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.


Diagnostic Investigations



-       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-


-       t(15;17)

-       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


Risk Classification


WBC <10 – Low to intermediate risk disease

WBC >10 – High risk disease


Supportive Treatment


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


Definitive Treatment


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


ATRA Toxicity


Pseudotumour Cerebri

-       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.


At relapse

-       Induce 2nd CR if aim to harvest PCR negative cells for autograft

-       Consider Allograft in patients in whom PCR negativity cannot be achieved.