acute lymphoblastic leukemia.ppt

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Acute Lymphoblastic Leukemia

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Page 1: Acute Lymphoblastic Leukemia.ppt

Acute Lymphoblastic Leukemia

Page 2: Acute Lymphoblastic Leukemia.ppt

Incidence Acute lymphoblastic leukemia (ALL) is the

commonest childhood cancer. It constitutes one fourth to one third of all

paediatric malignancies and 75% of all leukemias.

In India,each year over 4000 children < 15 years of age will develop ALL. Indonesia with 200 millions people >2000childrens

Page 3: Acute Lymphoblastic Leukemia.ppt

Epidemiology Age peak age of developing ALL is 4-5

years with the most frequent age range being 2 – 6 years.

Boy are more frequently affected than girls (1,2:1)

World wide, frequency, age distribution, and subtypes of ALL show striking geographic difference that could reflect variability in genetic susceptibility, environmental factor, or both.

Page 4: Acute Lymphoblastic Leukemia.ppt

Etiology Childhood ALL, as with most other cancers

remain a diseases with few proven etiology factor. Genetic and immunology factors.

High incidence ALL amongst identical twins (inheritance); amongst patients with Bloom’s syndrome and Fanconi anemia (genetic, faulty DNA repair); Down’s and Klinefelter’s syndrome (genetic);

Environment factors : radiation (atomic bomb); benzene, pesticides and herbicides.

Viral infection: Epstein-Barr virus (ALL L3; Burkit limphoma); HTLV I and II (adult T cell and hairy cell leukemia) and HIV (non Hodgkin’s lymphoma).

Page 5: Acute Lymphoblastic Leukemia.ppt

Morphologic classification(Frence-American-British)

Cytologic Features

L1 L2 L3

Cell size Small cell predominant

Large,heterogenous in size

Large and homogenous

Nuclear chromatin

Nuclear shape

Homogenous in any one case

Regular, occasional clefting or indentation

Variable, heterogenous in any one case

Irregular , clefting and indentation common

Finely stippled and homogeneous

Regular – oval to round

Nucleoli Not visible or small and inconspicuous

One or more present, often large

Prominent,one or more

Amount cytoplasm

Basophilic cytoplasm

Scanty

Slight or moderate

Variable, often moderate

Variable, deep in some

Moderately abundant

Very deep

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Immunologic subclasses of ALL

Type Antigen Expression Frequency (%)

Early pre B cCD22’,CD79a,CD19’,CD22’,clg(mu),slg

57

Pre - B Clg+ (mu) 22

Transitional pre - B

Clg+(mu),slg+,slg-(kappa), slg- (lambda)

4

B-Cell Slg+,slg-(kappa), or slg+ (lambda)

2

T - Cell cCD3+, CD17+,CD5+, or CD2+

15

Page 10: Acute Lymphoblastic Leukemia.ppt

Clinical featuresThe clinical features reflect underlying marrow

failure including manifestation: Anemia: fatigue, irritability, pallor Trombocytopenia (petecchiae;purpura, bleeding) Neutropenia (fever, sepsis)Extra medullary diseases manifestation: Lymphadenopathy (50%); hepatosplenomegaly

(68%); bone (28%); and joint paints (leukemic infiltrate of joint)

CNS leukemia: raised intracranial pressure; headache; vomiting, neck stiffness, papilloedema; and/or focal neurologic symptooms like cranial nerve palsies.

Page 11: Acute Lymphoblastic Leukemia.ppt

Differential Diagnosis Non Malignant conditions:

- Juvenile rheumatoid arthritis

- Infectious mononucleosis

- Idiopathic Thrombocytopenic Purpura

- Aplastic anemia

- Acute infectious lymphocytosis Malignant conditions:

- Neuroblastoma

- Retinoblastoma

- Rhabdomyosarcoma Unusual presentation:

- Hyereosinopilic sndrome

Page 12: Acute Lymphoblastic Leukemia.ppt

Diagnosis Bone marrow aspirate smear: 30% or more

blast in marrow is diagnostic of acute leukemia.The distinction between ALL and AML is made by morphology of blast in the marrow and the characteristic pattern of staining with cytochemical stainFAB Classificaation

* Immunobiology studies (phenotypes)

Page 13: Acute Lymphoblastic Leukemia.ppt

Essential Laboratory Work-upHb, total and differential WBC countBone marrow aspirateChest X- ray (mediastinal mass)Uric acd and electrolyte: Na;K;Ca;PO4LDH/LFT/KFTDiagnostic spinal tap

Page 14: Acute Lymphoblastic Leukemia.ppt

Prognostic factorsThere are number of prognostic parameters which could

help tailor the intensity of treatment. Some of these are:- WBC count at diagnosis- Age at diagnosis- Rapidity of leukemic cytoreduction during the early period of treatment- Cytogenetics [t(8;14),t(4;11),t(1;19) unfavourable; t(12;21) favourable

- Ploidi (DNA index>1,1,, favourable)- Mediastinal mass (unfavourable)- CNS disease at presenation (UNFAVOURABLE)

Page 15: Acute Lymphoblastic Leukemia.ppt

Treatment:Supportive care and specific therapySupportive care:Improvement in supportive care has contributes a great

deal to improvement in survival of ALL and is the backbone of ALL treatment.

Infection in induction therapy need to be treated urgently with high generation broad spectrum antibiotics.

Bleeding and anemia need appropriate blood product support in the form of packed red cell and platelet transfusions.

Another complication that is likely to occur immediately after start of induction therapy patients with high WBC counts is hyperuricemia

Page 16: Acute Lymphoblastic Leukemia.ppt

Treatment (cont’d)Specific therapy:

The specific approach to a patient differs somewhat depending upon the risk categorization, however the four main components of therapy remain the same.

These include : Induction; CNS prophylaxis, consolidation and maintenance therapy.

Induction: aim therapy is induction of remission. Drug combination most frequently used ; Vincristine, L Asparaginase with or without Daunorubicine.

CNS prophylaxis: methotrexate intrathecal

Consolidation: use same drugs as in induction and call it Re-induction treatment

Maintenance.(under guidance of the paediatric oncologist)

Page 17: Acute Lymphoblastic Leukemia.ppt

When to refer

1. Immediately after suspecting acute leukemia either clinically or by laboratory parameters.

2. Early referral by the paediatrician can avoid many disease related potentially life threatening conditions like severe infection, bleeding and metabolic problem.

Page 18: Acute Lymphoblastic Leukemia.ppt

Treatment for relapse

Side of relapse in ALL: bone marrow; CNS; testes.

Patients who develop hematologic relapse on therapy or shortly thereafter allogeneic haematopoietic stem cell transplantation is the treatment of choice.

Autologous transplantation offers no substantial advantage over chemotherapy as post induction treatment.

Page 19: Acute Lymphoblastic Leukemia.ppt

Late sequelae Few complications are as devastating as a

second cancer, especially brain tumors or acute myeloid leukemia.

Treatment with antracycline cardiomyopathy Cranial irradiation:

brain tumors;neuropsychological deficit.

endocrine dysfunction resulting in obesity

short stature; precocious puberty

osteoporosis Complication are seen in girls more then boys