Hematological Malignancy Flashcards
How can the stage of haemopoiesis affect the cancer’s aggression
Name of cancers based on each cell in haemopoiesis
- blasts
- mature RBC, platelets, granulocytes
- plasma
- mature lymphocytes
Precursor cells - acute (more aggressive)
Mature cells - chronic (less aggressive
Blasts - acute leukemia
Mature RBC, platelets, granulocytes - MPNs
Plasma - myeloma
Maturę lymphocytes - B, T, NK lymphomas
What is the main defining feature of acute leukemias
2 main types of acute leukemia and their main characteristics
- acute lymphoblastic leukemia
- acute myeloid leukemia
20%+ blasts in blood or BM
Acute lymphoblastic leukemia
- childhood cancer but incidence increases with age
- curable in children but less in adults
Acute myeloid leukemia
- elderly cancer
- prognosis depends on genetic abnormalities
- an umbrella term that covers leukemic changes at any point in hematopoiesis
Presentation of acute leukemias
- pathophysiology
- past medical history
Dysfunctional leukoblasts are made in the BM, not released => affects other cell lines and leukemia cells leak out
Abrupt onset Loss of BM function - pancytopenia -anemia, fatigue -fever, infection -bruising, easy bleeding
Organ infiltration - hepatomegaly, splenomegaly
-lymphadenopathy in ALL
CNS - headache, nausea, nerve palsy
AML can have strong FHx
MPN, MDS can develop into AML
Investigations to diagnose acute leukemia (ALL, AML)
Blood and BM morphology
Immunophenotyping - identify antigens present
Karyotyping - chromosomal abnormalities
Genetic analysis - assess for mutations
Management of acute leukemias
Combination chemotherapy with repeated courses
Allogenic hemopoietic stem cell transplant if
- relapse
- poor prognosis
Treatment guided by flow cytometry, PCR, sequencing
Pathophysiology of tumour lysis syndrome
Rapid release of cellular components into circulation after rapid destruction of rapidly proliferating malignant cells
Release of DNA => increased uric acid
Release of Ca, PO4 => arrythmias
Both can lead to AKI
Hydration
Allopurinol (xanthine oxidase) => prevent uric acid formation
Monitor K, manage if needed
Dialysis is an option
Acute promyelocytic leukemia
- pathophysiology
- management
Aggressive form of AML
MEDICAL EMERGENCY
- promyelocytes release cytokines => DIC
- platelet production low => bleed risk
Can manage with vitamin A analogues and arsenic trioxide
What are lymphoid neoplasms
Clonal tumours of B, T, NK cells
-malignancy can form at any stage of development and maturation
Myeloma
- epidemiology
- pathophysiology
- presentation
BM plasma cell neoplasm => excess IgG, IgA released into serum, urine
- can arise from MGUS
- 60-70 years
Bone pain, lesions, osteoporosis => high Ca
Fatigue, infection
Renal failure from high Ca, dehydration, amyloid
Myeloma
- investigations
- diagnosis
IgG, IgA monoclonal proteins in serum, urine
Increased plasma cells in BM
Whole body MRI - bone lesions
BM aspirate - identify myeloma cells
Presentation of myeloma in kidneys
Light chains block tubules => form cast nephropathy
Light chain accummulate in glomerulus => nephrotic syndrome
-can accumulate in other areas => macroglossia, peripheral neuropathy, HF, GI, liver
Describe the impact myeloma can have on the spinal cord
-management
SC compression - sensory loss, paraesthesia, limb weakness, difficulty walking, sphincter changes
Management
Supportive - bed rest, backbrace
Imaging - urgent MRI
Medical - high dose steroids to reduce plasma cell burden
If soft tissue lesion - local radio
If bony compression/SC unstable - surgery
What is hyperviscosity syndrome
- presentation
- management
High levels of paraprotein => increase viscosity => reduces O2 delivery => end organ dysfunction
Bleeding into skin, retina
