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Acute leukemia

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Biphenotypic acuteleukemia (BAL,ALL AML) Classification of Leukemia Morphology of FAB 1.Acute lymphoblastic leukemia (ALL) L1 small ... – PowerPoint PPT presentation

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Title: Acute leukemia


1
Acute leukemia

2
Aim and claim1Understand the classification and
pathogenesis of leukemias.2Familiar with the
clinical features investigations of
leukemias.3Get hold of the ALL management.
3
DEFINITION
Accumulation of leukemic cells
myeloid(myelogenous,myeloblastic)
lymphoid(lymphoblastic) in Bone
Marrow(BM) Peripheral Blood(PB)
Other Tissues
4
Biological Features of Leukemia Cells
  • 1.Over proliferation
  • 2.Poor differentiation
  • 3.Less apoptosis(programmed cell death)

Accumulation of Leukemia Cell
5
LEUKEMIA
1. Clonal disease 2. Somatic mutation
of a single
progenitor/ stem cell 3. Malignant disease
6
Epidemiology
7
  • Incidence 40 Per Million
  • New case about 2000 per year
  • Mortality 2th or 3th cause

8
Etiology
  • Genetic predisposition
  • Ionizing radiation
  • Chemical exposure
  • Previous chemotherapy
  • Other drug
  • Predisposing diseases

9
Etiology
  • 1.Environment of cause of leukemia
  • Physical Agent
  • Ionizing Radiation
  • Ultraviolet Irradiation
  • 2.Chemical Agents
  • Benzene
  • Alkylating Agents
  • Phenytoin
  • Chloramphenicol
  • Topoisomerase inhibitors

10
Viruses
  • RNA Viruses type c RNA v,Retroviruses
  • DNA Viruses Epstein-Barr Viruses
  • PAPOVA Viruses

11
Host Factor
  • Patient with such diseases
  • 1.Immunodeficiency state
  • 2.Chromosomal abnormalities
  • Down syndrome , Fanconi syndrome

12
Classification of Leukemia
  • Depend on
  • diffirentiation degree of leukemia cell
  • natural course
  • Classification
  • Acute leukemia(AL)
  • Chronic leukemia(CL)

13
Acute Leukemia
  • 1. Acute lymphoblastic(lymphoid, lymphocytic)
    leukemia (ALL)
  • 2. Acute myeloid(myelogenous,myelogenous)
    leukemia(AML),Acute non-lymphocytic
    leukemia(ANLL)
  • 3. Biphenotypic acuteleukemia (BAL,ALL?AML)

14
Classification of Leukemia
  • Morphology of FAB
  • 1.Acute lymphoblastic leukemia (ALL)
  • L1 small little cytoplasm
  • L2 larger increased
    cytoplasm
  • L3 basophilic
    cytoplasm with vacuolation

15
Acute Nonlymphocytic leukemia (ANLL)
  • M1 or M0 myeloblastic no maturation
  • M2 myeloblastic some maturtion
  • M3 hypergranlar promyelocytic
  • M4 myelomomocytic
  • M5 monocytic
  • M6 erythroleukemia
  • M7 megakryocytic

16
Laboratary Evaluation-4
Cytochemisry in Acute Leukemia
B-ALL T-ALL AML
Myeloperoxidase (POX) - - ?
Sudan black - - ?
Non-specific esterase - - ?(M4,M5)
Periodic acid-Schiff ? (coarse) - ?(fine except M6)
Acid phosphatase - ? -
17
Immunophenotype of All
  • A T cell from 15-20.
  • B B cell from 70-75.
  • (a) B cell (SIg)
  • (b)pre B cell (CIg, CD10, CD19 )
  • (c) early pre B cell (TdT ,CD19)
  • (d)common B cell (CD10 ,CD19)
  • C mixed B/T
  • DNull cell from lt10

18
EPICS XL/XL-MCL??????????(???)
????????
  • ?????

??????
????
?????
19
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20
Classification of cytogenetics
  • Associated Chromosomal Subtype
  • Abnormality
  • ALL t (1114) T
  • t (814)
    B
  • t (119)
    pre B
  • t (922)
    pre B
  • t (411)
    early pre B
  • t (1221)
    early pre B

21
  • Associated Chromosomal Subtype
  • Abnormality
  • ANLL t (821) M2
  • t (1517)
    M3
  • del(11)
    M5a
  • t (922)
    M1 or M2
  • inv/del(16)
    M4

22
Clinical Features
  • Leukemia cell accumulation
  • ?Normal Hemopoiesis?
  • 1.Anemia
  • 2.Bleeding
  • 3.Infection
  • 4.Infiltration
  • 5.Hypermetabolism

