Acute Promyelocytic Leukaemia (APML) (Blood 2009)
10-15% of AML cases
Usually young, with leukopenia and life-threatening coagulopathy
A balanced translocation between PML (Promyelocyte) & RARA (Retinoic Acid Receptor-a) generates a fusion protein —> leukaemic promyelocytes have the unique ability to differentiate when exposed to retionoic acid.
- Kidney-shaped/bi-lobed nucleus, cytoplasm densely packed with granules/auer rods
- Hypogranular variant exists, differential diagnosis of acute monocytic leukaemia
- CD45+, MPO+, CD117+, CD33+, CD13+, CD64+/-, Aberrant CD9+
- CD34-, HLADR-, CD11b-, CD11c-
- PCR as gold standard – able to detect PML-RARA in leukopenic patients. Takes 48 hours.
- FISH – can give an answer in 6 hours
- Karyotyping – expensive and time consuming
WBC <10 – Low to intermediate risk disease
WBC >10 – High risk disease
Coagulopathic bleeding responsible for 50-60% of early deaths (CNS, lung and GI)
Risk of bleeding may persist up to 20 days
- Twice or thrice daily FBC, PT, APTT and FGN
- Keep platelets >30-50
- Keep PT/APTT normal
- Keep FGN >1.5g/l
Treatment should start based on morphological assessment, do not wait for FISH.
- Overrides the t(15;17) protein induced blockade of the retinoic acid receptor
- 45mg/m2 daily in two divided doses to start on day 1
- Continued until haematological CR and for a maximum of 60 days
- 12mg/m2 on days 2,4,6 and 8. Or start on day 1 if WBC >10
Arsenic + ATRA is a highly effective (97% CR) non-chemo regimen, not currently available first line in UK
- Arsenic degrades the fusion protein and induces apoptosis
- Usually patients <20 y.o.
- Severe headache, nausea, vomiting and visual disturbance
- Bili/ALT/AlkP >5x the ULN
ATRA/APL Differentiation Syndrome
- 10 days after starting ATRA
- Fluid retention, capillary leak – cough, hypoxia, effusion, oedema, weight gain, fever
- Associated with rising WBC count. Risk lower when ATRA given with chemo.
- Rx: Stop ATRA, give IV Dexamethasone, Cautious re-introduction when Sx resolve
Other adverse effects
- Rash (Sweet’s Syn)
- Pancreatitis, hypercalcaemia, bone marrow necrosis
Consolidation & F/up
>90% CR after induction + 2 cycles of consolidation. No role for transplant in CR1
MRD monitoring 3-monthly for two years after completion of treatment
Relapse inevitable if PCR positive in two consecutive samples à treat at molecular relapse.
- Induce 2nd CR if aim to harvest PCR negative cells for autograft
- Consider Allograft in patients in whom PCR negativity cannot be achieved.