Prediction of Nonrelapse Mortality in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia Receiving Allogeneic Stem Cell Transplantation with Posttransplantation Cyclophosphamide-based Graft Versus Host Disease Prophylaxis

Sjoerd J.F. Hermans, Jurjen Versluis, Myriam Labopin, Sebastian Giebel, Yvette Van Norden, Ivan Moiseev, Didier Blaise, Jose L. Díez Martín, Ellen Meijer, Montserrat Rovira, Goda Choi, Anna Maria Raiola, Yener Koc, Péter Reményi, Jan Vydra, Nicolaus Kröger, Simona Sica, Massimo Martino, Gwendolyn Van Gorkom, Patrice ChevallierAlessandro Busca, Concepcion Herrera Arroyo, Eolia Brissot, Zinaida Peric, Arnon Nagler, Roni Shouval, Fabio Ciceri, Jan J. Cornelissen, Mohamad Mohty

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Abstract

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.

Original languageEnglish
Pages (from-to)E846
JournalHemaSphere
Volume7
Issue number3
DOIs
StatePublished - 21 Mar 2023
Externally publishedYes

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