Haematological

malignancies
KMTC, Kitui campus
• Haematological neoplasms are diseases of older patients, exceptions
being :
• Acute lymphoblastic leukaemia that affects children
• Hodgkin lymphoma- affects people aged 20–40 years
Leukaemias
• Increased numbers of white cells in the bone marrow and/or peripheral
blood
• Leukaemias are classified into four main groups:
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML).
• Lymphocytic and lymphoblastic – derived from lymphoid stem cells ,B and
T cells – there's immature B and T cells
• Other forms –precursors of red cells eg. Granulocytes, monocytes, platelets
Risk factors for leukaemia
• Ionising radiation- After atomic bombing of Japanese cities (myeloid leukaemia) ,
Radiotherapy
• Cytotoxic drugs eg. alkylating agents
• Retroviruses- Rare Adult T-cell leukaemia/lymphoma (ATLL) caused by human T-cell
lymphotropic virus 1(HTLV-1)
• Genetic
• Immunological
• Smoking
• Having previously undergone cancer treatment, including chemotherapy or
radiation therapy
• Having a history of other blood cell diseases, including types of myeloproliferative
neoplasms (MPN) or myelodysplastic syndrome (MDS)
1) Acute leukaemia
• Mutations in haematopoietic stem cells produce leukaemic stem
cells.
• Cells do not mature hence accumulation of primitive cells that take
up more marrow space at the expense of the normal
haematopoietic cells
• Eventually, this proliferation spills into the blood.
• Acute myeloid leukaemia (AML) is about four times more common
than acute lymphoblastic leukaemia (ALL) in adults
Clinical manifestations (AML AND ALL)
• Fever
• Loss of appetite
• Night sweats
• Weight loss
• Anemia - cause tiredness, headaches, pale skin, shortness of breath,
and feelings of weakness or dizziness
• Leukopenia -which leads to frequent infections and fevers
• Thrombocytopenia- causes easy bruising and bleeding problems,
including nosebleeds, bleeding gums, and heavy periods
• ALL- has lymphadenopathy. Rare in AML
Investigations
• FBC
• Shows anaemia with a normal or raised MCV
• Leucocyte count may vary from as low as 1 × 109 /L to as high as
500 × 109 /L or more
• Severe thrombocytopenia
• Blood film- blast cells
• A bone marrow examination – (hypercellular, with replacement of
normal elements by leukemic blast cells) confirm the dx
Management
• Make a decision whether or not to embark on speficic therapy
• Give supportive therapy
• Treat infections.fever (>38°C) lasting over 1hour (sepsis)-
aminoglycoside (e.g. gentamicin) and a broad-spectrum penicillin
• Gram-positive infection may require vancomycin
• Disseminated fungal infection-a liposomal amphotericin B
• Prophylaxis with co-trimoxazole is given during chemotherapy-
prevent PCP
• Analgesics-
• Anaemia corrected by red cell concentrate transfusion
• Thrombocytopenic bleeding controlled by platelet transfusions
• Central venous catheter
• Palliative chemotherapy- hydroxycarbamide and mercaptopurine are used
• Metabolic problem
 Frequent monitoring of fluid balance and renal, hepatic and haemostatic
function
Allopurinol and intravenous hydration are given to try to prevent renal
failure
• Psychological problems
Patients kept informed, and their questions answered and fears
allayed
Prognosis
• Without treatment, survival of patients with acute leukaemia is about 5
weeks.
Specific therapy
Acute myeloid leukaemia (AML)-
• Old age disease,
• First decision must be whether or not to give specific treatment
• A lot of side-effects which may not be appropriate in older patients and
those with comorbidities.
Three phases of specific treatment for AML:
Remission induction- Phase 1
• A tumour is killed by combinations of chemotherapy drugs.
• Daunorubicin with cytosine arabinoside given for 7–10 days in two
cycles
Remission consolidation- phase 2
• Attacking the residual disease after remmision
• 1–2 courses of high-dose cytosine arabinoside
Remission maintenance.-phase 3
• 1 yr of maintenance with midostaurin . other patients may benefit
from azacitidine.
2. Chronic leukaemias

a) Chronic myeloid leukaemia (CML)

• Is a myeloproliferative stem cell disorder resulting in
proliferation of all haematopoietic lineages
• Manifestation is in the granulocytic series
• Occurs at 30 and 80 years, with a peak incidence at 55 years
• Xsome abnormality known as the Philadelphia (Ph)
chromosome (shortened chromosome 22)
 Natural history
3 phases:
• A chronic phase- in which the disease is responsive to treatment and is
easily controlled, which used to last 3–5 years.
• An accelerated phase- (not always seen), disease control becomes more
difficult.
