Abstract

From 11/01 until 04/05, 832 patients under 60 (median age = 46, 18–60) were included in AML1 protocol for treatment of de novo AML (AML3 and previous diagnosis of MDS or MPS were excluded, unlike previous diagnosis of solid tumor and/or chemo-radiotherapy without subsequent MDS). Among these 8 patients presented with exclusion criteria (acute phase of CML = 5, AML3 = 1; age > 61 = 2).

All patients received induction therapy according to:

1st randomisation: classical 3 + 7 (Dauno 60 mg/m2/d, ARAC 200 mg/m2/d CI) vs 5 + 7(Ida 8 mg/m2/d);

residual blasts in bone marrow at D15: if > 5%: second course with same anthracyclin 2 d + intermediate dose ARAC 1 g/m2 × 2/d for 4 days.

82% were considered in complete remission (CR) after 1 or 2 (26%) induction courses. At remission patients were allowed to following arms according to:

  1. presence of an HLA identical sibling: arm M) if age < 50: prompt bone marrow allograft with myeloablative conditioning regimen; arm m) if age > 50: peripheral blood stem cells (PBSC) allograft after reduced intensity conditioning regimen and previous intensive consolidation (IC) with HD ARAC; arm C) no allograft (and 2 IC with HD ARAC) if good prognosis (CBF AML and CR after 1 course)

  2. absence of such a donor and subsequent 2nd randomization: arm A) IC followed by single autologous PBSC autograft (Busulfan 16 mg/kg and HD Melphalan 140 mg/m2); arm B) IC followed by to 2 PBSC autografts ( HD Mel 200 mg/m2 then BuMel as previous arm)

Preliminary results were presented at the 2006 ASH meeting (Abstr 319 and 608). In the present study, we tried to establish prognostic value for DFS and OS of absolute lymphocyte count (ALC) at 1st CR: 629 patients were assessable for this analysis. Median follow up is 35 months. Median ALC was 1,17 +/− 0,74 (range 0,08–7,9).

In univariate analysis, patients with ALC at 1st CR above the median value have significant better DFS but no significant different OS (Logrank test). For patients not receiving allografts, this advantage remains significant for both DFS and OS. Best OS advantage was observed for good prognosis patients (CBF AML) as it was not significant for DFS and other prognostic groups according to cytogenetics.

 ALC above median ALC under median p 
All patients (n = 629) 
Median DFS undefined 30 months 0,038 0,08 
Median OS undefined 63 months  
Patients not receving an allograft ( n = 428) 
Median DFS undefined 21 months 0,041 0,039 
Median OS undefined 59 months  
Patients with CBF AML not receving an allograft ( n = 87) 
Median DFS undefined undefined 0,159 
Median OS undefined undefined 0,029 
 ALC above median ALC under median p 
All patients (n = 629) 
Median DFS undefined 30 months 0,038 0,08 
Median OS undefined 63 months  
Patients not receving an allograft ( n = 428) 
Median DFS undefined 21 months 0,041 0,039 
Median OS undefined 59 months  
Patients with CBF AML not receving an allograft ( n = 87) 
Median DFS undefined undefined 0,159 
Median OS undefined undefined 0,029 

Difference occurs as soon as soon as 12 months after diagnosis as shown in survival curves below (i.e. short term relapses).

Conclusions:

  1. these results confirm in a large prospective trial previous data establishing good prognostic value of higher ALC value at 1st CR of AML;

  2. this effect is mostly seen among patients not proceeding to allograft as consolidation for 1st CR and for patients with CBF AML;

  3. this may represent an immunological platform for other additional therapies with immunostimulant properties (as may be lenalinomide for example) applied during or soon after consolidation courses.

Disclosures: No relevant conflicts of interest to declare.

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