Influence of Cytogenetic, Molecular Abnormalities and Other Risk Factors on the Outcomes of Children with Acute Myelogenous Leukemia Given An Unrelated Cord Blood Transplantation. A Survey on Behalf of Eurocord, ALWP and PDWP of EBMT
Bibliographic record
Abstract
Abstract Abstract 834 Several cytogenetic and molecular abnormalities have a major prognostic implication in patients with AML treated with conventional chemotherapy. However, the impact of such aberrations on outcomes after unrelated cord blood transplantation (UCBT) is, currently, unknown. The purpose of this study was to analyze the outcomes and prognostic factors after UCBT for paediatric AML, with a special emphasis on cytogenetic and molecular abnormalities. We performed a retrospective multicentre study on 390 AML children, who received a single UCBT. Transplants were performed from 1994 through 2010 in EBMT centers. Median age was 6 years and median weight 22 Kg at time of transplant. At time of UCBT, 37% of patients were in CR1, 42% in CR2 and 21% in a more advanced disease status. In addition to hematological disease status classification, 253 children (65%) were stratified in unfavourable (35%), intermediate (22%) and favourable (8%) groups based on cytogenetic and molecular biology whenever possible. The majority of grafts were HLA 5/6 (44%) or 4/6 (37%) and 5% of patients received UCBT as a second transplant. Median infused total nucleated (TNC) and CD34+ cells were 4.95×107/kg and 1.9 ×105/kg of recipient body weight, respectively. The majority of patients (86%) received myeloablative conditioning regimen with TBI (26%) or busulphan (60%); ATG was used in 80% of cases. GvHD prophylaxis was included CSA+steroids in 70%, CsA+MMF in 17% and MTX+ others in 8% of patients. Median follow-up time was 24 months. The median time to achieve neutrophil and platelet recoveries was 24 and 42 days, respectively. Cumulative incidence (CI) of ANC recovery was 85%; in a multivariate model, it was favourably associated with a higher TNC dose (> median, HR: 1.40, p=.008) and transplantation in CR1 (HR: 1.39, p=.015). At day +100, CI of grade II–IV acute GvHD was 34% (11% grade III, 5% grade IV). At 2 years, CI of NRM (Non Relapse Mortality) was 24%. Multivariate analysis showed that TNC dose (>median, HR: 0.58, p=.024) and disease status at time of UCBT (CR1-2, HR: 0.55, p=.026) were associated with decreased NRM. There was a trend towards a decreased NRM in patients transplanted with a 6/6 or 5/6 HLA graft (p=.06). CI of relapse at 2 years was 17% for patients transplanted in CR1, 26% in CR2 and 44% in more advanced disease. Estimated 2 y-LFS was 63% in CR1, 43% in CR2 and 22% in more advanced disease patients. There was a trend towards a better LFS in patients receiving an UCBT with TNC >4.9 107/kg (>median, HR: 1.38, p=.05). The multivariate analysis identified favorable cytogenetic and molecular risk group (HR: 2.14, p=.03) and disease status at time of UCBT (advanced, HR: 0.44, p<.001) as factors independently associated with LFS. Forty nine children transplanted in CR1 with unfavourable disease had LFS of 70 ± 7%, not statistically different from the overall CR1 group. For those transplanted in CR2, 2y-LFS was 71 ± 9%, 33 ± 9% and 40 ± 7% in the favorable, intermediate and unfavorable subgroups, respectively. Multivariate analysis demonstrated the following significant prognostic factors: favorable cytogenetic and molecular risk group (HR: 3.74, p=.005) and previous CR1 duration longer than 7 months (first quartile, HR: 1.85, p=.03). These data demonstrate that UCBT is an attractive stem cell source for children with AML when no HLA-identical donor is available. The cell dose remains an important factor for engraftment and NRM. The results are particularly encouraging for the use UCBT in patients with unfavorable cytogenetic and molecular biology risk classification diseases in CR1. Disclosures: Mohty: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".