MALIGNANT HAEMATOLOGY

SUMMER CRASH COURSE

FIFTH SESSION
 CDM CONDITIONS

• Bone marrow failure

• Leukemia
• Lymphoma
• Myeloma
• Myeloproliferative disorders
HAEMATOPOESI
S
 1)
MYELOFIBROSIS
 DEFINITION

• CLONAL STEM CELL DISEASE

• Proliferation of multiple cell lineages and progressive marrow fibrosis
• Commonly JAK2, CALR, MPL mutation
• MORE AGGRESSIVE compared to ET and PV
• PV can progress to MYELOFIBROSIS
 CLINICAL FEATURES

• Weight loss
• NIGHT Sweats
• Itch
• Massive splenomegaly
• Bone marrow failure (infections,
bleeding)
• Risk of ACUTE LEUKAEMIA
• Usually ANAEMIC
• Low/high platelets/WCC
depending on the stage
• BLOOD FILM - leucoerythroblastic
blood film with tear drop cells
 MANAGEMENT

1. Supportive care
2. ANEMIA - EPO injections, Transfusions
3. SPLEEN SIZE - Ruxolitinib (JAK2 inhibitor)
4. HIGH PLATELETS/WCC - hydroxycarbamide
5. Allogeneic hematopoietic stem cell transplant
 2) ACUTE
MYELOID
LEUKEMIA
 DEFINITION

• Most common type of leukemia

• IMMATURE MYELOBLASTS undergo proliferation and replace bone marrow cells with leukemia
cells and this results in a drop of other cell lineages like RBC, platelets
• This results in BONE MARROW FAILURE
• AUER RODS - crystal aggregates in myeloblasts

RISK FACTORS
• >45 age
• Myelodysplastic syndromes
• Myeloproliferatuve neoplasms
• Chemo/radiotherapy
• Benzene (painters, petroleum, rubber manufacturers)
 TYPES OF AML

• Many types exist (MO-M7)

• Most important being:
•
1. ACUTE PROMYELOCYTIC LEUKEMIA M3
• Promyelocytic protein fuses with retinoinc acid receptor so blocks maturation of myeloblats causing PROMYELOCYTE
ACCUMULATION
• AUER RODS present
• Common in YOUNGER
• THROMBOCYTOPENIA AND DIC seen
• Good prognosis
•
2. ACUTE MONOCYTIC LEUKEMIA M5
• MONOBLAST accumulation
• AUER ROD absent
• GUM INFILTRATION
• Poor prognosis
 CLINICAL FEATURES

• Fatigue
• Lymphadenopathy
• Hepatosplenomegaly
• Weight loss
• Fever
• Recurrent infections
• Bruising and mucosal bleeding
 INVESTIGATIONS AND MANAGEMENT

• FBC : leukocytosis, thrombocytopenia, anemia

• Blood flim, clotting screen
• Bone marrow aspirate and biopsy : >20% myeloblasts DIAGNOSTIC

MANAGEMENT
•INDUCTION
1. Combination of CYTRABINE and ANTHRACYCLINE (DAUNORUBICIN)
2. Add TRETINOIN in APML
•
•CONSOLIDATION
1. CHEMOTHERAPY
2. STEM CELL TRANSPLANTATION
2) CHRONIC
MYELOID
LEUKEMIA
 DEFINITION

• Translocation between chromosome 9 and 22 resulting in Philadelphia chromosome,

BCR-ABL1 fusion gene
• Proliferation of MATURE MYELOID CELLS (granulocytes)
• Good prognosis when treated with TKI
• 40-60 years

CLINICAL FEATURES
• Asymptomatic
• Splenomegaly
• Vague symptoms : weight loss, bone pains
 INVESTIGATIONS AND MANAGEMENT

• FBC : leukocytosis, thrombocytosis, anemia, granulocytosis

• Blood film : maturing granulocytes
• Bone marrow biopsy : myeloblast infiltration in BM

MANAGEMENT
• FIRST LINE - IMATINIB (tyrosine kinase inhibitors)
• SECOND LINE - NILOTINIB, DASATINIB, BOSUTINIB (TKI)
• THIRD LINE - PONATINIB (more potent, more side effects)
• Monitor BCR-ABL1 fusion transcripts and FBC if not sufficient switch to 2nd line
• 4th LINE - ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANT
 3) ACUTE
LYMPHOID
LEUKEMIA
 DEFINITION

