Table 1 Key studies of hypomethylating agents as maintenance therapy in AML patients after allo-HSCT

Jabbour [14]

Retrospective, single arm

8 acute leukemia (7 AML, 1 ALL)

low-dose AZA daily × 5 days every 28 days for a median of 8 cycles

3/8 (37.5%)

5 alive with CR, 2 alive with leukemia

de Lima [15]

Phase I

45 high-risk AML/ MDS (37 AML, 8 MDS)

low-dose AZA daily × 5 days every 30 days for a maximum of 4 cycles

24/45 (53.3%)

1-year OS: 77%; 1-year LFS: 58%

Maples [18]

Retrospective, 2 arms

25 (18 AML, 7 MDS)

AZA 32 mg/m²/day × 5 days every 28 days for 4–6 cycles

16% (AZA) versus 14% (Control)

1-year OS: 60% (AZA) versus 64% (Control)

Oshikawa [19]

Retrospective, 2 arms

10 high-risk AML

AZA (30 mg/m²/day on days 1–7) and GO (3 mg/m² on day 8) every 4 weeks for up to 4 cycles

AZA-GO: 4/10 (40.0%)

AZA-GO versus Control

1-year OS: 70.0% versus 59.8%; 1-year LFS: 60.0% versus 42.8%

Pusic [16]

Phase I

22 (17 AML, 5 MDS)

DAC × 5 days every 6 weeks for a maximum of 8 cycles

2-year CIR: 28%

2-year OS: 56%; 2-year LFS: 48%

Ma [17]

Retrospective, 2 arms

21 high-risk AML

DAC 20 mg/m²/day × 5 days every 3 months for up to 4–6 cycles

3-year CIR: 5.9% (DAC) versus 45.3% (Control)

3-year OS: 92.9% (DAC) versus 51.8% (Control)

Platzbecker [20]

Phase II

24 high-risk AML or MDS with MRD-positive post-transplantation

preemptive therapy with AZA 75 mg/m²/day on days 1–7 of a 29-day cycle for a minimum of 6 cycles

8/24 (33.3%)

2-year OS: 62%; 2-year LFS: 54%,

de Lima [21]

Phase I/II

30 (26 AML, 4 MDS)

CC-486 daily × 7 days every 28 days for up to 12 cycles

1-year CIR: 21%

1-year OS in the 7-day and 14-day dosing cohorts of 86% and 81%

Gao [22]

Phase II RCT

202 high-risk MRD- negative AML (G-DAC: 100; Non-G-DAC: 102)

G-DAC: 5 mg/m² of DAC on days 1–5 and 100 mg/m² of rhG-CSF on days 0–5 every 6–8 weeks for up to 6 cycles; Non-G-DAC: no intervention

2-year CIR: 15.0% (G-DAC) versus 38.3% (Non-G-DAC)

G-DAC versus Non-G-DAC

2-year OS: 85.8% versus 69.7%; 2-year LFS: 81.9% versus 60.7%