Influence of Stem Cell Source (bone marrow versus peripheral blood) on Outcome after Reduced-Intensity Conditioning Regimens for Acute Leukemia- a Report from the Acute Leukemia Working Party of the EBMT

Background:  Patients (pts) with acute leukemia are increasingly receiving RIC allo-SCT. Previously we have shown that peripheral blood (PB) or bone marrow (BM) grafts are associated with similar outcome after RIC MRD or MUD allo-SCT for AML in remission. In current analysis we have expanded study populations to include transplants until 2012 from matched and mismatched (MM) donor in both AML and ALL at any disease stage at transplant.

Methods: Pts who underwent related or unrelated donor RIC PB or BM transplant from Jan 2000 to Dec 2012 were included in the study. All unrelated donors were HLA-allele matched (10/10) or 1 allele MM (9/10) (-A, -B, -C, DRB1, -DQB1). Survival (OS) and DFS were estimated by Kaplan-Meier. Relapse incidence (RI), NRM, engraftment, acute and chronic GVHD were calculated using cumulative incidence (CInc) methods. Risk factors for outcomes were analyzed by Cox and Fine models.

Results: 837 pts transplanted with BM and 9011 with PB after RIC regimens were compared. Among related donor, 5139 (52.6%) were geno-identical (BM=388, PB=4751) and 538 (5.5%) were MM (BM=122, PB=416). Of unrelated donor, 3114 (31.6%) were 10/10 matched (BM=220, PB=2894) and 1057 (10.7%) were 9/10 MM (BM=107, PB=950). Median follow-up was 27 months for entire cohort (BM 29, PB 27; p=0.27).  8777 (89.1%) pts had AML (BM=702, PB=8075) and ALL 1071 (10.9%) (BM=135, PB=936). 5668 pts were in CR1 (BM=475, PB=5193), CR2+ 1690 (BM=177, PB=1513) and 2490 had advanced disease (BM=185, PB=2490). There were no statistically significant differences in cytogenetic risk categories among AML or ALL for pts receiving BM or PB allo-SCT. CInc of engraftment was lower in BM pats, 88 vs. 95.4% (p<0.0001). Grade II-IV aGVHD was lower in BM (19.4%) vs. 23.8% in PB (p=0.005). cGVHD was more frequent after PB (36.2 vs. 28.9%, p=0.0003). RI was significantly higher among BM recipients (43 vs. 35.4%, p=0.0004) whereas NRM was not significantly different with the either stem cell source (p=0.19). In multivariate analysis, OS (HR 0.90, 95% CI 0.81-1.0; p=0.05) and DFS (HR 0.88, 0.79-0.97; p=0.01) were higher in pts transplanted with PB compared to BM. Furthermore, PB was also associated with decreased risk of relapse (HR 0.78, 95%CI 0.69-0.88; p=0.00006).NRM was not significantly different between BM and PB and cGVHD was significantly lower after BM grafts (HR 1.38, 95%CI 1.18-1.61; p=0.00008). When analyzing separately ALL and AML pts, multivariate analysis showed PB grafts was significantly associated higher LFS for AML, but not for ALL and no significant difference OS between PB and BM groups.

Conclusion: Despite the limitation of a retrospective registry based study, our study shows that transplants with PB from matched or MM related or unrelated donor after RIC gives the best outcomes. However, increased risk of cGVHD after PB grafts is alarming and long term follow-up is needed to see if cGVHD related deaths might increase risk of late NRM.