Incidence and Risk Factors of Early Bacterial Infections after Unrelated Cord Blood Transplantation

Incidence and characteristics of early bacterial infection within 100 days after unrelated cord blood transplantation (UCBT) were assessed for 664 pediatric and 1208 adult recipients in Japan. Cumulative incidence of early bacterial infection at day 100 post-UCBT was 11% (95% confidence interval [CI], 8%-13%) for children and 21% (CI, 19%-24%) for adults (P < .0001). Early bacterial infection in adults had a significant impact on mortality (hazard ratio [HR] = 2.1, CI, 1.7-2.6; P < .0001), although no significant risk factors were identified. Multivariate analysis identified older age group (6-10, and 11-15 years versus 0-5 years of age) at transplant (HR = 2.0 and 2.7, CI, 1.1-3.5 and 1.4-4.9; P = .020 and .002, respectively) as an independent risk factor of early bacterial infection for children. Early bacterial infection in children did not have a significant impact on mortality when adjusted. Of 315 bacteremia, 74% were caused by Gram-positive microorganisms. Pneumonia occurred in 39 patients including 13 cases of Stenotrophomonas maltophilia pneumonia. Early bacterial infection had a negative effect on survival for adults and the median day of development was 10 days after transplant, suggesting that the prevention of bacterial infection in the very early post-UCBT phase is important.     

Acute Kidney Injury in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation: Incidence,Risk Factors,and Outcomes

Acute kidney injury (AKI) is a common adverse event after hematopoietic cell transplantation (HCT). AKI is associated with early death or chronic kidney disease among transplant survivors. However, large-scale pediatric studies based on standardized criteria are lacking. We performed a retrospective analysis of 1057 pediatric patients who received allogeneic HCT to evaluate the incidence and risk factors of AKI according to AKI Network criteria within the first 100 days of HCT. We also determined the effect of AKI on patient survival. The 100-day cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT) were 68.2%?±?1.4%, 25.0%?±?1.3%, and 7.6%?±?.8%, respectively. Overall survival at 1 year was not different between patients without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%, respectively) but was significantly different between patients without AKI and patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3% versus 7.5%, respectively; P?<?.001). Age, year of transplantation, donor type, sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD) were independent risk factors for stages 1 through 3 AKI. Age, donor, conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk factors for AKI requiring RRT. Our study revealed that AKI was a prevalent adverse event, and severe stage 3 AKI, which was associated with reduced survival, was common after pediatric allogeneic HCT. All patients receiving allogeneic HCT, especially those with multiple risk factors, require careful renal monitoring according to standardized criteria to minimize nephrotoxic insults.     

冠状动脉旁路移植术后急性肾损伤的危险因素分析

目的 对比冠状动脉旁路移植术(coronary artery bypass grafting,CABG)后急性肾损伤(acute kidney injury,AKI)诊断标志物的表达水平,分析CABG后AKI的危险因素.方法 选取73例CABG患者作为研究对象,以CABG是否发生AKI分组为AKI组与对照组;对比两组患者术后24h血清肌酐(serum creatinine,Scr)、血清尿素氮(serum urea nitrogen,BUN)、尿液胱抑素C(urine cystatin C,Cys C)及肾损伤分子-1(kidney injury molecule-1,KIM-1)的表达水平;以AKI为作因变量,而患者的临床资料作为自变量,分析CABG后AKI的危险因素,并进行多因素及单因素Logistic回归分析,为CABG后AKI的预防策略提供依据.结果 AKI组与对照组术前Scr、BUN、Cys C及KIM-1的表达水平对比,差异均无统计学意义(P ＞0.05);AKI组术后Scr、BUN、Cys C及KIM-1的表达水平均显著高于对照组,两组数据差异具有统计学意义(t分别为3.586、3.728、4.325、3.089,P均小于0.05);单因素Logistic回归分析显示,年龄、高血压、移植血管桥数量、机械通气时间及术后低心排作为CABG后AKI的危险因素;多因素Logistic回归分析显示,年龄、移植血管桥数量及术后低心排作为CABG后AKI的独立危险因素,具有统计学意义(P＜0.05).结论 CABG后应密切监测患者的Scr、BUN、Cys C及KIM-1的表达水平,作为AKI的诊断标志物;年龄、移植血管桥数量及术后低心排作为CABG后AKI的独立危险因素,应严格进行术前评估、降低手术风险、围术期保护及改善肾功能,降低CABG后AKI发生的风险.     

