LEUKAEMIA : LEUKAEMIA Definition : Definition Malignant disease characterised by uncontrolled proliferation of WBCs precursors. Epidemiology : Epidemiology Incidence :
The most common form of childhood cancer about one third of newly cases each year .
Peak incidence of age is 2 - 7 years .
Male to Female ratio is 2 : 1 .
White > Black . Etiology : Etiology Exact cause is unknown and the following factors are thought to be responsible , which are :
Hereditary & chromosomal abnormality .
Exposure to irradiation .
Exposure to chemicals .
Viral infections . Types of leukaemia : Types of leukaemia Acute :
Acute lymphocytic 76%
Acute non lymphocytic 20%
Chronic myelogenous leukaemia Acute lymphocytic leukaemia : Acute lymphocytic leukaemia Slightly boys more than girls
There is increase risk with :
Chromosomal abnormality (down syndrome)
Ataxia telangiectasia pathology : pathology Classified according to :
Morpholopgy of the blast
L1 lymphoblast: which is 85% , has small cells , little cytoplasm . The prognosis is better .
L2 lymphoblast: which is 14% , has a large cells ,greater cytoplasm ,irregular nucleous membranes ,prominent nuclei . The prognosis is poor
L3 lymphoblast: which is 1% ,has large cells ,prominent nuclei ,cytoplasmic vaculations . The prognosis is worst Slide 8: 2.Immunology of the blast :
B cell :
Pre B cell
Early pre B cell
Most of the patients with leukaemia almost always have disseminated disease at time of diagnosis with marrow involvement at all sites, with leukaemic blast cells in blood ,liver ,spleen and lymph nodes are also usually involved so no staging system like solid tumors . Clinical manifestations : Clinical manifestations First symptoms are usually non specific:
History of viral respiratory tract infection without full recovery
Frequent early manifestations: anorexia ,irritability ,lethargy
Progressive failure of bone marrow function: pallor ,bleeding ,fever cont : cont O / E
Petechiae or mucous membrane bleeding 50%.
Spleenomegaly <6 cm b.c.m. 66%.
Hepatomegaly less common.
Bone pain propably 2ndry to marrow infarction
Rarely signs of increased ICP due to leukaemic infiltration of meninges.
Children with T-CELL ALL often have mediastinal mass. investigations : investigations Complete blood picture:
RBC:normocytic normochromic anaemia
WBC:leukaemic lymphoblast in peripheral picture.sometimes the number is normal or leukopenic.
Bone marrow examination:hypercellular , increased lymphoplast ,decreased erythropoietic tissue or absent.
Chest X-ray :for mediastinal mass.
CSF:for leukaemic cells.
Renal function test: during therapy the malignant cells are destroyed leading to increase in the level of uric acid from catabolism of DNA&RNA uric acid nephropathy leading to renal failure.
Liver function test.
Microbiological studies: blood culture. Differentional diagnosis : Differentional diagnosis Bone marrow infiltration by other tumours (neuroblastoma,rhabdomyosarcoma,retinoblastoma…)
Aplastic anaemia or myelofibrosis.
Leishmania. TREATMENT : TREATMENT the treatment of ALL varies with clinical risk features. A patient at standard risk at the time of diagnosis is
>2 yrs and <10 yrs
Normal mediastinum on chest X-ray
No evidence of a leukaemic CNS involvement
The blast cells do not have B or T cell features
The high risk PTs are the reverse of the above criteria. CONT ; : CONT ; General:
prevention and treatment of infections.
correction of anaemia and control of bleeding (fresh blood or packed cell or platelet transfusion).
Induction therapy: until bone marrow no longer show leukaemic cells and is performed by the following drugs: Vincristine 0.05---0.07mg/kg once weekly I.V. Prednisolone 2mg/kg/day t.d.s. Asparaginase 10000 units/m twice weekly.the management is continued for 4---6weeks.
For CNS prphylaxis intrathecally the following drugs:
Cytosine arabinoside 10---15mg/dose.
These drugs are used weekly for 6 weeks during the induction phase then every 8 weeks for 3 yrs.
Systemic continuation phase: mercaptopurine 50mg/m/day. Methotrexate 2.5mg/kg/day.contiued for 2.5----3 yrs cont : cont The pt should be followed regularly by S&S &investigations and some centers can do bone marrow at regular intervals.
Bone marrow relapse after continuation phase need intensive treatment with acombination such as cytosine arabinoside and epipodophyllotoxin vm 26 the response is 15—20% .and bone marrow transplantation is considered. cont : cont When relapse occur in both standard and high risk it is often from an extramedullary site .the most important sites are :
CNS: the common early manifestations are due to increased ICP .these symptoms may be due to chemical meningitis from the intrathecal therapy. other symptoms include convulsions and 6th &7th cranial nerve palsy which may be due to vincistine toxicity. WT gain & behavioral disturbances due to hypothalamic invasion. CSF examination showed leukaemic cells. the management include intrathecal methotrexate weekly for 4—6 weeks &craniospinal irradiation.
