Clinical guidelines for the management of

Acute Myeloid Leukaemia (AML)

Agreed: Haematology Clinical Network Group: February 2010

For review: February 2011

Prepared by: Dr Salaheddin Tuegar. Countess of Chester Hospital

The patient should be considered for available NCRN/MRC trials at

diagnosis and relapse. All clinical teams are encouraged to enter patients
into trials.

MCCN AML Guidelines

Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 1 of 8
 Management of non APML patients <60 (or fit >60) years, fit for intensive
chemotherapy and not entered into a clinical trial

DA 3+10+Gemtuzumab ozogomycin
(Mylotarg)
(PCT funding may need to be sought)
OR ADE

CR or PR Refractory
(5-15% disease
blasts) (>15%blasts)

Not CR
DA 3+8 or ADE
High dose cytosine or
other relapse regimen
Poor risk cytogenetics e.g. (FLAG-Ida)
CR -5, -7, del (5q),
complex, abn 3q
normal risk with CR; discuss with No CR
FLT3ITD positive, transplant centre
NPM1 negative
Good risk
inv 16, t(8;21) Donor
Standard risk; discuss with
sibling or No Donor
transplant centre
unrelated or unfit for
transplant

MACE or high No sibling Sibling Donor

dose ara-C donor or unfit and <55 (or
for allogeneic <65 for RIC
transplant or allo) Consider Consider
FLT3ITD allogeneic further
negative, transplant consolidation
NPM1 Full/RIC/Sib chemotherapy
positive Consider
allogeneic /VUD or experimental
MidAC transplant therapy

Palliative treatment
Best supportive care
Consider experimental
MCCN AML Guidelines therapy
Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 2 of 8
 Management of Non APML patients >60 years and fit for
intensive treatment not entered into a clinical trial

DA 3+10 +/- Gemtuzumab

Ozogomycin (Mylotarg)
(Funding may need to be sought)

CR or PR (5-15% blasts) Resistant disease blasts >15%

DA 3+8

CR No CR

DA 2+5

Best supportive care

Palliative treatment
Consider
Consider RIC allo experimental therapy
if patient fit

If unfit for intensive therapy, patients should be entered into the non-intensive arm
of AML 16 if possible. If not eligible or not entered then low dose cytosine or
hydroxycarbamide and best supportive care should be offered.

For relapsed disease in patients >60 years treatment is likely to be palliative with
low dose cytosine or hydroxycarbamide. If a prolonged 1st remission was achieved
and the patient is fit, re-induction with DA followed by a RIC allo could be considered
OR Gemtuzumab Ozogamicin (Mylotarg) (Funding may need to be sought)

MCCN AML Guidelines

Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 3 of 8
 Management of Non APML patients <60 (of fit>60) years
with relapsed disease

Relapsed
disease

CR1 <12 months CR1 >12

months

High dose cytosine

High dose cytosine containing regimen
containing regimen or repeat first
remission inducing
treatment

CR2 No CR2

Donor available Best supportive care

(sib or No donor or Palliative treatment
unrelated) and unfit for allo Consider experimental
fit for allo therapy

Consider autograft if cells stored from first CR

Consider Allo or further consolidation chemotherapy/
transplant experimental therapy
Sib/VUD/full/RIC Consider haploidentical SCT in patients <30
years

MCCN AML Guidelines

Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 4 of 8
 Management of APML for patients >60 years not fit for intensive ‘MRC
type’ chemotherapy

There is little evidence to guide management of these patients however

various therapeutic options include the elderly variation of ‘Spanish’ type
therapy which may be less intensive than AIDA based regimens
Or
Arsenic + ATRA as first line treatment
Or
Mylotarg has some activity as a sole agent in APML but remissions are
usually short lived
Or
Low Dose chemotherapy with ATRA
Or
Experimental therapy

MCCN AML Guidelines

Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 5 of 8
 Management of APML patients <60 years (or fit >60)
not entered into a clinical trial

APML suspected treat as below. If t(15;17) not

confirmed stop ATRA and treat as per non APML
protocol

Correct coagulopathy
Hydration
Avoid leukapheresis for high white counts
Samples to be sent for MRD PCR monitoring

AIDA protocol (see section 19.4 of AML17 protocol)

If no CR by Day 60 proceed to high risk protocol –

(see below)

MCCN AML Guidelines

Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 6 of 8
 Management of patients with relapse/refractory APML

Confirm presence of PML/RARA

translocation + send samples for MRD
monitoring (BM+PB)

Arsenic trioxide therapy 0.30mg/kg for 5 days followed by

0.25mg/kg twice weekly for up to 7 weeks

Assess MRD at 28 days

MRD negative MRD positive or no

haematological CR

Further 4 weeks of
arsenic therapy then Continue arsenic
+Idarubicin 10mg/m2 on 2 consecutive
days – reassess MRD after further 2/52
Autologous stem cell
transplant from MRD
negative cells if
harvested in first CR
or following arsenic
re-induction MRD MRD
negative positive
If not fit for autologous
transplant consider further
consolidation therapy with Haematological No haematological
arsenic trioxide (up to 4 CR CR
courses in total) or
maintenance therapy with
MTX/6-MP and ATRA or
Consider Consider
experimental therapy
allogeneic stem Mylotarg
cell transplant therapy
If not fit for transplant consider
maintenance therapy with MTX/6-
MP and ATRA
If not fit for Mylotarg or no response,
consider ATRA alone, best supportive
MCCN AML Guidelines
Agreed Haematology CNG: February 2010 treatment or experimental therapy
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 7 of 8
Management of APML for patients >60 years not fit for Intensive ‘MRC type’
chemotherapy
There is little evidence to guide management of these patients however various
therapeutic options include the elderly variation of ‘Spanish’ type therapy which
may be less intensive than AIDA based regimens
Or
Arsenic + ATRA as first line treatment
Or
Mylotarg has some activity as a sole agent in APML but remissions are usually
short lived
Or
Low Dose chemotherapy with ATRA
Or
Experimental therapy

MCCN AML Guidelines

Agreed Haematology CNG: February 2010
Due for Review: February 2011
Prepared by: Dr Tuegar, Countess of Chester Hospital Page 8 of 8