Dual T-Cell Depletion with a Very Low Dose of ATG and Ptcy Provides an Effective Control of Acute Gvhd in PBSC RIC Allo-HSCT
Bibliographic record
Abstract
Introduction As has been described by Dr. Viswabandya et al, the combination of anti-thymoglobulin (ATG), post-transplant cyclophosphamide (PTCy) and cyclosporine (CsA) provides an effective control of graft-versus host disease (GVHD) in peripheral blood (PB) allo-HSCT. We aim to report our experience in reduced intensity conditioning (RIC) allo-HSCT using a novel GVHD prophylaxis composed by a very low dose of ATG, PTCy and CsA for GVHD prophylaxis. Patients and methods Between May 2018 and April 2019, 106 adult patients underwent RIC allo-HSCT with the present GVHD prophylaxis. All these recipients were included in the study. RIC regimen was composed by fludarabine, busulfan, and 200cGy of total body irradiation. For GVHD prophylaxis all recipients received a total dose of 2mg/kg of rabbit-ATG on day -3 (0.5mg/kg) and -2 (1.5mg/kg), PTCy 50mg/m2/day on day +3 and +4, and CsA since day +5. Data was collected retrospectively and updated on July 2019. The median follow-up was 7.6 months (range: 0.4-14.6) and survival percentages were calculated at 6 months. The cum.Inc of GVHD was assessed accounting relapse and death as competing events. Results The main baseline and post-transplant information is summarized in the Table 1 and 2. The cum.Inc of grade II-IV and III-IV acute GVHD at day +100 was 19% and 7.7%. The cum.Inc of grade II- IV was not significantly affected by donor type (P=0.787). However, the cum.Inc of grade III-IV was significantly higher in those recipients who received haploidentical or 9/10 matched unrelated donor (MUD) grafts (p=0.048). Rates of CMV and EBV reactivation were respectively 62.3% and 68.9%. No patients were diagnosed with CMV disease. Biopsy proven post-transplant lymphoproliferative disorder was diagnosed in only 1 recipient and successfully resolved after rituximab. Thirty-two (30.2%) recipients died and 16 (15.1%) relapsed during the follow-up. Main causes of death were relapse 13 (12.3%) and infection 6 (5.7%). The main outcome information is reported in the Table 2 and Plot 1 and 2. Those recipients who received grafts from matched related and unrelated donors had a significant better non-relapse mortality (NRM) (P=0.001), overall survival (OS) (P=0.02), relapse-free survival (RFS) (P=0.03) and GVHD-free/RFS (P=0.006). Table 3 shows the impact of risk factors in transplant outcomes. Those recipients with an HCT-CI score ≥3 had a significant worse OS (HR 2.5; P=0.024) and RFS (HR 2.5; P=0034). Those recipients who received grafts from 9/10 MUD and haploidentical donors had a significant worse RFS (HR 2.1; P=0.049). Disease risk index was not a significant risk factor for OS or RFS. Lastly, those recipients who received grafts from haploidentical donors had a significant worse GRFRS (HR 2.9; P=0.04). Conclusion The dose of ATG for GVHD prophylaxis is not well established. The combination of ATG (2mg/kg), PTCy, and CsA is safe and provides an effective acute GVHD prophylaxis in PB RIC allo-HSCT. Further investigations are required to analyze the effect of this prophylaxis in chronic GVHD to better state long-term outcome conclusions and to improve post-transplant outcomes in those recipients who received grafts from mismatched donor sources (haploidentical and 9/10 matched unrelated donors). Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".