Acute Lymphoblastic Leukaemia Terri Boyer 17 th October 2006.
Acute Lymphoblastic Leukaemia
-
Upload
stanley-medical-college-department-of-medicine -
Category
Health & Medicine
-
view
7.200 -
download
7
Transcript of Acute Lymphoblastic Leukaemia
![Page 1: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/1.jpg)
ACUTE LYMPHOBLASTIC LEUKEMIA
PROF.S.TITO’S UNIT M5
DR.M.ARIVUMANI
![Page 2: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/2.jpg)
Acute lymphoblastic leuKemia is malignant disease of marrow in which early lymphoid precursors proliferate and replace the normal haematopoietic cells
![Page 3: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/3.jpg)
Normal marrow
![Page 4: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/4.jpg)
Entire marrow replaced by blast
![Page 5: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/5.jpg)
Marrow showing blasts
![Page 6: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/6.jpg)
Relative frequencies of lymphoid malignancies
NHL(62.4%)
![Page 7: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/7.jpg)
• Epidemiology peaK incidence in 2 to 6 years more in boys than girls. median age in adults-35years• Etiology less studied environmental and genetic factors
![Page 8: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/8.jpg)
Chromosomal abnormalities in ALL
ABNORMALITIES ADULTS(%) CHILDREN(%)
Normal karyotype 16-34 9
hypodiploidy 4-9 1
hyperdiploidy 2-9 25
t (9;22) 11-30 4
t (4;11) 3-7 6
t (10;14) 4-6 4
t (8;14) 4 2
t ( 1;19) 3 5
9p abnormality 5-16 7-13
6q abnormality 2-6 4-6
12p abnormality 4-5 22
![Page 9: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/9.jpg)
Factors predisposing ALL
GENETIC ENVRONMENTAL
Downs,turner, klinefelter Ionising radiation
Fanconi,diamond blackfan Drugs
NF Type1 alkylating agents
Ataxia telengiectasia nitrosourea
SCID epipodophyllotoxin
PNH benzene exposure
Li-fraumeni syndrome advanced maternal age
Blooms syndrome paternal smoking
![Page 10: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/10.jpg)
FAB CLASSIFICATION OF ALL
CYTOLOGIC FEATURES
L1 L2 L3
Cell size Small cells predominate,homogenous
Large,heterogenous in size
Large homogenous
cytoplasm Scanty Variable,often moderately abundant
Moderately abundant
nucleoli Small One or more,often large
One or more,prominent
Nuclear shape Homogenous Variable, heterogenous
Stippled, homogenous
Nuclear shape Regular Irregular clefts regular
Cyt.basophilia variable variable Intensely basophilic
Cyt.vacuolation variable variable prominent
![Page 11: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/11.jpg)
Immunologic subtype
% of cases FAB subtype Cytogenetic abnormalites
Pre B ALL 75 L1,L2 t(9;22),t(4;11)t(1;19)
Tcell ALL 20 L1,L2 14q11 or 7q34
Mature Bcell ALL(burkitt leukemia)
5 L3 t(8;14)
Classification of ALL(WHO)
![Page 12: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/12.jpg)
Pre B ALL(L1)Small blasts wth thin rim of cytoplasm
![Page 13: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/13.jpg)
T Cell ALL(L1)
![Page 14: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/14.jpg)
T Cell ALL (L2)Irregular clefts of nucleus
![Page 15: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/15.jpg)
Burkitt leukemia-Mature B Cell ALL(L3)-vacuolations
![Page 16: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/16.jpg)
CNS Leukemia(csf showing blasts)
![Page 17: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/17.jpg)
B Cell ALL (85%)type tdt CALLA Surface Ig
Early pro B ALL positive negative negative
Pre Bcell ALL positive positive negative
Mature B ALL negative positive positive
![Page 18: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/18.jpg)
T Cell ALL(15%)
• Early subtype• CD3 -, CD4-,CD8- or• CD3-,CD4+,CD8+.• Later subtype• CD3+ with CD4+ or CD8+
![Page 19: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/19.jpg)
T Cell ALL(CD3 Positive)
![Page 20: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/20.jpg)
CLINICAL FEATURES
Due to infiltration of marrow• SYMPTOMS Due to decreased production of normal marrow elements
![Page 21: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/21.jpg)
Symptoms symptoms percentage
fatigue 92
Bone or joint pain 79
fever 71
Weight loss 66
Abnormal masses 62
purpura 51
Other haemorrhage 27
infection 17
![Page 22: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/22.jpg)
Physical findings
Physical findings percentage
splenomegaly 86
lymphadenopathy 76
hepatomegaly 74
Sternal tenderness 69
purpura 50
Fundic changes 14
![Page 23: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/23.jpg)
Investigations
CBC-Anemia,thrombocytopenia,leucopenia or leucocytosis.
Peripheral smear study-circulating blast can be seen.
![Page 24: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/24.jpg)
Confirmatory Bone marrow aspiration/biopsy
![Page 25: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/25.jpg)
Bone marrow biopsy(gross specimen)
![Page 26: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/26.jpg)
Criteria for diagnosis
• Bone marrow or peripheral smear showing
Aleast 30% blast(FAB) Atleast 20%blast (WHO)MPO Negative,tdt positive is hallmark
ofLymphoblast,however in L3 tdt is
negative
![Page 27: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/27.jpg)
Investigation (cont)
• Cytogenetics.• Flow cytometry.
