The EBMT Cytogenetic Risk Score maintains its prognostic significance in acute myeloid leukemia following allogeneic stem cell transplantation in a cohort with 40% of patients transplanted with in vitro partial T-cell depleted graft

Abstract

Cytogenetic [1] and molecular pattern [2] of acute myeloid leukemia (AML) is prognostic for survival and relapse incidence and also for patient undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) for consolidation. Different validated prognostic scores, such as the disease risk index [3, 4], have demonstrated the impact of cytogenetic pattern of AML in this context. Recently, a new prognostic score, the AML EBMT Cytogenetic Risk score (EBMT-CRS) [5, 6] was published, combining cytogenetics and FLT3-ITD status for AML patients in complete remission (CR) at transplant time. The EBMTCRS is prognostic for leukemia-free survival (LFS), overall survival (OS), GVHD-free/relapse-free survival (GRFS) and cumulative incidence of relapse (CIR). This model was initially investigated in first CR (CR1) for AML patients undergoing alloHSCT with matched donor (MD) (fullymatched related and unrelated donor) without ex-vivo manipulation grafts and was also validated for patients with positive minimal measurable disease (MRD+). In our transplant center (Geneva University Hospitals), we frequently offer in-vitro partial T-cell depleted graft (pTDEP) for patient in CR [7]. Graft is initially T-cell depleted with alemtuzumab (Sanofi, France), infused at Day 0, followed with an addback of T cells (100 × 10 cells) on day +1 to decrease morbidity and mortality associated with graft-versus-host disease (GvHD). We previously demonstrated that pTDEP significantly improves GRFS and GVHD without harming OS, DFS, or RI in selected patients [8, 9]. Currently, The EBMT-CRS has not been evaluated in pTDEP patients. In this retrospective monocentric study, we investigated the impact of the EBMT-CRS for 2 years LFS, OS, GRFS, CIR, NRM, acute and chronic GVHD in a cohort with patients allografted with pTDEP graft. All consecutive ≥18 years patients in CR at transplant time who received a first allograft for AML between 2008 and 2018 with data available to determine the EBMT-CRS were included. OS, LFS, GRFS were investigated with the Kaplan–Meier method. CIR (with NRM as competing event), NRM (with relapse as competing event) and acute and chronic GvHD (with relapse as competing event) were investigated with the cumulative incidence estimator as defined by Fine and Gray. All patients provided written consent authorizing the use of their data for research publication. This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practices guidelines. A total of 135 consecutive patients were included. Median age at transplant time was 56 years (range: 19–74), 44% were female, 82% has Karnofsky index ≥ 90. 21% of graft were from HLA identical, 57% from matched unrelated donor, 10% from mismatched unrelated donor and 12% from haploidentical donor. Stem cell source was peripheral blood in 89% and bone marrow in 11%. Partial in* Yves Chalandon [email protected]