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Previous studies investigating the outcome of allogeneic hematopoietic cell transplantation (allo-HCT) in relapsed patients with acute myeloid leukemia (AML), have established that certain factors such as duration of first complete remission (CR1) or age at relapse, could predict the likelihood of CR2. Achieving CR2 has been shown to provide a benefit for subsequent allo-HCT.1
However, so far there are no available data from large series, which assess the impact of conditioning regimen intensity on the outcomes of HCT in patients with AML in CR2.
Maria H Gilleece, Leeds Teaching Hospitals Trust, Leeds, UK, and colleagues, conducted a study2 on behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Bone Marrow Transplantation (EBMT) to evaluate the difference between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) in patients with AML who were in CR2, including by age (<50 versus ≥50 years).
Two-year survival outcomes are shown in Table 1 (whole cohort) and Table 2 (by conditioning regimen).
|
Percentage (%) |
95% CI |
---|---|---|
LFS |
52 |
49.4-54.5 |
OS |
58.7 |
56.2-61.2 |
RI |
28.9 |
26.7-31.2 |
NRM |
19 |
17.2-21 |
GFRS |
38.7 |
36.2-41.1 |
cGvHD |
37.2 |
34.7-39.7 |
Extensive cGvHD |
15.9 |
14.1-17.8 |
|
LFS (%) |
OS (%) |
NRM (%) |
GRFS (%) |
---|---|---|---|---|
Patients <50 years old |
||||
MAC |
54 |
61 |
18 |
38 |
RIC |
54 |
62 |
15 |
42 |
p value |
0.61 |
0.7 |
Not reported (NR) |
NR |
Patients ≥50 years old |
||||
MAC |
52 |
58 |
27 |
42.4 |
RIC |
49 |
55 |
19 |
36 |
p value |
0.7 |
0.3 |
NR |
NR |
In order to assess the impact of conditioning regimens and other parameters on transplant outcomes, multivariate analysis was conducted (Table 3).
Factor |
Outcome |
Effect |
Hazard ratio (HR) and confidence interval |
p values |
---|---|---|---|---|
Conditioning regimen, RIC |
NRM |
Favored RIC |
0.65 (0.5–0.84)
|
0.001
|
Conditioning regimen RIC, and age ≥50 years |
NRM |
Favored RIC |
0.54 (0.38–0.76) |
<0.001 |
Conditioning regimen RIC, and age ≥50 years |
cGVHD |
Increased |
1.38 (1.03–1.85) |
0.03 |
Age <50 years |
GRFS |
Adverse |
1.13 (1.01–1.26) |
0.03 |
Age <50 years |
NRM |
Increased |
1.25 (1.01–1.53) |
0.034 |
Age ≥50 years |
NRM |
Increased |
1.6 (1.21–2.03) |
0.001 |
Karnofsky performance scores (KPS) >80% and age <50 years |
NRM |
Lowered |
0.447 (0.219–0.914) |
0.03 |
KPS >80% and age ≥50 years |
NRM |
Lowered |
0.265 (0.162–0.435) |
<10-5 |
KPS >80% and age ≥50 years |
aGvHD grade II-IV aGvHD grade III-IV |
Lowered
|
0.562 (0.322–0.982) 0.338 (0.152–0.748) |
0.043 0.007 |
KPS >80% and age ≥50 years |
OS LFS GRFS |
Improved |
0.437 (0.297–0.645) 0.486 (0.331–0.715) 0.363 (0.254–0.518) |
<10-4 <10-3 0.000 |
Longer interval from diagnosis to allo-HCT and age <50 years |
RI LFS OS GRFS |
Improved
|
0.96 (0.948–0.975) 0.982 (0.974–0.99) 0.982 (0.974–0.991) 0.991 (0.985–0.997) |
<10-5 10-5 <10-4 0.003 |
Longer interval from diagnosis to allo-HCT and age ≥50 years |
RI LFS OS GRFS |
Improved |
0.974 (0.963–0.986) 0.987 (0.98–0.995) 0.988 (0.98–0.996) 0.993 (0.986–1) |
10-5 0.001 0.002 0.037 |
Donor selection: MMVUD or Haplo-ID or donors and age <50 years |
NRM
|
Increased |
MMVUD: 1.986 (1.168–3.377) Haplo-ID: 2.096 (1.097–4.002) |
0.01 0.02 |
Donor selection: MMVUD or Haplo-ID or donors and age ≥50 years |
NRM
|
Increased |
MMVUD: 2.241 (1.419–3.539) Haplo-ID: 1.948 (1.069–3.552) |
0.001 0.029 |
Donor selection: MMVUD or Haplo-ID donors and age ≥50 years |
aGvHD grade II–IV |
Increased |
MMVUD: 2.685 (1.692–4.26) Haplo-ID: 2.434 (1.341–4.417) |
<10-4 0.003 |
Donor selection: MMVUD donors and age <50 years |
aGvHD grade II–IV |
Increased |
2.679 (1.721–4.17)
|
<10-4
|
Donor selection: female donors and age <50 years |
Extensive cGvHD |
Increased |
1.515 (1.047–2.194) |
0.028 |
Donor source: PBSC and age <50 years |
cGvHD |
Increased |
1.784 (1.253–2.539)
|
0.001 |
Donor source: PBSC and age ≥50 years |
cGvHD |
Increased
|
1.683 (1.08–2.624) |
0.021 |
Advantages |
Limitations |
---|---|
Wide range of regimens included |
Retrospective |
Long follow-up |
Only addresses patients in CR2 rather than relapse after CR1 |
Large sample size |
Unknown reasons that allo-HCT was used in CR2 |
The high relapse rates in patients with AML in CR2 indicate an unmet need for more active therapies.
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