1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China 2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100044, China
The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n=47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms’ tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P=0.377) and 9.1% and 0.0% (P=0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P=0.891) and 84.3% and 84.6% (P=0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.
Median time from allo-HSCT to intervention, days (range)
192 (39–1016)
194 (84–1552)
0.625
Sex, male/female, n
22/11
9/5
1.000
WHO classification, n (%)
RCMD
5 (15.1)
1 (7.1)
0.708
RAEB-1
13 (39.4)
4 (28.6)
RAEB-2
15 (45.5)
9 (64.3)
Cytogenetic risk, n (%)
Good
1 (3.0)
1 (7.2)
0.094
Intermediate
28 (84.8)
8 (57.1)
Poor
4 (12.1)
5 (35.7)
Severe anemia, n (%)a
19 (57.6)
5 (35.7)
0.212
WPSS risk, n (%)
High
26 (78.8)
6 (42.9)
0.037
Very high
7 (21.2)
8 (57.1)
Chemotherapy prior to HSCT, n (%)
9 (27.3)
6 (42.9)
0.324
Disease status at transplantation, n (%)
CR
7 (21.2)
2 (14.3)
0.704
Non-CR
26 (78.8)
12 (85.7)
Donor type
HLA-identical sibling donor
11 (33.3)
7 (50.0)
0.464
HLA-haploidentical related donor
19 (57.6)
7 (50.0)
HLA-unrelated donor
3 (9.1)
0 (0.0)
Number of HLA-A, HLA-B, HLA-DR mismatches, n (%)
0
13 (39.4)
7 (50.0)
0.661
1
4 (12.1)
0 (0.0)
2
1 (3.0)
0 (0.0)
3
15 (45.5)
7 (50.0)
MRD status before immunotherapy, n (%)
MRDsin+b
18 (54.5)
0 (0.0)
<0.001
WT1 positive once
17 (51.5)
0 (0.0)
LAIPs positive once
1 (3.0)
0 (0.0)
MRDco+, two BM samples
12 (36.4)
6 (42.9)
WT1 positive twice
12 (36.4)
4 (28.6)
LAIPs positive twice
0 (0.0)
2 (14.3)
MRDco+, one BM sample
WT1 positive and LAIPs positive simultaneously
3 (9.1)
8 (57.1)
MRD level before immunotherapy, n (%) c
Low level
11 (33.3)
3 (21.4)
0.503
High level
22 (66.7)
11 (78.6)
Discontinuing immunosuppression before immunotherapy, n (%)
19 (57.6)
9 (64.3)
0.753
Median duration of follow-up after immunotherapy, days (range)
559 (77–1410)
498 (94–1685)
0.675
Tab.1
Fig.2
Fig.3
Outcome
HR (95% CI)
P
Treatment failure as defined by OS
Intervention type
IFN-a treatment
1
0.389
Chemo-DLI
0.38 (0.04–3.39)
Other significant factors
MRD status after intervention
Positive
1
Negative
0.12 (0.02–0.61)
0.011
Treatment failure as defined by DFS
Intervention type
IFN-a treatment
1
0.388
Chemo-DLI
0.52 (0.12–2.29)
Other significant factors
MRD status after intervention
Positive
1
Negative
0.21 (0.06–0.72)
0.014
Relapse
Intervention type
IFN-a treatment
1
0.519
Chemo-DLI
0.52 (0.07–3.87)
Non-relapse mortality
Intervention type
IFN-a treatment
1
0.241
Chemo-DLI
6.24 (0.29–133.69)
Other significant factors
MRD status after intervention
Positive
1
Negative
0.06 (0.01–0.65)
0.021
Tab.2
Fig.4
Fig.5
Fig.6
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