Improved Survival in Acute Myeloid Leukaemia Patients Aged over 40 Given Cladribine in Combination with Standard Remission Induction (DA 3+7) and Consolidation Treatment (HD AraC). Seven Year Follow-Up of Prospective, Cooperative PALG Study.

The aim of this study was to evaluate long-term outcome of acute myeloid leukemia (AML) patients treated within the PALG 1999 DAC vs. DA Study. [b][Within 3 years (1999–2002) 445 patients, aged 18–60, were randomized 1:1 to the induction treatment DAC-7: daunorubicin 60 mg/m²/d iv 1–3; cytarabine 200 mg/m²/d ci d 1–7; cladribine (2-CdA) 5 mg/m² 2h inf. iv d 1–5 and standard DA-7 regimen (the same therapy excluding cladribine). Patients achieving CR received two courses of subsequent intensive consolidation:

1. HAM (HD AraC, mitoxantrone)

2. HD AraC with or without cladribine in the DAC-7 or DA-7 arm, respectively.

In case of PR after the first induction course the same regimen was repeated, Post-consolidation therapy was comparable in both arms with following proportions of autoHCT, alloHCT and maintenance: DAC-7 17%, 14%, 69%; DA-7 21%, 14%, 65%, respectively.

As previously reported, a single course of DAC-7 induction resulted in 17% higher CR rate compared to the DA-7 treatment (p=0,0008). The difference was particularly pronounced in patients: aged >40 years and with initial WBC >100x10⁹/L. In the latter subgroup also the overall CR rate (achieved after entire induction program) was higher in the DAC-7 arm (71% vs. 43%). [

In the present report we analyzed seven-year long-term outcome (median follow-up 5 yrs) in the whole study population and in subgroups stratified according to age, initial WBC, cytogenetics, sex, FAB subtype, and preceding myelodysplasia. In the whole group the overall survival (OS) rate equaled 29,5% for DAC-7 and 24% for DA-7 arm (p=NS) and leukemia free survivall (LFS) 30% vs. 28% (p=NS), respectively.

Of note, in patients aged >40 years, the therapy containing cladribine was associated with improved OS (26% vs. 14,5%, p=0.03), and LFS (28% for DAC-7 vs. 18,5% for DA-7, p=0.02).

Other subgroup analyses revealed higher probability of the OS in patients with initial WBC ≥ 50 G/l assigned to DAC-7 compared to DA-7 arm (32% vs. 20,5%, p=0.04). The LFS rate equaled 35% and 27% (p=NS), respectively.

In women receiving DAC-7 induction therapy in comparison with those treated in arm without 2-CdA reached higher OS: 29% vs. 19,5%, p=0,03, respectively. LFS in these subgroups was comparable: 25% vs. 22%, p=NS, respectively.

We conclude that addition of cladribine to induction and consolidation therapy of AML improves long-term outcome in patients: older than 40 y, as well as in those with high tumour burden. The better outcome in older patients results mainly from reduced risk of relapse, whether that in cases with high WBC seems to be linked to a higher CR rate.