Testicular relapse: presented with painless swelling of one or both testicles (thus testicular size assessment in all PTs should be done).diagnosed by biopsy . Treated by irradiation of gonads +systemic ttt + CNS preventive measures Bad prognostic factors : Bad prognostic factors Age :<2yrs or>10yrs.
Sex: being a male.
Immunologic subtype B &T cells.
Resistant to treatment.
Presence of pheladelphia chromosome
Types of blast: L3. Tumor lysis syndrome : Tumor lysis syndrome It is an emergency result from lysis of tumour cells before or during early stages of chemotherapy especially burkitt lymphoma &leakemia(esp T cell acute ALL).
It presented by hyperuricemia, hypocalcemia, hyperkalemia,hyperphosphatemia &can lead to acute renal failure.
Regular check of K, Ca,Ph,uric acid ,@urine analysis.
Correction of electrolytes. Acute none-lymphcytic leukemia : Acute none-lymphcytic leukemia Occurs in about 20% of chilldren.
More common in older children.
Male: female is equal to 1:1.
Predisposing factors :fanconi anaemia, bloom syndrome (excessive chromosomal breakage or as a second tumour after cancer therapy. pathology : pathology According to the cytomorphology is divided into:
Myeloblastic with no maturation -----M1.
Myeloblastic with some maturation ---M2.
Megakaryocytic------------------------------M7. clinical manifestation : clinical manifestation Duration of S&S is brief < 6 weeks afew present after 12 months .
It is diffecult to distinguish b/w ALL & ANLL .
A findings relatively specific are gingival swelling due to inflteration by leukaemic cells : Hepato splenomegaly 60%, lymphadenopathy is marked in 20%
Menorrhagia in older girls. investigations : investigations CBC
Bone marrow (cytology, chromosomal analysis, monoclonal antibodies). MANAGEMENT : MANAGEMENT Induction therapy :
Successful induction seems to require a period of bone marrow aplasia .
Cytosine arabinoside 100 mg/m/24hr via I.V infusion for 7 days .
Daunorubicin 45 mg/m/24hr via I.V line for 3 days .
N:B ; in promyelocytic leukaemia heparin is given to prevent the fatal haemorrhage from D.I.C .
Maintenance therapy :
Duration is up to 2 yrs .
Prophylactic for C.N.S .
N:B ; 30 – 40 % of children expected to be cured with chemotherapy alone . And bone marrow transplantation is being studied . Chronic Myelocytic Leukaemia : Chronic Myelocytic Leukaemia It is of two types :
The adult type of C.M.L is an a clonal panmyelopathy involving all haemopoietic cell lineages and at least some of lymphoid .
3% of cases of leukaemia in children .
Incidence is 10 – 12 yrs.
Increase frequency with exposure to atomic bombs radiations. Pathology of Adult C.M.L : Pathology of Adult C.M.L Increase number of differentiating myeloid cells in blood & bone marrow .
If the pathognomic ph 1 chromosome present , it is diagnostic for C.M.L . Clinical features : Clinical features On set of symptoms generally incidious .
Diagnosis may not suspected till spleenomegaly ;spleen may become firm and enlarge as far as into the pelvis. Or abnormal blood count found in routine examination . investigation : investigation CBC
Bone marrow examination .
Laboratory abnormalities are noted early. Treatment : Treatment No treatment will reverse under lying process of disease CML
Therapy should be aimed at preserving stem cells .
WBCs count should propably be kept <100,000 to avoid increased blood viscosity that can lead to CVA by using hydroxy urea .
Spleen irradiation if it produces severe discomfort .
Marrow transplantation may be effective early in the disease.
Some responses to interferon have been seen. Slide 29: Terminal phase of the disease is characterised by gradual increase in blast cells (blast crises ) and development of anaemia and thrombocytopenia. With the onset of blast crises treatment is changed to that of AL. Survival from diagnosis is about 3 yrs. Juvenile CML : Juvenile CML Rare disease .
Usually under 2yrs .
It is a clonal pan myelopathy with elevated WBCs count , prominent involvement of monocytic series ,spleenomegaly , cutaneous manifestations ,serum vit B12 is increased , ph1 chromosome absent .
It is thought to represent abnormal sensitivity to growth factors . Congenital leukaemia : Congenital leukaemia Leukaemia occuring in neonatal period and usually of myelocytic morphology .
Often present with cutaneous inflteration (blue berry muffin lesions ) ,haemorrhage ,
and high WBCs count .
It has a high fatality rate .
Some times an infant with chromosomal abnormality particularly trisomy 21 may be born with hepato spleenomegaly , high WBCs with immature myeloid forms and thrombocytopenia . It is unclear that it represent a true leukaemic process . treatment : treatment Platelet transfusion if needed for bleeding .
Single agent chemotherapy only if needed to control WBCs count. Slide 33: THE END