Haem proliferations/malignancies

Question 1

MM - high risk patients for progression

Answer 1

• Translocations (on FiSH): t(4;14) or t(14;16) or 17p del
• Serum β2-microglobulin >5.5
• LDH increased
• (Plasma cells >60% in BM)
• (Very skewed free light chain ratio eg >100:1)
• (Discrete skeletal lesions >5mm usu)

Brackets = more likely to Rx even if asx

Question 2

MM criteria for categories

Answer 2

MGUS:

• Paraprotein <30 g/L
• BM plasma cells <10%
• *No CRAB/SLIM**

Smouldering: either

• Paraprotein >30 g/L (OR)
• BM plasma >10%
• *No CRAB/SLIM**

Active myeloma: CRAB/SLIM

Question 3

MM: CRAB & SLiM criteria

Answer 3

SLiM:

• plasma cells >60% Sixty
• Light chain ratio >100 (either chain)
• MRI - multi focal lesions

Question 4

MM - Rx

Answer 4

1st line: VRD/VRC = Bortezomb + Cyclophosphamide/Revlimid (lenalidomide) + Dex
Immunomodulators (Thalidomide, Lenalidomide, Pomalidomide) - VTE

Typically given during autologous SCTx

Gold std: Daratumumab (mAb CD38 - expressed on plasma cells / immune/RBC)
Use in first relapse w/ Pomalidomide (prev Bortzeomib)
NEED TO UNDERGO EXTENSIVE CROSS MATCHING PRIOR

Question 5

DLBCL - subtypes & prognosis

Answer 5

GCB: germinal centre

ABC: activated B cell like - worse prognosis

Triple hit: mutations in MYC, BCL2, BCL6 - very poor survival <1y

Question 6

DLBCL - Rx & general toxicities

Answer 6

R-CHOP (H=Doxo, O=Vincrist)
Vincristine = PN
Doxorubicin = CM

Polatuzumab vedotin (Ab-drug conjugate)
CAR-T cells
Bispecific T-cell engagers (Blinatumomab - anti CD19)

Question 7

HL - Rx

Answer 7

Chemo (ABVD) + Radio : to lower doses of both re; long term effects

Brentuximab vedotin; antiCD30 Ab-drug conjugate
Not sustained response so bridge to Autologous SCTx or relapse only

Pembrolizumab (relapsed/refractory)

Question 8

AML - cytogenetic profiles & Rx

Answer 8

Good: t(8;21), APML, inv(16): HiDAC (induction/consolidation)

Poor (-5 -7 abN 3q): as above w/ allogenic SCTx

If FLT3 mutated - Midostaurin

Question 9

ET - Rx

Answer 9

HIGH RISK Pts
>60y w/ hx thrombosis/CV RF or JAK2 (MPL) mutations
Aspirin (?BD) + Hydroxyurea (if plts >1000) + AC (if venous thrombosis only)

LOW RISK
CALR mutations in young ppl - can watch
If treating young ppl could consider PEG-IFN, also consider acqVWD if plts>1500

Question 10

ET - Rx

Answer 10

HIGH RISK Pts
>60y w/ hx thrombosis/CV RF or JAK2 (MPL) mutations
Aspirin (?BD) + Hydroxyurea (if plts >1000) + AC (if venous thrombosis only)

LOW RISK
CALR mutations in young ppl - can watch
If treating young ppl could consider PEG-IFN, also consider acqVWD if plts>1500

Question 11

PMF - Pathophys & exam findings

Answer 11

Pathophysiology - megakaryocyte disorder
- Cytokine release causes BM fibrosis (can be pre-fibrotic or overt)

Fx

• BM bx showing fibrosis
• Thrombocytosis / Leucocytosis / Teardrop RBC
• Presence of driver mutation (50% JAk2, 25% CALR _BEST, 10% MPL. Triple neg 15% _WORST but epigenetic regulator mutations also predict poor survival)
• often ‘asx’ but cytopenias, spleenomegaly, film abN, pain, gout

Question 12

PMF - Rx

Answer 12

Pre-PMF: consider aspirin, cytoreductive Rx (HC) to prevent thrombosis.

Observe unless sx, spleenomegaly >10cm, Leucs >25, Plts >1000, anaemia

2nd line Rx: Ruxolitinib (JAK-inh, use independent of mutation); HSTx if high risk

Question 13

CLM - Rx for mutation

Answer 13

T315i mutation - use 3rd gen TKI: Ponatinib

S/E: CV hence can’t use 1st line.
Pancreatisis
rash