Maryse Power - CBMTG

ALLOGENEIC STEM CELL TRANSPLANT IN FIRST
COMPLETE REMISSION OVERCOMES THE POOR
PROGNOSIS ASSOCIATED WITH THE FLT-3
INTERNAL TANDEM DUPLICATION IN ACUTE
MYELOID LEUKEMIA
Maryse M. Power, Giovanna Di Sauro, Ryan Brinkman,
Angela Brooks-Wilson, Stanley Wong, Yasser R. Abou
Mourad, Michael J. Barnett, John D. Shepherd, Clayton A.
Smith, Heather J. Sutherland, Donna L. Forrest, Julye C.
Lavoie, Kevin W. Song, Steven H. Nantel, Cynthia L. Toze,
Thomas J. Nevill, Sujaatha Narayanan, Steve Leach, Donna
E. Hogge

Introduction
• Prognosis in AML –Karyotype powerful
prognostic indicator AND helps to guide
therapeutic decisions
• Most patients fall into the “intermediate risk”
karyotype group (46-74% of patients), with 40-
50% of patients displaying a normal karyotype
at diagnosis
• Newly identified molecular abnormalities add
further prognostic information in this group.

Survival-Cytogenetic Risk Group
HETEROGENOUS

Impact of FLT3 mutations on
outcome in AML
Thiede, C. et al. Blood 2002;99:4326-4335

NPM1 mutation status and
AML outcome
Dohner, K. et al. Blood 2005;106:3740-3746

Aim
• Define prevalence, prognostic significance
of mutations in FLT3 and NPM1 in a
cohort of AML patients under the age of
60 years in first complete remission
• Compare the results obtained using
allogeneic SCT in first CR to chemotherapy
consolidation in FLT3 and nucleophosmin
mutated patients

Patient Characteristics
• Patients treated at Vancouver General Hospital
between 1980 and 2006
• All had achieved complete remission with one or
two cycles of induction chemotherapy
• Retrospective analysis
• Treatment decisions not based on molecular
data

Patients
Database identified 695 patients with diagnosis of AML who
achieved CR1 with one or two cycles of induction therapy and
were aged < 60 years
298 patients of this group had sufficient DNA in diagnostic
samples available for analysis
Further 31 patients excluded for clinical reasons: eg; failure to
achieve CR per Cheson criteria, MDS diagnosis rather than
AML, No therapy given beyond CR1
267 patients in final group

Patients
230 patients
ALLO SCT in CR1
n=92
Chemo in CR1
N=138

Patient Characteristics
• CHEMO Group
– Of the CHEMO group, 92% received high dose ARA-C
consolidation therapy
– 86% received more than one cycle of chemotherapy
consolidation
– This group included 9 patients who were treated with
autologous SCT in first CR as consolidation therapy

Patient Characteristics
• ALLO Group (n=92)
– 62 patients SIB ALLO
– 22 patients VUD with full HLA match
– 7 patients with mismatch VUD
– 1 haploidentical

Results
• FLT 3 ITD mutation in 24% of patients
(41% of normal karyotype group)
• Nucleophosmin NPM1 mutation in 28% of
patients (47% of normal karyotype group)
• FLT 3 D835 point mutation in 9% of the
total group

Entire Group: ALLO vs CHEMO

Survival- Induction Failure

Survival-Cytogenetic Risk Group

Overall Survival- All Patients
According to FLT3 ITD Status

Intermediate Risk (IR) Group-
FLT3 ITD Status

IR Group- NPM1 and FLT3
D835 Mutation Status and OS

Interaction of FLT3 ITD and
NPM1 Mutation with OS

Survival
• 50% of FLT3 ITD positive patients are alive
following ALLO SCT in CR1
• 30% of FLT3 ITD positive patients are alive
following CHEMO consolidation in CR1
• Relapse rate: 39% in ALLO SCT in CR1
76% in CHEMO in CR1

Intermediate Risk Cytogenetics-
Allograft group

Intermediate Risk Cytogenetics
Group- CHEMO

ITD Positive Patients- CHEMO vs
ALLO

Conclusions
• Mutations in FLT3 and NPM1 - similar
prevalence in our cohort to other groups
• Induction failure, cytogenetic classification
and FLT3 ITD mutation status predictive
of overall survival
• No effect of NPM1 or FLT3 D835 mutation
on overall survival

Conclusions
• Higher relapse risk in AML patients with
FLT3 ITD treated with chemotherapy in
CR1
• Negative prognostic effect of the FLT3 ITD
appears to be overcome by allogeneic SCT
in CR1

Acknowledgments
• Leukemia and BMT Program of BC/ BC Cancer Agency
• Dr Donna Hogge MD,PhD
• Giovanna di Sauro BCCRC, Angela Brooks Wilson, BC
Centre for Genome Science
• Ryan Brinkman, Stanley Wong, Yunfeng Dai, BCCRC
• Janet Nitta and Roomana Bajwa, Data Coordinators VGH