Modifiye Endotelyal Aktivite ve Stres İndeksinin (mEASIX) Graft-Versus-Host-Hastalığında (GVHH) Ruksolitinib Yanıtını Öngördücü Değeri

Öz

Allojenik hematopoetik kök hücre nakli (allo-kit) sonrası greft-versus-host hastalığı (GVHH), nüks dışı morbidite ve mortalitenin önemli bir nedenidir. Ruksolitinib steroid refrakter veya bağımlı akut ve kronik GVHH olgularında ikinci basamak tedavi olarak kullanılmaktadır ancak tedavi yanıtını öngörebilecek güvenilir biyobelirteçler hâlâ yetersizdir. Laktat dehidrogenaz, C-reaktif protein ve trombosit sayısını içeren Modifiye Endotelyal Aktivite ve Stres İndeksi (mEASIX), endotel disfonksiyonu ve sistemik inflamasyonu yansıtmaktadır. Bu tek merkezli retrospektif çalışmada, mEASIX skorunun Ruksolitinib yanıtını öngörmedeki değeri 23 yetişkin GVHH hastasında değerlendirildi. Hastaların 11’i steroid-refrakter/bağımlı akut GVHH, 12’si ise kronik GVHH idi. Ruksolitinib’e genel yanıt oranı %65,2 olup, en düşük yanıt bronşiolitis obliterans hastalarında izlendi. Ruksolitinib’e dirençli hastalarda tedavi başlangıcındaki mEASIX skoru, yanıtlı hastalara göre anlamlı düzeyde yüksekti (37,09’a karşı 5,38; p=0,008). ROC analizine göre Ruksolitinib direncini öngörmede en uygun mEASIX eşik değeri 22,2 olarak belirlendi (AUC: 0,842; duyarlılık: %75; özgüllük: %86,7; p<0,001). Çok değişkenli lojistik regresyon analizi sonucunda mEASIX Ruksolitinib yanıtını öngörmede bağımsız bir değişken olarak saptandı (OR: 0,051; p=0,008). Ayrıca, yüksek mEASIX skoruna sahip hastalarda 1 yıllık genel sağkalım daha düşük saptandı (%50’ye karşı %92,3; p=0,078). Bulgularımız, GVHH’de mEASIX’in erken dönemde değerlendirilmesinin, Ruksolitinib direnci açısından riskli hastaların belirlenmesine ve zamanında tedavi değişiklikleriyle klinik sonuçların iyileştirilmesine katkı sağlayabileceğini göstermektedir. Bulguların doğrulanması için ileriye dönük çok merkezli çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Allojeneik hematopoetik kök hücre nakli (Allo-kit)
• Graft-versus-host-hastalığı (GVHH)
• Modifiye Endotelyal Aktivite ve Stres İndeksi
• Ruksolitinib

Destekleyen Kurum

destekleyen kuruluş yoktur.

Etik Beyan

Bu çalışma etik ilkelere uygun olarak yürütülmüş ve Bursa Uludağ Üniversitesi Tıp Fakültesi Klinik Araştırmalar Etik Kurulu’ndan onay almıştır (Karar no: 2025/577-7/10, Onay Tarihi: 19.03.2025)

Predictive Value of Modified Endothelial Activation and Stress Index (mEASIX) for Ruxolitinib Response in Graft-versus-Host Disease

Öz

Graft-versus-host disease (GVHD) continues to be a predominant cause of non-relapse morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Ruxolitinib is an established second-line treatment for steroid-refractory or steroid-dependent acute and chronic GVHD; however, predictive biomarkers for treatment response are lacking. The modified Endothelial Activation and Stress Index (mEASIX) is determined by measuring lactate dehydrogenase, C-reactive protein, and platelet count, and it indicates both endothelial damage and systemic inflammation. In this single-center retrospective study, we evaluated the predictive value of mEASIX for ruxolitinib response in 23 adult patients with GVHD. To assess the predictive capability of the mEASIX score, both receiver operating characteristic (ROC) analysis and logistic regression analysis were conducted. The median age was 37 years, and acute myeloid leukemia was the most common indication for transplantation (65.2%). Eleven patients had steroid-refractory/dependent acute GVHD, while 12 had steroid-refractory/dependent chronic GVHD. The overall response rate to ruxolitinib was 65.2%, with the lowest response observed in patients with bronchiolitis obliterans. Patients with ruxolitinib resistance had significantly higher mEASIX scores at treatment initiation compared to responders (37.09 vs. 5.38, p=0.008). Based on the ROC curve analysis optimal mEASIX cut-off value for predicting ruxolitinib resistance was 22.2 (sensitivity: 75%, specificity: 86.7%, AUC: 0.842, p<0.001). In multivariate analysis, mEASIX remained an independent predictor of ruxolitinib response (OR: 0.051, p=0.008). Patients with high mEASIX scores had lower 1-year overall survival compared to those with low scores (50% vs. 92.3%, p=0.078). Our findings suggest that early evaluation of mEASIX can identify patients at risk of ruxolitinib resistance, allowing timely treatment modifications to improve clinical outcomes in GVHD. Prospective multicenter studies are needed to validate these results.

Anahtar Kelimeler

• Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
• Graft-versus-host disease (GVHD)
• Ruxolitinib
• Modified Endothelial Activation and Stress Index (mEASIX)

Destekleyen Kurum

no funding

Etik Beyan

This study was conducted in accordance with ethical principles and received approval from the Clinical Research Ethics Committee of the Bursa Uludag University Faculty of Medicine (Decision no:2025/577-7/10, Approval Date: 19.03.2025).

Kaynakça

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