Haematological cancers Flashcards
CML
a) Presentation and diagnosis
b) Aetiology
c) Phases
d) Management (drug also used in what other cancer?)
e) vs. myelofibrosis
a) Very high WCC (often >100), splenomegaly, infections, commonly thrombocytosis (unlike any other leukaemia)
- “Left shift” - myelocytes, metamyelocytes and banded neutrophils present in higher levels
- Basophilia, neutrophilia, myeloid cells on blood film
- Diagnose via cytogenetics - PCR for BCR-ABL (serum analysis)
- May then proceed to a bone marrow biopsy (to know % blast cells)
b) Philadelphia chromosome:
- BCR from Ch22 translocates to ABL on Ch9
- Tyrosine kinase activation
c) - Chronic phase (< 10% blasts)
- Accelerated phase (10 - 19% blasts)
- Blast transformation (>20% blasts)
d) Tyrosine kinase inhibitors, which all end in -tinib (e.g. imatinib), given orally. Also used to treat GIST cancers
- Monitor PCR for BCR-ABL levels
- If blast transformation present, treat as for AML
e) - Both conditions can cause raised WCC with myeloid cells of varying stages seen, and both have massive splenomegaly, however:
- CML will have a grossly elevated WCC (>100 often)
- Both may cause a raised PLT*
- Myelofibrosis causes dry tap (so diagnosis requires a bone marrow ‘trephine’ - core biopsy)
- Myelofibrosis will have a leukoerythroblastic picture with “teardrop” cells on blood film (CRY-elo-fibrosis)
- 50% myelofibrosis are JAK-2 positive and may have a history of PRV
*CML is only leukaemia to commonly cause thrombocytosis
AML treatment
a) Phases and usual treatment
b) What is remission defined as?
c) If very high WCC, what therapy may also be used?
d) Why is it important to do clotting screen on all likely AML diagnoses?
Induction:
- Cytarabine (ara-C) + anthracycline drug such as daunorubicin or idarubicin
- Given in a 7+3 regime
After induction, a bone marrow biopsy is done:
- Remission is defined as <5% blast cells.
- If >5% blast cells present, a further induction regime is given.
- If <5% blast cells, remission is successful and proceed to consolidation therapy
Consolidation
- Further cycles of cytarabine, or
- Allogeneic (donor) HSCT
- Autologous HSCT
Leukostasis:
- Respiratory (SOB, hypoxia) and neurological symptoms (headache, dizziness, confusion, vision loss, etc.)
- Treated with leukapheresis
d) Clotting screen:
- On all AML diagnoses to look for any evidence of DIC (would suggest APML)
Richter syndrome
a) Which cancers can transform into this? What is it? How common is it?
b) How does it present?
c) Treatment
a) - CLL or hairy cell leukaemia
- Transform into high grade B-cell lymphoma
- Around 2-10% of CLL
b) Presentation:
- B symptoms
- Enlarging LN
- Splenomegaly
- Hypercalcaemia
c) Diagnose with LN biopsy
Treatment as for high grade lymphoma:
- R-CHOP (rituximab, cyclophosphamide, doxyrubicin, vincristine, prednisolone)
+/- stem cell transplant
CLL
a) Aetiology
b) Poor prognostic factors
c) Presentation and diagnosis
d) Treatment - indications, strategies
a) Genetic abnormalities:
- del(13q), del(11q), or del(17p)
- Sometimes there is an extra chromosome 12 (trisomy 12)
b) - p53 gene
- Zeta associated protein (ZAP-70)
c) - Incidental high WCC
- Immunophenotype for diagnosis to look for circulating clonal B-lymphocytes expressing CD5, CD19, CD20, CD23, pathological expression of T-cell marker CD5 and absence of FMC-7 staining
- (do not routinely need a bone marrow biopsy)
- Autoimmune haemolytic anaemia
- Hypogammaglobulinaemia
d) - Most patients will be a W&W
- Indications for treatment: drenching night sweats, lymphadenopathy, weight loss, anaemia
- Types of treatment:
1. Fit, younger patients = R-FC (rituximab, fludarabine, cyclophosphamide)
2. Chlormabucil + rituximab
3. Tyrosine kinase inhibitor
- Splenectomy may be offered for resistant haemolytic anaemia
Graft versus host disease
a) What is it?