• Blast crisis- disease transforms into an acute leukaemia, either
myeloblastic (70%) or lymphoblastic (30%)- cause of death
Clinical features
• Lethargy
• weight loss
• abdominal discomfort
• gout and sweating
• 25% of patients are asymptomatic at diagnosis
• Splenomegaly is present in 90%
• Hepatomegaly occurs in about 50%
Investigations
FBC-
• normocytic, normochromic anaemia.
• very high platelet count
• The leucocyte count can vary from 10 to 600 × 109 /L.
Blood film
• granulocyte precursors, from myeloblasts to mature neutrophils are seen
• predominant cells are neutrophils and myelocytes
Cont’
Bone marrow examination- obtained to confirm the diagnosis and
phase
Blood LDH- elevated and uric acid may be high
Management
Chronic phase- tyrosine kinase inhibitors (TKIs)
• First-line - Imatinib ,Nilotinib , Dasatinib
• Second-line - Imatinib , Nilotinib , Dasatinib , Bosutinib , Ponatinib
• Hydroxycarbamide and interferon are also used
Accelerated phase and blast crisis
• TKI therapy is given eg. nilotinib or dasatinib.
• Response is better if disease is lymphoblastic rather than myeloblastic
• TKIs eg. dasatinib plus chemotherapy is used to try to achieve
remission.
• Hydroxycarbamide can be an effective single agent

ASSIGNMENT-
• Short notes on Chronic lymphocytic leukaemia (CLL)
 Lymphomas
• Arise from lymphoid tissues and diagnosed from the pathological
findings on biopsy as Hodgkin or non-Hodgkin lymphoma.
• The majority are of B-cell origin.
• Non-Hodgkin lymphomas( more common) are classified as:
• low- grade
 divide slowly
• high-grade tumours (on the basis of their proliferation rate. )
 divide rapidly
 may be life-threatening with high risk of extranodal involvement.
1. Hodgkin lymphoma
• Histological hallmark of HL is the presence of Reed–Sternberg cells
(RS cell): (large, malignant lymphoid cells of B-cell origin)
• Present only in small numbers, surrounded by large numbers of
reactive non-malignant T cells, plasma cells and granulocytes,
including eosinophils.
• 4 new cases/100 000 population/year
• Median age 31 years;1st peak at 20–35 years and 2nd at 50–70 years
WHO pathological classification of HL
• Nodular lymphocyte-predominant 5%
• Classical HL-
• Nodular sclerosing 70% (more common in young patients and in women)
• Mixed cellularity 20% (more common in older patients)
• Lymphocyte-rich 5%, (in men), It accounts for about 5% of Hodgkin’s lymphoma
cases.
• Lymphocyte-depleted –Rare and occurs in people in their 30s and in those
with compromised immune systems.
Risk factors
• Age: More cases are diagnosed in people between the ages of 20 and
30 years and in people over 55 years.
• Sex: Males are more likely than females to develop this type of
lymphoma.
• Family history: If a sibling is diagnosed with this type of cancer, your
risk of also developing it is higher.
• Infectious mononucleosis: An EBV infection can cause
mononucleosis. This infection can increase the risk of lymphoma.
• Immunodeficiency: Individuals with HIV have a greater risk of
developing lymphoma
Clinical features
• Painless, rubbery lymphadenopathy, usually in the neck or
supraclavicular fossae
• Large mediastinal mass that can cause dry cough and breathlessness
• Hepatosplenomegaly
• Loss of appetite
• Fatigue
• Pruritis-because of cytokines released by the body when trying to fight
the infection. Cytokines irritate the nerves and the skin
• ‘B symptoms’ of :
• drenching night sweats
• fever
• loss of 10% body weight.
Investigations
• FBC -may be normal. lymphopenia indicate poor prognostic factor
• ESR – raised
• Renal function tests- ensure function is normal prior to treatment.
• Liver function -may be abnormal or show hepatic infiltration
• LDH may be raised
• Chest X-ray may show a mediastinal mass.
• CT scan of chest, abdomen and pelvis for staging
• Positron emission tomography-CT (PET-CT) scanning – to identify the
node
• percutaneous needle biopsy of the Bone marrow or lymph node
under radiological guidance
Management
• Chemotherapy
• The ABVD regimen -doxorubicin (adriamycin), bleomycin, vinblastine and
dacarbazine are used.
• early-stage patients- 2 cycles of ABVD combined with radiotherapy
• Radiotherapy
NB- Over 90% of pnt with early-stage HL achieve complete remission
when treated with chemotherapy and radiotherapy
2. Non-Hodgkin lymphoma
• monoclonal proliferation of lymphoid cells of B-cell (90%) or T-cell (10%) origin
• Common than HL
• 12 new cases/100 000 people/year
• Age-Median age 65–70 years, M>F
• High-grade NHL –
• high proliferation rates
• Rapidly produces symptoms
• Fatal if untreated, but is potentially curable.