• Same cytogenic abnormality at PHILADELPHIA CHROMOSOME

• Leads to proliferation of immature lymphoblasts, accumulate in bone marrow causing bone marrow
failure
• B AND T CELLS will invade tissues like testicles, meninges, kidneys
• COMMON in children UNDER 6, white males, down syndrome
• Good prognosis in >90%

CLINICAL FEATURES
• Fatigue, fever, recurrent infections
• Lymphadenopathy, Hepatosplenomegaly
• Easy bruising, mucosal bleeding, prolonged bleeding
• Parotid, testicular swelling
• CNS involvement : meningism
 INVESTIGATIONS AND MANAGEMENT

• FBC : lymphocytosis, thrombocytopenia, anemia

• Blood film : lymphoblasts
• Bone marrow aspirate and biopsy : >20% lymphoblasts

MANAGEMENT
• Chemotherapy
• Bone marrow transplant
4) CHRONIC
LYMPHOID
LEUKEMIA
 DEFINITION

• Neo proliferation of B LYMPHOCYTES

• If they collect in LYMPH NODES - SMALL LYMPHOCYTIC LYMPHOMA (SLL)
• MOST COMMON TYPE IN ADULTS
• >70 AGE

CLINICAL FEATURES
• Fatigue
• Lymphadenopathy
• Hepatosplenomegaly
• Weight loss
• Fever
• Recurrent infections
• Bruising and mucosal bleeding
 INVESTIGATIONS AND MANAGEMENT

• FBC : leukocytosis, thrombocytopenia, anemia

• Blood film : mature lymphocytes and smudge cells
• Bone marrow biopsy and/or lymph node biopsy

MANAGEMENT
• Early disease is monitored
• Chemotherapy in advanced

RICHTER TRANSFORMATION:
Can transform into non-hodgkin
lymphoma, poor prognosis
5) MULTIPLE
MYELOMA
 DEFINITION

• MALIGNANT proliferation of PLASMA CELLS in bone marrow

• These release IMMUNOGLOBULINS (IgG, IgA) and free light chains
• These light chains can form amyloid proteins -> AMYLOIDOSIS
• FOLLOWS A RELAPSING AND REMITTING COURSE
• >65 common

CRAB (DIAGNOSTIC CRITERIA)

•
•CALCIUM
• HYPERCALCEMIA because neoplastic cells release cytokines -> activates OSTEOCLASTS -> BONE RESORPTION -> BONE PAIN AND LYTIC LESIONS ON IMAGING
•
•RENAL INSUFFICIENCY
• Occurs due to light chains (BENCE JOHNS) depositing on renal tubules -> renal failure
• Also due NEPHROCALCINOSIS (Ca deposition in renal parenchyma)
•
•ANEMIA
• Infiltrations by neoplastic plasma cells -> reduced hematopoiesis -> anemia, leukopenia, thrombocytopenia
•
•BONE LESIONS
• Lesions and pain caused by osteoclast activation as above
 CLINICAL FEATURES

• ALWAYS CONSIDER MYELOMA IN OLDER

PATIENTS WITH BONE PAIN
• Hypercalcemia symptoms : STONES, BONES,
MOANS, GROANS
• Anemia, bleeding, bruising
• Recurrent infections
 INVESTIGATIONS AND MANAGEMENT

• URINE and SERUM ELECTROPHORESIS : M spike

• FBC, BLOOD FILM, U&Es, BONE PROFILE, BETA-2-MICROGLOBULIN
• WHOLE BODY MRI (first line imaging)

MANAGEMENT
• CHEMOTHERAPY
• STEM CELL TRANSPLANTATION
• BORTERZOMIB MONOTHERAPY when FIRST RELAPSE
• BISPHOSPHONATES - ZOLEDRONATE (bone protection)
LYMPHOMA
 6) NON-
HODGKIN
LYMPHOMA
 DEFINITION

• Lymphoproliferative disorder
• Differs from leukemia because mostly affects lymph nodes and extra nodal sites
• Involves T,B,NK cells
• MORE COMMON THAN HL

RISK FACTORS
• >50
• Males
• INFECTIONS
• AUTOIMMUNITY - HASHIMOTOS, SJOGRENS
• IMMUNODEF - HIV
 CLINICAL FEATURES

• B SYMPTOMS : fever, weight loss, night sweats

• Lymphadenopathy : painless, hard, rubbery, fixed, non-contiguous spread
• Splenomegaly (more common in NHL vs HL)
• Extranodal disease: bone marrow, thyroid, salivary gland, GI tract, CNS
 INVESTIGATIONS AND MANAGEMENT

• FBC : leukocytosis/pancytopenia
• Blood film
• Ultrasound of lymph nodes
• Excisional biopsy of lymph nodes : DIAGNOSTIC!!
• Bone marrow biopsy and CT CAP : staging