![Page 28: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/28.jpg)
Investigation (cont)
• LDH,Serum uric acid• Coagulation profile• LFT,RFT• Chest xray,CT chest• Blood culture• Baseline Echo,ECG
![Page 29: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/29.jpg)
TreatmentPre Chemotherapy supportive careChemotherapy Preinduction Remission induction-phase 1 & 2 Reinduction CNS preventive therapy consolidation Maintenance therapyAllogenic stem cell transplantationNewer drugsSupportive careTreatment of relapseEffects of treatment
![Page 30: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/30.jpg)
Supportive care
Treat metabolic complications hyperuricemia-hydration,rasburicase hyperphosphatemia-po4 binders hypocalcemia-Ca supplements Hyperleuckocytosis-leukopharesis Infection control-broad spectrum
antibiotics Hematologic support
![Page 31: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/31.jpg)
Preinduction
• Prednisolone 1mg/kg p.ofor 5 days • Recheck blast after 5 days, if blast
count dropped-good response.
![Page 32: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/32.jpg)
Treatment of ALLInduction 1
cycle chemotherapy Dose and schedule
Induction Prednisolone or 1mg/kg p.o days 1-28 days
vincristine 1.5mg/m2 i.v weekly one dose x 4 weeks
doxorubicin 30mg/m2 i.v weekly one dose x 4 weeks
L-Asparginase 1,00,000 u/m2(total dose) in divided doses of 10,000 u daily for 10 days
CNS Preventive therapy methotrexate 12mg IT days 1,8,15,22
![Page 33: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/33.jpg)
Reassess
• After 4 weeks of phase 1 induction assess marrow for remission.
• If there is remission taper prednisolone
and after 1 week of restart phase2 induction,
• If there is no remission give 2 more weekly doses of vincristine and doxo and then assess, if still no remission go for alternate regimen.
![Page 34: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/34.jpg)
Induction 2Induction2 drugs Dose and schedule
Cyclophosphamide
Cytosine arabinoside
650mg/m2 i.v days 1 and 1575mg/m2 i.v x 4 days a weeks for 4 weeki.e day 1-4,8-11,15-18,22-25
methotrexate 12mg/m2 IT days 1,8,15,22
Cranial radiation 200 cGy x 9days
![Page 35: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/35.jpg)
ReinductionReinduction drug Dose and schedule
vincristine 1.5 mg/m2 i.v weekly one dose on day 1 and 8
doxorubicin 30mg/m2 i.v. weekly one dose on day 1 and 8
prednisolone 1mg/kg p.o daily for 14 days
![Page 36: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/36.jpg)
consolidation consoldation drugs Dose and schedule
cyclophosphamide 750/m2 .i.v days 1 and 15
Cytosine arabinoside 75mg/m2 doses days 1-4 and 15-18
![Page 37: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/37.jpg)
Maintenance phase duration- upto 2 years
maintenance drug Dose and schedule
1st month methotrexate 12.5mg i.t on day 1
vincristine 1.4mg/m2 .v day 1
prednisolone 1mg/kg p.o daily day 1-7
6 mercaptopurine 60mg/m2 p.o. daily for next 3 weeks
methotrexate 15mg/m2 p.o. once a week for 3 weeks.
2nd month 6 MCP and T.Methotxerate for 4 weeks.
![Page 38: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/38.jpg)
Follow up
If the patient completes chemotherapy for 2 years without relapse-stop chemo and follow up.
No relapse within 5 years-can be declared as cured.
![Page 39: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/39.jpg)
Refractory ALL
![Page 40: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/40.jpg)
Allogenic stem cell transpantation
• Usually done in second remission.• Can be done in first remission in high
risk patients WBC>25000 philadelphia chromosome positive poor initial response to remission induction
![Page 41: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/41.jpg)
Newer drugs
Monoclonal antibodies rituximab(CD20),epratuzumab(CD22) alemtuzumab(CD52),gemtuzumab(CD33)Antimetabolites clofarabine,nelarabineTyrosine kinase inhibitor imatinib,nilotinib,dasatinibVornistat,sirolimus,everolimus,oblimersen,
![Page 42: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/42.jpg)
Late effects of treatment
Cranial irradiation-cognitive and intellectual impairment,cns neoplaysms
Chemotherapeutic drugs-secondary AMLEndorine dysfunctions-short
stature,obesity,growth retardationAnthracycline-cardiotoxicitySteroid-avascular necrosis of bone.
![Page 43: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/43.jpg)
RelapseReappearance of blast at any site in the body after initial
remisson during chemotherapy or after comleting chemo.Marrow relapse-poor outcome Hyper CVAD regimen allogenic BM transplantCNS relapse -Triple IT –alternate days till csf clears,then
twice weekly 6 doses.then one dose every week 6 doses. - cranial irradiationTesticular relapse -chemotherapy plus b/l testicular radiation
![Page 44: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/44.jpg)
Cns relapse
![Page 45: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/45.jpg)
Prognostic factors in ALL
Determinants Favourable unfavourable
WBC Counts <10,000 >2,00,000
Age 2-10 years <1yr,>10yr
Gender female male
Ethnicity white blac
Node,liver,splenomegaly absent massive
Testicular enlargement absent present
CNS involvement absent Csf blast and pleocytosis
FAB Type L1 L2
Cytogenetics T(12;21)(TEL-AML1)Trsomies 4,10,17
t(9;22)(bcr-abl)t(4;11)(MLL-AF4)
Ploidy hyperdipoidy hypodiploidy
Time to remission <14days >28days
![Page 46: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/46.jpg)
References. 1.Harrison’s principles of internal medicine 17th edition 2.Williams hematology 8th edition 3.Wintrobe’s clinical hematology 4.Nelson textbooK of paediatrics 5.ash.hematologylibrary.com/image bank.
![Page 47: Acute Lymphoblastic Leukaemia](https://reader035.fdocuments.net/reader035/viewer/2022081504/55648487d8b42a8c5e8b559b/html5/thumbnails/47.jpg)
THANK THANK YOUYOU