--- module: 039-02 language: en chapter: 39 title: "White-Cell Disorders, Marrow Failure, and Haematological Malignancy" module_title: "Marrow pattern recognition, clonal disease, and haematological emergencies" source_sha256: 32ece85cf27d1c94471909f640de6e19731af6b80bd467b9ec327e8060247534 --- # Marrow patterns, clonal disease, emergencies ## Counts as dynamic marrow output ### Unit is count plus trend, film, lineages, tempo ### Niche regulates dormancy and lineage commitment ### Early stem-cell injury reduces all lineages #### Lineage-specific immune process: isolated cytopenia ### Clones fail to make useful cells in cellular marrow #### Pancytopenia does not mean empty marrow ## Leukocytosis and lymphocytosis ### Absolute differential and film come first ### Reactive: bands, toxic granulation, Döhle-like bodies ### Clonal: broad maturation, basophilia, blasts ### Glucocorticoids raise neutrophils rapidly #### Demargination and reduced tissue migration #### Lymphocytes and eosinophils often fall ### Monomorphic lymphocytes suggest a clone #### Flow cytometry shows light-chain restriction ## Neutropenic infection ### Inflammation becomes diagnostically silent #### Mucositis and devices breach barriers #### No pus, infiltrates, or local tenderness ### Fever may be the sole sign ### Cultures, then antipseudomonal regimen ### Low-risk discharge needs support and contact ### Persistent fever is not automatically resistance #### Abscess, mould, virus, drug, marrow recovery ### Avoid rectal procedures: mucosal injury ### Growth factor does not replace antibiotics ## Pancytopenia and marrow sampling ### Organised by cellularity and destruction #### Nutritional: macrocytosis, hypersegmentation #### Aplastic: hypocellular, no malignant replacement #### Infiltration: leukoerythroblastic film #### Hypersplenism sequesters several lineages ### Aspirate: morphology, flow, cytogenetics #### Dry tap with fibrosis or dense disease ### Trephine: architecture, fibrosis, focal infiltration ### Interpret mutations with morphology ### Inadequate sample negative is not absence ## Myelodysplastic and myeloproliferative neoplasms ### Clonal stem cells yield ineffective descendants #### Mutations predict progression to leukaemia #### Alcohol, copper, vitamins, drugs mimic dysplasia ### Allogeneic transplantation principal curative route ### Polycythaemia vera raises viscosity #### Leukocytes and platelets add thrombosis ### Thrombocythaemia bleeds via von Willebrand loss ### Myelofibrosis shifts production to spleen, liver ## Acute leukaemia and bleeding ### Differentiation failure with blast expansion #### May present with pancytopenia ### Flow sets lineage, genetics define entity ### Promyelocytes activate coagulation, fibrinolysis #### Differentiation therapy on suspicion ### Platelet count alone misstates bleeding risk #### Frequent coagulation tests, fibrinogen targets #### Avoid intramuscular injection and procedures ## Leukostasis ### Poorly deformable cells obstruct microvessels #### Lung and brain most affected ### Risk count differs by lineage ### Emergency cytoreduction and specialist care ### Transfusion further raises viscosity ### Leukapheresis cannot replace definitive therapy ## Lymphoma and plasma-cell disease ### Lymphoma diagnosis depends on architecture #### Excisional biopsy preferred when feasible #### Steroids shrink tissue and obscure diagnosis ### Biology outweighs stage for urgency ### Plasma-cell clones injure by mass and protein #### Osteoclast activation: lytic bone, hypercalcaemia #### Free light chains damage tubules ### Small clones cause amyloid or neuropathy ## Tumour lysis syndrome ### Release outpaces homeostasis #### Potassium causes arrhythmia #### Calcium phosphate deposits in kidney #### Uric acid obstructs tubules ### Prevention starts before cytotoxic treatment ### Allopurinol prevents, rasburicase degrades urate #### Post-rasburicase samples need cooling ### Casual calcium correction increases deposition ## Supportive care and transfusion ### Treatment trades control against reserve ### Residual disease is assay- and disease-specific ### Transfuse to symptoms and goals, not number ### Reaction: stop, recheck identity, assess ### Monitor alloimmunisation, iron, overload ### Irradiated or leukocyte-depleted by transplant plan ### Clear discharge thresholds and contacts