Haematological Malignancies Flashcards
Describe pathogenesis of haematological malignancy
Multi step process
Acquired genetic alterations in a long lived cell
Proliferative/survival advantage to mutated cell
This produces malignant clone
Malignant clone grows to dominate tissue
Leukaemia v lymphoma
leukaemia bone marrow
lymphoma lymphoid tissue
Describe features of acute leukaemia
Leukamic cells do not differentiate
Bone marrow failure
Rapidly fatal if untreated
Potentially curable; childhood acute lymphoblastic leukaemia
Describe features of chronic leukaemia
Leukaemic cells retain ability to differentiate
Proliferation without bone marrow failure
Survival for a few years
Potentially curable with modern therapy; tyrosine kinase inhibitors in CML
What are the parts of a lymph node?
Medulla
Paracortex
Cortex
B cell follicle; germinal centre, mantle zone, marginal zone
What can cause localised, painful lymphadenopathy?
Bacterial infection in draining site
What can cause localised, painless lymphadenopathy?
Rare infections, catch scratch fever, TB
Metastatic carcinoma from draining site; hard
Lymphoma; rubbery
Reactive, no cause identified
What can cause generalised, painful/tender lymphadenopathy?
Viral infections, EBV, CMV, hepatitis, HIV
What can cause generalised, painless lymphadenopathy?
Lymphoma
Leukaemia
Connective tissue diseases, sarcoidosis
Reactive, no cause identified
Drugs
How can lymphoma present?
Nodal disease
- > 90% HL present with nodal disease
- ~60% NHL present with purely nodal disease
Extranodal disease
Systemic symptoms; fever, drenching sweats, wt loss, pruritis, fatugue
What are symptoms of acute lymphoblastic leukaemia?
Lymphadenopathy
Hepatosplenomegaly
Pallor, echymoses, petechiae
Neurological signs
Investigations for acute lymphoblastic leukaemia
FBC Peripheral blood smear Serum electrolytes Renal function Liver function
Describe treatment of acute lymphoblastic leukaemia
Chemotherapy
Fluid therapy + allopurinol/rasburicase
Prophylactic antimicrobials
What is acute myeloid leukaemia?
Clonal expansion of bone marrow blasts in bone marrow, peripheral blood or extramedullary tissues
Bone marrow blasts of at least 20% are diagnostic
What are symptoms of acute myeloid leukaemia?
Pallor Fatigue Ecchymoses or petechiae Infection (due to neutropenia) Palpitations Dizziness Dyspnoea Infection or fever Lymphadenopathy
What are investigations for acute myeloid leukaemia?
FBC; WCC high but possible neutropenia Peripheral blood smear Coagulation pannel Bone marrow aspirate Cytogenics Serum electrolytes Renal function
What is the treatment for acute myeloid leukaemia?
Chemotherapy
Fluid + allopurinol/rasburicase
Allogenic stem cell transplantation
If unable to tolerate chemo then cytarabine
What are symptoms of chronic myeloid leukaemia?
Splenomegaly Left upper quadrant discomfort Dyspnoea Wt loss Excess sweating Pallor Fever Gout
Investigations for chronic myeloid leukaemia
FBC
Metabolic profile
Peripheral blood smear; mature or maturing myeloid cells, increased basophils
Bone marrow biopsy; granulocytic hyperplasia, hypercellular
Treatment of chronic myeloid leukaemia
First presentation; tyrosine kinase inhibitor (end in ‘inib’)
Progression after TKI therapy; allogeneic HSCT plus high dose chemo
Symptoms of chronic lymphocytic leukaemia
Dyspnoea Fatigue Lymphadenopathy Splenomegaly Hepatomegaly
Investigations for chronic lymphocytic leukaemia
WBC Count Blood film; smudge cells Haemoglobin; low Platelet count; low Flow cytometry; positive for dim surface Ig
Treatment of chronic lymphocytic leukaemia
Observation if early stage
Chemoimmunotherapy or ibrutinib
What is Rai staging?
Classification of CLL
0-IV
0 ; lymphocytosis but not other physical signs
I ; lymphocytosis and lymphadenopathy
II ; Lypmhocytosis, hepato/splenomegaly and might have lymphadenopathy
III ; lymphocytosis and anaemia. Maybe hepato/splenomegaly and lymphadenopathy
IV ; lymphocytosis and low platelets, all other signs possible
What are the cells in Hodgkin’s lymphoma?
Arises from mature B cells
Characterised by presence of Hodgkin’s cells and Reed-Steinberg cells
What are the cells in Hodgkin’s lymphoma?
Arises from mature B cells
Characterised by presence of Hodgkin’s cells and Reed-Sternberg cells
Investigations for Hodgkin’s lymphoma
FBC Metabolite panel CXR ESR Lymph node biopsy
Treatment of Hodgkin’s lymphoma
Chemotherapy + Radiotherapy in classical HL
Radiotherapy in early nodular lymphocyte-predominant HL
Chemotherapy in late nodular lymphocyte-predominant HL
Symptoms of non-hodgkins lymphoma
Night sweats Fever Malaise/fatigue Wt loss Lymphadenopathy Splenomegaly
Investigations for non-hodgkins lymphoma
FBC
Blood smear; nucleated red blood cells, left shift
Lymph node biopsy
Skin biopsy
Treatment for non-hodgkins lymphoma
R-CHOP-21 + radiotherapy
Chemotherapy
What is R-CHOP-21?