23
Anemia
  • 1.Lethargy
  • 2.Weakness
  • 3.Dyspnea
  • 4.Pallor
  • 5.Dizziness
  • 6.Palpitation

24
Bleeding
  • Petechialusually
  • Skin
  • Mucous membrane
  • CNSmost severe
  • DICM3(APL)

25
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26
Infection
  • 1. Bacterial in early stage
  • 2. Fungal in patients with prolonged period of
    time
  • 3. Site
  • skin,mouth,pharynx,perianal,perineal
  • lung,septicemia

27
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28
Infiltration
  • Skin M5.widespread raised nonitchy hemorrhagic
    rash,swelling of gum,nodular
  • Lymphadenopathy ALL.
  • T-ALL(thymic mass/upper mediastinal enlarge)
  • Hepatosplenomegaly
  • CNS meningeal.ALL(children,younger)
  • nausea,vomiting,headache,visual
    disturbance,
  • photophobia,cranial nerve palsy
  • Testes testicular swelling
  • Bone pathologic fracture,bone pain.sternal tender

29
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30
Hypermetabolism
  • 1.Night sweat
  • 2.Low fever
  • 3.Higher uric acid(urate)
  • 4.Weight loss

31
Frequency of Clinical Findings at Diagnosis in ALL
Clinical Features Percentage
Symptoms Fatigue Bone or joint pain Fever without infection Weight loss Abnormal masses Purpura Other hemorrhage Infection 92 79 71 66 62 51 27 17
32
Frequency of Clinical Findings at Diagnosis in ALL
Clinical Features Percentage
Physical findings(signs) Splenomegaly Lymphadenopathy Hepatomegaly Sternal tenderness Purpura Fundic hemorrhage 86 76 74 69 50 14
33
Laboratory Evaluation-1
Laboratory Features Percentage
WBC(109/L) lt10/10-49/50-99/gt100 ANC (109/L) lt1/1-2/gt2 Platelets (109/L) lt50/50-150/gt150 40/34/15/11 73/9/18 62/30/8
34
Laboratory Evaluation-2
Bone Marrow Examination Hypercellular
Replacement of fat spaces and normal
marrow elements by leukemic cells
Lymphoblastdorminant Residual
myeloid/erythroid precursor
morphologic normal
Megakaryocyteabsent/decreased Dry tap
35
Treatment
  • Supportive care with antibiotics and blood
    products
  • Allopurinol?Hydration?Soda(sodium bicarbonate) to
    prevent acute tumour lysis syndrome(ATLS)

36
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37
Treatment
  • Cytotoxic chemotherapy
  • inductionVP,DNR,L-asp
  • consolidation
  • maintenance6-MP,MTX
  • CNSLMTX,Ara-C,Dex
  • Stem cell transplantation

38
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39
Treatment
  • Cytotoxic chemotherapy
  • induction DA,HA,MA,IA
  • (M3 ATRA,As2O3,As4S4)
  • postremission
  • HD-AraC
  • Auto-SCT
  • Allo-SCT
  • (M3-ATRA,As2O3,As4S4)

40
Prognosis
  • Children60 5-year survival.
  • Adults30 5-year survival.
  • Poor prognosic indicators include
  • increasing age
  • increasing white cell count Philadelphia(Ph)
    chromosome, t(411)
  • 11q23 abnormality
  • NR within 28days

41
Reviews and question
  • 1Try explaining the classification and
    pathogenesis of leukemia?
  • 2How are the clinical featrures and
    investigations of leukemia?

42
???

43
  • 1.????? ????????????????????
  • 2.???????,????????,????????,???????,?????,??,????
    ??
  • 3.???????4.52/10?,????,?gt?,70?NHL?

44
  • ???
  • 1.??EBV??Brkitt????
  • 2.???????????,??????????????
  • 3.??????,???
  • 4.???????

45
?????
  • ???? ???,????? ???,? ?????,????,????,??5????

46
Most patients present with a painless,
asymmetrical,firm and discrete enlargement of
superficial lymph nodes
Right-sided cervical lymphadenopathy. Scar of a
previous biopsy incision
47
????
  • 1.??????
  • 2.???? ????30?????
  • 3.???????????
  • (1)?????
  • (2)??????????
  • (3)????????,??
  • (4)??????????
  • (5)????
  • (6)???????,????????????

48
  • 4.???????
  • (1)???,??,????,40????????
  • (2)?????,??,??,???
  • (3)??????????,??????,???????
  • 5.??????,??,???
  • 6.????
  • (1)????
  • (2)???
  • ?? ???????????????