Incidence and Risk Factors of Acute Kidney Injury after Radical Cystectomy: Importance of Preoperative Serum Uric Acid Level

Background: Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. While radical cystectomy associates significantly with an increased risk of serious complications, including AKI, risk factors of AKI after radical cystectomy has not been reported. This study was performed to determine the incidence and independent predictors of AKI after radical cystectomy.Methods: All consecutive patients who underwent radical cystectomy in 2001-2013 in a single tertiary-care center were identified. Their demographics, laboratory values, and intraoperative data were recorded. Postoperative AKI was defined and staged according to the Acute Kidney Injury Network criteria on the basis of postoperative changes in creatinine levels. Independent predictors of AKI were identified by univariate and multivariate logistic regression analyses.Results: Of the 238 patients who met the eligibility criteria, 91 (38.2%) developed AKI. Univariate logistic regression analyses showed that male gender, high serum uric acid level, and long operation time associated with the development of AKI. On multivariate logistic regression analysis, preoperative serum uric acid concentration (odds ratio [OR] = 1.251; 95% confidence interval [CI] = 1.048-1.493; P = 0.013) and operation time (OR = 1.005; 95% CI = 1.002-1.008; P = 0.003) remained as independent predictors of AKI after radical cystectomy.Conclusions: AKI after radical cystectomy was a relatively common complication. Its independent risk factors were high preoperative serum uric acid concentration and long operation time. These observations can help to prevent AKI after radical cystectomy.     

Transplantation of Umbilical Cord Blood Stem Cells for Treating Spinal Cord Injury

Spinal cord injury (SCI) develops primary and secondary damage to neural tissue and this often results in permanent disability of the motor and sensory functions. However, there is currently no effective treatment except methylprednisolone, and the use of methylprednisolone has also been questioned due to its moderate efficacy and the drug’s downside. Regenerative medicine has remarkably developed since the discovery of stem cells, and many studies have suggested the potential of cell-based therapies for neural injury. Especially, the therapeutic potential of human umbilical cord blood cells (hUCB cells) for intractable neurological disorders has been demonstrated using in vitro and vivo models. The hUCB cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Their ability to produce several neurotropic factors and to modulate immune and inflammatory reactions has also been noted. Recent evidence has emerged suggesting alternative pathways of graft-mediated neural repair that involve neurotrophic effects. These effects are caused by the release of various growth factors that promote cell survival, angiogenesis and anti-inflammation, and this is all aside from a cell replacement mechanism. In this review, we present the recent findings on the stemness properties and the therapeutic potential of hUCB as a safe, feasible and effective cellular source for transplantation in SCI. These multifaceted protective and restorative effects from hUCB grafts may be interdependent and they act in harmony to promote therapeutic benefits for SCI. Nevertheless, clinical studies with hUCB are still rare because of the concerns about safety and efficiency. Among these concerns, the major histocompatibility in allogeneic transplantation is an important issue to be addressed in future clinical trials for treating SCI.     

Incidence and Risk Factors for Nontuberculous Mycobacterial Infection after Allogeneic Hematopoietic Cell Transplantation

Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT. This retrospective cohort study included all patients with allogeneic HCT at our institution during 2001 to 2013. Patients who developed significant NTM infection (NTM disease) were identified. Multivariable modeling was used to identify risk factors for NTM disease, and a risk score model was constructed to identify high-risk patients. Of 1097 allogeneic HCT patients, 45 (4.1%) had NTM isolated and 30 (2.7%) had NTM disease (28 [93.3%] exclusively pulmonary, 2 [6.7%] pulmonary plus another site). Incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9% to 4.0%). The median time to diagnosis was 343 days (range, 19 to 1967). In Fine-Gray proportional hazards modeling, only global severity of chronic graft-versus-host disease (cGVHD) (HR,?1.99; 95% CI, 1.12 to 3.53; P?=?.019,) and cytomegalovirus (CMV) viremia (HR,?5.77; 95% CI, 1.71 to 19.45; P?=?.004) were significantly associated with NTM disease. Using these variables a risk score was calculated: 1 point for CMV viremia or moderate cGVHD and 2 points for severe cGVHD. The score divided patients into low risk (0 to 1 points, n?=?820 [77.3%], 3-year NTM risk 1.2%), intermediate risk (2 points, n?=?161 [15.4%], 3-year NTM risk 7.1%), and high risk (3 points, n?=?56 [5.4%], 3-year NTM risk 14.3%). NTM disease after allogeneic HCT is common. Severe cGVHD and CMV viremia are associated with increased risk, permitting risk stratification.     

