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 outcome  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 Molecular genetics Short Spread 10 Other 10 NPM1 + FLT3 ITD neg 34 Normal 15 NPM1 pos 4 Inv 16 1 Complex 2 8;21 6 15;17 15 Unavailable 126 Total 185

All AML from Diagnosed in 2007 to 2009 - Overall Survival 100 90 80 70 60 50 40 30 20 10 0 0 10 20 30 40 Time

Impact of Age on Overall Survival of AML Patients (1 = Age <55 years 2 = Age >55 years) 100 90 <55y 127pt 28m 80 <55y 51pt 4m 70 60 50 40 30 20 10 0 0 10 20 30 40 Time

Ov erall Surv iv al of AML Patients according to Age Young <65 years Old > 65 years 100 <65y 141 17m >65y 24 2.5m 80 60 Age_more_or_less_than_65 Old Young 40 20 0 0 10 20 30 40 T ime

Overall Survival of AML patients according to treatment 100 Allo 21 (NR) Auto 14 (NR) Chemo 109 (16m) 80 No Rx 28 (2m) 60 Treatment ALLO Auto CHEMO No treatment 40 20 0 0 10 20 30 40 Time

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) 100 80 60 Cytogenetic_Group Favourable NA Normal other short spread 40 20 0 0 10 20 30 40 Time

Overall Survival of AML patients > 55 years Overall Survival of AML patients less than 55 years 100 100 80 80 Cytogenetic_Group 60 Cytogenetic_Group 60 Favourable Favourable NA NA Normal Normal other other 40 short spread 40 short spread 20 20 0 0 0 10 20 30 40 0 10 20 30 40 Time Time

Overall Survival of AML patients more than 55 years 100 80 60 Cytogenetic_Group Favourable NA Normal other 40 20 0 0 10 20 30 40 Time

KM curves of Overalll survival of All AML with MRD positivity during treatment 100 Pos 44 Neg 27 90 MS 16m vs NR p = 0.0146 80 70 60 MRD 50 Negative Positive 40 30 20 10 0 0 10 20 30 40 Time

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) 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 0 5 10 15 20 25 30 35 40 Time

Outcome of AML transplants 1999-2009 (n=133) Kaplan Meier Curve of Overall Survival of All Transplanted Patients 100 90 80 70 60 50 40 30 20 10 0 0 20 40 60 80 100 120 140 Time

Kaplan Meier Curve Survival Analysis of All AML patients undergoing transplants Overall Survival 100 Total (n=133) 80 Allo matched siblings 73 60 Autologous 53 Type_Of_Transplant Allogenic Matched Sibling Autologous Haploidentical MUD 3 Matched Unrelated Mismatched cord blood transplant 40 Cords 3 Haplo 1 20 0 0 20 40 60 80 100 120 140 Time

Overall Survival (1 = <20y 2 = 20-40y 3 = >40y) 100 <20y n=42 90 20-40 n=71 >40y n=20 80 p=0.6679 70 60 Age 1 50 2 3 40 30 20 10 0 0 20 40 60 80 100 120 140 Time

Kaplan Meier Curves of Overall Survival Of AML Patients who were transplanted - Comparison of Auto vs Allo 100 90 80 70 60 TypeOfTransplant 50 Allogenic Autologous 40 30 20 10 0 0 20 40 60 80 100 120 140 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) 100 90 80 70 60 50 40 30 20 10 0 0 20 40 60 80 100 120 140 Time

Favourable AML Transplanted Overall Survival for Favourable Cytogenetics AML 100 95 90 85 Allo n=6 80 Auto n=15 75 p = 0.4281 70 65 60 55 Type_Of_Transplant 50 Allogenic Matched Sibling Autologous 45 40 35 30 25 20 15 10 5 0 0 20 40 60 80 100 120 Time

Overall Survival in Favourable Cytogenetics AML 100 CR1 (n=5) >CR1 (n=15) 80 p = 0.0354 60 RemissionStatus CR 1 CR > 1 Relapsed/ refractory 40 20 0 0 20 40 60 80 100 120 Time

Acknowledgement  Clinical  Laboratory  Dr Jameela S  Dr Subramanian Yegappan  Dr V Purushothaman  Dr Rita Puri  Dr Ong Tee Chuan  Molecular lab  Dr Tan Sen Mui  Cytogenetic lab  Dr Lau Ngee Siang  Leukaemia lab  Dr Zanapiah M  Stem cell lab  Dr Lim Soo Min  HPE lab  Dr Guan Yong Khee  Coag lab  Dr Kuan Jew Win  Nursing team  Dr Jay Suriar  Pharmacy  Dr Jerome Tan  Dr Liew Hong Khee  Hospital ampang  Dr Ahlam Nair  CRC  Dr Bahariah  Haem physicians  Dr Agnes Yong