b) Risk factors
c) Presentation of acute vs chronic
d) Acute GvHD staging
e) Management
f) Reducing the risk of tranfusion associated GvHD
a) - T-cells in the graft attack the host’s cells following bone marrow or stem cell transplant, as a result of HLA-mismatch (type 4 hypersensitivity reaction)
- It is where the GRAFT rejects the host
- May also rarely occur following blood transfusion in immunocompromised individuals
b) Degree of HLA mismatch, sex difference between donor-recipient, older age of recipient, reduced intensity pre-chemo
c) Diagnosis is clinical
Acute GvHD:
- Classically presents <100 days post-transplant (if >100 days with features of acute GvHD, termed late-onset acute GvHD)
- Classically attacks cells in the gut (abdo cramp, diarrhoea), skin (sunburn like rash), liver (LFT derangement), bone marrow (pancytopenia)
- Skin - maculopapular rash (starts on palms and soles), may ulcerate, may produce TEN-like reaction in severe cases
- GI - diarrhoea, vomiting, pain, anorexia, mucosal ulceration (poor prognosis), might have “ribbon sign” on CT abdomen
- LFT derangement - high bilirubin, cholestatic picture
Chronic GvHD:
- Classically presents >100 days post-transplant
- Skin - poikiloderma, lichen planus, alopecia, nail dystrophy, dyspigmentation
- Lichen-type changes on mucous membranes (such as the mouth or genitals)
- MSK - fasciitis, joint contractures, myositis
- Other - mouth ulceration, xerostomia, conjunctivitis
- Can affect heart, lungs, kidneys, GI tract, etc.
- May also have features of acute GvHD in an overlap syndrome
d) Stage 1: skin rash <25% body, bilirubin 26-60, GI losses 500-1000ml per day
Stage 2 and 3 - in between
Stage 4: bullous desquamation of skin; bilirubin >257, GI losses >2500 ml/day or ileus
e) - Topical steroids/tacrolimus* if pure skin involvement and mild
- Systemic steroids if more severe/extensive
- Other immunosuppressants if steroids ineffective
- Tacrolimus and ciclosporin are useful in GvHD as they are T-cell mediators
f) Gamma-irradiated blood - should be used in any severely immunocompromised individual (e.g. chemotherapy)
Myeloma
a) Chemotherapy regime
b) MGUS vs smouldering myeloma vs active myeloma
c) Risk of progression to myeloma for MGUS and smouldering myeloma
d) Renal disease associated with findings
a) Thalidomide containing regimes (e.g. CTD - cyclophosphamide, thalidomide, dexamethasone)
b) MGUS:
- Serum monoclonal protein < 3 g/dL (no urinary paraprotein)
- Clonal bone marrow plasma cells < 10%, and
- Absence of end-organ damage (CRAB)
Smouldering:
- Serum monoclonal protein (IgG or IgA) ≥ 3 g/dL and/or clonal bone marrow plasma cells ≥ 10%, and
- Absence of end-organ damage (CRAB)
Active myeloma:
- Plasma cells >10%, and
- Presence of urinary or serum paraprotein, and
- End-organ damage (CRAB)
c) - MGUS: 1% per year
- Smouldering: 10% per year for the first 5 years, then risk reduces
d) Cast nephropathy, caused by light chains forming plugs (eosinophilic, dense, homogenous casts) in the tubules and resulting in renal failure
Which haematological malignancy is a more common cause of DIC?
Acute promyelocytic leukaemia
Hodgkin lymphoma
a) Classification. Which has better prognosis?
b) Ann Arbor staging (used for HL and NHL)
c) Common skin presentation
d) Renal disease associated
e) Most common chemotherapy regime
a) Lymphocyte predominant Hodgkin’s lymphoma (better prognosis)
Classical Hodgkin’s lymphoma - i) nodular sclerosis, ii) mixed cellularity, iii) lymphocyte-rich, iv) lymphocyte-depleted
b) - I = Single LN (or single extra-lymphatic organ including spleen)
- II = 2 or more LNs on same side of diaphragm
- III = LNs on both sides of diaphragm
- IV = diffuse/disseminated involvement of 1 or more extra-lymphatic organs, or affecting liver/bone marrow/pleura/CSF
Also substaged A or B for asymptomatic or B symptoms present (fever >38, or drenching night sweats, or weight loss >10%)
c) - Erythema nodosum
(note: in Adult T-cell lymphoma - may have scaly rash)
d) Minimal change disease
e) ABVD:
Doxorubicin, bleomycin, vinblastine and dacarbazine
Adult T-cell leukaemia/lymphoma
a) What is it?
b) Cause
c) Presentation
d) Treatment
a) Type of NHL:
- Most commonly acute high-grade lymphoma (60%)
- 15% leukaemia
- 15% chronic lymphoma
- 10% smouldering
b) HTLV-1 virus
(Adult T cell - hTlv1)
c) - Lymphadenopathy, hepatosplenomegaly, B symptoms, infections
- Hypercalcaemia
- Skin rash - plaque like lesions, may ulcerate, may be cancerous lesions
d) R-CHOP (note: poor prognosis)
HSCT
Hairy cell leukaemia
a) What is it?
b) Presentation
c) Diagnosis
d) Treatment
a) A type of slow-growing B-cell leukaemia
b) Pancytopenia - anaemia, infections, bleeding, etc.