CNS - headache, blurred vision, poor conc, low GCS, tinnitus, seizures
CV - HF, intermittent claudication
Resp - pulmonary congestion, SOB
Treat underlying disease
DO NOT TRANFUSE RED CELLS
-plasmapheresis
-isovolemic venesection with saline replacement
Myeloma management
Chronic disease - only treat supportively if symptomatic
- bisphosphonates - bone protection
- radio - pain, palliation
- repeated chemo/steroids/meds
What are the main 2 types of lymphoma
-risk factors
Replacement of normal lymphoid structures with malignant cells
Can be nodal/extranodal
Hodgkin - 20s and increased incidence with age
Non Hodgkin - mainly associated with age
-B cell most common
Risk factors
- increasing age
- viruses (EBV, HIV, HepB, C)
- chronic inflammation (Hpylori, AI)
- IC (organ transplant, meds)
Presentation of lymphoma
Fever, night sweats, weight loss, fatigue
Lympadenopathy
Hepatosplenomegaly
Symptoms in extranodal sites
Hodgkin
- itch or alcohol induced pain
- mediastinal mass => SVC obstruction, SOB
- cyclical changes in fever (PelEbstein)
Diagnosis and staging of lymphoma
LN biopsy
Stage
-CT/PET
-BM aspirate - assess liquid, can be used to immunophenotyping, cytogenetics
-BM trephine - assess solid section of bone for immunohistochemistry
Also can assess for genetic abnormalities that will guide diagnosis and treatment
Treatment of lymphomas in general
Treatment of Hodgkin lymphoma
High grade - urgent with curative intent
Early low grade - radio with curative intent
Symptomatic low grade - treat
Asymptomatic low grade - wait
Gastric MALT (caused by HPylori) can be cured => HPylori eradication
Hodgkin lymphoma treatment depends on staging
- cycles of chemo and radio
- monoclonal AB
- stem cell rescue can be used for relapse
What is autologous stem cell transplant
Why is this used in chemotherapy
For myeloma, Hodgkin and high grade lymphoma
Remove and freeze patient’s own stem cells
Chemo destroys the patient’s normal hemopoetic tissue => pancytopenia
Thawed stem cells are reinfused to aid recovery of BM
What are the side effects of chemotherapy
N+V+D Hair loss Myelosuppression, neutropenic sepsis Fatigue Lung, nerve damage, cardiomyopathy Infertility Secondary cancer Steroid related side effects
What is neutropenic sepsis
-what is the general management
ONCOLOGICAL EMERGENCY
Fever and neutrophil count U0.5x10^9
Broad spec ABx with G-ve coverage
-tazocin
What is diffuse large B cell lymphoma
What is follicular lymphoma
Most common lymphoma
High grade CD20+ tumour
Common in older adults, males
Most common low grade lymphoma CD20+ Only treated when symptomatic or early -chemo + rituiximab Common in older adults, females
Characteristics of chronic lymphocytic leukemia
Proliferation of mature B cells in BM, LN and spill out into blood
Often accidentally found
Risk factors
-increased age, male
Presentation
- cancer red flags
- recurrent infection
- AI hemolytic anemia, thrombocytopenia
- BM failure
- lymphadenopathy
- splenomegaly
MPN pathophysiology
Polycythemia vera presentation
BM making too many blood cells PV - too many RBCs, neutrophils, platelets -JAK2 common -hyperviscosity -splenomegaly -easy bleeds -plethoric
MPN - essential thrombocytopenia
- presentation
- pathophysiology
Megakaryocyte proliferation => too many platelets
-JAK2 common
- burning feeling in hands
- high platelets
- thrombosis and haemorrhage
MPN - myelofibrosis
- pathophysiology
- presentation
Hyperplasia of abnormal megakaryocytes => BM fibrosis => dysfunctional blood cells made in BM => haematopoiesis occurs in liver and spleen but cannot make enough RBCs to keep up with demand
Anemia, fatigue
Massive splenomegaly
Weight loss, night sweats
MDS pathophysiology
Abnormal growth of blood cells that accumulate in BM => spill out into blood
- pancytopenia
- splenomegaly
