TLDR;
This video provides a comprehensive overview of acute leukemias, focusing on their pathophysiology, clinical findings, complications, diagnostic approaches, and treatment strategies. It differentiates between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), highlighting key subtypes and genetic translocations. The video also covers oncologic emergencies like tumour lysis syndrome, leukostasis, and disseminated intravascular coagulation (DIC), offering insights into their management.
- Pathophysiology of Acute Leukemia
- Clinical Findings and Complications
- Diagnostic and Treatment Approaches
Lab [0:00]
The video begins with an introduction to acute leukemias, dividing them into two main types: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It emphasises that these are disorders of haematopoiesis, which is the production of blood cells in the red bone marrow. The presenter explains how a haemocytoblast, a pluripotent stem cell in the bone marrow, differentiates into lymphoid and myeloid stem cells, eventually forming various blood cells like granulocytes, red blood cells, and platelets. Abnormalities in this differentiation process can lead to either ALL or AML, depending on where the disruption occurs.
Pathophysiology of Acute Leukemia [0:41]
The discussion continues into the specifics of AML, noting that it involves an overproduction of myeloblasts in the bone marrow, constituting at least 20% of the marrow cells. The presenter mentions that there are eight subtypes of AML, labelled M0 to M7, with the M3 subtype, also known as acute promyelocytic leukemia (APL), being particularly important due to its distinct treatment and prognosis, as well as its association with disseminated intravascular coagulation (DIC). Myeloblasts can be identified by the presence of Auer rods and myeloperoxidase (MPO) enzyme.
Moving on to ALL, the video explains that it involves the accumulation of lymphoblasts, which also need to be greater than or equal to 20% in the bone marrow. ALL has two main subtypes: T-cell ALL and B-cell ALL, with B-cell ALL being more common. T-cell and B-cell lymphoblasts are differentiated by the presence of terminal deoxynucleotidyl transferase (TDT) and cluster differentiation proteins such as CD2 to CD8 for T-cells and CD10, CD19, and CD20 for B-cells. The presenter also notes that acute leukemias involve blasts, which lead to rapid disease progression, while chronic conditions involve more mature cells and progress more gradually.
Classic Findings of Acute Leukemia [26:08]
The video transitions to the classic clinical findings of acute leukemias, starting with pancytopenia, which results from the bone marrow being crowded out by either myeloblasts in AML or lymphoblasts in ALL. This crowding leads to reduced production of red blood cells (anaemia), platelets (thrombocytopenia), and functional white blood cells (leucopenia). Anaemia presents with fatigue and pallor, thrombocytopenia with bleeding and bruising, and leucopenia with frequent infections or fevers. Neutropenic fever, defined as an absolute neutrophil count less than 500 with a fever, is highlighted as an oncologic emergency. Bone pain is more common in ALL due to bone marrow expansion, particularly in the pelvis, femur, and tibia, leading to limping or refusal to bear weight. In specific AML subtypes (M4 and M5), monoblasts can infiltrate mucous membranes and cutaneous tissue, causing gingival hyperplasia and leukemia cutis.
Complications of Acute Lymphoblastic Leukemia [38:26]
The discussion shifts to the complications of ALL, beginning with lymphadenopathy, where lymphoblasts deposit in lymph nodes, causing painless enlargement, particularly in the cervical, axillary, and inguinal regions. These lymphoblasts also release cytokines, leading to B symptoms like fevers and chills. Hepatomegaly and splenomegaly can occur as lymphoblasts infiltrate the liver and spleen, causing stomach compression and early satiety. Thymic enlargement, specific to T-cell ALL, can cause mass effects such as dysphagia, dyspnoea, and superior vena cava (SVC) syndrome, which presents with face, neck, chest, and arm swelling. SVC syndrome can lead to increased intracranial pressure and laryngeal oedema, causing respiratory distress. Meningeal leukemia, where leukemic cells infiltrate the meninges, can cause headaches, nausea, vomiting, nuchal rigidity, and cranial nerve palsies, requiring intrathecal chemotherapy. Tumour lysis syndrome, more common in ALL, results from the rapid death of cancer cells during chemotherapy, releasing potassium, phosphate, and uric acid into the bloodstream.
Complications of Acute Myeloid Leukemia [1:00:38]
The video addresses the complications of AML, noting that while tumour lysis syndrome can occur, it is less common than in ALL. Leukostasis, characterised by a white blood cell count greater than 100,000, is more frequently seen in AML. It increases blood viscosity and causes microvascular occlusions, leading to decreased oxygen delivery and organ ischaemia. This can manifest as headaches, dizziness, transient ischaemic attacks (TIAs), strokes, blurred vision due to dilated retinal veins and retinal haemorrhages, and hypoxia due to pulmonary artery occlusions. Disseminated intravascular coagulation (DIC) is specifically associated with acute promyelocytic leukemia (APL), the M3 variant of AML. Promyelocytes release tissue factors and coagulation factor activators, triggering the coagulation cascade and leading to widespread microthrombi. This process consumes platelets and clotting proteins, resulting in both clotting and bleeding. Promyelocytes also release annexin 2, which increases plasmin activity, breaking down fibrin and fibrinogen, further worsening bleeding. Red cells are shredded by microthrombi, forming schistocytes.
Diagnostic Approach to Acute Leukemia [1:17:18]
The video outlines the diagnostic approach to acute leukemia, which begins with recognising symptoms such as fatigue, pallor, easy bruising, bleeding, frequent infections, and fevers, indicative of pancytopenia. Bone pain suggests ALL, while mucocutaneous lesions suggest AML. A complete blood count (CBC) with differential is performed to assess cell lines and identify blasts. A peripheral blood smear helps determine if the blasts are lymphoblasts or myeloblasts. Lymphoblasts suggest ALL, while myeloblasts with Auer rods are indicative of AML. A bone marrow biopsy is essential to confirm the diagnosis, with greater than or equal to 20% lymphoblasts indicating ALL and greater than or equal to 20% myeloblasts indicating AML. Flow cytometry and immunohistochemistry are used to differentiate T-cell and B-cell ALL based on CD proteins and TDT. Cytogenetic studies identify chromosomal translocations, such as 12;21 (good prognosis in paediatrics) and 9;22 (poor prognosis in adults). For AML, cytogenetics can detect the 15;17 translocation associated with APL.
Treatment of Acute Leukemia [1:24:28]
The video concludes with a discussion on the treatment of acute leukemia, starting with the management of acute complications. For tumour lysis syndrome, IV fluids are administered to maintain euvolemia, and allopurinol is used prophylactically to decrease uric acid formation. Rasburicase is used acutely to convert uric acid into a less toxic form. Leukostasis is treated with hydroxyurea to reduce cell production and leucopheresis to rapidly remove white cells. DIC is managed with supportive care, including platelet transfusions, packed red blood cell transfusions, and fresh frozen plasma (FFP). All-trans retinoic acid (ATRA) is a specific treatment for APL. Intrathecal chemotherapy with methotrexate is used prophylactically in ALL to prevent meningeal leukemia. SVC syndrome is treated with steroids and radiation therapy, but emergent cases with high ICP or laryngeal oedema require stent placement. The underlying disease is treated with chemotherapy regimens such as CAVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone) for ALL and cytarabine and daunorubicin for AML. Tyrosine kinase inhibitors (e.g., imatinib) are used for ALL with the 9;22 translocation. Bone marrow transplantation is considered for high-risk patients to replace abnormal stem cells with normal ones.