Maintenance with Hypomethylating Agents after Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Meta-Analysis
Bibliographic record
Abstract
Abstract Background: After allogeneic hematopoietic stem cell transplantation (allo-SCT), 35%-45% of patients suffer disease relapse, resulting in dismal outcomes. Several strategies have been adopted to prolong disease-free intervals. Hypomethylating agents (HMA) seem to have a range of properties favorable to post-allo-SCT maintenance. They mediate a direct anti-leukemic effect in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), regardless of their molecular mutation profile. Moreover, their abilities to induce a CD8+ tumor-specific T cell response, together with the expansion of regulatory T cells, leads to an epigenetically enhanced graft-versus-leukemia effect that is not counterbalanced by an increased risk of graft-versus-host disease (GVHD). Materials and Methods: Two investigators independently searched the Embase and MEDLINE databases for relevant studies published from inception to 31 January 2021. The inclusion criteria were as follows: (1) the studies had to be either randomized controlled trials or cohort studies; (2) the patients underwent allo-SCT for AML or MDS; (3) the studies compared 2 patient groups: one receiving HMA maintenance post-allo-SCT, and the other being an observational group; and (4) the studies needed to report at least one of our primary outcomes of interest; overall survival (OS), relapse-free survival (RFS), grade II-IV acute GVHD, and chronic GVHD. Results: Eleven eligible studies compared HMA maintenance to observation following allo-SCT for AML or MDS. The OS of the HMA maintenance group was superior to the observation group, with a pooled odds ratio (OR) of 2.52 (95% CI, 1.60-3.94; I 2, 51%; Figure 1A). Similarly, a pooled meta-analysis found that the RFS was significantly better for patients receiving HMA maintenance, with a pooled OR of 2.64 (95% CI, 1.79-3.90; I 2, 0%; Figure 1B). Moreover, the cumulative incidence of relapse (CIR) was significantly lower in patients who received HMAs. The HMA group also had lower non-relapse mortality (NRM) compared with the observation group. Overall, the incidences of grade II-IV acute GVHD and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone. Conclusions: The current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD. Figure 1. Forest plots of the meta-analysis of HMA maintenance compared with observation. (A) OS rate. (B) RFS rate. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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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 | 0.009 | 0.017 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.030 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".