Acute Leukaemia its causes and newest treatment

•          Acute Leukaemia
Def: Progressive proliferation of immature leucocytes which diffusely infiltrate all organs and tissues and displace  normal haematopoeitic cells from the bone marrow

•           Incidence : 1: 10,000 for AML ( 80% of adult AL) and 1; 70,000 for ALL ( 80% of children AL)

•          Clinical features:

•          1- Symptoms of bone marrow failure: anaemia, thrombocytopenia, neutropenia

•           2- Infiltration of tissues: LN enlargement, hepatosplenomegaly, gum hypertrophy, CNS involvement

•          Lab. Invest

•          Peripheral blood film: increased WCC ( not always), anaemia, thrombocytopenia

•          BM aspiration± Biopsy: increased cellularity with blast cells > 20%

•          Bone marrow cytogenetics

•          Immunophenotyping of Blood or marrow blasts

•          D.D. : AA,     EBV,      ITP,     BM infiltration with other malignancies

•          Classification of AML
FAB classification : M0, M1, M2, M3, M4, M5, M6, M7 is based on predominant differentiation pathway and the degree of differentiation.

•          WHO 1999 classification tries to correlate morphological, genetic and clinical features to classify cases of AML into subgroups

•          Classification of ALL
FAB classification  into L1, L2 and L3 on morphological basis

•          Immunological classification of ALL :

   * Immature B-ALL

   * mature B -ALL

   * T- ALL

Management of Acute leukaemia

•          The disease is invariably fatal if not treated

•          Supportive

•          1- Give explanation and offer councelling

•          2- Insert IV line or tunnelled central venous catheter

•          3- RBCs and platelet transfusion support will continue throughout treatment

•          4- Start neutropenic regimen prophylaxis

•          5- Start hydration and allopurinol PO

•          Seek expert help immediately

Specific treatment of AML

•          After informed consent, Induction of remission ( bone marrow blasts < 5%) usually induced by 1-2 courses of combination chemotherapy.

•          Consolidation therapy to reduce leukaemia burden and to decrease the risk of relapse

( usually 2-4 courses that may include intensification therapy or stem cell transplant)

Chemotherapy used for AML management usually includes Anthracyclines ( usually daunorubicin) + Cytosine arabinoside. For M3 ATRA is given with Chemotherapy

•          Prognosis:   70-80% of pts under 60ys will enter CR but about 3/5 will have relapse in 1-3 ys . The rest will be cured

•          Specific Treatment of ALL
Remission induction: using vincristine, prednisolone, daunorubicin and asparaginase

•          CNS prophylaxis: cranial irradiation and intra-thecal methotrexate

•          Consolidation therapy to reduce the risk of relapse usually includes 1-2 intensification phases

•          Maintenance Therapy for 2-3  years  of 6-MP and methotrexate

•          Allogeneic Stem transplant  is an option sometimes in young patients with high risk disease

•          Prognosis of ALL: about  75% of adults achieve CR with modern therapy , good supportive care. 5-year survival rate for children is around 70%. For adults < 30% (for < 50ys it is less than 20%)

•          Emergencies that are frequently encountered in haematological malignancies:
In acute leukaemia

•          DIC with severe bleeding

•          severe thrombocytopenia with possibility of I.C.Hge

•          Neutropenic fever and septic shock particularly when neutrophil count is less than 500/cubic mm

•          Tumor lysis syndrome and acute renal failure