Acute Kidney Injury after CAR-T Cell Therapy: Low Incidence and Rapid Recovery

Chimeric antigen receptor (CAR) T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies. Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are recognized toxicities of CAR-T, whereas kidney injury remains less well recognized. The objective of the present study was to identify the incidence of acute kidney injury (AKI) after CAR-T cell therapy, potential risk factors, and recovery of kidney function. We performed a retrospective review of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T therapy between February 2018 and February 2019 at our institution. Serum creatinine values before CAR-T therapy through day 100 were used to assess AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5- to <2-fold of baseline; grade 2, 2- to <3-fold of baseline; grade 3, ≥3-fold of baseline. CRS and ICANS were graded using the consensus criteria of the American Society of Transplantation and Cellular Therapy. The overall incidence of CRS was 78.3% (95% confidence interval [CI], 66% to 90.5%), of whom 13% (95% CI, 3.3% to 22.8%) developed grade 3-4 CRS, whereas the overall incidence of ICANS was lower at 45.7% (95% CI, 3.1% to 60.3%). The cumulative incidence of any grade AKI by day 100 was 30% (95% CI, 16.9% to 43.9%), with a grade 1 AKI incidence of 21.7% (95% CI, 9.7% to 33.8%) and a grade 2-3 AKI incidence of 8.7% (95% CI, .4% to 17%). No patients developed severe AKI necessitating renal replacement therapy. Patients with previous autologous or allogeneic stem cell transplantation, those requiring intensive care unit level care and with grade 3-4 CRS had a higher incidence of AKI. Most patients recovered, with kidney function returning to baseline within 30 days. We conclude that with early recognition and management of CAR-T complications, the incidence of AKI is low, the severity of injury is mild, and most patients recover kidney function within 30 days.     

Platelet Transfusion Refractoriness in Single-Unit Cord Blood Transplantation for Adults: Risk Factors and Clinical Outcomes

Platelet transfusion refractoriness (PTR) is frequently observed after allogeneic hematopoietic cell transplantation (HCT). However, the incidence of and risk factors for PTR, and impact of PTR on transplant outcomes after cord blood transplantation (CBT) have not been fully investigated. We retrospectively analyzed 185 adult patients who received single-unit CBT in our institute. The mean 16-hour corrected count increment (CCI) for the 5840 platelet transfusions was 3.68?×?10⁹/L. Among them, 3196 transfusions (54.7%) were associated with a PTR with 16-hour-CCI <4.5?×?10⁹/L. Results of multivariate analysis indicated that the following factors were significantly associated with decreased platelet transfusion responses: female sex with pregnancy history, male sex, the presence of HLA class I antibody, lower cord blood total nucleated cell dose, lower cord blood CD34⁺?cell dose, 3 locus HLA disparities, body temperature ≥38°C, C-reactive protein ≥10?mg/dL, cytomegalovirus reactivation, use of foscarnet, and use of liposomal amphotericin B. By contrast, graft-versus-host disease prophylaxis including methotrexate, ABO minor mismatch, use of ganciclovir, and use of linezolid were significantly associated with better platelet transfusion responses. PTR had a significant effect on poor neutrophil and platelet recovery, and overall mortality after CBT. These data suggest that early phase PTR may be predictive of engraftment and mortality after single-unit CBT for adults.     

Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome

Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P < .001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.     

Urinary Liver-Type Fatty Acid-Binding Protein Linked with Increased Risk of Acute Kidney Injury after Allogeneic Stem Cell Transplantation

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.     

