Leukemia Study Guide

📖 Core Concepts Leukemia – a group of malignant blood cancers that begin in bone‑marrow and produce excess immature cells (blasts). Acute vs. Chronic – Acute: rapid proliferation of immature cells, needs immediate therapy. Chronic: slower accumulation of more mature abnormal cells, may be observed initially. Lymphoid vs. Myeloid Lineage – Lymphoid (B‑cell or T‑cell precursors) → ALL, CLL. Myeloid (RBC, some WBC, platelets) → AML, CML. Four Main Categories – Acute Lymphoblastic (ALL), Acute Myeloid (AML), Chronic Lymphocytic (CLL), Chronic Myeloid (CML). Key Pathogenesis – DNA mutations → activation of oncogenes or loss of tumor‑suppressor genes → uncontrolled proliferation/differentiation block. Philadelphia chromosome – t(9;22) translocation → BCR‑ABL fusion, hallmark of CML (≈95 % cases). 📌 Must Remember ALL = most common childhood leukemia; treatment = multi‑phase chemo + CNS prophylaxis. AML = adult‑predominant; induction = cytarabine + anthracycline; 5‑yr survival ≈ 20 %. CLL = adults >55 yr, male predominance; 5‑yr survival ≈ 85 %; incurable but manageable. CML = adults; first‑line = imatinib (TKI); 5‑yr survival ≈ 90 %. Risk factors – smoking, ionizing radiation, benzene, prior chemo, Down syndrome, family history. Common symptoms – bruising/petechiae (thrombocytopenia), infections (neutropenia), anemia (fatigue, pallor), organomegaly (splenomegaly/hepatomegaly). Diagnostic cornerstone – CBC + bone‑marrow biopsy; peripheral blood may be normal in early/remission phases. 🔄 Key Processes Diagnosis workflow CBC → abnormal WBC, Hb, platelets? → peripheral smear. If suspicion persists → bone‑marrow aspirate/biopsy → morphologic + immunophenotypic classification. ALL treatment sequence Induction: prednisone + vincristine + anthracycline → achieve remission. Consolidation/Intensification: high‑dose multi‑drug regimens. CNS prophylaxis: intrathecal methotrexate ± cranial RT. Maintenance: low‑dose methotrexate + 6‑mercaptopurine (≈3 yr). CML TKI algorithm Start imatinib → assess response. If intolerance/resistance → switch to second‑generation TKI (e.g., dasatinib) or consider transplant. 🔍 Key Comparisons Acute vs. Chronic – rapid blast surge & severe cytopenias vs. gradual rise of mature abnormal cells. ALL vs. AML – Cell of origin: lymphoid precursors vs. myeloid precursors; Age: children (ALL) vs. adults (AML); Key drug: vincristine (ALL) vs. cytarabine (AML). CML vs. CLL – Molecular hallmark: BCR‑ABL t(9;22) (CML) vs. no specific translocation (CLL); Therapy: TKI (CML) vs. chemo + steroids (CLL). Imatinib vs. Second‑gen TKI – imatinib = first‑line, well‑tolerated; second‑gen = used for resistance/intolerance, often more potent. ⚠️ Common Misunderstandings “All leukemias need immediate chemo.” Chronic leukemias (especially low‑risk CLL) may be observed (watchful waiting). “CML is always acute.” CML is a chronic disease; acute phase (blast crisis) is a later complication. “Philadelphia chromosome appears in ALL.” It is characteristic of CML; rare in ALL. “CNS prophylaxis is only for children.” Adults with ALL also require intrathecal methotrexate to prevent CNS spread. 🧠 Mental Models / Intuition “Blast vs. Mature” – Think of a traffic jam: Acute = many stalled cars (blasts) blocking the road; Chronic = a steady flow of slightly broken cars (mature abnormal cells). “Lineage ladder” – Visualize a two‑branch tree: left = lymphoid → ALL/CLL; right = myeloid → AML/CML. Knowing the branch tells you expected treatment class. 🚩 Exceptions & Edge Cases Philadelphia‑positive ALL – rare subset; may respond to TKIs similar to CML. Elderly >65 yr with ALL – higher toxicity; regimens may be attenuated. Down syndrome – dramatically ↑ risk of AML (especially megakaryoblastic) and ALL; treatment protocols may be modified. 📍 When to Use Which Imatinib → first‑line for any confirmed BCR‑ABL‑positive CML. Second‑gen TKI → if patient cannot tolerate imatinib or shows resistance (e.g., rising BCR‑ABL transcript levels). Allogeneic stem‑cell transplant → high‑risk ALL, relapsed AML, or CLL in younger fit patients. Watchful waiting → low‑risk CLL without cytopenias, massive splenomegaly, or rapid lymphocyte rise. 👀 Patterns to Recognize Cytopenia triad (anemia, neutropenia, thrombocytopenia) → suggests marrow infiltration → think leukemia. Organomegaly + high WBC → chronic leukemias (CML, CLL). Sudden severe fatigue + blasts on smear → acute leukemia. t(9;22) on cytogenetics → CML (or rare Ph‑positive ALL). 🗂️ Exam Traps “Treatment of CML is chemotherapy.” Wrong – the standard is a targeted TKI (imatinib). “ALL occurs only in children.” Incorrect – also seen in adults >65 yr. “All leukemias present with high WBC count.” Chronic lymphocytic leukemia may have modest leukocytosis; acute leukemias often show blasts but can have low total WBC. “Presence of the Philadelphia chromosome always means CML.” Misleading – can appear in a minority of ALL cases. --- All information derived directly from the provided outline.