recommendations, guidelines and local experience K M Chang - - PowerPoint PPT Presentation

Acute myeloid leukaemia – recommendations, guidelines and local experience

K M Chang Hospital Ampang

WHO classification (2008)

Acute leukaemias of ambigous lineage

WHO 2008

Initial work-up

European Leukaemia Net Consensus, Blood Jan 2010

Prognostic factors

Prognostic groups

ELN Blood 2010

Normal cytogenetics – NPM1+/Flt3-ITD-

Induction therapy

 3 & 7

 DNR 60-90mg/m2  Ida 10-12mg/m2  Mitoxantrone 10-12mg/m2  Cytarabine 100-200mg/m2 continuous infusion  CR 60-80%, treatment delay >5d may impact on

• utcome

 Alternatives

 HiDAC increased toxicity  G-CSF priming better DFS and OS in intermediate

risk

 Gemtuzumab

DNR 45mg/m2 vs 90mg/m2

ECOG Fernandez HF, Sun Z et al. NEJM 2009

Post remission therapy

 HiDAC

 4 cycles 3g/m2 12h D1,3,5 superior to int- and std dose

Ara C

 Benefit to CBF and less to CN-AML but not to others

 CALGB NEJM 1994

 Maintenance

 Not routine  No benefit to remission duration or OS  ?elderly patients

 Autologous HSCT

 Outcome as good as post remission consolidation  ? No improvement

 Allogeneic HSCT

 Lowest risk of relapse  OS improved in int- and hi-risk AML

HiDAC consolidation

NEJM 1998 Blood 2005

Older pt > 60y

 Prognostic factors

 Adverse cytogenetics

 CR < 30%, OS < 5%

 Performance status  Comorbidity

 Post remission therapy

 May benefit CBF AML and mutNPM+/-FLT3-

ITD

 RIC HSCT  Investigational therapies

Elderly AML

OS based on age and cytogenetics : MRC/NCRI AML

Prognostic index for relapse AML

Breems DA. JCO 2005

Moving to a new home………Nov 2006

AML Ampang 2007-9

FAB Not specified 73 M0 1 M1 5 M2 13 M3 25 M4 35 M5 28 M6 3 M7 2 Total 185

Cytogenetics at diagnosis

Cytogenetics Short Spread 10 Other 10 Normal 15 Inv 16 1 Complex 2 8;21 6 15;17 15 Unavailable 126 Total 185

Molecular genetics NPM1 + FLT3 ITD neg 34 NPM1 pos 4

All AML from Diagnosed in 2007 to 2009 - Overall Survival 10 20 30 40 100 90 80 70 60 50 40 30 20 10 Time

Impact of Age on Overall Survival of AML Patients (1 = Age <55 years 2 = Age >55 years) 10 20 30 40 100 90 80 70 60 50 40 30 20 10 Time

<55y 127pt 28m <55y 51pt 4m

Age_more_or_less_than_65 Old Young Ov erall Surv iv al of AML Patients according to Age Young <65 years Old > 65 years 10 20 30 40 100 80 60 40 20 T ime

<65y 141 17m >65y 24 2.5m

Treatment ALLO Auto CHEMO No treatment Overall Survival of AML patients according to treatment 10 20 30 40 100 80 60 40 20 Time

Allo 21 (NR) Auto 14 (NR) Chemo 109 (16m) No Rx 28 (2m)

Cytogenetic_Group Favourable NA Normal

• ther

short spread Overall Survival Of AML Patients Based on Cytogenetics (Favourable = 15;17, 8;21, Inv 16) (NA - Not Available) (Other - cytogenetics other than normal or favourable) 10 20 30 40 100 80 60 40 20 Time

Cytogenetic_Group Favourable NA Normal

• ther

short spread Overall Survival of AML patients > 55 years 10 20 30 40 100 80 60 40 20 Time Cytogenetic_Group Favourable NA Normal

• ther

short spread Overall Survival of AML patients less than 55 years 10 20 30 40 100 80 60 40 20 Time

Cytogenetic_Group Favourable NA Normal

• ther

Overall Survival of AML patients more than 55 years 10 20 30 40 100 80 60 40 20 Time

MRD Negative Positive KM curves of Overalll survival of All AML with MRD positivity during treatment 10 20 30 40 100 90 80 70 60 50 40 30 20 10 Time

Pos 44 Neg 27 MS 16m vs NR p = 0.0146

Postremission FLAG/FLAG-GO in elderly AML > 55y

 11 pt  TRM 1/11  8 evaluable  Age 55.4y – 72.3 y (median 60y)  M 3: F 5  Cytogeneitcs

 Normal 1, t(8;21) 1, NA 6

Overall Survival of AML patient undergoing upfront consolidation with FLAG or FLAG-Myelotarg in patients > 55 years (total 8 patients included, 1 loss to follow-up and 2 with incomplete records wereexcluded) 5 10 15 20 25 30 35 40 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 Time

Outcome of AML transplants 1999-2009 (n=133)

Kaplan Meier Curve of Overall Survival of All Transplanted Patients 20 40 60 80 100 120 140 100 90 80 70 60 50 40 30 20 10 Time

Kaplan Meier Curve Survival Analysis of All AML patients undergoing transplants

Type_Of_Transplant Allogenic Matched Sibling Autologous Haploidentical Matched Unrelated Mismatched cord blood transplant Overall Survival 20 40 60 80 100 120 140 100 80 60 40 20 Time

Total (n=133) Allo matched siblings 73 Autologous 53 MUD 3 Cords 3 Haplo 1

Age 1 2 3 Overall Survival (1 = <20y 2 = 20-40y 3 = >40y) 20 40 60 80 100 120 140 100 90 80 70 60 50 40 30 20 10 Time

<20y n=42 20-40 n=71 >40y n=20 p=0.6679

TypeOfTransplant Allogenic Autologous Kaplan Meier Curves of Overall Survival Of AML Patients who were transplanted - Comparison of Auto vs Allo 20 40 60 80 100 120 140 100 90 80 70 60 50 40 30 20 10 Time

Kaplan Meier Curves of Overall Survival of Transplanted AML patients based on Cytogenetics (Orange dotted - t(8;21) Brow n - t(15;17) Green - Normal Gold - Other Blue - Unavailable or short spreads Pink dotted - Complex) 20 40 60 80 100 120 140 100 90 80 70 60 50 40 30 20 10 Time

Favourable AML Transplanted

Type_Of_Transplant Allogenic Matched Sibling Autologous Overall Survival for Favourable Cytogenetics AML 20 40 60 80 100 120 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 Time

Allo n=6 Auto n=15 p = 0.4281

RemissionStatus CR 1 CR > 1 Relapsed/ refractory Overall Survival in Favourable Cytogenetics AML 20 40 60 80 100 120 100 80 60 40 20 Time

CR1 (n=5) >CR1 (n=15) p = 0.0354

Acknowledgement

 Clinical

 Dr Jameela S  Dr V Purushothaman  Dr Ong Tee Chuan  Dr Tan Sen Mui  Dr Lau Ngee Siang  Dr Zanapiah M  Dr Lim Soo Min  Dr Guan Yong Khee  Dr Kuan Jew Win  Dr Jay Suriar  Dr Jerome Tan  Dr Liew Hong Khee  Dr Ahlam Nair  Dr Bahariah  Haem physicians  Dr Agnes Yong

 Laboratory

 Dr Subramanian

Yegappan

 Dr Rita Puri  Molecular lab  Cytogenetic lab  Leukaemia lab  Stem cell lab  HPE lab  Coag lab

 Nursing team  Pharmacy  Hospital ampang  CRC