Incidence,Risk Factors,Outcomes, and Risk Score Model of Acute Pancreatitis after Allogeneic Hematopoietic Stem Cell Transplantation

Acute pancreatitis (AP) has been recognized as an uncommon yet potentially lethal complication after hematopoietic stem cell transplant (HSCT). This retrospective, nested, case-control study reviewed data from 5284 consecutive patients who underwent allogeneic (allo)-HSCT between 2009 and 2018 at a single center, identifying 40 patients (0.76%) with AP after allo-HSCT. The diagnosis and severity of AP were established and classified according to existing criteria. Younger age (P = .008), grades II to IV acute graft-versus-host disease (P = .010), a history of donor lymphocyte infusion (P = .033), and pre-existing gallstones (P = .003) were independent risk factors of AP after allo-HSCT. Post-transplant AP had a trend to negatively influence overall survival (OS) and nonrelapse mortality (NRM) (P = .063) for allo-HSCT recipients, but no significant difference was found. Patients with moderately severe and severe AP had significantly lower OS (P = .002) and higher NRM (P = .000) than other patients. Based on these findings, a risk score model was also established to predict the occurrence of AP. Our risk score model performed well in terms of discrimination when applied to derivation samples. Patients were classified into a low-risk group (0 to 1 point), a medium-risk group (2 to 3 points), and a high-risk group (4 points or more). Significant difference was observed in AP incidence among the 3 groups. The predictive tool explored by our study might contribute to target high-risk patients and guide personalized AP prevention in allo-HSCT recipients.     

Unrelated Cord Blood Transplantation after Myeloablative Conditioning in Adults with Acute Myelogenous Leukemia

We analyzed the disease-specific outcomes of adult acute myelogenous leukemia (AML) patients treated with unrelated cord blood transplantation (CBT) after myeloablative conditioning. Between August 1998 and February 2008, 77 adult patients with AML were treated with unrelated CBT. All patients received 4 fractionated 12 Gy total body irradiation (TBI) and chemotherapy as myeloablative conditioning. The median age was 45 years, the median weight was 55 kg, the median number of nucleated cells was 2.44 × 10⁷/kg, and the median number of CD34-positive cells was 1.00 × 10⁵/kg. All patients received a single and HLA mismatched cord blood unit. The cumulative incidence of neutrophil recovery at day 50 and platelet recovery at day 200 was 94.8% and 91.7%, respectively. A higher CD34-positive cell dose was associated with faster hematopoietic recovery. The cumulative incidence of grade III to IV acute graft-versus-host disease (aGVHD) and extensive-type chronic GVHD (cGVHD) was 25.1% and 28.6%, respectively. With a median follow-up of 78 months, the probability of event-free survival (EFS) at 5 years was 62.8%. The 5-year cumulative incidence of treatment related-mortality (TRM) and relapse was 9.7%, 25.8%, respectively. In multivariate analyses, the risk factor identified for event free survival (EFS) was disease status and cytogenetics. These results suggest that unrelated CBT after myeloablative conditioning could be safely and effectively used for adult patients with AML.     

Impact of Acute Kidney Injury on Long-Term Mortality after Nonmyeloablative Hematopoietic Cell Transplantation

Acute kidney injury (AKI) occurs frequently after nonmyeloablative hematopoietic cell transplantation (HCT). The severity of AKI after nonmyeloablative HCT has association with short-term mortality. However, the long-term effect of AKI on survival after nonmyeloablative HCT is not known. We performed a retrospective analysis of patients who underwent an HLA matched nonmyeloablative HCT between 1997 and 2006. Patients were followed for a median of 36 (range: 3-99) months. AKI occurring up to day 100 was defined as a >2-fold increase in serum creatinine or requirement of dialysis. Of the 358 patients who were included in the analysis, 200 (56%) had AKI, 158 (44%) had no AKI. Overall, 158 patients (43%) died during follow-up. After controlling for potential confounders, the adjusted hazard ratio for overall mortality associated with AKI was 1.57 (95 % confidence interval [CI] 1.2-2.3; P = .0006). The adjusted hazards ratio of nonrelapse mortality (NRM) associated with AKI was 1.72 (95% CI 0.9-3.1; P = .07). AKI is an independent predictor of overall mortality after nonmyeloablative HCT. This finding reiterates the importance of identifying preventative strategies in nonmyeloablative HCT for attenuating incidence and severity of AKI.     