49
Involvement of retroperitoneal lymph
nodes Splenomegaly 50
Pitting edema
HDgross edema of the legs,genitals and lower
abdominal wall with umbilical herniation due to
lymphatic obstruction resulting from extensive
involvement of inguinal and pelvic lymph
nodes.There is a staphylococcal infection in skin
folds of groins
50
Extensive skin deposit
Pedunculated skin deposit
Of the extranodal sites,the bone marrow shows
focal or diffuse involvement in about 20
patients.After marrow,liver and spleen,the
gastrointestinal tract is involved most
frequently and patients may present with acute
abdominal symptoms.The skin is affected not
infrequently.
51
Mediastinal,hilar node or lung involvement Detect
ed by radiography
Liver involvement by percutaneous
biopsy,para-aortic or pelvic lymph node
involvement by abdominal radiography and
lymphangiography
52
Plain abdominal radiograph
Bilateral massive para-aortic lymph node
enlargement
lymphangiogram
53
Chest
Abdomen
Pelvis
Computerized tomographic(CT) scanning is now used
extensively in the search for thoracic and
abdominal lymph node and organ involvement
As staging procedures are not always reliable,
laparotomy may be performed,combined with
abdominal node and liver biopsies,and splenectomy
in cases considered to be Stage?or? after
clinical examination and the initial staging
procedures
54
  • ????
  • (1)???????(LP)40?
  • ??????????,???????????????,???????????,
    R-S?????
  • ???

55
  • 2.?????(NS)40
  • ?????????????????????,R-S?????????
  • ?????
  • 3.?????(MC)10
  • ?????????,?????????? ????.????.????.????
    ,???,??,???R-S???
  • ????

56
  • 4.???????(LD)10
  • ?????????,?????,R-S???????

57
????? nodular sclerosis
58
HISTOLOGY
Typical multinucleate Reed-Sternberg cell
MicroscopicallyCharacteristic polypoid
Reed-Sternberg cell
59
????
  • I.??????????,??????(IE)?
  • II.????????2??2???????(II)??????????????(II E)?
  • III.????????(III),?????(III E)????(III
    S),????(III ES)?
  • ?.??????????????????????,???????????

60
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61
????
  • ?????????,???????,BM,?????????????????????,?????
    ?????,??????????????????
  • E ????????????????????????(??)???????,??????????
    ,??????
  • A?B??B?????????6????????????10,???????

62
???????
  • ??
  • 1.?????
  • 2.??????
  • ????
  • 1.???????,????,??,???????
  • 2.???????

63
???????
  • ??????,????????
  • ??MOPP COPP COEP ABVD
  • ????
  • 1.CR?1?
  • 2.PR ?????????????50?
  • 3.??????????50,?????25,??1??
  • 4.??(PD)???????25,???????

64
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65
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66
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67
??????
68
??????
  • ????
  • ???????, ??????
  • ???????
  • ??????
  • ????????????
  • ???????

69
  • ????
  • 1.???????70-80?T
  • 2.??????(????)95?B
  • 3.???????
  • ??
  • ???????
  • ?ALL??????
  • ??????,???,??

70
B???????B???
  • ????
  • ????
  • ???? CD19,CD20,CD10,SmIg
  • ??????(Burkitts)

71
T???????T???
  • ????
  • ????
  • ???? CD7,CD5,CD1,CD3,CD4,CD8,CD2
  • ????????

72
Classification
  • KielMIpattern(follicular,diffuse)
  • RappaportMpattern
  • Lukes-CollinsMI
  • National Cancer Institute(NCI) Working
    FormulationMpattern
  • REAL(1994)MIpatternCM
  • WHO(2001)

73
  • ???????????
  • 1.?????????? ?????B
  • 2.???(???) ??100B
  • 3.??????? 53B17T

  • 30Null
  • 4.??????? 70B30Null
  • 5.?????? Bor T
  • 6.?????? ?????T
  • 7.???????Bark??? ????B

74
  • ??
  • ?????? ??
  • ???? ??
  • ?????????????? ,??NHL????????
  • ??????????,IT????
  • ????CHOP

75
  • ??????(T)
  • ??????
  • ALL??
  • ASP
  • HD MTX
  • HD ARA-C
  • ?????(gt18?)
  • ????(B)
  • ??????
  • ??????
  • ?????
  • HD MTX
  • HD ARA-C
  • ????
  • T,B??????
  • B???????

76
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78
T-NHLIII-IV?????
79
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80
T-NHL I-II? ????
81
  • ????(HSCT)?? ?
  • ABMT?????????
  • ???????

82
  • ????
  • 1.????
  • 2.??????????????
  • 3.????????????

83
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84
??
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