Leukemia's
Dr H AlMukharraq
Leukemia's
Acute leukemia 97% of childhood leukemia's
Acute lymphoblastic leukemia 75%
Acute myeloblastic leukemia(ALL) 20%
Acute undifferentiated leukemia(AUL) <0.5% Acute mixed lineage leukemia(AMLL)
Chronic myeloid leukemia's 3%
Philadelphia chromosome positive Juvenile myelmonocytic leukemia (JMML)
Acute lymphoblastic leukemia
ALL 3 4 per 100,000 children Peak age 2 5 years 25 30 % of all childhood cancers
Etiology
Unknown Risk factors Ionizing radiation Chemicals e.g. benzene Drugs e.g. alkylating agents Genetic factors
Identical twins 20% Siblings 4 times greater than G.P Chromosomal abnormalities Downs syndrome
Clinical & Laboratory features at diagnosis in children with ALL
Clinical & laboratory findings Symptoms & signs Fever Bleeding Bone pain Lymphadenopathy Splenomegaly Hepatosplenomegaly Laboratory features Leukocyte count (mm) <10,000 10,00 49,000 > 50,000 Hemoglobin (g/dl) < 7.0 7.0 11.0 > 11.0 % of patients
61 48 23 50 63 68
53 30 17 43 45 12
Clinical & Laboratory features at diagnosis in children with ALL
Clinical & laboratory finding Platelets count (mm) < 20,000 20,000 99,000 > 100,000 Lymphoblast morphology L1 L2 L3 Immunophenotyping Pre-B cell
Transitional pre
% of patients
28 % 2 47 % 8 !2 % 4 7 84 % 2 15 % 5 1%
8 4 1 80 % 5 1 1-2 % 15-20 %
Common ALL antigen Mature B-cell T cell
Diagnosis
1. blood count
Hb WBC Platelets Blood smear
2. Bone marrow
Histochemistry Immunophenotyping Cytogeitics
[Link] x-ray 4. Blood chemistry 5. CSF 6. Coagulation profile 7. Cardiac function 8. Infectious diseases profile 9. Immunologic screening
Prognosis in ALL
Good WBC Sex Immunophenotyping Age Cytogeitics Time to clear blast Time to remission CNS disease at presentation Minimal residual disease 4-years EFS Poor High>50x10 Boys B-ALL <2 y->12y Ph+ve,11q23 >1 week >4 weeks Present +v at 3-6 month 65%
Low
Girls C-ALL 2-12 years N or hyperdiploidy <1 week <4 weeks Absent -ve at 1-3 month 80%
Treatment
General supportive treatment [Link] of a central line. [Link] of vomiting. [Link] products support . 4. Allopurinol and intravenous fluids. [Link] and treatment of infection. Specific therapy
Remission induction Vinicristine, prednisolone,
asparaginase,daunorubicin Consolidation/intensification Cycclophosamide cytosine arabinoside,thioguanine Central nervous system (CNS) directed therapy High dose methotrexate Maintenance Mercaptopurine,methotrexate
Acute myeloid leukemia
Incidence of AML increases with age The median age at diagnosis is 63 years About 90% of all acute leukemia in adults Rare in children
Male-to-female ratio of 1.3:1
New cases each year 10.500 in the USA
Accounting for 1.2% of cancer deaths in US
Risk factors for developing AML
Pre-leukemic" blood disorders such as myelodysplastic Exposure to anti- cancer chemotherapy e.g. alkylt. agents Exposure to ionizing radiation
Occupational chemical exposure to benzene & other
aromatic organic compounds
Several congenital conditions
The risk of developing AML is increased threefold in the first-degree relative of patients with AML
Diagnosis
Complete blood count
Bone marrow examination
light microscopy
flow cytometry cytogenetics
Classification
The French-American-British (FAB) classification
MO Acute undifferentiated leukemia M1 -- Myeloblastic leukemia without maturation M2 Myeloblastic leukemia with differentiation M3 Acute Promyelocytic leukemia(APML) M4 Myelmonocytic M4 EOSMyelmonocytic with BM eosinophilia M M5 Monocytic M leukemia M6 Erythroleukemia M M8 Megakaryocytic leukemia
World health organization )WHO( classification
AML with characteristic genetic abnormalities AML with multilineage dysplasia AML and MDS, therapy-related AML not otherwise categorized Acute leukemia's of ambiguous lineage
Prognosis
* Cytogenetics and prognosis in AML
Risk category Favorable Abnormalities t(8;21), t(15;17), inv(16) Normal, +8, +21, +22, del(7q), del(9q) ,abnormal 11q23 Adverse ,del(5q), Abnormal 3q ,7- ,5Complex cytogenetics 5-years survival 70%
Intermediate
48%
15%
* Antecedent MDS and prognosis * Other prognostic markers (receptor tyrosine kinase mutation)
Overall expectation of cure
Cure rates in clinical trials have ranged from 20-45%
Cure rates for Promyelocytic leukemia can be 98%
Treatment
Induction
Cytarabine(Ara-c),Daunorubicin Regimen ; DCTER or MRC 10
Complete remission is obtained in about 50%-75%
Consolidation
Good-prognosis leukemia's (i.e. inv(16), t(8;21), and t(15;17) typically undergo an additional 3-5 courses
Hematopoietic stem cell transplantation
For patients at high risk of relapse high-risk cytogenetics, underlying MDS, or therapy-related AML
BMT
Disease Treatment-related Relapse Leukemiastage morality probability Free survival
Allogeneic CR1 CR2 rel/refr Autologous CR1 CR2 MUD CR2
20%
2-8% 48%
26% 47% 71% 51% 70% 22%
51% 34% 20% 42% 24% 39%