MANAGEMENT
• CHEMOTHERAPY AND/OR RADIOTHERAPY
• RCHOP REGIMEN in HIGH GRADE - RITUXIMAB, CYCLOPHOSPHAMIDE,
HYDROXYDAUNORUBICIN, ONCOVIN, PREDNISOLONE
7) HODGKIN
LYMPHOMA
 DEFINITION Subtype Characteristics Pathology Prognosis

Nodular sclerosing Most common subtype (70%) Nodules of Reed-Sternberg cells and lymphoid tissue Good
separated by sclerosis prognosis
Young females

Cervical or mediastinal

• LYMPHOPROLIFERATIVE lymphadenopathy

Mixed cellularity 20% of cases Abundant eosinophils on histology Good

DISORDER prognosis

• REED-STERNBERG CELLS - Linked to EBV infection Reed-Sternberg cells

large B cells with OWL'S Abdominal lymphadenopathy

EYE NUCLEI THAT RELEASE Lymphocyte rich 5% of cases Reed-Sternberg cells and reactive lymphocytosis BEST
prognosis

CYTOKINES AND ATTRACT Cervical or axillary

lymphadenopathy
INFLAMMATORY CELLS Lymphocyte Rare Reed-Sternberg cells and decreased number of Poor
• NHL does NOT have these depleted lymphocytes prognosis
Linked to HIV infection
• 15-35, >60 common
Lymphadenopathy below the
diaphragm
 CLINICAL FEATURES

• B symptoms
• Lympadenopathy
• Splenomegaly (less common in HL)
• PEL-EBSTEIN FEVER (intermittent every couple of weeks)
• Alcohol-induced lymph node pain
• Pruritus
ANN-ARBOR STAGING

•EACH STAGE IS EITHER

1. A - no systemic symptoms
2. B - weight loss >10%, unexplained fever, night sweats
 INVESTIGATIONS AND MANAGEMENT

• FBC
• LDH : monitor disease
• Ultrasound and Excisional Biopsy of lymph nodes : DIAGNOSTIC!!

MANAGEMENT
• Chemotherapy:
• An example regimen would be ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). The number of cycles depends on the severity
• An alternate regimen is BEACOPP: bleomycin, etoposide, adriamycin (doxorubicin), cyclophosphamide, oncovin (vincristine), procarbazine
and prednisolone
• Radiotherapy:
• Usually administered after completing a number of cycles of chemotherapy

• Rituximab:
• This monoclonal antibody targets CD20 on lymphocytes and is used in CD20+ lymphoma, i.e. nodular lymphocyte-predominant HL (atypical)
• It is often used alongside chemotherapy and/or radiotherapy
 CHEMOTHERAPY COMPLICATIONS

• NEUTROPENIC SEPSIS
- Neutropenia <0.5 and fever
- Manage with antibiotics (piperacillin and tazobactam) within 60 mins

• TUMOR LYSIS SYNDROME

- hyperuricemia, hyperphosphatemia, hyperkalemia, secondary hypocalcemia
- Treat with hydration, allopurinol, rasburicase
 QUESTION 1

• A 63-year-old man presents to his GP with persistent back pain. His past medical history includes
pneumonia, cellulitis, and pyelonephritis, all of which occurred over the past year. Upon performing a
systemic inquiry, he mentions he has noticed that he bruises quite easily, and has experienced frequent
fatigue, and increased thirst over the past few months. His blood test shows the following results:
• Given the likely diagnosis, what are the blood test results of this patient likely to show?

A) Hypercalcaemia, low phosphate, normal ALP

• B) Hypercalcaemia, normal / high phosphate, normal ALP
• C) Hypocalcaemia, low phosphate, high ALP
• D) Hypocalcaemia, normal / high phosphate, normal ALP
• E) Normal calcium, normal / high phosphate, normal ALP
 QUESTION 2

• A 23-year-old woman has been recently diagnosed with Hodgkin's lymphoma. She had been feeling
fatigued and was found to have multiple palpable lymph nodes when she originally saw the GP. She
has now seen the oncologist and is told that her lymphoma is stage III.

What feature would have resulted in this classification?

A) Lymph nodes greater than 4cm in diameter

• B) Lymph nodes in both the left and right axilla
• C) Lymph nodes in neck and groin
• D) Presence of 'B' symptoms
• E)Splenomegaly
 QUESTION 3

• A 78-year-old woman presents to her GP with stomach cramps and mid-back pain. Her GP notes she has recently been seen in
the practice 2 months earlier with complaints of tiredness and a normocytic, normochromic anaemia was found. She was
referred on a 2-week wait to gastroenterology and an OGD and colonoscopy found no evidence of gastrointestinal malignancy.

