ACUTE MYELOID LEUKEMIA - THERAPY, EXCLUDING TRANSPLANTATION:

PEDIATRIC AND ADULT AML THERAPY | NOVEMBER 19, 2010

Study AML-BFM 2004: Improved Survival In Childhood

Acute Myeloid Leukemia without Increased Toxicity
1 *,2 *,3
Ursula Creutzig, MD, Martin Zimmermann, Michael Dworzak, Jean-Pierre Bourquin, MD,
4 *,5 *,5 *,6 7
PhD, Christine Neuhoff, Annette Sander, Jan Stary, Dirk Reinhardt, MD, PhD
1
Hematology/Oncology, University Children's Hospital Muenster, Muenster, Germany,
2
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany,
3
St. Anna Children's Hospital, Vienna, Wien,
4
Div. of Pediatric Oncology, Universitaets-Kinderklinik Zurich, Zurich, Switzerland,
5
Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany,
6
Department of Pediatric Hematology and Oncology, 2nd Faculty
of Medicine, Charles University Prague, Prague, Czech Republic,
7
Department of Pediatric Hematology /Oncology, Medical School of Hannover, Hannover, Germany

Blood (2010) 116 (21) : 181.

http://doi.org/10.1182/blood.V116.21.181.181

Abstract
Abstract 181

Acute Myeloid Leukemia - Therapy, excluding Transplantation: Pediatric and Adult AML Therapy

Study AML-BFM 2004 was designed to improve outcome of children and adolescents with AML
without increasing toxicity. Patients were stratified into a standard- (SR)* or high-risk (HR)** group
according to morphology, cyto-/molecular genetics including FLT3-ITD, and therapy response on day
15. Notably, reclassification of SR patients to the HR group in case of FLT3-ITD positivity was newly
established in this study. Improvement of prognosis was attempted by intensification of chemotherapy: (1)
Randomized introduction of liposomal daunorubicin (L-DNR) in a higher equivalent dose than idarubicin
2
during induction in both risk groups (L-DNR 80mg/m /day/3x) in comparison to standard induction
2
using idarubicin 12mg/m /day/3x, each combined with cytarabine and etoposide (L-DNR may offer an
increased therapeutic window due to lower cardiotoxicity) and (2) randomised introduction of 2-chloro-2-
 2
deoxyadenosine (2-CDA, 2×6mg/m ) as intensification during the cytarabine/idarubicin (AI) consolidation
in HR patients only.

Overall results improved compared to the previous study AML-BFM 98: Survival estimates at 5 year
(pOS) in patients (excluding Myeloid leukemia in Down syndrome) were 72% + 3% vs. 64% + 2% (AML-
BFM 04 n=566 vs. AML-BFM 98 n=472), plogrank=0.02; the 5-year event-free survival (pEFS): was 54%
+ 3% vs. 50% + 2%, plogrank=.40. Results in the 197 SR patients were excellent: pOS 88% + 3% vs. 78%
+ 3% (n=182), plogrank=.01, EFS 69%, + 4% vs. 64% + 4%, plogrank=.40. Results in the 368 HR patients
also improved: pOS 63% + 4% vs. 56% + 3% (n=290), plogrank=.07, EFS 46%, + 3% vs. 41% + 3%,
plogrank=.43. OS improvement was partly due to better results after treatment of relapse or nonresponse
(3-year pOS after nonresponse/relapse in 171 patients of study 2004 40% + 5% vs. 32% + 4% in 198
patients in AML-BFM 98, plogrank=.017).

st
Results for the 1 randomization L-DNR vs. idarubicin during induction were similar (pOS 78% + 4% vs.
70% + 4%, plogrank=.15, pEFS 60% + 4% vs. 54% + 4%, plogrank=.17). There were less early deaths (4
vs. 8 patients) and less treatment related deaths in remission in the L-DNR group (2 vs. 5 patients). The
rate of severe infection was slightly lower with L-DNR (pFisher 0.15). Two L-DNR vs. 6 idarubicin patients
nd
showed grade III/IV cardiotoxicity after induction. Results of the 2 randomization in HR patients (AI/2-
CDA vs. AI) were also similar: p=OS 75% + 5% vs. 65% + 5%, plogrank=.18, pEFS 51% + 5% vs. 51% +
5%, plogrank=.98. Toxicity rates of the intensification with 2-CDA were tolerable.

In conclusion, compared to the previous study AML-BFM 98, results of study AML-BFM 2004 show
significant improvement in both risk groups. This appears attributable to a combination of factors
including therapy intensification, better supportive care and improved treatment of patients with relapse
or nonresponse. Given the reduced toxicity of L-DNR and a trend towards better survival rates by adding
L-DNR during induction and 2-CDA during HR consolidation, these agents will be further used in the
forthcoming AML-BFM study.

*Standard risk group definition: FAB M1/M2 with Auer rods, FAB M4eo or favorable cytogenetics [t(8;21)
or inv(16)] and blasts in the bone marrow on day 15 <5%, and FAB M3 (all patients)

**High-risk group definition: all others.

Disclosures:
Off Label Use: liposomal daunorubicin is used, which is off label for pediatric AML. It was used because
it offers a possibility to increase cumulative dosages of anthracyclines with lower cardiotoxicity.

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Author notes
* Asterisk with author names denotes non-ASH members.

© 2010 by the American Society of Hematology