Leukaemia
Acute Lymphoblastic Leukaemia
Definition & DDx - In ALL bone marrow is hypercellular
Uncontrolled proliferation of immature with lymphoblasts
lymphoid precursor cells within the bone CLL
marrow - unregulated cell growth leads to - Typically affects older adults
bone marrow failure and increased Non-Hodgkin Lymphoma
presence of lymphoblasts in the peripheral - In ALL bone marrow is
blood, disrupting normal production of predominantly affected
blood cells - In lymphoma, LNs are 1º site of
Most common type = B-cell ALL involvement
DDx Anatomy & Risks
Aplastic anaemia Most common type of leukaemia in
- Can also lead to pancytopenia childhood – peak incidence 2-5yo
- In aplastic anaemia bone marrow is Predisposition in certain genetic conditions
hypocellular - Down / Klinefelter’s / Fanconi
anaemia
Symptoms & Complications
- Fatigue (anaemia) - Unexplained persistent/recurrent
- Abnormal bleeding/bruising (low infection/fever
platelets/thrombocytopenia) - Generalised lymphadenopathy
- Infections (low white - Unexplained bruising/bleeding
cells/neutropenia) /petechiae/hepatosplenomegaly
Also: Complications
- Painless lymphadenopathy - Infections (esp. during chemo)
- Hepatosplenomegaly o Prophylactic abx and
- CNS involvement antifungals
o More common in ALL - Bleeding
- Painless unilat. testicular o May need platelet
enlargement transfusion
o Testicular infiltration - CNS involvement
Urgent FBC <48hrs if: o Intrathecal chemotherapy
- Pallor - Chemo-related toxicities
- Persistent fatigue o Mucositis, neutropenic
fever, cardiotoxicity
A&E for any CYP with unexplained - T-ALL
petechiae/hepatosplenomegaly - Incomplete response to therapy
Investigations Treatment/Management & Side effects
- FBC = leucocytosis Combination chemotherapy – induces
- Blood film = blast cells remission then consolidation with stronger
Poor prognostic factors chemo
- Age <1yr / >10yo - CNS prophylaxis due to CNS
- Male ‘sanctuary site’
- WCC >50 - Maintenance therapy for 2yrs
- CNS disease - Response to treatment monitoring:
- Genetic features o Blast count in bone marrow
,Chronic Lymphocytic Leukaemia
Definition & DDx
Monoclonal proliferation of well-
differentiated lymphocytes (normally B-
cells) Complications
- Often slow-growing and crowd out - Anaemia
healthy blood cells - Hypogammaglobulinaemia
- Most common in M>60yo o Recurrent infections
Symptoms & Complications - Warm autoimmune haemolytic
- Often no features anaemia
o Can be picked up by - Transformation to high-grade
incidental finding of lymphoma (Large B-Cell)
lymphocytosis o Richter’s transformation
- Anorexia/weight loss/night o Pts become unwell very
sweats/fever = B symptoms suddenly
- Bleeding/Infections o LN swelling/fever without
o Less common than acute infection/night sweats/abdo
leukaemias pain
- Lymphadenopathy more marked
than CML
Investigations
FBC
- Lymphocytosis
- Anaemia; due to either:
o Bone marrow replacement
o Autoimmune haemolytic anaemia
- Thrombocytopenia; due to either:
o Bone marrow replacement
o Immune thrombocytopenia (ITP)
Blood film
- Smudge cells (also known as smear cells)
Immunophenotyping
- Panel of abs for CD5/19/20/23
Treatment/Management & Side effects
Staging based on Binet’s system of lymphoid tissue enlargement
Allogeneic stem cell transplant can be considered in fit patients who have failure of chemo or
have Richter’s transformation
Prognostic factors
- Disease stage
- Lymphocyte doubling time <12mths
- Genetic abnormalities
- Male
, Acute Myeloid Leukaemia
Definition & DDx
Can occur as 1º disease or following 2º transformation of myeloproliferative disorder
Uncontrolled proliferation of myeloid precursors in the bone marrow
- Leading to bone marrow failure and accumulation of immature WBC (blasts) in
peripheral blood
Symptoms & Complications Complications
Related to bone marrow failure - High incidence of DIC
- Anaemia - Organ infiltration
o Pallor/lethargy/weakness - Treatment related toxicities
- Neutropenia - Death within 2mths without
o High WCC but functioning treatment
neutrophil level may be low
o Leading to frequent Investigations
infections Poor prognostic features
- Thrombocytopenia - >60yo
o Bleeding - >20% blasts after first course of
- Splenomegaly chemo
- Bone pain - Chromosome deletions
- Gum hypertrophy Bone marrow biopsy
CNS involvement is rare - Auer rods
- Hypercellular marrow
- >50% blasts
Treatment/Management & Side effects
Classification based on French-American-British (FAB) criteria
Chemotherapy
- 3-4 courses lasting 5-10 days
- Initial induction to remove bulk of leukemic cells
- Consolidation chemo to remove residual cells
Bone marrow transplantation
- Destruction of leukemic cells with conditioning chemotherapy and radiotherapy to
clear bone marrow before donor stem cells given
- Immunogenic response from receiving donor cells helps destroy any remaining
leukemic cells
o Graft v leukaemia effect
Prophylactic antimicrobials, blood products, growth hormone therapy
