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PBSC with ATG vs. BM
ther investigated whether there was a statistical interac- tion between the use of TBI in the conditioning regimen and the impact of graft type on relapse risk. Among patients given graft from MSD, there was no such interac- tion (P-value for the interaction test = 0.97).
The 2-year CI of NRM was 11.5% in both groups (Figure 1D). In multivariate analyses, PBSC with ATG was associated with a similar risk of NRM to BM (HR=1.1, 95% CI: 0.8-1.4, P=0.7). In contrast, older age at transplan- tation (HR=1.5, 95% CI: 1.4-1.7, P<0.001) and secondary versus de novo AML (HR=1.5, 95% CI: 1.0-2.1, P=0.03) were associated with a higher NRM while a more recent year of transplantation was associated with a lower NRM (HR=0.7, 95% C1: 0.6-0.8, P<0.001).
OS and LFS
The 2-year OS and LFS were 70% (95% CI: 68-73%) and 64% (95% CI: 62-66%) in BMT without ATG patients versus 68% (95% CI: 64-71%, P=0.1) and 61% (95% CI: 58-64%, P=0.06) in PBSC with ATG patients, respectively (Figure 1A-B). After adjusting for potential confounding factors by multivariate analyses, the use of PBSC with ATG was no different to BM with respect to OS (HR=1.0, 95% CI: 0.8-1.2, P=0.8) and LFS (HR=1.0, 95% CI: 0.8-1.2, P=0.9). In contrast, second CR at trans- plantation (HR=1.3, 95% CI: 1.0-1.5, P=0.03), and older patient age (HR=1.2, 95% CI: 1.1-1.3, P<0.001) were asso- ciated with worse OS. The same factors were also signif- icantly associated with worse LFS: second CR at trans- plantation (HR=1.2, 95% CI: 1.0-1.5; P=0.04), and older patient age (HR=1.2, 95% CI: 1.1-1.2, P<0.001).
GRFS
At 2 years, GRFS was 50% (95% CI: 48-53%) in BMT without ATG patients versus 52% (95% CI: 48-55%) in the PBSC with ATG group (P=0.8) (Figure 1F). This was con- firmed on multivariate analysis including data from all patients (HR=0.9, 95% CI: 0.8-1.1, P=0.5) as well as in fur- ther sensitivity analysis restricted to patients given a com- bination of a calcineurin inhibitor and methotrexate as GvHD prophylaxis (HR=1.0, 95% CI: 0.8-1.2, P=0.9). In contrast, female donor to male recipient (HR=1.2, 95% CI: 1.0-1.3, P=0.01), and older patient age (HR=1.1, 95% CI: 1.1-1.1, P<0.001) were associated with a worse GRFS.
BM without ATG versus PBSC with ATG in MUD recipients
Patients
P<0.001). No other factor was significantly associated with grade II-IV aGvHD in multivariate analysis (Online Supplementary Table S4).
The 2-year CI of cGvHD was 43% (95% CI: 37-49%) in BM without ATG recipients versus 30% (95% CI: 28-32%) in PBSC with ATG patients (P<0.0001) (Figure 2E). On multivariate analysis, PBSC with ATG, in comparison to BM without ATG, was associated with a lower incidence of cGvHD (HR=0.6, 95% CI: 0.5-0.8, P=0.0006) (Table 2), but no other factor was significantly associated with cGvHD.
Relapse and non-relapse mortality
The 2-year CI of relapse was 23% (95% CI: 19-29%) in BMT without ATG recipients versus 24% (95% CI: 23- 26%) in PBSC with ATG patients (P=0.4) (Figure 2C). On multivariate analysis, as observed in the MSD cohort, there was no significant impact of the graft type on relapse (HR=1.0, 95% CI: 0.8-1.3, P=0.9), but a more recent trans- plantation was significantly associated with a higher risk of relapse (HR=1.2, 95% CI: 1.0-1.4, P=0.03) (Online Supplementary Table S1). There was no interaction between the association of graft type and the risk of relapse and year of transplantation (interaction test P=0.13). Unadjusted comparison of relapse incidence between the two groups per 6-year periods is shown in the Online Supplementalry Table S2. We further investigated whether there was a sta- tistical interaction between the use of TBI in the condition- ing regimen and the impact of the graft type on the relapse risk. Among patients given graft from MUD, there was such an interaction (P-value for the interaction test=0.05). Specifically, in the subgroup of patients given TBI-based
Table 2. Outcomes (multivariate Cox models).
ìOutcomes
MSD
Grade II-IV acute GvHD
Chronic GvHD
Relapse incidence
Non relapse mortality Leukemia-free survival
Overall survival
GvHD-free and relapse-free survival
MUD
Grade 2-4 acute GvHD
Chronic GvHD
Relapse incidence
Non relapse mortality
Leukemia-free survival
Overall survival
GvHD-free and relapse-free survival2
HR (95% CI) PBSC P
with ATG vs BMT without ATG
value1
A total of 2,621 recipients met the inclusion/exclusion criteria. Comprising 303 patients in the BM group and 2,318 in the PBSC with ATG group (Table 3). In compari- son to BM recipients, PBSC with ATG patients were older (median 48 years vs. 42 years old), were transplanted more recently (median year of transplantation 2013 versus 2012) and were more frequently transplanted in the first CR (79% vs. 71%).
GvHD
The 100-day incidence of grade II-IV aGvHD was 44% in BMT without ATG recipients vs. 24% in PBSC with ATG recipients (P<0.0001). For grade 3-4, the figures were 17% (95% CI: 13-21%) and 7% (95% CI: 6-8%), respec- tively (P<0.001). In multivariate analysis, PBSC with ATG patients had a significantly lower incidence of grade II-IV aGvHD than BM recipients (HR=0.5, 95% CI: 0.4-0.7;
0.82 (0.64-1.05) 0.12 0.74 (0.59-0.93) 0.01 0.96 (0.79-1.16) 0.64 1.07 (0.79-1.44) 0.68 0.99 (0.84-1.16) 0.89 0.97 (0.81-1.16) 0.75 0.94 (0.81-1.1) 0.45
0.54 (0.41-0.71)
0.62 (0.47-0.81)
<0.001 <0.001
0.99 (0.77-1.27) 0.93
0.72 (0.50-1.02) 0.07
0.87 (0.72-1.06) 0.17
0.80 (0.65-0.99) 0.04
0.76 (0.64-0.90) 0.001
HLA: human leucocyte antigen; MSD: HLA-identical sibling donor; MUD: 10/10 HLA-
matched unrelated donors; HR: hazard ratio; CI: confidence interval; BM: bone mar-
row; BMT: bone marrow transplant; PBSC: peripheral blood stem cells; ATG: anti-thy-
mocyte globulin; GvHD: graft-versus-host disease.1Factors included in the models are:
disease status at transplantation, female donor to male recipient or not,
cytomegalovirus (CMV) serostatus, use or not of total body irradiation (TBI), year of
transplantation, age at transplantation, primary versus secondary acute myeloid 2
leukemia (AML), cytogenetic risk and frailty center effect; defined as no death, no relapse, no grade III-IV acute GvHD and no extensive chronic GvHD.
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