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Secondary acute myeloid leukemia (sAML) evolves from underlying hematological conditions, such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN) and bone marrow failure disorders. sAML can also arise following subjection to radio- or chemotherapy, resulting in a unique subtype known as therapy related AML (tAML).1
Relative to de novo AML, the prognosis of sAML is poor, and patients respond inadequately to conventional chemotherapy and autologous stem cell transplants (auto-SCT). The front-line therapy for sAML is allogenic SCT (allo-SCT), however many patients lack human leukocyte antigen identical siblings.2
It remains unanswered whether sAML is, itself, a contributor to poor outcomes following allo-SCT. The Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT) aimed to address this question; conducting a retrospective comparison of patient outcomes following allo-SCT for the treatment of sAML vs de novo AML. Ann-Kristin Schmaelter and coinvestigators published the findings in Blood Cancer Journal and the AML Hub hereby presents a summary.2
Table 1. Baseline characteristics for patients receiving allo-SCT for the treatment of de novo AML and sAML
allo-SCT, allogenic stem cell transplantation; AML, acute myeloid leukemia; CR1/2, first/second complete remission; MAC, myeloablative conditioning; MSD, matched sibling donor; PIF, primary induction failure; RIC, reduced-intensity conditioning; sAML, secondary AML; SCT stem cell transplantation; UD, unrelated donor *Allele compatibility for the human leukocyte antigen (HLA) † Nine out of ten donor allele match to HLA |
||
Characteristic, p < 0.001 |
De novo AML (n = 11,439) |
sAML (n = 1325) |
---|---|---|
Median age at SCT, years (range) |
49.3 (18–76.8) |
57.7 (18.3–76) |
Status at SCT, % CR1 CR2 PIF Relapse |
67.23 18.64 5.31 8.82 |
68.6 7.02 15.02 9.36 |
Donor MSD UD 10/10* UD 9/10† Haploidentical donor |
55.99 28.68 9.05 6.28 |
43.62 39.09 10.49 6.79 |
Cytogenetics Favorable Intermediate Adverse |
13.04 68.27 18.69 |
4.38 63.09 32.53 |
Graft source Bone marrow Peripheral blood |
17.53 82.47 |
12.23 87.77 |
Conditioning regimen MAC RIC |
55.13 43.32 |
44.87 56.68 |
Table 2. Patient outcomes to allo-SCT by diagnosis
allo-SCT, allogenic stem cell transplantation; AML, acute myeloid leukemia; aGvHD, acute graft-versus-host disease; cGvHD, chronic GvHD; GRFS, GvHD/relapse-free survival; LFS, leukemia free survival; OS, overall survival; RI, incidence of relapse; sAML, secondary AML; SCT stem cell transplantation |
||
Outcome, % |
De novo AML (n = 11,439) |
sAML (n = 1325) |
---|---|---|
Engraftment |
98.2 |
96.6 |
Patient outcome at 3 years OS LFS NRM RI GRFS |
54.6 48.9 18 33 34.3 |
43.1 37.9 24.8 37.3 25.8 |
Grade 3–4 GvHD aGvHD cGvHD |
23.5 40.6 |
24.4 35.4 |
Table 3. The 3-year outcomes of patients receiving allo-SCT during CR1
AML, acute myeloid leukemia; CR1, first complete remission; GRFS, graft-versus-host disease (GvHD)/relapse-free survival; LFS, leukemia free survival; OS, overall survival; sAML, secondary AML |
|||
Outcome, % |
De novo AML (n = 11,439) |
sAML (n = 1325) |
p |
---|---|---|---|
OS |
60.8 |
46.7 |
< 0.00001 |
Relapse |
28.5 |
35 |
0.000086 |
NRM |
16.4 |
23.4 |
< 0.00001 |
LFS |
55.1 |
41.6 |
< 0.00001 |
GRFS |
38.6 |
28.4 |
< 0.00001 |
Table 4. Multivariate analysis of patients receiving allo-SCT during CR1
CI, confidence interval; GRFS, graft-versus-host disease (GvHD)/relapse-free survival; HR, hazard ratio; LFS, leukemia free survival; NRM, non-relapse mortality; OS, overall survival; RI, incidence |
|||
Outcome |
HR |
95% CI |
p |
---|---|---|---|
OS |
1.33 |
1.21–1.48 |
< 0.00001 |
LFS |
1.32 |
1.19–1.45 |
< 0.00001 |
GRFS |
1.20 |
1.10–1.31 |
< 0.0001 |
NRM |
1.37 |
1.17–1.59 |
< 0.001 |
RI |
1.27 |
1.12–1.44 |
< 0.0001 |
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