Tuesday, March 28, 2023
| Patients | ||
|---|---|---|
| Characteristic | n | % |
| Full cohort, n | 295 | 100 |
| Recipient age, median (range) | 66 (6-76) | |
| Recipient sex | ||
| Female | 117 | 40 |
| Male | 178 | 60 |
| HCT-CI score | ||
| 0 | 83 | 28 |
| 1-2 | 81 | 27 |
| 3+ | 120 | 40 |
| Missing | 11 | 4 |
| Type of AML (clinically defined) | ||
| De novo | 173 | 59 |
| Secondary | 91 | 31 |
| Therapy-related | 31 | 11 |
| Cytogenetics* | ||
| Normal | 136 | 46 |
| Core binding factor | 6 | 2 |
| Complex karyotype | 41 | 14 |
| Other | 112 | 38 |
| 2017 ELN risk group | ||
| Favorable | 53 | 18 |
| Intermediate | 85 | 29 |
| Adverse | 152 | 52 |
| Missing | 5 | 2 |
| Initial therapy | ||
| Intensive induction | 249 | 84 |
| Non-intensive induction | 46 | 16 |
| Reinduction | ||
| Yes | 90 | 31 |
| No | 204 | 69 |
| Missing | 1 | 0.3 |
| Remission quality | ||
| CR with hematologic recovery | 225 | 75 |
| CRi | 67 | 23 |
| Missing | 1 | 0.3 |
| Donor type | ||
| Matched related | 54 | 18 |
| Matched unrelated | 154 | 52 |
| Mismatch related | 7 | 2 |
| Mismatch unrelated | 29 | 10 |
| Haploidentical | 51 | 17 |
| Conditioning regimen | ||
| Myeloablative | 28 | 9 |
| Reduced intensity | 267 | 91 |
| T-cell depletion | 25 | 9 |
| Stem cell source | ||
| Peripheral blood | 216 | 73 |
| Bone marrow | 71 | 24 |
| Umbilical cord blood | 8 | 3 |
Table 1. Cohort characteristics
Shown are the pretransplant characteristics of the 295 patients included in the cohort. HCT-CI: hematopoietic cell transplant comorbidity index score. CRi denotes complete remission with incomplete recovery of at least 1 hematopoietic cell lineage.
ELN, European Leukemia Network.
* Core binding factor: inv(16) or t(8;21); complex karyotype: 3 or more chromosomal abnormalities within a single clone.
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Patients who were diagnosed with AML at age ≥60 and underwent allogeneic transplantation in CR1, with or without hematologic recovery (CR or CR with incomplete recovery [CRi]) at 1 of 6 participating centers (Dana-Farber Cancer Institute, Johns Hopkins University, Memorial Sloan Kettering Cancer Center, The Ohio State University, Roswell Park Comprehensive Cancer Center, and the University of Pennsylvania) were eligible for inclusion (supplemental Table 1 available on the Blood Web site). Patients with acute promyelocytic leukemia or isolated extramedullary disease were excluded. Conditioning regimens and graft-versus-host disease prophylaxis strategies were administered according to the discretion of the treating physician. A total of 295 patients met the inclusion criteria and had a banked bone marrow or peripheral blood sample collected before the initiation of induction chemotherapy. Of those, 192 (65.1%) also had a sample collected in CR1 before transplant. The median age at the time of AML diagnosis was 66 years (range, 60-76). The median follow-up time for survivors was 44 months (range, 6.7-155.3), median time from diagnosis to transplant was 4.8 months (range, 1.9-21), and median time to relapse after transplant was 4.8 months (range, 1-60.8). For patients with remission samples, the median time from remission sample collection to transplant was 2.5 months (range, 0.1-14). Most patients in the remission cohort (121 of 192) received consolidation after CR1 and before transplantation. Five of the 40 patients in the remission cohort with a FLT3-internal tandem duplication (ITD) received a FLT3 inhibitor as part of their consolidation therapy. Additional characteristics of the 295 included patients are reported in Table 1, and a comparison of baseline characteristics between those with and without a remission sample is shown in supplemental Table 2. The study was conducted with the approval of and with waivers of consent from the institutional review boards at the respective institutions.
For diagnostic samples, we performed targeted sequencing of 113 genes known to be recurrently mutated in AML or in germline syndromes predisposing to development of myeloid malignancies (supplemental Table 3). For remission samples, we performed duplex unique molecular identifier-tagged targeted sequencing of 76 genes recurrently mutated in myeloid malignancies (supplemental Table 4). We classified variants as pathogenic on the basis of accepted genetic criteria.[15] Annotation of mutations was blinded to clinical characteristics and genetic analysis was locked before merging with clinical data. For remission samples, we performed initial mutation annotation blinded to diagnostic sequencing results, then assessed each remission sample for the presence or absence of mutations present in the paired diagnostic sample (supplemental Table 5).
The primary end point was leukemia-free survival (LFS), defined as the time from transplantation until death or relapse of the original AML, whichever occurred first. Overall survival (OS) was defined as the time from transplantation until death from any cause or until censoring at the time last known to be alive. OS and LFS were estimated by the Kaplan-Meier method, and the difference was determined with log-rank tests. Cumulative incidences of NRM and relapse were estimated in competing risk frameworks that treated relapse and NRM as competing events and were compared using the Gray test. Multivariable analysis was performed with Cox models for OS and LFS and Fine and Gray models for NRM and relapse. Risk groupings were derived from the results of univariable and multivariable models. Additional details are provided in the supplemental methods.
