Allogeneic Stem Cell Transplantation with Reduced Intensity Conditionning Regimen (RIC) for Adult Patients with AML: Same Results in Secondary and De Novo AML.

We have evaluated the outcome of RIC in 114 adult pts with AML either de novo (74) or secondary to cancer or MDS (40). There were 43 men, median age was 55 yo (22–65). Cytogenetic was available in 104 and was abnormal in 55 (favorable: 13; intermediate: 21; poor: 21). Pts had received a median of 1 line of Tx before RIC (0–3). Twenty had a previous autologous transplant. At time of RIC, 28 patients were refractory or in relapse while 71 were in CR (1st: 48; 2d: 20). The donor was an id sib for 80 and a MUD in 34 (with1allelic mismatch in 6). The cond regimen was of Slavin type in 56, only 11 pts received the Seattle program. Overall 74 had ATG as part of cond reg. GVHD prophylaxis consisted of CSA or CSA-MTX in 95 pts, 14 had CSA-MMF.

With a median FU of surviving pts of 21 m (3–73) the 3y survival (OS) and EFS are 40% and 38% respectively. Sixty pts died with the main cause of death being relapse. The probability of TRM at 100 d and 1 y are 7% and 14% respectively. The 2y probability of relapse is 50%. These figures are strictly superimposable for pts with de-novo or secondary AML.

The factors affecting significantly (p<0.05) the 3y OS and EFS were: disease status at time of RIC (50% vs 0 to 24% in pts in CR vs not), the N° of previous lines of Tx (55% vs 0 to 24% after one line vs more), an id sib as donor ( 45% vs 32% for OS and 44% vs 19% for EFS), having an aGVHD grade 1 or 2 ( OS: 75% vs 25% if aGVHD grade 3–4 vs 38% if no aGVHD), and a CGVHD limited or extensive (OS: 50% or 78% respectively vs 29% if no CGVHD; EFS: 50% or 56% respectively vs 29% if no CGVHD). The single factors that affected the risk of relapse was the occurence of an acute and or chronic GVHD. The TRM was significantly increased in pts with previous autologous transplant, a MUD, an aGVHD and a female donor.

Conclusion: RIC allo is well tolerated ( max TRM :14% at 1 y) and allows the same result in de-novo and secondary AML. The best results are achieved in patients in CR1 ( 3y OS and EFS: 63% and 62% respectively) whatever was the type of donor. As most of the pts beyond CR1 were transplanted with a MUD, it is not possible to separate the negative impact of advanced disease or MUD. An active search of a donor at the time of diagnosis, particularly in patients with secondary AML, could allow early RIC with MUD in pts with an indication of allogeneic stem cell transplantation.