Defining Incidence and Risk Factors for Catheter-Associated Bloodstream Infections in an Outpatient Adult Hematopoietic Cell Transplantation Program

Allogeneic hematopoietic cell transplantation (HCT) patients are at an increased risk of developing central line–associated bloodstream infections (CLABSIs) due to prolonged periods of myelosuppression, immunosuppression, and indwelling catheter days. CLABSIs are among the most serious complications in HCT recipients and can lead to prolonged hospitalizations, intensive care unit admissions, lengthy antimicrobial therapies, and increased mortality. There is a lack of data regarding the incidence and risk factors associated with the development of CLABSIs in the HCT population undergoing outpatient transplantation. This was a single-center, retrospective analysis of adult patients who underwent allogeneic HCT between July 2012 and July 2016 in an outpatient transplant unit at a tertiary academic medical center. The primary outcome was the cumulative incidence of CLABSIs from the date of central line placement through the first 100 days post-transplantation. Secondary outcomes included risk factors for CLABSI, number of hospitalizations due to CLABSI, mortality rate at 6 months post-transplantation, and the cumulative incidence, speciation, and presence of multidrug resistance in identified microorganisms. Three hundred fifty-nine patients underwent allogeneic HCT at Vanderbilt University Medical Center and 352 were included for analysis. The cumulative incidence of CLABSIs was 9%, with the majority occurring within the first 30 days post HCT (67%). The use of a matched unrelated donor (MUD) and/or haploidentical donor (odds ratio, 3.993; 95% confidence interval [CI], 1.329 to 12.001; P?=?.0136) and use of an ablative conditioning regimen (odds ratio, 2.394; 95% CI, 1.052 to 5.446; P?=?.0374) were independently associated with development of a CLABSI on multivariate analysis. The most common organism implicated in CLABSI was Staphylococcus epidermidis (34%). Patients who developed a CLABSI had an almost 5 times higher risk of mortality at 6 months post-transplantation compared with patients who did not develop a CLABSI (hazard ratio, 4.932; 95% CI, 2.463 to 9.878; P?<?.001). There is a low incidence of CLABSIs in patients undergoing HCT in the outpatient setting. Patients who underwent HCT using a MUD or haploidentical donor and received ablative conditioning were at higher risk for developing CLABSIs. Overall mortality at 6 months post-transplantation was higher in patients who developed a CLABSI. Additional prospective studies are needed to confirm these observations.     

COMT-Val158Met-Polymorphism Is Not a Risk Factor for Acute Kidney Injury after Cardiac Surgery

Background. Cardiac surgery-associated acute kidney injury (CSA-AKI) depicts a major complication after cardiac surgery using cardiopulmonary bypass (CPB). Objective. CSA-AKI has clearly been linked to increased perioperative morbidity and mortality. Dysregulations of vasomotor tone are assumed to be causal for CSA-AKI. While catechol-O-methyltransferase (COMT) is involved in metabolizing catecholamines, a single-nucleotide polymorphism (SNP) in the COMT gene leads to different enzyme activities according to genotype. Pilot studies found associations between those COMT genotypes and CSA-AKI. Methods. We prospectively included 1741 patients undergoing elective cardiac surgery using cardiopulmonary bypass (CPB). Patients were genotyped for COMT-Val158Met-(G/A) polymorphism (rs4680). Results. Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between COMT genotypes and the RIFLE criteria could be detected. A multiple linear regression analysis for postoperative creatinine increase revealed highly significant associations for aortic cross-clamp time (P < 0.001), CPB time (P < 0.001), norepinephrine (P < 0.001), and age (P < 0.001). No associations were found for COMT genotypes or baseline creatinine. With an R² = 0.39 and a sample size of 1741, the observed power of the regression analysis was >99%. Conclusions. Based on our results, we can rule out an association between the COMT-Val158Met-(G/A) polymorphism and the appearance of CSA-AKI.