Mobilized Peripheral Blood Stem Cells (PBSC) Compared with Bone Marrow (BM) as the Stem Cell Source for Unrelated Donor Allogeneic Transplantation with Reduced Intensity Conditioning (RIC-alloSCT) in Patients with Acute Myeloid Leukemia (AML) in Complete Remission (CR): a Retrospective Analysis From the ALWP of EBMT.
Authors: Nagler Arnon , Labopin Myriam , Shimoni Avichai , Niederwieser Dietger , Basara Nadezda , Mufti Ghulam J , Zander Axel R. , Arnold Renate , Greinix Hildegard , Cornelissen Jan J. , Jackson Graham H , Craddock Charles , Bunjes Donald W. , Ganser Arnold , Russell Nigel H. , Kyrcz-Krzemien Slawomira , Mohty Mohamad , Rocha Vanderson 
Published: October 2019

Abstract
Abstract 527
RIC-alloSCT is being increasingly used for AML patients with high comorbidities not eligible for standard myeloablative conditioning. Few published data advocate the use of PBSC instead of BM in RIC in the HLA identical sibling setting, however only scarce data is availabel in RIC-alloSCT using unrelated donors. Moreover, sometimes volunteer donors are reluctant to use G-CSF. Therefore, we compared outcomes of PBSC vs. BM RIC-alloSCT, using the EBMT ALWP data set. Between 2000 and 2008, 803 patients with AML in CR underwent RIC-alloSCT from HLA compatible unrelated donors with PBSC (690) or BM (113) grafts. Recipient‘s age was higher in the PBSC vs. BM groups 57y (range, 19-77) and 52y (range, 18-76), respectively (P<0.0001), while gender was comparable between the 2 groups. Leukemia features were also comparable between the PBSC vs. BM groups, such as WBC at diagnosis (10.4×109/L vs. 8.6×109/L), cytogenetics–good risk (6.7% vs. 9.6%), intermediate risk (73.9% vs. 75%) and poor risk (19.4% vs. 15.4%) as well as for FAB classification. Disease status at RIC-alloSCT was not statistically different between the 2 cohorts: in the BM group 57% were in first CR and 43% in second CR compared to 64% and 36% in the PBSC group, respectively (p=0.13). Time from diagnosis to transplant was 239d in PBSC group vs. 332d in the BM group (P<0.0001) and low-dose TBI-based conditioning was more frequently used in PBSC (33.2%) compared to 6.2% in the BM group (P<0.0001). Donor gender and CMV serostatus were not statistically different in both groups. There was a difference in year of transplant as it was 2006 (2000-2008) vs. 2005 (2000-2008) for the PBSC vs. BM RIC-alloSCT (P<0.001). Results: Engraftment was achieved in 95% of the patients in both groups. Acute GVHD grade > II was significantly higher in the PBSC group, 28% compared to 12% in BM group, (P<0.0001). Similarly, chronic GVHD (2y) was higher in the PBSC with 55±3% vs. 48±9% in the BM group, respectively (P=0.05). The 2-year probabilities of LFS and relapse incidence were 44±3% and 38±3% for the PBSC transplants in comparison to 42±6% and 51±7%, for the BM group (NS), while, non relapsed mortality was significantly higher for the PBSC vs. BM group, 29±3% vs. 14±5%, respectively (P=0.007). In multivariate analysis, after statistical adjustments of differences, the PBSC group was associated with a higher incidence of aGVHD (II-IV) (HR=3.2, p=0.01), higher NRM (HR=2.6, p=0.005), a trend of decreased relapse incidence (HR 1.47, p=0.06) and no statistical difference of LFS between the two groups (p=0.62). In conclusion: 1) The vast majority (86%) of the unrelated RIC - alloSCT for AML performed in Europe are from PBSC rather than from BM grafts. 2) Our results indicate significantly higher incidence of acute GVHD and NRM, but not statistically different LFS comparing unrelated PBSC to BM grafts following RIC conditioning. Therefore, there is no disadvantage for using unrelated BM rather than unrelated PBSC grafts in the RIC-alloSCT setting. Whether PBSC should be preferred in advanced phase of the disease, where outcome is dominated by relapse incidence, need to be further investigated.

Disclosures:
No relevant conflicts of interest to declare.