PMID- 32045652 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20210623 IS - 1523-6536 (Electronic) IS - 1083-8791 (Linking) VI - 26 IP - 5 DP - 2020 May TI - Endothelial Activation and Stress Index (EASIX) at Admission Predicts Fluid Overload in Recipients of Allogeneic Stem Cell Transplantation. PG - 1013-1020 LID - S1083-8791(20)30061-6 [pii] LID - 10.1016/j.bbmt.2020.01.028 [doi] AB - Fluid overload (FO) grade >/=2 (more than 10% weight gain from baseline) has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation (AHCT). The causes for FO remain unclear. We hypothesized that endothelial damage, possibly due to treatments received prior to AHCT, may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index (EASIX) (defined as lactate dehydrogenase [U/L] x creatinine [mg/dL]/platelets [10(9) cells/L]) correlates with grade >/=2 FO in 2 cohorts of recipients of AHCT at our institution. We tested our hypothesis in a cohort of 145 consecutive recipients (study cohort) of AHCT transplant from HLA-haploidentical donors and validated the findings in a cohort of 449 (validation cohort) recipients of AHCT from HLA-matched donors who underwent transplantation between 2010 and 2015. Predictors of grade >/=2 FO were evaluated using competing risks regression in univariate analysis and classification and regression tree (CART) analysis in multivariate analysis. The cumulative incidence of grade >/=2 FO was estimated considering death as a competing risk. EASIX scores were evaluated based on log(2)-transformed values. Optimal predictive EASIX cutoff values were determined based on receiver operating characteristics curve analysis. Grade >/=2 FO occurred in 21% and 6% of the study and validation cohorts, respectively, with the majority of these cases being diagnosed before the day of AHCT. Median log(2) EASIX score at admission was 2.4 (interquartile range [IQR], 1.3, 3.7) and 2.5 (IQR, 1.4, 3.9) in the 2 respective cohorts. In univariate analysis, high EASIX at admission was a significant predictor of grade >/=2 FO in the study (cutoff: 4.4, hazard ratio [HR] = 4.8, P < .001) and in the validation (cutoff: 4.3, HR = 4.8, P < .001) cohorts. The significant effect of EASIX persisted in multivariate CART analysis in the study (HR = 6.3, P < .001) and the validation (HR = 28, P = .002) cohorts. Additional predictors in multivariate analysis included body weight below 80 kg in recipients older than 55 years (HR = 4.5, P < .001) in the study cohort and diabetes (HR = 34, P = .001) and age >60 years (HR = 9.6, P = .04) in the validation cohort. At admission, the prevalence of EASIX score of >4.3 (18% versus 17%, P = .9) was not different between the diabetics and nondiabetics. EASIX score at admission is a significant predictor of grade >/=2 FO in recipients of AHCT from HLA-haploidentical or HLA-matched donors. Independently of EASIX, older patients with low weight were associated with increased risk of grade >/=2 FO for recipients of HLA-haploidentical transplants. For the HLA-matched cohort, diabetes and older age were associated with increased FO risk. These findings require validation in external cohorts. CI - Copyright (c) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Varma, Ankur AU - Varma A AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, Illinois. FAU - Rondon, Gabriela AU - Rondon G AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Srour, Samer A AU - Srour SA AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Chen, Julianne AU - Chen J AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Ledesma, Celina AU - Ledesma C AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Champlin, Richard E AU - Champlin RE AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Ciurea, Stefan O AU - Ciurea SO AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Saliba, Rima M AU - Saliba RM AD - Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: rsaliba@mdanderson.org. LA - eng PT - Journal Article DEP - 20200209 PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 SB - IM MH - Aged MH - Cohort Studies MH - *Graft vs Host Disease MH - *Hematopoietic Stem Cell Transplantation/adverse effects MH - Humans MH - Middle Aged MH - Proportional Hazards Models MH - Tissue Donors MH - Transplantation, Homologous OTO - NOTNLM OT - Diabetes OT - EASIX OT - Fluid overload OT - Haploidentical OT - Toxicity EDAT- 2020/02/12 06:00 MHDA- 2021/06/24 06:00 CRDT- 2020/02/12 06:00 PHST- 2019/09/18 00:00 [received] PHST- 2020/01/28 00:00 [revised] PHST- 2020/01/29 00:00 [accepted] PHST- 2020/02/12 06:00 [pubmed] PHST- 2021/06/24 06:00 [medline] PHST- 2020/02/12 06:00 [entrez] AID - S1083-8791(20)30061-6 [pii] AID - 10.1016/j.bbmt.2020.01.028 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2020 May;26(5):1013-1020. doi: 10.1016/j.bbmt.2020.01.028. Epub 2020 Feb 9.