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J. Woo et al.
trend toward higher relapse incidence in patients given pre-HCT intensive cytotoxic chemotherapy and hypomethylating agents, and toward lower relapse inci- dence with achievement of complete remission at trans- plant (Table 3). Year of transplant did not have an influ- ence on relapse incidence, overall survival (Table 3), or NRM (for years 2000-2010: HR, 0.7; 95% CI: 0.38-1.50; P=0.57; for years after 2010: HR, 1.05; 95% CI: 0.49-2.25; P=0.60).
Mutational landscape
In a subcohort of 52 patients for whom pre-transplant bone marrow samples were available, we carried out a mutational analysis of 75 genes. At least one somatic mutation was identified in 44 of the 52 patients (85%) (median number/patient = 5; range, 0–21) (Online Supplementary Figure S2 and Online Supplementary Tables S1 and S2). The most common mutations were those in ASXL1 (52%), TET2 (42%), and SRSF2 (25%), consistent
Table 3. Univariate regression analyses. Parameter
Conditioning by intensity Myeloablative conditioning Reduced-intensity conditioning
Age at transplant <55years 55+ years
CMV serostatus
Recipient –ve and Donor –ve Recipient +ve or Donor +ve
Sex match Others
Female to male
HCT-CI 0,1 2,3
4+
Interval (diagnosis to transplant) <6months
6–18 months
> 18 months
Pre-transplant therapy† Supportive care
Low intensity
Induction chemo ± HMA HMA
Status at transplant Non-complete remission Complete remission
Individual mutations
ASXL1 TET2 RUNX1 SETBP1 NRAS WT1 ATRX
Overall survival (mortality) Relapse/progression N. HR(95%CI) P HR(95%CI) P
103 23
62
67
32 95
90
37
31 47 45
29 66 34
32 34 38 25
64
64
27 22 9 5 6 10 6
15
12,3,4,6 10
7
16, 11, 10, 4, 4, 7
1
1.10 (0.7–1.9) 0.71 1.32 (0.6–2.8) 0.46
1 1
1.13 (0.7–1.7) 0.57
1
1.11 (0.7–1.8) 0.67
1
0.94 (0.6–1.5) 0.78
1
1.10 (0.6–1.9) 0.73 1.99 (1.2–3.4) 0.01
0.95 (0.5–1.8) 0.88
1
0.92 (0.5–1.8) 0.81
1
0.48 (0.2–1.1) 0.07
1
0.94 (0.4–2.0) 0.87 1.08 (0.5–2.4) 0.84
1 1
1.02 (0.6–1.7) 0.95
1.34 (0.7–2.4) 0.33
1
1.01 (0.6–1.8) 0.99 1.31 (0.7–2.3) 0.36 1.37 (0.7–2.6) 0.32
1
1.00 (0.7–1.5) 0.99
1.4 (0.7–2.8) 0.33 1.8 (0.9–3.6) 0.10 1.1 (0.4–2.6) 0.90 0.8 (0.2–2.6) 0.67 1.9 (0.7–5.1) 0.22 4.3 (1.7–11) 0.004 4.9 (1.8–13) 0.005
1.5 (0.7–3.2) 0.30
1.2 (1.0–1.5) 0.09 1.5 (0.7–3.4) 0.33
2.3 (0.9–5.9) 0.09
1.1 (0.9–1.3) 0.58
0.97 (0.4–2.2) 0.93
1.72 (0.7–4.1) 0.22
1
1.87 (0.7–5.1) 0.22 2.23 (0.9–5.9) 0.09 2.28 (0.8–6.4) 0.12
1
0.58 (0.3–1.1) 0.1
1.1 (0.4–3.0) 0.89 1.6 (0.6–4.6) 0.40 1.9 (0.6–6.1) 0.29 0.6 (0.1–4.3) 0.54 4.7 (1.4–16) 0.03 6.3 (1.6–24) 0.01
Total number of mutations
≥10
17.3 (4.1–73)
3.4 (1.2–9.6) 0.02
1.5 (1.1–2.0) 0.02
0.0005
Functional groups‡
Epigenetic
Trend over 0, 1, 2, 3, 4, 5+ mutations
16, 11,
≥4
Tumor suppressor
5.4 (1.9–16)
0.003
Presence
Signaling
Trend over 0, 1, 2, 3, 4, 5+ mutations
3.1 (0.8–11) 0.13
1.1 (0.8–1.5) 0.57
*According to Such E, et al.28 †Supportive care includes transfusion, treatment with granulocyte colony-stimulating factor and erythropoiesis-stimulating agents. Low intensity treatments include hydroxyurea,lenalidomide,steroids,azathioprine,imatinib,and ruxolitinib. Hypomethylating agents include azacitidine and decitabine.‡According to Online Supplementary Table S1. HR: hazard ratio; 95% CI: 95% confidence interval; CMV: cytomegalovirus; HCT-CI: Hematopoietic Cell Transplantation - Comorbidity Index: HMA: hypomethylating agents.
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