Abstract

Abstract 1066

Different approaches have been investigated to improve the prognosis of adult patients with primary acute myeloid leukemia. In two consecutive phase II trials our group has explored the use of intermediate-dose cytarabine in induction associated with idarubicin and etoposide, the addition of G-CSF priming to the previous combination, and risk-adapted postremission therapy.

Objective:

To compare the results of two consecutive trials for primary AML and to analyze the factors influencing the outcome.

Patients and methods:

Adult patients between 17 and 60 years of age with de novo AML, diagnosed between 1999 and 2009, were included in the CETLAM AML-99 and AML-03 trials. Induction chemotherapy (CT) included one or two courses of idarubicin 12 mg/m2 IV days 1,3,5, cytarabine 500 mg/m2/12h over 2h IV days 1,3,5,7 and etoposide 100 mg/m2 IV days 1,2,3. This was followed by one consolidation with mitoxantrone 12 mg/m2 IV from day 4 to 6, and cytarabine 500 mg/m2/12h IV from day 1–6. In the AML 03 trial, patients also received G-CSF priming, 150 mg/m2 subcutaneously (SC) from day 0 to the last day of induction and consolidation CT. Postremission therapy consisted of high-dose cytarabine (CBF AML), autologous or allogeneic hematopoietic transplantation depending on cytogenetics, courses to complete remission (CR), and in the AML-03 protocol also based on molecular abnormalities involving FLT3 or MLL genes and/or the persistence of minimal residual disease after consolidation.

Results:

Overall, 788 patients were included, 353 in the AML-99 trial and 435 in the AML-03. Median age of the patients was 46 years (range 17–60). There were no differences between patients included in the two protocols regarding age, gender, leukocyte counts, cytogenetics and proportion of favourable and unfavourable molecular cases in the group with intermediate-risk karyotype. The main results achieved appear in the table.

AML-99AML-03P-value
CR/Refract/Death % 72%/17%/11% 79%/10%/11% 0.017 
Favourable cytog (n=113) 83%/11%/6% 95%/0%/5% 0.083 
Intermediate cytog (n=490) 75%/15%/10% 80%/9%/11% 0.160 
Unfavourable cytog (n=106) 45%/39%/16% 72%/19%/9% 0.018 
5-yrs Survival 35±3% 43±3% 0.008 
Favourable cytog 57±7% 79±6% 0.055 
Intermediate cytog 36±3% 41±4% 0.130 
Unfavourable cytog 9±4% 13±7% 0.004 
AML-99AML-03P-value
CR/Refract/Death % 72%/17%/11% 79%/10%/11% 0.017 
Favourable cytog (n=113) 83%/11%/6% 95%/0%/5% 0.083 
Intermediate cytog (n=490) 75%/15%/10% 80%/9%/11% 0.160 
Unfavourable cytog (n=106) 45%/39%/16% 72%/19%/9% 0.018 
5-yrs Survival 35±3% 43±3% 0.008 
Favourable cytog 57±7% 79±6% 0.055 
Intermediate cytog 36±3% 41±4% 0.130 
Unfavourable cytog 9±4% 13±7% 0.004 

Multivariate analysis confirmed the favourable impact of AML-03 protocol on outcome. Other significant factors influencing survival were age, leukocyte counts and cytogenetics.

Conclusion:

G-CSF priming improved the CR rate of adult patients with primary AML and favourable or unfavourable cytogenetics. This fact and a more precise risk-adapted therapy taking into account genetic data and MRD studies translated into improved overall survival.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.