Chronic Graft-Versus-Host Disease and Its Association with Treatment-Related Mortality, Relapse, Leukemia-Free and Overall Survival After Umbilical Cord Blood Transplantation (UCBT) In Children and Adolescents with Acute Leukemia
Bibliographic record
Abstract
Abstract Abstract 213 Chronic graft-versus-host disease (cGVHD) is the leading cause of late transplant-related mortality (TRM) after unrelated adult donor transplantation. However, limited, mild or moderate cGVHD may be associated with higher survival in part due to an association with lower relapse risk in adults with acute and chronic leukemia. While cGVHD rates are generally lower in children, we sought to determine the impact of cGVHD after UCBT on risk of relapse, TRM, leukemia-free survival (LFS) and overall survival (OS) as well as to identify risk factors for cGVHD after UCBT. Patients <18 years with acute lymphoblastic or acute myeloblastic leukemia transplanted with a single UCB unit after myeloablative conditioning between 1995–2007 who survived without recurrent leukemia for more than 3 months were eligible for analysis. Of the 657 patients, 59% were male, 26% were >10 years of age, 24% were transplanted in third remission or beyond, 74% were conditioned with TBI, 83% had pre-transplant anti-thymocyte globulin and 11% received tacrolimus, rather than cyclosporine, for acute GVHD prophylaxis. The cumulative incidence of cGVHD was 25% at 5 years with mild, moderate and severe disease in 91, 38 and 19 patients, respectively. cGVHD rates did not vary with donor-recipient HLA disparity. We constructed Cox proportional hazard-regression models to examine the effects of cGVHD on TRM, relapse, treatment failure (relapse or death; inverse of LFS) and overall mortality adjusting for age, disease, disease status, transplantation period, GVHD prophylaxis and donor-recipient HLA match. The risks of TRM (hazard ratio [HR] 9.33, p<0.0001), treatment failure (HR 2.96, p<0.0001) and overall mortality (HR 4.79, p<0.0001) were significantly higher in patients who developed cGVHD compared to those who did not develop cGVHD. In contrast to reports in adults transplanted with bone marrow or peripheral blood, mortality risk did not vary in those with mild, moderate or severe cGVHD after UCBT. Notably, relapse risk was not altered by the development of cGVHD (HR 0.73, p=0.38). In multivariate analysis, after adjusting for age and transplantation period, cGVHD risks were higher in patients who received tacrolimus (HR 3.12, p<0.0001) and in those with a prior history of grade 2 acute GVHD (HR 2.04, p=0.0001) or grade 3–4 acute GVHD (HR 5.51, p<0.0001) with a higher risk of cGVHD in patients with grade 3–4 versus grade 2 acute GVHD (HR 2.70, p<0.0001). These data suggest cGVHD of any severity has a markedly negative impact on survival after UCBT in children with acute leukemia without the associated graft-versus-leukemia effect previously reported for other stem cell sources. This analysis compels us to reevaluate our current acute GVHD prophylaxis strategies, including how tacrolimus is typically used, in an attempt to reduce the risk of cGVHD and its deleterious effect on LFS and OS after UCBT. Disclosures: Weisdorf: Genzyme: Research Funding; Hospira:Wagner:CORD:USE: Membership on an entity's Board of Directors or advisory committees; VidaCord: Membership on an entity's Board of Directors or advisory committees.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".