Sociodemographic and patient-related determinants of outcomes after unrelated donor hematopoietic cell transplantation using posttransplant cyclophosphamide-based GVHD prophylaxis
Notice bibliographique
Résumé
Abstract Background Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for several hematologic disorders. While disease- and transplant-related factors significantly impact post-transplant outcomes, sociodemographic and patient-related determinants may also play a crucial role in the success of allo-HCT. We aimed to investigate the influence of sociodemographic and patient-related determinants on outcomes after unmatched allo-HCT using post-transplant cyclophosphamide (PT-Cy)-based graft-versus-host disease (GVHD) prophylaxis. Methods A retrospective multicenter analysis was conducted using the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2017 to 2021 using P-5891 data by Shaffer et al. We evaluated the impact of recipient age, gender, race and ethnicity, graft source, disease type, disease risk index, donor age, donor-recipient CMV status, karnofsky performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) on overall survival (OS), relapse, non-relapse mortality (NRM), grade II-IV acute GVHD (aGVHD), grade III-IV aGVHD, moderate/severe chronic GVHD (cGVHD), and GVHD-free relapse-free survival (GRFS). Patient-, disease- and transplant-related factors were compared between groups using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. Cox proportional hazards regression analyses were performed to assess outcomes. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p < 0.1 in univariable analysis and clinically relevant variables were included in the multivariable models. Statistical analyses were conducted using Stata version 18, and significance was defined at p < 0.05. Results We included a total of 2,271 unrelated allo-HCT recipients receiving PT-Cy-based GVHD prophylaxis. Mean age was 57.0 (SD 13.9) years, and 56.1% were male. The graft source was bone marrow in 90% of patients and peripheral blood in 10%. The primary hematologic malignancies included acute myeloid leukemia (AML) (54%), myelodysplastic syndrome (MDS) (29.5%), and acute lymphoblastic leukemia (ALL) (16.5%). The race of patients was Caucasian (87%), African American (4.8%), Asian, and others (9%). The conditioning regimen was myeloablative in 39.8% of patients. The KPS was <90 in 44.8% of patients. The HCT-CI was ≥3 in 53% patients. The median OS was 24 (IQR 11.6-36) months. Grade II-IV aGVHD, grade III-IV aGVHD, moderate/severe cGVHD, relapse, and mortality rates were 29.1%, 6.4%, 11.4%, 27.1%, and 36.9%, respectively. After adjusting for significant variables in multivariate regression analysis, recipient age (HR = 1.010, 95% CI 1.004-1.017; p = 0.003), <90 KPS at transplant (HR = 1.20, 95% CI 1.04-1.38; p = 0.013), and higher HCT-CI (HR = 1.11, 95% CI 1.08-1.15; p < 0.001) predicted inferior OS. Lower risk of relapse was observed in patients with ALL (HR = 0.71, 95% CI 0.54-0.93; p = 0.014). However, risk of relapse was higher among patients receiving non-myeloablative conditioning (HR = 1.43, 95% CI 1.12-1.82; p = 0.004). In addition, recipient age (HR = 1.03, 95% CI 1.02-1.04; p < 0.001), <90 KPS (HR = 1.27, 95% CI 1.03-1.56; p = 0.025), ALL (HR = 1.58, 95% CI 1.17-2.14; p = 0.003), and higher HCT-CI (HR = 1.15, 95% CI 1.10-1.20; p < 0.001) predicted worse NRM. For GRFS, higher risk was observed with Black race (HR = 1.38, 95% CI 1.06-1.78; p = 0.016), higher HCT-CI (HR = 1.08, 95% CI 1.04-1.10; p < 0.001), donor age (HR = 1.008, 95% CI 1.000-1.015; p = 0.042), and reduced intensity conditioning (HR = 1.18, 95% CI 1.01-1.37; p = 0.034). Moreover, higher HCT-CI also predicted a higher risk of aGVHD III-IV (HR = 1.12, 95% CI 1.04-1.20; p = 0.003). High and very high-risk disease status at the time of transplant predicted worse OS, relapse rate, and GRFS. Conclusion In this multicenter analysis, we found that recipient age, performance, and comorbidity status, disease type, disease risk, and conditioning intensity consistently predict worse outcomes in patients undergoing unmatched allo-HCT with PT-Cy prophylaxis. Donor age and race may also impact outcomes; however, further investigation is warranted. Sex, graft source, donor-recipient CMV status, and ethnicity do not appear to influence outcomes.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».