Search

Introduction: We have recently reported that the evaluation CD25 expression on leukemic blasts at the time of disease onset could be an alternative non-molecular tool for predicting transplant outcomes in patients with cytogenetically intermediate acute myeloid leukemia (AML). We herein focus on patients with refractory or relapsed AML and examine the clinical correlation of the surface CD25 expression measured by flow cytometry at the time of transplantation and subsequent transplant outcomes. Patients and methods: A total of 60 AML samples with primary induction failure (n = 32), first relapse (n = 23) or second relapse (n = 5) were analyzed by means of flow cytometric CD25 antigen expression on leukemic blasts at the time of transplantation. Survival outcomes were compared with regard to the CD25 expression. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meiyer. Factors associated with at least borderline significance (p< 0.10) on univariate analyses were subjected to multivariate analysis using backward stepwise proportional hazard modeling. Multivariate analysis was performed using the Cox proportional hazards regression model. Results: CD25 antigen expression (>10%) on leukemic blasts was observed in 24 patients (40%). There was no significant difference between CD25 positive and negative groups in terms of clinical characteristics including cytogenetic risk, WHO classification, marrow or peripheral blasts % at transplantation, comorbidity, conditioning regimen, donor source or interval between diagnosis and transplantation. Although more early relapse cases within 180 days were observed in the CD25 positive group (p = 0.01), cumulative incidence of relapse, non-relapse mortality, acute or chronic graft-versus-host disease were not different between 2 groups. However, there was a significant difference in OS or PFS between 2 groups: 2-years OS; 8.3% vs. 34.0%, p=0.004 (Fig 1A), 2-years PFS; 8.3% vs. 26.3%, p=0.003 (Fig 1B). Moreover, multivariate analysis showed that CD25 expression was an independent adverse factor for OS (hazard ratio: 2.01, 95% confidence interval: 1.10-3.67, p = 0.02). Conclusion: Our cohorts with total 60 patients with refractory or relapsed AML showed that CD25 endowed these patients with an adverse prognostic impact, which might not be overcome even by transplantation. AML patients with residual CD25+ blasts at the time of transplantation might require additional therapy before or after transplantation for better survival. However, our small experience clearly desires larger series patients for evaluating the real impact of CD25 expression. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Stem cell transplantation (SCT) involves a great risk of acute kidney injury (AKI), which is largely committed to fatality derived from SCT. Liver-type fatty acid-binding protein (L-FABP) is a 15kDa protein expressed in human renal proximal tubular cells, and is shed into urine in response to renal tissue ischemia or oxidative stress. Urinary L-FABP (uL-FABP) has been reported to be not only a sensitive biomarker to detect incipient AKI but also a potential marker for something more than a measure of renal insult. This study addressed utility of uL-FABP, as it has not been fully understood on the clinical platform of SCT. Patients and Methods: A prospective cohort study was conducted in 81 patients who received allogeneic SCT in our hospital from April 2009 to March 2012 (median age, 49 years; median [range] follow-up period, 771 [2-1923] days). All had hematological malignancies, and were recipients of the first SCT. Associations of increased uL-FABP before executing conditioning therapy (at baseline) and clinical outcomes including incidence of AKI, non-relapse mortality (NRM), and overall survival (OS) were investigated. AKI was defined, based on the creatinine (Cr) criteria of the 2013 Kidney Disease Global Outcomes. AKI that developed within the first 30 days after SCT was considered in this study. The recipients were stratified into an elevated and a normal uL-FABP group at baseline, according to the reference value for healthy adult individuals (8.5µg/gCr). Hazard ratio (HR) with its 95% confidence interval (CI) of uL-FABP elevation was calculated for OS using the Cox proportional hazard model and for NRM using the Fine-Gray proportional hazards model, adjusted for confounders which had P -values ≤ 0.2 in univariate analyses. Results: Patients had been diagnosed with acute myeloid leukemia (n = 36), acute lymphoid leukemia (n = 23), myelodysplastic syndrome (n = 17), and myeloproliferative neoplasm (n = 5). The elevated and normal uL-FABP groups included 17 (21%) and 64 (79%) patients, respectively. The proportion of high disease risk was significantly greater in the elevated than in the normal uL-FAB P group (70.6 % vs. 31.3%, P = 0.005). There were no significant differences in age, serum Cr level, and the proportion of gender, hematopoietic cell transplantation comorbidity index (HCT-CI) ≥3, myeloablative conditioning regimen, stem-cell sources (bone marrow, peripheral blood, cord blood), related donor type and matched human leukocyte antigen compatibility. AKI emerged in 28 recipients (34.6%) at day 30? following SCT (median [range], 14 [0-30] days). The cumulative incidence [95% CI] of AKI was significantly greater in the elevated than in the normal uL-FABP group (64.7% [36-83.1 %] vs. 26.6% [16.4-37.8 %], P Conclusions: uL-FABP is a simple and non-invasive measurement to target patients at increased risk of AKI, NRM and OS following allogeneic SCT. The presence of antecedent subclinical renal injury, which can be detected by uL-FABP elevation at baseline, may provide prognostic information beyond renal outcome after allogeneic SCT. Disclosures No relevant conflicts of interest to declare.

