Leukemia

• Leukaemia

• Leukemia are group of malignant diseases in which genetic abnormalities in a hematopoietic cell give rise to an unregulated clonal proliferation of cells.
• i.e., uncontrolled monoclonal proliferation of hematopoietic precursor cell line, which replace the normal hematopoietic cells of the marrow.

Hematopoietic

stem cell

Neutrophils

Eosinophils

Basophils

Monocytes

Platelets

Red cells

Myeloid
progenitor






Lymphoid
progenitor

B-lymphocytes

T-lymphocytes

Plasma
cells
germinal center
naïve


ALL

AML

• Epidemiology

• The leukemia are the most common malignant neoplasm in childhood, accounting for about 41% of all malignancies that occur in children <15 yr of age.
• Most common age: 2-5 years
• Male > Female.
• ALL : 77%
• AML : 11%
• CML : 2-3%
• JCML : 1-2%

• Causes of acute leukaemia

• idiopathic (most)
• hematologic disorders (e.g., Fanconi anemia, Kostmann syndrome, Diamond-Blackfan anemia)
• chemicals, drugs
• ionizing radiation

• Clinical features

Duration: few weeks – few months
• Symptoms: Anorexia, fatigue, irritability, intermittent low-grade fever , bone pain, joint pain, pallor, bruising, or epistaxis .
• Signs: pallor, purpuric and petechial skin lesions, or mucous membrane hemorrhage, lymphadenopathy, Splenomegaly, hepatomegaly.
• Rarely, patients show signs of increased intracranial pressure, meningeal irritation signs, papilledema, retinal hemorrhages, and cranial nerve palsies .


• Non-malignant conditions mimicking leukemia
• ITP
• Aplstic anemia
• streptococcal/viral pharyngitis
• Trauma, rheumatologic diseases, collagen vascular diseases, osteomyelitis
• CMV, EBV infection

• Laboratory investigations

• CBP(complete Blood Picture)
• -Hb : mostly low <10 g/dL (s.t. Normal)
• -Total WBCs: low, normal, or high (normal 4-11 X 10^9/L). May be very high (hyperleukocytosis) > 100 X10^9/L; causing increasing viscosity of blood, bleeding diathesis, ARDS, CVA.
• Leukopenia→ infection.
• -Platelets: usually thrombocytopenia ( plt<50 X10^9/L cause mucocutaneous bleeding).
• -Blood film: normochromic normocytic anemia. Blasts in peripheral blood (%).
• -ESR: increased (not specific).

• Bone marrow examination:-

• necessary for diagnosis, useful for determining type of leukaemia
• ALL is defined by the presence of >25% blasts in bone marrow (% of nucleated marrow cells)
• AML is defined by the presence of >20% blasts
• Done in diagnosis, during therapy and during follow-up in certain spots; and when suspect BM relapse.


• Classification of subtypes of leukemia depends on
• Morphology: FAB classification
• ALL : L1, L2, L3
• AML : M0, M1, M2, M3, M3v, M4, M4 Eo, M5, M6, M7
• Immunophenotype: flowcytometry;e.g ALL: Pre-B, B-cell , T-cell
• Cytogenetic:
• ALL : t(12,21)
• AML : t(15,17)in M3
• CML : t(9,22) – Philadelphian chromosome

• Biochemical investigations

• -S.uric acid : (NV: 120-420 mmol/L).
• DNA (destructed by chemotherapy)→purine nucleotide→hypoxanthine→xanthine→urate→ nephropathy
• -LFT: SGOT, SGPT, S.Alk Ph, TSB (direct & indirect)
• -RFT: S. creatinine, BUN
• -S. electrolyte: Na, Cl, K
• -S. minerals: Ca, Ph, Mg
• -Others: bl. Sugar, S. albumin

• Imaging studies

• -Chest X-ray (AP & lateral): anterior mediastinal mass, pulmonary infiltrates, ARDS, pneumonia.
• X-ray of long bones and vertebrae: osteoporosis, pathologic fracture .
• - abdominal U/S: size and texture of liver, spleen, abdominal LN groups, kidneys, GB, UB, ascites,…
• -CT scan of brain (ICH), of lungs (pneumonia, pul. hemorrhage), of abdomen (liver & spleen)
• -MRI : rarely requested


• Treatment
• Supportive measures
• -For anemia --- packed RBCs (10 mL/Kg)
• -For infections--- broad-spectrum antibiotics(often 3rd generation cephalosporin+ aminoglycoside) , antifungal, antiviral; systemic & local
• -For bleeding--- platelets concentrate,antifibrinolytic
• -Hydration --- twice maintenance i.e., 3000mL/m2/d (dilutional effect, increase GFR, corrects electrolyte imbalance, enhance excretion of toxic metabolites e.g. uric acid)
• -Nutrition

• Specific measures(CHEMOTHERAPY)

• ALL
• Induction of remission: vincristine, prednisone, daunorubicin, L-asparginase
• CNS prophylaxis: intrathecal(methotrexate ,cytosar, steroid), cranial radiation Consolidation of remission: cytosar, cyclophosphamide, methotrexate, etoposide
• Maintenance of remission: 6-MP, oral MTX
• Total duration of Rx: for boys 3 years
• for girls 2.5 years

• Bone Marrow Transplantation

• Autologous: from the patient
• Allogeneic : from matched related or unrelated donor
• S.E.: life-threatening infections, GVHD, secondary malignancies,….
• Indication: very HR ALL, relapse, many cases of AML


• Prognosis
• Acute lymphoblastic leukemia
• Criteria
• Good prognosis
• Bad prognosis
• Age (yr)*
• 1-10
• <1 , >10
• Gender
• Female
• Male
• Race
• White
• Black, Hispanics
• Mediastinal mass
• No
• Yes
• Extramedullary involvement
• No
• Yes
• WBCs count X 10^9/L*
• <50
• >50


• Prognosis in AML
• Good prognosis:
• Down’s syndrome
• AML-M3 (APL) with t(15,17)
• AML-M4Eo with inv(16)
• Bad prognosis:
• Secondary AML
• Monosomy 7

• Complications

• Of disease:-
• BM infiltration(anemia, thrombocytopenia, neutropenia)
• Medullary &/or extramedullary relapse (CNS, testis)
• Hyperuricemia, hyperleukocytosis
• SVC syndrome & tracheal obstruction (mediastinal mass)
• Delayed growth.
• Psychologic problems (chronic disease)

• Of chemotherapy:-

• myelosuppression (most drugs except VCR & steroid),
• nephrotoxicity (MTX, cyclophosphamide)
• hepatotoxicity (MTX, 6-MP)
• cardiotoxicity (adriamycine)
• alopecia, infertility, mucositis (MTX, cytosar)
• secondary malignancies (etoposide)


• Of radiotherapy:-
• neurocognetive defects
• poor growth
• psychatric disorders
• poor school performance
• Amnesia
• secondary endocrine disorders
myelosuppression
• secondary malignancies
• Of supportive measures:- transfusion-related infections (HBV, HCV, HIV, CMV), allergic reactions, fluid overload, S.E. of antibiotics