Prolonged Duration of Systemic Immunosuppression after Allogeneic Hematopoietic Cell Transplantation Associates with the Use of Peripheral Blood Stem Cells, Severe Grade of Chronic Gvhd, Progressive Type Onset of Chronic Gvhd, Grade 2-4 Acute Gvhd and Older Age, but Not with T-Cell Depletion or Conditioning Regimen
Bibliographic record
Abstract
Abstract Background: Prolongedsystemic immunosuppression (SIS) post allogeneic hematopoietic cell transplantation (HCT) results in increased unnecessary complications. In our previous study of avascular necrosis (AVN; ASBMT 2015), one of common complications occurring after allogeneic HCT related to the use of prolonged immunosuppression including corticosteroids, we demonstrated a strong correlation between the duration of SIS and the risk of AVN. The probability of remaining on SIS was higher in the group developed AVN than those without episode of AVN (46.4% vs 11.7% at 4 years post-HCT). The question remains what are the risk factors related to prolonged SIS after allogeneic HCT. The present study attempted to evaluate potential risk factors for prolonged SIS. Methods: A retrospective review of 845 consecutive patients ≥18 years of age who underwent alloHCT at Princess Margaret Cancer Centre from 2002 to 2013 was conducted to determine the probability of SIS discontinuation considering death and relapse as competing risks. Univariate and multivariate analyses were conducted using cumulative incidence method considering competing risk to identify the risk factors for failure from SIS discontinuation. Results: Out of 845 patients, the probability of remaining on SIS, SIS discontinuation and death at 4 years is 19.6%, 30.5%, 49.9%, respectively. The median follow up duration among survivors was 3.5 years. Univariate analysis for successful SIS cessation revealed following risk factors: aGVHD grade 2-4 (p<0.001, HR 0.53), cGVHD by NIH consensus criteria (p<0.001, HR 0.52), cGVHD severity (p<0.001,HR 0.44), progressive type onset of cGVHD (p<0.001, HR 0.62), stem cell source (p<0.001,HR 0.54 for PBSC), T cell depletion (p<0.001, HR 1.42), donor type (p=0.0028, HR 1.45 for matched related donor), HLA match (p=0.0039, HR 0.30 for mismatched) and age (p<0.001, HR 0.98). Multivariate analysis confirmed that younger age (p<0.001, HR 0.97), aGVHD grade 2-4 (p<0.001, HR 0.51), progressive type of cGVHD (p<0.001, HR 0.53), cGVHD by NIH consensus criteria (p<0.001, HR 0.53), stem cell source (p<0.001, HR 0.51 for PBSC) and use of matched related donor (p<0.001, HR 1.68) were significant risk factors. ROC analysis was performed which revealed an age ≤ 50 to be a categorical risk factor for SIS discontinuation. A risk score model was generated assigning a score to each risk factor. A score of 1 was assigned to aGVHD grade 2-4, younger patient of age ≤50 years, progressive type of cGVHD, cGVHD by NIH consensus criteria, PBSC stem cell source and the use of matched related donor. Total score was calculated with risk score 0 (n=16, 2%), risk score 1 (n=55, 7%), risk score 2 (n=109, 14%), risk score 3 (n=215, 28%), risk score 4 (n=232, 30 %), risk score 5 (n=119, 16%), risk score 6 (n=14, 1%). Three risk groups were created: low (score 0-2, n=181, 21.4%), intermediate (score 3, n=216, 25.6%) and high (score 4-6, n=365, 47%). This risk score group could stratify the patients according to their success rate of SIS cessation (p<0.0001): 48.0% in low vs. 40.8% in intermediate vs. 28.5% in high risk group for SIS discontinuation rate at 4 yrs. Conclusions: Younger age, aGVHD grade 2-4, progressive type of cGVHD, cGVHD by NIH consensus criteria, peripheral stem cell source and use of matched sibling donor predicts for prolonged immunosuppression use post allogeneic transplant. Figure 1. Figure 1. Disclosures Kim: Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.
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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 | 0.001 | 0.001 |
| 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".