Introduction Cardiac diastolic dysfunction plays a crucial role in the development of heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e') reflects left ventricular end-diastolic pressure and is used in the diagnosis of diastolic heart failure. Although cardiac complication is one of the most serious problems in hematopoietic stem cell transplantation (HSCT), the impact of diastolic dysfunction on clinical outcomes after allogeneic HSCT is unclear. Thus, we investigated the effects of diastolic dysfunction on HSCT using E/e'. Patients and Methods We retrospectively reviewed the records of 102 evaluable patients who underwent their first allogeneic HSCT at our hospital between November 2010 and July 2012, and investigated whether elevated E/e' would affect the clinical outcomes such as incidence of cardiac complications, overall survival (OS) and non-relapse mortality (NRM). Patients were classified into high- E/e' group if E/e' was ≥9 and classified into low- E/e' group if E/e' was Results This study analyzed 58 males and 44 females with a median age of 47 years (range: 15-71). Forty one patients were classified into the high- E/e' group and 61 classified into the low- E/e' group. High- E/e' patients were older than low- E/e' patients (median: 57 years in E/e'-high vs. 41 years in E/e'-low, P=0.027). Reduced intensity regimen was more frequent in the high- E/e' group (39% vs. 16%, P=0.019) and there were also more men in the high- E/e' group compared with patients in the low- E/e' group (68% vs. 49%, P=0.07). Twelve patients developed cardiac complications during the first 100 days after HSCT (Day100) and its cumulative incidence was11.9%. Of them, 6 patients developed heart failure, 5 developed arrhythmia, and 1 developed both myocardial ischemia and heart failure. The cumulative incidence of cardiac complications at Day 100 was significantly higher in the high- E/e' group (22.4%) than that in the low- E/e' group (22.4% vs. 5%, P=0.0087, Figure 1a). Non-relapse death occurred in 17 patients within 1 year after HSCT. Nine patients died of infection, 3 died of hemorrhage, 2 died of graft-versus-host disease, 1 died of heart failure, 1 died of thrombotic microangiopathy, and 1 died of veno-occlusive disease/sinusoidal obstruction disease. NRM was higher in the high- E/e' group than in the low- E/e' group (28.8% vs. 10.5% at 1year, P=0.0165, Figure 1b). A multivariate analysis revealed that high- E/e' and high disease status were significant risk factors for high NRM (other co-variates were HLA compatibility and HCT-CI). Conversely, the relapse rate did not significantly differ in both groups (23% in the high- E/e' vs. 17% in the low- E/e' at 1 year, P=0.44). The OS was significantly poorer in the high- E/e' group than in the low- E/e' group (55.2% vs. 75.6% at 1 year, P=0.0085, Figure 1c). On multivariate analysis, E/e', disease status, and donor source were defined as independent prognostic factors for OS (other co-variates were HLA compatibility, preparative regimens, disease status, and QTc). Conclusions Diastolic dysfunction is associated with iron overload, anemia, diabetes, kidney disease, heart failure, cardiomyopathy, aging, and hypertension. Thus, pre-transplat E/e' value might reflect the potential risk of these diseases in transplant candidates and be associated with poor outcomes. Our results suggest that pre-transplant E/e' value would be an early predictor of cardiac complications and survival after HSCT. Disclosures: No relevant conflicts of interest to declare.

Stem cell transplantation (SCT) involves a great risk of acute kidney injury (AKI). Urinary liver-type fatty acid-binding protein (uL-FABP) is a sensitive biomarker to detect kidney damage before an increase in serum creatinine (Cr); however, the utility of uL-FABP is not fully understood in the platform of SCT. A prospective study was conducted in 84 allogeneic SCT recipients to ascertain a link between the uL-FABP level before preparative procedures and AKI incidence after SCT. The association between them was analyzed using Gray's method and a multivariate Fine-Gray proportional hazards regression model. The recipients were stratified into high and low uL-FABP groups, according to the reference value for healthy subjects (8.4 μg/g Cr). AKI developed more frequently in the high (n = 20) than low (n = 64) group (55.0% versus 26.6% at day 30, P = .005), and high uL-FABP was an independent risk for the emergence of AKI (hazard ratio, 2.78; 95% confidence interval, 1.24 to 6.22, P = .01). In conclusion, increased baseline uL-FABP, which may indicate previous incipient kidney injury, is linked with a high risk of AKI after allogeneic SCT.