The GP takes some additional blood tests:

• She is referred to haematology. They organise imaging and perform bone marrow aspiration.

What is the aspiration likely to show?

A) Dry tap
• B) Hyperplastic lymphoblasts
• C) Hyperplastic megakaryocytes
• D) Plasma cells
• E) Reticular fibrosis
 QUESTION 4

• A 67-year-old man comes in complaining of lethargy, weight loss and night sweats in the last
3 months. As part of his investigation, the man has a bone marrow aspiration which shows an
increase in granulocytes at different stages of maturation under the microscope.

What is the first-line treatment for this condition?

A) Hydroxyurea
• B) Imatinib
• C) Interferon-alpha
• D) Radiotherapy
• E) Steroids
 QUESTION 5

• A 34-year-old man is referred to the emergency department by his GP with weakness, bone pain, and
splenomegaly. Over the last few weeks he has been gradually feeling more tired and weak when trying to
carry out his daily activities. On examination, he appears very pale and there are petechiae present on his
lower limbs. Following bone marrow sampling he is diagnosed with acute promyelocytic leukaemia
(APML).

Which of the following would most likely be seen on his blood film?

A) 'Tear-drop' poikilocytes
• B) Auer rods
• C) Smear cells
• D) Spherocytes
• E) Target cells
 QUESTION 6

• A 80-year-old man attends his GP complaining of persistent mid-back pain for the past 6 months. This
is described as 7/10 in severity and has recently been preventing him from sleeping at night. Past
medical history is unremarkable aside from stable angina and hypertension. On examination there is
bony tenderness particularly in the thoracic spine and restricted range of movement. Blood tests
reveal a raised corrected calcium level as well as a leucopenia. Which one of the following is the most
appropriate action?

A) Measure serum PTH levels

• B) Urgent protein electrophoresis and Bence Jones protein testing
• C) Refer to physiotherapy
• D) Refer for an urgent MRI of the spine
• E) Prescribe an appropriate analgesia regim
 QUESTION 7

• During your ward round on the paediatric unit you review a 5-year-old Caucasian male who has been admitted for
chemotherapy as he has recently been diagnosed with acute lymphoblastic leukaemia (ALL). His mother worriedly
asks you what his chance of survival is and how you work this out.

On reviewing the patient notes, you see he is on the 95th percentile for weight and the 60th for height. His white cell
count at diagnosis was 12 * 10^9/l and there were no noted T or B cell markers on his blood film.

Which feature from this case is a poor prognostic factor?

A) Caucasian
• B) Male sex
• C) Presentation under the age of 5
• D) White cell count over 11 * 10^9/l at diagnosis
• E) Obesity
 QUESTION 8

• A 65-year-old man presents with a progressive history of headaches, fatigue and generalised bone pain. Base-
level blood tests are performed and identify normocytic anaemia, raised calcium and renal impairment therefore a
diagnosis of multiple myeloma is suspected.

The patient is admitted for corrects of his electrolyte imbalance and a plan for bone marrow biopsy is considered.

What imaging should be conducted as the first line for this patient’s suspected diagnosis?

A) Skeletal survey
• B) Skull x-ray
• C) Whole-body CT scan
• D) Whole-body MRI scan
• E) Whole-body PET scan
 QUESTION 9

• A 27-year-old female of Afro-Caribbean origin presents to the oncology clinic following a referral by her
general practitioner. She has been noticing some lumps on her neck that have been classified as painless,
non-tender, asymmetrical lymphadenopathy. She complains of increasing night sweats and she noticed
some pain when she drinks alcohol.

Given the most likely diagnosis, which one of the following features is associated with a poor prognosis?

A) Afro-Caribbean origin
• B) Alcohol-induced pain
• C) Asymmetrical lymphadenopathy
• D) Female sex
• E) Night sweats
 QUESTION 10

• An 80-year-old woman is seen in GP due to weight loss, night sweats and fatigue over the preceding weeks. On
examination, she is pale and palpation of her abdomen reveals hepatosplenomegaly. She has a past medical history of
polycythaemia vera. A full blood count reveals pancytopaenia. Blood film shows a characteristic finding associated with
the new condition.

What characteristic finding on blood film is most associated with this patient's new condition?

A) Heinz bodies
• B) Pencil poikilocytes
• C) Schistocytes
• D) Spherocytes
• E) Tear drop poikilocytes