Cells differentiate from a pluripotent haemopoietic stem cell
Normal haemopoiesis = proliferationdifferentiationapoptosis
Neoplasic change in cascade = leukaemia (cancer of WBC/BM)
Uncontrolled proliferation by either: excessive proliferation of resistance to apoptosis
Acute L: short, aggressive, easier to tx and so better outcome
Chronic L: indolent, refractory and worse outcome.
Causes: chemicals (benzenes, smoking, alcohol, hair dye), drugs (CT, alkylating agents), benign medical conditions (Ank Spon, fibroids, medical radiation), virus, genetic.
Quick fatal proliferation = accumulation of malignant ‘blast’ cells (immature cells). Blast cells occupy space in BM and cause reduction in normal cell production = pancytopaenia.
AML: adult disease, most (>65yo), myeloid transformation = accumulation of myeloblasts, anaemia, neutropaenia, thrombocytopaenia. 50% cure rate by BM transplant in you. Can use induction/consolidation CT regimens (alemtuzumab/chlorambucil) to control. Remission in 70-80%
ALL: childhood disease, average age on onset = 4yo, M>F, accumulation of lymphoblasts, often short disease <3/12, p/c = anaemia, neutropaenia, thrombocytopaenia. Curable by aggressive CT (cranial irradiation / intrathecal CT) and methotrexate therapy. Remission in 90%.
Long history, indolent disease = slower cell turnover = less treatable
CML: in older population (40-60yo), often caused by radiation, p/c = neutrophilia and hyperleukocytosis, haemolytic anaemia, HSM, visual disturbance, gout. A myeloproliferative disorder – arsien from a stem cell mutation (reciprocal translocation between C 9:22) = philidelphia chromosome = bcr-abl fusion (has tyrosine kinase activity). Fatal in longterm. Tx can include = SC/BM transplant, or alpha-IFN and Glivec (TK inhibitor) therapy.
CLL: disease of elderly, a lymphoproliferative disorder of B-cells, lymphoblasts accummulate in BM, LNs, spleen. Caused by mutation or chormosome deletion preventing apoptosis of blasts. Diagnosis based on microscopy of peripheral blood = stageA-c (A = favourable, C=very aggressive). Tx is based on staging. Tx CT and chlorambucil. Incurable but so indolent 50% of pts die of a different cause.
Other acute lymphoid disorders:
Lymphoma: is a malignant cancer of lymphoid cells which typically form a large solid mass in lymph nodes. They are similar to lymphocytic leukaemias, except they exist soley in LNs and do not circulate in blood or BM like lymphocytic leukaemias do. There are various forms of lymphomas – affecting B-cells, T-cells and NK-cells. Specific symptoms: LN enlargement, back pain, HSM… Systemic symptoms may include: anorexia, dyspnea, fatigue, fever of unknown origin, lymphadenopathy, night sweats, pruritus, weight loss (so-called ‘B-signs’- indicating a worse prognosis). Tx is with CT (CHOP regimen), RT and BM transplant, and depending on staging, histology and type – can be cured. If low grade, ‘watchful waiting’ may be the best course of action.