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Acute lymphoblastic leukemia (ALL) relapsed after allogeneic hematopoietic cell transplantation (allo-HCT) has a catastrophic prognosis. Blinatumomab, a CD3/CD19-directed bispecific T cell engager, is reportedly effective for advanced B-cell ALL (B-ALL), even after allo-HCT. However, the efficacy of blinatumomab in extramedullary relapse (EMR) is controversial. Donor lymphocyte infusion (DLI) is another immunological treatment worth considering for ALL relapsed after allo-HCT. We report the case of a 56-year-old woman with B-ALL. Allo-HCT was performed during the second complete remission (CR). Thirteen months after allo-HCT, isolated EMR (iEMR) of B-ALL developed without bone marrow lesions. A third CR was achieved with 2 cycles of blinatumomab. An additional four cycles each of blinatumomab and DLI were then administered. The patient did not develop graft-versus-host disease and has confirmed 2-year treatment-free remission without a second allo-HCT. Therefore, blinatumomab was considered an effective salvage therapy for iEMR of B-ALL after allo-HCT, because iEMR could have a lower tumor burden than that seen in systemic relapse, and low tumor burden was a prognostic factor for response to blinatumomab. Furthermore, immunological consolidation therapies could only provoke graft-versus-leukemia effects if the imbalanced effector/target ratio was restored and the tumor burden was lowered through immunosurveillance. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34–8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT. [ABSTRACT FROM AUTHOR]

A study published in the Blood Cancer Journal examines the effects of venetoclax (VEN) on the immune response in patients with relapsed acute myeloid leukemia (AML) after a specific type of stem cell transplant. The study shows that VEN therapy, when combined with azacitidine, improves survival rates and reduces the risk of relapse in these patients. The researchers also found that VEN therapy increases the number of specific immune cells that have the ability to target and kill leukemia cells. These findings suggest that VEN therapy could be a potential treatment option for AML patients who do not respond to standard treatments. However, more research with larger groups of patients is needed to confirm these results. The report is written by a group of experts in the field and is culturally sensitive, respecting different perspectives. It provides a comprehensive analysis of the topic and can be a valuable resource for library patrons conducting research in this area. [Extracted from the article]

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1–42.4%) and 3.5% (95%CI, 1.1–5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS. [ABSTRACT FROM AUTHOR]

Hepatomegaly is an extramedullary disease (EMD) manifestation of hematological malignancy. Although EMD before allogeneic hematopoietic stem cell transplantation (allo-HCT) is a risk factor for relapse in patients not in complete remission (NonCR) patients, the significance of hepatomegaly to allo-HCT is unclear. We conducted a single-center retrospective observational study of 140 patients with acute leukemia and myelodysplastic syndrome who underwent allo-HCT at our institution from 2014 to 2019. Hepatomegaly was assessed by ultrasonography using the liver index (LI). In the univariable analysis, the LI/height ratio was significantly associated with relapse (hazard ratio [HR] per standard deviation [sd]: 1.51, 95% confidence interval [CI] 1.18–1.93, p = 0.001, sd = 13.8) in NonCR patients (n = 62), but showed no significant association in CR patients (n = 78) (HR per sd: 0.95, 95% CI 0.64–1.39, p = 0.780, sd = 8.7). In multivariable analysis, the LI/height ratio was significantly associated with relapse (HR per sd: 1.34, 95% CI 1.02–1.78, p = 0.037) after adjusting for the refined disease risk index and conditioning intensity. Interaction analysis showed a noteworthy but not statistically significant association between the LI/height ratio and CR status (p = 0.110). In conclusion, our findings suggest that the LI may be a risk factor for relapse in NonCR patients after allo-HCT. [ABSTRACT FROM AUTHOR]

Control and prevention of invasive alien species (IAS) are important issues for the environmental management of dam reservoirs. Recently, environmental DNA (eDNA) analysis has been used for monitoring IAS in aquatic ecosystems. In this study, as a simple and user-friendly eDNA method for monitoring IAS, we developed an eDNA chip analysis for monitoring three IAS, largemouth bass Micropterus salmoides, smallmouth bass Micropterus dolomieu and bluegill sunfish Lepomis macrochirus, in dam reservoirs. The eDNA chip analysis using each IAS-specific primer and probe only amplified and detected the target species. The developed eDNA chip detected three IAS from water samples collected in five dam reservoirs, indicating that eDNA chip analysis can be used as a monitoring tool for IAS. However, IAS were not detected by the eDNA chip at some survey sites where the qPCR assays showed low eDNA concentrations, indicating a lower sensitivity of the eDNA chip at low eDNA concentrations. For the establishment of an eDNA chip for biomonitoring, some challenges faced by other techniques like qPCR and metabarcoding remain, such as sensitivity at low target concentrations and "real-time" detections in the field and further improvement of performance in eDNA chip will be required. [ABSTRACT FROM AUTHOR]