Used in non-hodgkins lymphoma treatment
R - rituximab C - cyclophosphamide H - doxorubicin hydrochloride O - vincristine (previously oncovine) P - prednisolone
R-CHOP-21 is the name given if the treatment course is 3 weeks
Symptoms of multiple myeloma
Anaemia Bone pain Infections Fatigue Renal impairment
Cells in multiple myeloma
Clonal proliferation plasma cells in bone marrow and typically associated w/monoclonal component in serum and/or urine
Investigations for multiple myeloma
Whole body low dose CT; osteolytic lesions, pathological fractures
Serum/urine electrophoresis
Skeletal survey; osteolytic lesions, pathological fractures
Serum free light chain assey
Bone marrow aspirate and biopsy; monoclonal plasma infiltrate ≥10%
Serum calcium; hypercalcaemia
Treatment for multiple myeloma
Induction therapy prior to stem cell transplant (if non-tranaplant candidate then non-transplant induction therapy)
DVT prophylaxis; i.e. aspirin
Bone disease - bisphosphonate ± analgesics
What is myelodysplastic syndrome?
Group clonal stem cell disorders , ineffective haematopoeisis
Pre-leukaemic
Symptoms of myelodysplastic syndrome
Older age Often asymptomatic Fatigue Exercise intolerance Spleno/hepatomegaly
Investigations for myelodysplastic syndrome
FBC
Reticulocyte count
Bone marrow aspiration with iron stain; single or multilineage dysplasia, bone marrow blasts <20%
Treatment of myelodysplastic syndrome
Asymptomatic cytopenia; monitoring
Symptomatic without 5q31 deletion; haematopoietic growth factors first line, DNA methyltransferase inhibitors second line
Symptomatic with 5q31 deletion; lenalidomide first line, haematopoietic growth factors second line, DNA methyltransferse third line
What are some myeloproliferative neoplasms?
Polycythaemia Vera (PV)
Essential thrombocythaemia (ET)
Idiopathic myelofibrosis (IM)
What are the tumour markers in ALL?
CD34, TDT; early immature cells
What is CAR?
Chimeric antigen receptor T cells
ALL treatment
What are side effects of T cell immunotherapy?
Cytokine release syndrome
Neurotoxicity
Describe cytokine release syndrome
Side effect of T cell immunotherapy
- fever, hypotension, dyspnoea
- CAR T cells correlated to presence of RRS; significant number require ITU support
Describe neurotoxicity
Side effect of T cell immunotherapy
Confusion with normal conscious level
Seizure, headache, focal neurology, coma
What is Binet staging?
CLL staging
A; <3 lymph node areas
B; ≥3 lymph node areas
C; B + anaemia or thrombocytopenia
What are the most common subtypes of lymphoma?
Diffuse large B-cell lymphoma most common
Follicular lymphoma second most common
Which type of infection do the different WBCs attack?
Neutrophils; bacterial and fungal
Monocytes; fungal infection
Eosinophils; parasitic infections
T lymphocytes; fungal and viral, PJP
B lymphocytes; bacterial infection
What measures are used to reduce risk of sepsis in haematological malignancy?
Prophylaxis Growth factors Stem cell rescue/transplant Protective environment IV Ig replacement Vaccination
What are some factors in neutropenic risk?
Cause of neutropenia; marrow failure risk higher than immune destruction
Degree of neutropenia
- <0.5 x 10^9 = significant risk
- <0.2 x 10^9 = high risk
Duration
- >7days high risk
What type of bacteria more commonly cause febrile neutropenia?
Gram positive bacteria
i.e. Staph, strep, enterococcus, corynebacterium, bacillus
What are some gram negative bacteria?
E.coli Klebsiella Pseudomonas aeruginosa Enterobacter Acinetobacter Citrobacter Stenotrophomonas
Describe fungal infection in immunocompromised patients
e.g. candida, aspergillus
Life threatening deep seated infection, lung, liver, sinuses, brain
Monocytopenia and monocyte dysfunction contributes to risk of fungal infection
Describe presentation of neutropenic sepsis
Fever with no localising signs
- single reading of >38.5 or two of 38 one hour apart
- rigors
- chest infection/pneumonia
- skin sepsis; cellulitis
- UTI
- septic shock
How is neutropenic fever investigated?
History and exam
Blood cultures; Hickman line and peripheral
CXR
Throat swab and other clinical sites of infection
Sputum if productive
FBC, renal and liver function, coagulation screen
How is neutropenic sepsis managed?
Resus; ABC
Broad spectrum IV abs; tazocin or gentamicin
If gram positive identified; + vancomycin or teicoplanin
If no response at 72hrs add IV antifungal e.g. caspofungin
CT chest/abdo/pelvis for source
Modify treatment based on culture
What can cause monocytopaenia?
Hairy cell leukaemia, ALL, Hodgkin Lymphoma
Infections i.e. HIV, EBV
Corticosteroid or Ig therapy
Chemotherapy
What puts patients at risk of being severely lymphopenic?
Stem cell transplant patients esp allogenic; Graft V Host Disease
Recipients of total body irradiation
Nucleoside analogues or ATG
Lymphoid malignancy
Describe infection in lymphopenic patients
Atypical pneumonia;
- pneumonitis jirovecii, CMV, RSV
Viral
- shingles, mouth ulcers, adenovirus, EBV
What is monitored in the blood of allogeneic transplant patients ?
CMV
Adenovirus
EBV
Need early intervention if become infected
