|Leukaemias in General
|Acute Promyelocytic Leukaemia
|Acute Myeloblastic Leukaemia (AML)
|Acute Lymphoblastic Leukaemia (ALL)
|Chronic Lymphocytic leukaemia (CLL)
|Chronic Myeloid Leukaemia (CML)
|Hairy Cell Leukaemia
|Tretinoin (All-trans-retinoic acid (ATRA) )
|Immune(Idiopathic) Thrombocytopenic Purpura (ITP)
CLL is commonly complicated by panhypogammaglobulinaemia. Although IV immunoglobulin prevents recurrent infections it does not prolong survival.
- Usually a benign slow-growing malignant clone of B lymphocytes
- May see Smear cells
- CLL is the commonest leukaemia in adults
- It is commonest in those over 60 years of age
- Older patients in a blood film with raised WCC
- Usually B cell origin and Indolent and slow-growing
- Commoner in Farmers ? insecticides ? chemicals
- Asymptomatic and diagnosed on a routine FBC
- Some may have Lymphadenopathy, Hepatosplenomegaly
- Recent shingles infection
- Haemolytic anaemia - usually a warm antibody IgG haemolytic anaemia may be seen but oddly not by the leukaemic cells! The mechanism is unknown
- Infections due to hypogammaglobulinaemia
- Thrombocytopenia and marrow failure
- Richter's syndrome is seen in less than 10% where the CLL transforms to a high-grade Non-Hodgkin B cell lymphoma with a poor prognosis
- Hb and platelets may be low and WCC high
- WCC > 15 x 109/L with > 40% lymphocytes in the peripheral film.
- Excess lymphocytes are B lymphocytes (95%) the remaining 5% are T lymphocytes)
- 'Smear cells' are seen on blood film - artefact as cells damaged in process of making a film. CLL cells are fragile and burst.
- Immunotyping - shows a clone of B cells expressing CD19 and CD23
- Plasma protein electrophoresis: kappa or lambda immunoglobulin light chains
- Flow cytometry : CLL cells at a level less than 5 × 109/L called monoclonal B lymphocytosis of uncertain significance
- Reticulocyte count and a direct Coombs test for autoimmune haemolytic anaemia
- Rarely a monoclonal band can be seen. More usually low IgG IgA IgM
- Bone marrow examination by aspirate and trephine not essential to make a diagnosis
- Cytogenetics: loss of chromosome 17p or mutation in the TP53 gene helps prognostically
Differential: Myelofibrosis vs CML
- Myelofibrosis - abnormal megakaryocyte precursors release a factor increasing localised fibrosis within the bone marrow. This leads to extramedullary haemopoiesis
- Myelofibrosis - absent Philadelphia chromosome but seen in CML
- Myelofibrosis - A leukoerythroblastic blood film with "teardrop" shaped cells
- Myelofibrosis - hepatosplenomegaly
- Myelofibrosis - high platelets and white cells which eventually falls and anaemia
- Myelofibrosis - possible high LAP score, Low in CML
- Stage 0 - lymphocytosis only (WCC > 5x109) > 15 year survival
- Stage 1 - lymphocytosis (WCC > 5x109) and lymphadenopathy- 8 year survival
- Stage 2 - lymphocytosis (WCC > 5x109) and splenomegaly - 6 year survival
- Stage 3 - lymphocytosis (WCC > 5x109) and Hb < 11g/dl - 3 year survival
- Stage 4 - lymphocytosis (WCC > 5x109) and Thrombocytopenia (<100 x109) - 2 year survival
- Prognosis is also related to the levels of Beta2-microglobulin, thymidine kinase and soluble CD23
- Low levels of ZAP-70 indicated a good prognosis ZAP = zeta associated protein. Measured using flow cytometry
Indication for Treatment
- Progressive marrow failure: worsening of anaemia and/or thrombocytopenia. This is importing and when assessing needs for therapy.
- Massive (>10 cm) or progressive lymphadenopathy
- Massive (>6 cm) or progressive splenomegaly
- Progressive lymphocytosis: > 50% increase over 2 months or lymphocyte doubling time < 6 months
- Systemic symptoms: weight loss > 10% in previous 6 months, fever >38°C for > 2 weeks, extreme fatigue, night sweats
- Autoimmune cytopaenias e.g. ITP
- Acutely treat any bacterial infections or shingles.
- Many patients require no treatment but just regular follow up and life expectancy may be unaltered.
- Treatment needed for bone marrow failure, massive lymphadenopathy, weight loss, sweats, rise in WCC, autoimmune haemolytic anaemia or thrombocytopenia
- Younger pts (<70) and TP53 mutation-negative, fludarabine, cyclophosphamide and Rituximab (FCR) is standard care.
- Older, less fit patients, Rituximab with bendamustine or oral chlorambucil.
- A more potent type 2 anti-CD20 antibody, obinutuzumab, has is superior to Rituximab
- Ibrutinib inhibits Bruton's tyrosine kinase and may also be useful
- Steroids are useful for those with a Coomb's positive haemolytic anaemia, Splenectomy if that fails
- Ultimately patients become immunoparesed, anaemic and vulnerable to infection with bone marrow failure
- Radiotherapy for massive lymphadenopathy or splenomegaly causing symptoms
- CLL can transform to aggressive high-grade lymphoma, called Richter's transformation.