• Low-grade NHL –
• Low proliferation rates
• May be asymptomatic for many months or even years before presentation
• Disseminate quickly at dx
• Not curable by conventional therapy.
• Other forms of NHL include:
• Burkitt lymphoma
• mantle cell lymphoma,
• mucosa-associated lymphoid tissue (MALT) lymphomas
• T-cell lymphomas
Risk factors
• Immunodeficiency: This could be due to a weak immune system from HIV or
taking an immune system-suppressing drug
• Age: Lymphoma is most common in older individuals
• Sex: NHL is higher in males than females
• Infection: People who’ve had infections such as the human T-cell
lymphotrophic virus, Epstein Barr virus
• Chemical and radiation exposure
Clinical features
• Widely disseminated at presentation, including in extranodal sites,
unlike HL
• Lymph node enlargement
• weight loss
• Sweating
• Fever
• Itching
• Hepatosplenomegaly
Management
• Asymptomatic patients may not require therapy - managed by
‘watching and waiting’.
• Indications for treatment include marked systemic symptoms eg.
Lymphadenopathy
• Radiotherapy- used for localised stage 1 disease
• Chemotherapy- use chlorambucil
• Monoclonal antibody therapy-to target surface antigen on tumour
cells
 Multiple myeloma
• Malignant proliferation of plasma cells
• Normal plasma cells are derived from B cells and produce immunoglobulins that
contain heavy and light chains
• In MM excess of light chain or only light chains are produced
• This appears in the urine as Bence Jones proteinuria
Eg. Abnornal plasma cells produce abnormal ab which then produce Monoclonal
protein (M protein)
• Majority of malignant plasma cells are present in the bone marrow, minority in
blood
• Malignant plasma cells produce cytokines > stimulate osteoclasts > bone
resorption> Lytic lesions > bone pain, fractures and hypercalcaemia.
• Marrow involvement can result in anaemia or pancytopenia.
• 4/100 000 new cases per annum
• Male-to-female ratio of 2:1.
• Age at diagnosis is 60–70 years
Clinical features
• Bone pain/fracture-Plasma cells destroy bone tissue causing soft spots on bone(Osteolytic
lesions)
• Renal failure -due to Paraprotein blocking filtering process ,hypercalcaemia ,Infection
• Spinal cord compression – due to vertebral bones collapse collapse
• Hyperviscosity syndrome – M proteins causes blood hyperviscosity leading to Retinal
bleeds ,heart failure and Cerebral ischemia
• Anemia- General body weakness and fatigue
• N/V –because of hypercalcemia
• Poor appetite and feeling thirsty- because of hypercalcemia
CF….
• Unexplained weight loss
• Bacterial infections
• Bruising and bleeding because of thrombocytopenia
• Amyloidosis- when M proteins build up in organs.
Investigations
• Bone marrow aspiration and biopsy- plasmacytosis seen
• Quantitative immunoglobulin test
• plasma and urine electrophoresis-Type M protein, Bence Jones
proteinuria
• X-rays-Lytic lesions and bone fractures
• CT scan or whole-body MRI
• ESR is elevated
• UECs- renal function
• FBC- Normo- or macrocytic Anemia,Pancytopenia
Criteria for diagnosing MM
i. Increased malignant plasma cells in the bone marrow
ii. Serum and/or urinary M-protein
iii. Skeletal lytic lesions.
Management
• Asymptomatic with no evidence of end-organ damage- RX not
required but monitored closely
Immediate support
• High fluid intake to treat renal impairment and hypercalcemia
• Analgesia for bone pain
• Bisphosphonates for hypercalcaemia
• Allopurinol to prevent urate nephropathy
• Plasmapheresis, for hyperviscosity
• Antibiotic prophylaxis with levofloxacin
a) Chemotherapy-With 3 drugs
• Older patients -thalidomide combined with the alkylating agent
melphalan and pdl
• RX is administered until paraprotein levels have stopped falling
(‘plateau phase)
• In younger pnts-cyclophosphamide, thalidomide and
dexamethasone (CTD) is given
• NB- prolongs survival, but does not cure myeloma.
b) Radiotherapy
c) Bisphosphonates-reduces bone pain and skeletal events
Assignment
Read
• Coagulation disorders eg.
Haemophilia A and B
Von Willebrand disease
• Thrombotic disorders eg.
• venous thromboembolism
• Disseminated intravascular coagulation(DIC)