Hermans Sjoerd J F, Versluis Jurjen, Labopin Myriam, Giebel Sebastian, van Norden Yvette, Moiseev Ivan, Blaise Didier, Díez Martín Jose L, Meijer Ellen, Rovira Montserrat, Choi Goda, Raiola Anna Maria, Koc Yener, Reményi Péter, Vydra Jan, Kröger Nicolaus, Sica Simona, Martino Massimo, van Gorkom Gwendolyn, Chevallier Patrice, Busca Alessandro, Herrera Arroyo Concepcion, Brissot Eolia, Peric Zinaida, Nagler Arnon, Shouval Roni, Ciceri Fabio, Cornelissen Jan J, Mohty Mohamad
Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
Department of Hematology, Hôpital Saint Antoine, Paris, France.
Hemasphere. 2023 Feb 21;7(3):e846. doi: 10.1097/HS9.0000000000000846. eCollection 2023 Mar.
Graft versus host disease (GVHD) prophylaxis with posttransplantation cyclophosphamide (PTCY) has been established to reduce severe GVHD, and thereby potentially reducing nonrelapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). We evaluated the predictive capacity of established NRM-risk scores in patients receiving PTCY-based GVHD prophylaxis, and subsequently developed and validated a novel PTCY-specific NRM-risk model. Adult patients (n = 1861) with AML or ALL in first complete remission who received alloSCT with PTCY-based GVHD prophylaxis were included. The PTCY-risk score was developed using multivariable Fine and Gray regression, selecting parameters from the hematopoietic cell transplantation-comorbidity index (HCT-CI) and European Group for Blood and Marrow Transplantation (EBMT) score with a subdistribution hazard ratio (SHR) of ≥1.2 for 2-year NRM in the training set (70% split), which was validated in the test set (30%). The performance of the EBMT score, HCT-CI, and integrated EBMT score was relatively poor for discriminating 2-year NRM (c-statistic 51.7%, 56.6%, and 59.2%, respectively). The PTCY-risk score included 10 variables which were collapsed in 3 risk groups estimating 2-year NRM of 11% ± 2%, 19% ± 2%, and 36% ± 3% (training set, c-statistic 64%), and 11% ± 2%, 18% ± 3%, and 31% ± 5% (test set, c-statistic 63%), which also translated into different overall survival. Collectively, we developed an NRM-risk score for acute leukemia patients receiving PTCY that better predicted 2-year NRM compared with existing models, which might be applicable to the specific toxicities of high-dose cyclophosphamide.
移植后环磷酰胺（PTCY）预防移植物抗宿主病（GVHD）已被证实可降低严重GVHD，从而可能降低异基因干细胞移植（alloSCT）后的非复发死亡率（NRM）。我们评估了既定的NRM风险评分对接受基于PTCY的GVHD预防患者的预测能力，随后开发并验证了一种新的PTCY特异性NRM风险模型。纳入了1861例处于首次完全缓解期的急性髓系白血病（AML）或急性淋巴细胞白血病（ALL）成年患者，这些患者接受了基于PTCY的GVHD预防的alloSCT。PTCY风险评分通过多变量Fine和Gray回归分析得出，从造血细胞移植合并症指数（HCT-CI）和欧洲血液与骨髓移植组（EBMT）评分中选择参数，在训练集（70%分割）中2年NRM的亚分布风险比（SHR）≥1.2，并在测试集（30%）中进行验证。EBMT评分、HCT-CI和综合EBMT评分在区分2年NRM方面表现相对较差（c统计量分别为51.7%、56.6%和59.2%）。PTCY风险评分包括10个变量，分为3个风险组，估计2年NRM分别为11%±2%、19%±2%和36%±3%（训练集，c统计量64%），以及11%±2%、18%±3%和31%±5%（测试集，c统计量63%），这也转化为不同的总生存率。总体而言，我们为接受PTCY的急性白血病患者开发了一种NRM风险评分，与现有模型相比，该评分能更好地预测2年NRM，可能适用于高剂量环磷酰胺的特定毒性。