Acute Lymphoblastic Leukaemia
Definition & DDx - In ALL bone marrow is hypercellular
Uncontrolled proliferation of immature with lymphoblasts
lymphoid precursor cells within the bone CLL
marrow - unregulated cell growth leads to - Typically affects older adults
bone marrow failure and increased Non-Hodgkin Lymphoma
presence of lymphoblasts in the peripheral - In ALL bone marrow is
blood, disrupting normal production of predominantly affected
blood cells - In lymphoma, LNs are 1º site of
Most common type = B-cell ALL involvement
DDx Anatomy & Risks
Aplastic anaemia Most common type of leukaemia in
- Can also lead to pancytopenia childhood – peak incidence 2-5yo
- In aplastic anaemia bone marrow is Predisposition in certain genetic conditions
hypocellular - Down / Klinefelter’s / Fanconi
anaemia
Symptoms & Complications
- Fatigue (anaemia) - Unexplained persistent/recurrent
- Abnormal bleeding/bruising (low infection/fever
platelets/thrombocytopenia) - Generalised lymphadenopathy
- Infections (low white - Unexplained bruising/bleeding
cells/neutropenia) /petechiae/hepatosplenomegaly
Also: Complications
- Painless lymphadenopathy - Infections (esp. during chemo)
- Hepatosplenomegaly o Prophylactic abx and
- CNS involvement antifungals
o More common in ALL - Bleeding
- Painless unilat. testicular o May need platelet
enlargement transfusion
o Testicular infiltration - CNS involvement
Urgent FBC <48hrs if: o Intrathecal chemotherapy
- Pallor - Chemo-related toxicities
- Persistent fatigue o Mucositis, neutropenic
fever, cardiotoxicity
A&E for any CYP with unexplained - T-ALL
petechiae/hepatosplenomegaly - Incomplete response to therapy
Investigations Treatment/Management & Side effects
- FBC = leucocytosis Combination chemotherapy – induces
- Blood film = blast cells remission then consolidation with stronger
Poor prognostic factors chemo
- Age <1yr / >10yo - CNS prophylaxis due to CNS
- Male ‘sanctuary site’
- WCC >50 - Maintenance therapy for 2yrs
- CNS disease - Response to treatment monitoring:
- Genetic features o Blast count in bone marrow
,Chronic Lymphocytic Leukaemia
Definition & DDx
Monoclonal proliferation of well-
differentiated lymphocytes (normally B-
cells) Complications
- Often slow-growing and crowd out - Anaemia
healthy blood cells - Hypogammaglobulinaemia
- Most common in M>60yo o Recurrent infections
Symptoms & Complications - Warm autoimmune haemolytic
- Often no features anaemia
o Can be picked up by - Transformation to high-grade
incidental finding of lymphoma (Large B-Cell)
lymphocytosis o Richter’s transformation
- Anorexia/weight loss/night o Pts become unwell very
sweats/fever = B symptoms suddenly
- Bleeding/Infections o LN swelling/fever without
o Less common than acute infection/night sweats/abdo
leukaemias pain
- Lymphadenopathy more marked
than CML
Investigations
FBC
- Lymphocytosis
- Anaemia; due to either:
o Bone marrow replacement
o Autoimmune haemolytic anaemia
- Thrombocytopenia; due to either:
o Bone marrow replacement
o Immune thrombocytopenia (ITP)
Blood film
- Smudge cells (also known as smear cells)
Immunophenotyping
- Panel of abs for CD5/19/20/23
Treatment/Management & Side effects
Staging based on Binet’s system of lymphoid tissue enlargement
Allogeneic stem cell transplant can be considered in fit patients who have failure of chemo or
have Richter’s transformation
Prognostic factors
- Disease stage
- Lymphocyte doubling time <12mths
- Genetic abnormalities
- Male
, Acute Myeloid Leukaemia
Definition & DDx
Can occur as 1º disease or following 2º transformation of myeloproliferative disorder
Uncontrolled proliferation of myeloid precursors in the bone marrow
- Leading to bone marrow failure and accumulation of immature WBC (blasts) in
peripheral blood
Symptoms & Complications Complications
Related to bone marrow failure - High incidence of DIC
- Anaemia - Organ infiltration
o Pallor/lethargy/weakness - Treatment related toxicities
- Neutropenia - Death within 2mths without
o High WCC but functioning treatment
neutrophil level may be low
o Leading to frequent Investigations
infections Poor prognostic features
- Thrombocytopenia - >60yo
o Bleeding - >20% blasts after first course of
- Splenomegaly chemo
- Bone pain - Chromosome deletions
- Gum hypertrophy Bone marrow biopsy
CNS involvement is rare - Auer rods
- Hypercellular marrow
- >50% blasts
Treatment/Management & Side effects
Classification based on French-American-British (FAB) criteria
Chemotherapy
- 3-4 courses lasting 5-10 days
- Initial induction to remove bulk of leukemic cells
- Consolidation chemo to remove residual cells
Bone marrow transplantation
- Destruction of leukemic cells with conditioning chemotherapy and radiotherapy to
clear bone marrow before donor stem cells given
- Immunogenic response from receiving donor cells helps destroy any remaining
leukemic cells
o Graft v leukaemia effect
Prophylactic antimicrobials, blood products, growth hormone therapy
