acute lymphoblastic leukemia.ppt
DESCRIPTION
ALLTRANSCRIPT
Acute Lymphoblastic Leukemia
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
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.
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).
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
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
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.
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
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)
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
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)
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
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)
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.
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.
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