Improved Leukemia-Free Survival after Post-Consolidation Treatment with Histamine Dihydrochloride and Interleukin-2 in AML: A Randomized Phase III Trial.
Bibliographic record
Abstract
Abstract Background: Histamine dihydrochloride (HDC) potentiates immune-based therapies by protecting pivotal anti-neoplastic lymphocytes from phagocyte-induced suppression. Previous results in AML indicated that post-consolidation treatment with HDC and low-dose interleukin-2 (IL-2) is safe and feasible, and that the combination may prolong leukemia-free survival (LFS). Aims: The primary objective was to determine if post-consolidation treatment with IL-2 and HDC could improve LFS for AML pts in complete remission (CR). Secondary objectives included overall survival (OS), LFS in CR1 and CR>1 subgroups, and safety. Methods: This international, randomized, open-label, phase III study was conducted at 92 centers. From June 1998 to October 2000, 320 AML pts [148 females, 172 males, median age 57 (18–84) yrs] were enrolled in CR after completion of standard consolidation therapy. Pts were stratified by CR1 or CR>1 and randomized to either treatment (n=160) or no treatment (control, n=160) arms. The treatment was self-administered at home and included 10 cycles of low-dose IL-2 (aldesleukin, Chiron Corp) 18 000 U/kg, sc bid plus HDC (Maxim Pharmaceuticals) 0.5 mg sc bid. For cycles 1–3, each cycle comprised 3 wks of treatment and 3 wks of rest, whereas in cycles 4–10 the rest periods were 6 wks. The study arms were well balanced with respect to age, sex, karyotype-based risk, time from CR to inclusion and frequency of secondary leukemia. Pts were followed for relapse and survival using an identical assessment schedule until 3 yrs after last enrollment. All efficacy analyses were intent-to-treat. Results: The median follow-up of living pts was 46 months. For the primary endpoint, treatment with HDC/IL-2 increased LFS in the entire study population (CR1/CR>1, n=320, p=0.026 stratified log-rank test). There was no significant difference in OS (p=0.33). In the analysis of pre-stratified subgroups, one pt was excluded. For CR1 pts (n=262), HDC/IL-2 significantly improved LFS (p=0.011, log-rank test), with 3-year Kaplan-Meier estimates of 26% (control group) and 40% (treatment group). The difference in OS did not reach significance (p=0.16). For CR>1 pts (n=57), outcome was not affected by treatment. Side effects attributable to IL-2 included fever and local inflammatory reactions. HDC treatment induced symptoms of transient vasodilatation. Serious adverse events occurred in approximately 20% of pts in both groups. There were no treatment-related deaths. Conclusions: For AML pts in CR, post-consolidation therapy with HDC and IL-2 was safe and significantly improved LFS compared to standard of care. The benefit observed of HDC/IL-2 treatment appears to be explained by a reduction of relapses in CR1 pts.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".