphology 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
![Page 10: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/10.jpg)
CRITICISM OF FAB CLASSIFICATION
1- It dose not include • Immunophenotyping• Cytogentics• Molecular characteristics2- immunological subtype of ALL3-biphenotypic leukemia4- Limited relevance to therapeutic or
prognostic implications.
![Page 11: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/11.jpg)
WHO CLASSIFIACTION OF ALL (2008)
1-B lymphoblastic leukemia/lymphoma nos2- 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
![Page 12: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/12.jpg)
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
![Page 13: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/13.jpg)
IMMUNOLOGICAL CLLASIFICATIONSUBTYPE HLA DR TdT CD 10 cIg smIg
Pro B ALL +_ + - - -
COMMON ALL + + + - -
Pre BALL + - - + -
Mature B ALL - - - - +
![Page 14: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/14.jpg)
T ALL
• PAS negative acid phosphatase positive • CNS involvement and mediastenal mass• CD3 ,2 and 7 positive
![Page 15: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/15.jpg)
Scoring system for biphenotypic leukemiapoints B lineage T lineage Myeloid
2.0 CD 79aCD 22.
CD 3 MPO
1.0 CD 10 CD 1 CD 13
0.5 TdT TdT, CD 7 CD 11bCD 11c
Score above 2 from two lineage is diagnostic of biphenotypic leukemia
![Page 16: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/16.jpg)
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 .
![Page 17: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/17.jpg)
Hand mirror variants
![Page 18: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/18.jpg)
• Peripheral Blood smear• Bone marrow aspiration smear• Cytochemistry• Immunophenotyping• Cytogenetic analysis• Molecular genetic analysis
DIAGNOSIS OF ACUTE LEUKEMIA
![Page 19: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/19.jpg)
PERIPHERAL BLOOD EXAMINATION
• Total leucocyte count raised , normal or low.• Normocytic normochromic anaemia.• Thrombocytopenia.
![Page 20: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/20.jpg)
![Page 21: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/21.jpg)
• 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.
![Page 22: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/22.jpg)
BONE MARROW EXAMINATION
• Hypercellular• Normal hematopoietic elements diminished
![Page 23: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/23.jpg)
ALL L1
Size – small.Cytoplasm scanty basophilic.N/C Ratio – high.Nuclear membrane – regular.
Nucleoli – invisible or indistinct.
![Page 24: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/24.jpg)
BONE MARROW SMEAR
BLAST
![Page 25: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/25.jpg)
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
![Page 26: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/26.jpg)
BONE MARROW SMEAR
![Page 27: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/27.jpg)
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
![Page 28: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/28.jpg)
BONE MARROW SMEAR
LYMPHOBLAST WITH CYTOPLASMIC VACUOLES & NUCLEOLI
![Page 29: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/29.jpg)
STARRY SKY PATTERN
![Page 30: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/30.jpg)
PAS STAIN
LYMPHOBLAST WITH BLOCK & COARSE GRANULAR STAINING
![Page 31: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/31.jpg)
STAINS
METHYL GREEN PYRONINE OIL RED O(VACUOLES)
![Page 32: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/32.jpg)
• Diagnosis and classification.• Assessment of prognosis.• Monitoring of minimum residual disease.
IMMUNOPHENOTYPING
![Page 33: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/33.jpg)
• Establishment of lineage-DNA analysis.• Identification of translocation.• Detection of relapse.• Detection of minimum residual disease.
Molecular Genetics-
![Page 34: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/34.jpg)
OTHER INVESTIGATIONS• Lumbar puncture.• Testicular biopsy.• X-Ray chest.
![Page 35: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/35.jpg)
DIFFERENTIAL DIAGNOSIS
• Leukemic phase of Non Hodgkins Lymphoma• Reactive lymphocytosis due to infections• Metastatic tumours in bone marrow• AML
![Page 36: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/36.jpg)
ALL Vs AMLALL 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
![Page 37: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/37.jpg)
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
![Page 38: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/38.jpg)
AML ALL
![Page 39: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/39.jpg)
PROGNOSTIC FACTORSFactor 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
![Page 40: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/40.jpg)
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
![Page 41: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/41.jpg)
![Page 42: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/42.jpg)
• MODERATOR— Prof. Dr. C. V. KULKARNI
• SPEAKER- DR. NARMADA PRASAD TIWARI
![Page 43: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/43.jpg)
• AML• CD34/CD33/HLA-DR/CD45• CD34/CD117/CD33/CD45• CD115/CD117/CD33/CD34• HLA-DR/CD117/CD33/CD34
• CLL• CD20/CD79a/CD19/CD5
![Page 44: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/44.jpg)
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
![Page 45: Acute lymphoblastic leukemia dr narmada](https://reader033.vdocument.in/reader033/viewer/2022061116/546605a1b4af9f583f8b51d7/html5/thumbnails/45.jpg)
• ENVIRONMENTAL FACTORS• Ionizing radiation • Drugs • Alkylating agents • Nitrosourea • Epipodophyllotoxin • Benzene exposure • Advanced maternal age