--- module: 039-01 language: en chapter: 39 title: "White-Cell Disorders, Marrow Failure, and Haematological Malignancy" module_title: "Foundations" source_sha256: f4b761ef37c0a612c95149ac93c7d96488dda894c97778190316b336c5cf25f5 --- # White-cell disorders and haematological malignancy ## Orientation and haematopoiesis ### Counts reflect production, release, destruction, clonality #### A count is not a diagnosis #### Morphology, lineage, tempo, molecular findings ### Stem cells balance self-renewal and differentiation #### Niches of stroma, matrix, vessels, cytokines ### Growth factors drive red-cell, platelet, granulocyte lines ### Clonal haematopoiesis rises with age #### Raises blood-cancer and cardiovascular risk #### Leukaemia is not inevitable ## Interpreting white-cell counts ### Use absolute counts, not percentages alone ### Neutrophilia: infection, inflammation, steroids, neoplasia #### Left shift means more immature granulocytes #### Toxic granulation and vacuoles support reaction #### Demargination raises count without production ### Lymphocytosis: reactive versus monomorphic clone ### Leukopenia: suppression, destruction, drugs, spleen #### Trends show one lineage or whole marrow ## Neutropenia and febrile neutropenia ### Risk rises with depth and duration #### Barrier, device, cellular-immune defects add risk ### Serious infection without pus, signs, or fever ### Fever in neutropenia is an emergency #### Cultures and site assessment #### Prompt broad antipseudomonal antibiotics #### Avoid rectal procedures ### Persistent fever prompts reassessment ### Colony-stimulating factor shortens treatment neutropenia #### Not a substitute in established sepsis ## Bone-marrow failure ### Aplastic anaemia: hypocellular pancytopenia #### Immune destruction of stem cells common #### No major nodes or spleen ### Transplantation cures selected patients #### Alloimmunisation from transfusion complicates it ### Immunosuppression with thrombopoietic support ### Aspirate gives cellular detail and flow cytometry ### Trephine shows architecture, fibrosis, infiltration ## Myelodysplastic and myeloproliferative neoplasms ### Myelodysplasia: ineffective dysplastic haematopoiesis #### Cytopenias and risk of acute myeloid leukaemia #### Exclude nutritional, toxic, drug, infectious mimics ### Myeloproliferative: excess mature myeloid cells #### Polycythaemia vera: thrombosis, itch, splenomegaly #### Essential thrombocythaemia: clot or bleed #### Myelofibrosis: fibrosis, leukoerythroblastic film ### Driver mutations activate growth signalling ### A high count alone does not set risk ## Acute leukaemia ### Blasts suppress marrow and infiltrate tissues #### Fatigue, infection, bleeding, bone pain ### Lineage and genotype set therapy and prognosis ### Promyelocytic leukaemia: severe coagulopathy #### Differentiation therapy on suspicion ### Induction, consolidation, transplantation by risk ### Hyperleukocytosis impairs microvascular flow #### Brain and lung symptoms need cytoreduction #### Red-cell transfusion raises viscosity ## Chronic leukaemias ### Chronic myeloid: translocation fusion kinase #### Chronic phase can progress to blast crisis #### Kinase inhibitors need response monitoring ### Chronic lymphocytic: clonal mature B cells #### Hypogammaglobulinaemia, autoimmune cytopenias #### Treat active indications, not count ## Lymphoma ### Hodgkin: malignant cells in reactive background #### Often spreads contiguously ### Non-Hodgkin: indolent and aggressive B, T, NK ### Persistent nodes, sweats, weight loss prompt assessment ### Excision or core biopsy preserves architecture #### Fine-needle aspiration often cannot classify ### Subtype and molecular risk outweigh stage ## Plasma-cell disorders ### Monoclonal immunoglobulin or light chain ### MGUS lacks organ injury but can progress ### Myeloma: bone, anaemia, kidney, calcium, infection ### Small clones can still damage organs ### Protein studies, light chains, marrow, imaging ## Emergencies and care principles ### Tumour lysis releases potassium, phosphate, nucleic acid #### Arrhythmia, seizure, urate kidney injury #### Prevent: fluid, monitoring, urate lowering ### Cord compression, vena-cava obstruction, airway ### Never dismiss persistent abnormality without trend ### Decisions weigh curability, frailty, goals ### Survivorship: vaccination, second cancers, fertility