Comparison of Busulfan and Cyclophosphamide (Bu-Cy)-Based Standard Myeloablative Conditioning (MAC) Vs. Fludarabine and Busulfan (Flu-Bu)-Based Reduced-Intensity Conditioning (RIC) Prior to Allogeneic Stem Cell Transplantation (allo-SCT) From An HLA Identical Sibling Donor for Acute Myeloid Leukemia (AML) Patients in First Complete Remission (CR1) Aged >40 Years: a Retrospective Analysis From the Acute Leukemia Working Party of EBMT.
Authors: Mohty Mohamad , Labopin Myriam , Socié Gerard , Milpied Noel-Jean , Attal Michel , Blaise Didier , Ringden Olle , Brown Paul , Lorentz Brinch , Brune Mats L , Hamladji Rose-Marie , Duarte Rafael F , Nagler Arnon , Rocha Vanderson 
Published: October 2019

Abstract
Abstract 3364
Poster Board III-252
RIC allo-SCT is an attractive treatment modality for AML patients not eligible for standard MAC regimens. While comorbidities may represent an obstacle to the use of a MAC regimen irrespective of age, most centres usually use an age threshold around 50 years for the use of a RIC regimen. Since RIC regimen proved to significantly decrease early non-relapse mortality (NRM) after allo-SCT, investigators are currently tempted by the use of RIC regimens in lower age groups with the aim to decrease NRM and optimize allogeneic immunotherapy.
The aim of this analysis was to compare outcomes (leukemia-free survival: LFS, NRM, and relapse incidence) between patients receiving the classical Bu-Cy MAC regimen vs. patients receiving a Flu-Bu RIC regimen prior to allo-SCT. Since the use of RIC in young patients is still limited, the analysis was restricted to patients aged >40 years, who were transplanted using an HLA identical sibling donor for AML in CR1.
Between 2000 and 2008, 452 patients with AML in CR1 were treated with standard MAC Bu-Cy and 376 received a Flu-Bu RIC regimen, and reported to the EBMT Registry. Patients received either allogeneic PBSC or BM from HLA-identical sibling donors.
As expected, patients receiving the RIC regimen were older (median: 56 y. vs. 47 y.; p<0.0001), but the median time from CR1 to allo-SCT was shorter (99 days vs. 111 d.; p<0.0001) in the MAC group. Both groups were comparable in terms of period (median year: 2005) of allo-SCT, and donor-recipient gender distribution. In terms of AML-related risk factors, WBC, cytogenetics risk groups (good: 4.1%; intermediate: 84.1%; and poor: 11.7%), and the FAB subtype (M1-M2: 50.1%; M3: 1.2%; M4-M5: 36.1%; M0-M6-M7: 12.6%) at diagnosis, were also comparable between both groups.
With a median follow-up of 13 (range, 1-100) months, the 3 years probabilities of LFS were 54±3% and 49±3% in the MAC and RIC groups respectively (p=0.32). The absence of difference in LFS is explained by a lower relapse incidence in the MAC group (25+/-3% vs. 39±3%; p<0.0001), but a higher rate of NRM (28±3 vs. 20±3%; p=0.004). However, when comparing the outcome of patients aged from 40 to 50 y. (n=351; 43%) and those aged >=50 y., the picture was different. In the 40-50 age group, LFS was 55±3% vs. 37±8%, p=0.049; relapse: 26±3 vs. 53±8%, p<0.0001; NRM: 25±3 vs. 21±9%, p=0.29, in the MAC and RIC groups respectively. On the other hand, in the >=50 y. age group, LFS was 52±5 vs. 51±3%, p=0.75; relapse: 23±5 vs. 36±3%, p=0.014; NRM: 33±4 vs. 20±3%, p=0.001, in the MAC and RIC groups respectively.
In summary, in this specific setting of AML in CR1, LFS is not statistically different when using MAC or RIC allo-SCT for patients older than 50 years. However, for younger patients (40-50 y. age group), the use of RIC is associated with a higher relapse rate. Prospective trials addressing the use of RIC in patients younger than 50 years are needed. Indeed, reducing toxicity without compromising disease control could be of significant benefit to many patients, but MAC (or “more intensive” RIC regimens as being tested prospectively at present), despite the hazard of increased toxicity, may be necessary in others. Thus, the trade-off between dose intensity, toxicity, and disease control will remain to be assessed for each individual patient.

Disclosures:
No relevant conflicts of interest to declare.