1. Acute Leukaemia Dr. Soheir Adam, MRCPath Assistant Professor Department of Haematology, KAUH

2. Acute Lymphoblastic Leukaemia ALL is a malignant clonal disorder in which early lymphoid precursors proliferate and replace normal marrow cells. ALL is a malignant clonal disorder in which early lymphoid precursors proliferate and replace normal marrow cells. Pathophysiology Pathophysiology Lymphoid precursors are arrested in the early stages of development. This arrest is caused by an abnormal expression of genes, often due to chromosomal translocations.

3. Acute Lymphoblastic Leukaemia Incidence Incidence - ALL is the most common cancer of childhood - In adults it is more common in men - It is less common in adults than AML

4. Acute Lymphoblastic Leukaemia Presentation Presentation - Symptoms related to depletion of normal marrow elements e.g. anaemia, bleeding - Bone pain due to infiltration of bone marrow by leukaemic cells - Organomegaly: splenomegaly - T-ALL can present with a mediastinal mass - Fever and/or weight loss

5. Acute Lymphoblastic Leukaemia Physical Examination Physical Examination -Signs of anaemia / infection -Lymphadenopathy / organomegaly -Petechiae / ecchymosis due to low platelets -Signs of CNS or testicular involvement -Less commonly signs of hyperleukostasis like mental confusion and headache

6. Acute Lymphoblastic Leukaemia Laboratory Investigation Laboratory Investigation - CBC - Peripheral smear - LDH and uric acid - LFT - U&Es - Blood cultures

7. Acute Lymphoblastic Leukaemia Radiological Investigation Radiological Investigation - CXR - Chest CT - Abdominal US - ECG & MUGA scan

8. Acute Lymphoblastic Leukaemia Bone marrow aspiration & trephine biopsy Bone marrow aspiration & trephine biopsy - Morphology - Cytochemistry - Flowcytometry - Cytogenetic analysis Lumbar puncture Lumbar puncture Testicular ultrasound Testicular ultrasound

9. Acute Lymphoblastic Leukaemia Cytochemical Stains Cytochemical Stains - Myeloperoxidase negative - Tdt positive Immunophenotyping Immunophenotyping - Detects B or T antigens expresed on the surface of blast cells =, antibodies are given CD numbers - Some ALL cells co-express myeloid markers

10. Acute Lymphoblastic Leukaemia Cytogenetic Analysis Cytogenetic Analysis -Determines prognosis and determines treatment plan -Bad prognostic chromosomal abnormalities e.g. t(9,22), t(4,11), t(8,14), t(2,8) & t(8,22) -Good prognosis with oter abnormalities e.g. t(10,14), hyperdiploidly > 50 and near tetraploidy -Philidelphia chromosome t(9,22) is found in 10-15% of adults and 2-5% of children with ALL

11. Acute Lymphoblastic Leukaemia Management 1 - Chemotherapy 1 - Chemotherapy - Induction - Consolidation - Late intensification - Maintenance

12. Acute Lymphoblastic Leukaemia Management 2 – CNS prophylaxis 2 – CNS prophylaxis - Intrathecal chemotherapy - Cranial irradiation - Systemic chemotherapy - If CNS disease  IT chemotherapy twice weekly until 3 consecutive clear CSF samples

13. Acute Lymphoblastic Leukaemia Management 3 – Bone marrow transplantation 3 – Bone marrow transplantation - Offered to young patients with high risk features who are in first remission - Young patients with no high risk features should be considered for BMT when in relapse - Older patients should be offered non- myeloablative BMT within clinical trials

14. Acute Lymphoblastic Leukaemia Management 4 – Mature B-ALL 4 – Mature B-ALL - Burkitt-like leukaemia - Not considered for early transplant as before - Special chemotherapy protocols are used in such cases - Hyper-CVAD regimen produces 81% CR and 61% event-free survival at 3 years

15. Acute Lymphoblastic Leukaemia Management 5 – Supportive care 5 – Supportive care - PRBCs transfusion if Hb < 9 g/dl - Platelets transfusion if < 20,000 or if patient is actively bleeding - Antibiotics for febrile neutropenia (gram negative organisms coverage) - Growth factors reduce the nadir and duration of neutropenia -Pneumocystis carinii prophylaxis