Predicting mortality from intracranial hemorrhage in allogeneic hematopoietic stem cell transplantation patients

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, 70 allo-HSCT patients with ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. We used these 2 cohorts to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors, lactate dehydrogenase level, albumin level, white blood cell count and disease status, were retained in the multivariable logistic regression model, and a simplified grading scale, termed the LAWS score, was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, p>0.05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic of 0.859, 95% CI 0.776-0.945) and the external validation cohort (C-statistic of 0.795, 95% CI 0.645-0.945). The LAWS score is the first scoring system capable of predicting the 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk-stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups.

Download Full-text

Nutritional risk factors predict severe acute graft-versus-host disease and early mortality in pediatric allogeneic hematopoietic stem cell transplantation

Pediatric Blood & Cancer ◽

10.1002/pbc.26853 ◽

2017 ◽

Vol 65 (2) ◽

pp. e26853 ◽

Cited By ~ 7

Author(s):

Eva H. Kerby ◽

Yimei Li ◽

Kelly D. Getz ◽

Elizabeth C. Smith ◽

Laura T. Smith ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Graft Versus Host Disease ◽

Early Mortality ◽

Nutritional Risk ◽

Hematopoietic Stem ◽

Graft Versus Host ◽

Acute Graft

Download Full-text

External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation

Blood Advances ◽

10.1182/bloodadvances.2019032268 ◽

2019 ◽

Vol 3 (12) ◽

pp. 1881-1890 ◽

Cited By ~ 10

Author(s):

Roni Shouval ◽

Joshua A. Fein ◽

Aniela Shouval ◽

Ivetta Danylesko ◽

Noga Shem-Tov ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Disease Risk ◽

Risk Index ◽

External Validation ◽

Prognostic Scores ◽

Hematopoietic Stem

Abstract Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores’ limited discriminative capacity.

Download Full-text

Urinary CXCL10 and CXCL9 Are Associated with Acute Kidney Injury in Children after Hematopoietic Stem Cell Transplantation: Results of a Discovery and Validation Cohort

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2018.12.332 ◽

2019 ◽

Vol 25 (3) ◽

pp. S185-S186 ◽

Cited By ~ 2

Author(s):

Daniella Levy Erez ◽

Kathleen E. Sullivan ◽

Michelle Denburg ◽

Nancy J. Bunin ◽

Sonata Jodele ◽

...

Keyword(s):

Acute Kidney Injury ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Validation Cohort ◽

Kidney Injury ◽

Hematopoietic Stem

Download Full-text

Plasma Brain Natriuretic Peptide Is Associated with Hepatic Veno-Occlusive Disease and Early Mortality After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.3348.3348 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3348-3348

Author(s):

Keisuke Kataoka ◽

Yasuhito Nannya ◽

Hiroshi Iwata ◽

Sachiko Seo ◽

Keiki Kumano ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cardiac Function ◽

Brain Natriuretic Peptide ◽

Prognostic Marker ◽

Peak Plasma ◽

Early Mortality ◽

Hematopoietic Stem ◽

Allogeneic Hsct

Abstract Abstract 3348 Poster Board III-236 Introduction: Fluid retention is usually the first sign and characteristic feature of hepatic veno-occlusive disease (VOD), a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Because brain natriuretic peptide (BNP) is a 32-amino-acid neurohormone synthesized in ventricular myocardium and secreted in response to volume expansion, we hypothesized that plasma BNP concentrations indicate onset and/or severity of VOD and serve as a prognostic marker after HSCT. Methods: We performed a retrospective analysis to see if plasma BNP is associated with VOD and early mortality after allogeneic HSCT. This analysis included 33 consecutive adult patients who underwent allogeneic HSCT at our institution between February 2008 and February 2009. Plasma BNP concentrations (normal range < 18.4 pg/mL) were measured once before transplantation for routine workup and weekly after transplantation, using fluorescence enzyme immunoassay. The diagnosis of VOD was based on modified Seattle criteria and the severity of VOD was defined according to the established criteria. Results: A total of 7 (21.2%) patients died before day 100, and 12 (36.3%) patients developed VOD (mild to moderate in 6 and severe in 6) between 1 and 15 days (median, 9.5 days) after transplantation. Plasma BNP concentrations were similar before and on day 0 between patients with and without VOD, but significantly increased on day 7 and later in those with VOD. Peak plasma BNP concentrations before engraftment in patients with VOD were significantly elevated compared with those without VOD (median values, 1686.9 pg/mL (range, 459.5 – 10390.9 pg/mL) vs. 87.6 pg/mL (14.3 – 378.8 pg/mL); P = 0.01). Comparison across the severity of VOD revealed that peak plasma BNP concentrations before engraftment were significantly higher in patients with severe VOD than in those with mild to moderate VOD (3678.0 pg/mL (2486.2 – 10390.9 pg/mL) vs. 525.1 pg/mL (459.5 – 887.5 pg/mL); P = 0.02). As most patients presented VOD before day 14, we investigated the impact of plasma BNP on early mortality using peak plasma BNP concentrations before day 14. Receiver operating characteristic curve analysis showed a BNP cutoff value of ≥ 380 pg/mL could effectively differentiate nonsurvivors from survivors at day 100, with a sensitivity of 85.7% and a specificity of 84.6%. Actually, survival at day 100 in patients with peak plasma BNP concentrations of ≥ 380 pg/mL was significantly worse than that in patients with peak plasma BNP concentrations of < 380 pg/mL (40.0% vs. 95.7%; P < 0.01). Because plasma BNP concentrations can be increased in various diseases including heart failure and sepsis, we investigated the associations between plasma BNP concentrations and these conditions. There was no significant difference in peak plasma BNP concentrations before engraftment between patients with and without documented infection (P = 0.72). With respect to cardiac function, pretransplant left ventricular ejection fraction (LVEF) showed no correlation with peak plasma BNP concentrations before engraftment (r = -0.09; P = 0.63). In 6 patients whose peak BNP concentrations were ≥ 1000 pg/mL, cardiac performance was normal or slightly reduced (LVEF ≥ 50%) in 4 patients and moderately deteriorated (LVEF 30 - 50%) in 2 patients when they had peak plasma BNP concentrations. Conclusion: We found plasma BNP concentrations are elevated in patients with VOD and associated with the severity of VOD and mortality at day 100, irrespective of pretransplant cardiac function and coexistence of documented infection. These findings suggest that plasma BNP may represent a prognostic marker of VOD and could offer a valuable tool toward therapeutic interventions. Disclosures: No relevant conflicts of interest to declare.

Download Full-text