B symptoms
Hepatosplenomegaly, lymphadenopathy
c) Blood film - “hairy” cells seen
d) - Watchful waiting
- If severe symptoms, significant pancytopenia or massive hepatosplenomegaly, chemotherapy started
- Chemo drugs - cladribine, or pentostatin
- May also have splenectomy if severely enlarged spleen
Burkitt’s lymphoma
a) Common translocation
b) Proto-oncogene
c) Presentation of endemic vs sporadic form
d) Diagnosis and typical finding
e) Prognosis
a) t (8: 14)
= 8urk14tts
b) c-Myc
c) Endemic - jaw/facial bone involvement with painless neck LN
Sporadic - abdominal involvement with ascites
d) LN biopsy - “starry sky” appearance of macrophages phagocytosing cell debris
(also seen in other high grade lymphomas)
e) 2/3 curative with intensive chemotherapy (even though it is a VERY high grade lymphoma)
Acute pro-myelocytic leukaemia (APML)
a) What is it?
b) Common presentation
c) Mutation
d) Cell types present
e) Treatments
a) Variant of AML
b) DIC
c) t (15: 17) - affecting the RAR-alpha gene on Ch15 and APML gene on Ch17
d) - Promyelocytes
- Faggot cells
e) ATRA - all trans retinoic analogues (vitamin A analogues)
Waldenstroms Macroglobulinaemia
a) What is it?
b) Presentation
c) Diagnostic tests
d) Treatment
a) Type of Non-Hodgkin B-cell lymphoma involving lymphoplasmacytic (LPL) cells*, which produce excess IgM monoclonal antibodies, resulting in hyperviscosity
*Halfway between a small lymphocyte and mature plasma cell
b) Pancytopenia, hepatosplenomegaly, lymphadenopathy
- Features of hyperviscosity*. Triad of neurological deficits, visual changes, and mucosal bleeding, e.g. headaches, dizziness, papilloedema, nosebleeds, thrombosis
*30% WM patients get HVS at some stage. Other causes of HVS include myeloma, cryoglobulinaemia, more rarely inflammatory diseases like RA/ Sjogren’s/ SLE, HIV.
Treat with IV fluids, PLEX +/- chemo
c) Serum protein electrophoresis - for IgM
d) - Watch and wait
- Chemotherapy (often with rituximab, e.g. R-CHOP)
- Stem cell transplant
- Plasma exchange (especially if HVS)
MDS
a) Primary vs secondary
b) Classification
c) Presentation
d) Diagnosis
e) Treatment
f) Complications
a) Primary (majority) - idiopathic
Secondary - related to previous chemo/RT
Risk factors include chemical benzene exposure
b) MDS-SLD:
- Single lineage dysplasia - 1 abnormal cell line (RBC, WBC or PLT) in bone marrow
1 or 2 out of anaemia, leukopenia or thrombocytopenia
MDS-MLD:
- Multiple lineage dysplasia - 2 or 3 abnormal cell lines in bone marrow
- 2 or 3 out of anaemia, leukopenia or thrombocytopenia
MDS-EB
- 1-3 abnormal cell lines and 1-3 cytopenias
- Excess blasts in bone marrow: 5-9% (EB-1) and 10-19% (EB-2).
- >20% would be AML
MDS with isolated del(5q)
- Chromosome del(5q) mutation - this mutation confers the worst prognosis in patients with AML
- 1-3 abnormal cell lines and 1-3 cytopenias
c) May be asymptomatic
May have features of cytopenia, HSM
d) - FBC, blood film (poikilocytosis: >10% abnormal cells)
- Suspect if macrocytic anaemia but normal folate/B12
- Bone marrow aspirate for Cytogenetic studies
e) HSCT
- chemo if not eligible (e.g. >75)
f) - Bone marrow failure (main cause of death)
- AML transformation
ALL
a) Poor prognostic features
b) Cause of stroke in AML and ALL
c) Why is intrathecal chemotherapy given?
d) Finding of mediastinal mass indicates what?
a) Philadelphia chromosome, male sex, uncommon phenotype, older age >60
b) Hyperleukocytosis and leukostasis
c) Some blast cells can cross BBB and cause CNS disease, so this is given to all ALL patients to treat any disease here
d) T lymphoblastic disease