We evaluated 413 adult patients with lymphoma who underwent unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning between 2002 and 2017 to investigate longitudinal changes in outcomes and the optimal melphalan dose and graft-versus-host disease (GVHD) prophylaxis regimen. Outcomes were compared between FM80/100 (melphalan dose: 80 or 100 mg/m2) and FM140 (melphalan dose: 140 mg/m2), as well as between calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved over time (OS: 27% in 2000s vs. 42% in 2010s, p < 0.001; NRM: 43% in 2000s vs. 26% in 2010s, p < 0.001). Multivariable analysis showed that in the 2000s, melphalan dose and GVHD prophylaxis regimen did not affect any outcomes. In the 2010s, FM80/100 (vs. FM140) related to better OS (hazard ratio [HR] 0.62, p = 0.01) and NRM (HR 0.52, p = 0.016). MTX + CNI and CNI alone (vs. CNI + MMF) related to worse OS (CNI + MTX, HR 2.01, p < 0.001; CNI alone, HR 2.65, p < 0.001) and relapse/progression (CNI + MTX, HR 2.40, p < 0.001; CNI alone, HR 2.13, p = 0.023). In recent years, the use of FM80/100 and CNI + MMF significantly reduced the risk of NRM and relapse/progression, respectively, and resulted in better OS after UCBT for lymphoma. [ABSTRACT FROM AUTHOR]

A combination of three post-transplant drugs, cyclophosphamide (PTCy), a calcineurin inhibitor, and mycophenolate mofetil, has long been used for prophylaxis of graft-versus-host-disease (GVHD) after HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT). Recently, this combination has been used following HLA-matched allo-HCT as well, but the optimal combination of drugs for GVHD prophylaxis in an HLA-matched setting remains unclear. This prospective phase II study evaluated the safety and efficacy of PTCy plus tacrolimus (TAC) for GVHD prophylaxis after allo-HCT from HLA-matched related donors (MRD) or HLA-matched unrelated donors (MUD). The cumulative incidences of grades II–IV and III–IV acute GVHD at 100 days post-transplantation were 18% and 5.9%, respectively, in the MRD group, and 18% and 9.1%, respectively, in the MUD group. The cumulative incidences of moderate to severe chronic GVHD at 1 year were 12% and 9.1% in the MRD and MUD groups, respectively. The 1-year overall survival rates in the MRD and MUD groups were 88% and 64%, respectively, and the 1-year GVHD-free, relapse free survival rates were 59% and 50%, respectively. These results suggest that GVHD prophylaxis with a less intensive double drug combination (PT/Cy and TAC) might be feasible after HLA-matched allo-HCT. Clinical Trial Notation This trial was a prospective single-center trial registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification number: UMIN000023890) and the Japan Registry of Clinical Trials (jRCTs051180143). [ABSTRACT FROM AUTHOR]

T-PLL progression accompanied a more prolonged APTT and systemic hemorrhage, which was indicated an exacerbated paraneoplastic coagulation disorder. Treatment of acquired coagulopathies requires inhibitor eradication, hemostatic therapy, and control of underlying disease. [Extracted from the article]

The pathophysiology of immune thrombocytopenia (ITP) is poorly understood, particularly aspects regarding abnormal homeostasis and dysregulation of B cells. In this study, we analyzed peripheral lymphocyte subsets in patients with untreated ITP and healthy controls, and examined correlations between cell percentages/counts and titers of serum cytokines and antibodies. We also compared ITP patients who later required second-line therapies and those who did not. The percentages of CD19 + CD24highCD38high regulatory B cells, pre-germinal center (GC) B cells, and plasmablast-like B cells were significantly higher in ITP patients than in healthy controls. Absolute counts of regulatory B cells and pre-GC B cells were significantly higher in those who needed second-line therapies. In addition, serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) levels and platelet-associated immune globulin G antibody titers correlated positively with regulatory B cell, pre-GC B cell, and auto-reactive B cell counts. Serum interferon-α (IFN-α) levels were elevated in four ITP patients with high auto-reactive B cell counts. These results indicate that increases in regulatory B cells and pre-GC B cells may reflect activated autoimmunity induced by BAFF and/or IFN-α. Consequently, evaluation of B cell subsets in untreated ITP patients may predict treatment response. [ABSTRACT FROM AUTHOR]

Nonlinear phenomena are universal in ecology. However, their inference and prediction are generally difficult because of autocorrelation and outliers. A traditional least squares method for parameter estimation is capable of improving short-term prediction by estimating autocorrelation, whereas it has weakness to outliers and consequently worse long-term prediction. In contrast, a traditional robust regression approach, such as the least absolute deviations method, alleviates the influence of outliers and has potentially better long-term prediction, whereas it makes accurately estimating autocorrelation difficult and possibly leads to worse short-term prediction. We propose a new robust regression approach that estimates autocorrelation accurately and reduces the influence of outliers. We then compare the new method with the conventional least squares and least absolute deviations methods by using simulated data and real ecological data. Simulations and analysis of real data demonstrate that the new method generally has better long-term and short-term prediction ability for nonlinear estimation problems using spawner–recruitment data. The new method provides nearly unbiased autocorrelation even for highly contaminated simulated data with extreme outliers, whereas other methods fail to estimate autocorrelation accurately. [ABSTRACT FROM AUTHOR]

We evaluated the impact of FLT3-ITD, NPM1 mutations, and double mutant CEBPa (dmCEBPa) on overall survival (OS) after relapse in patients with cytogenetically intermediate-risk acute myeloid leukemia (AML) who were treated with chemotherapy alone in the first remission (CR1). Patients aged 16–65 years diagnosed with cytogenetically intermediate-risk AML, and who achieved CR1 were included. We retrospectively analyzed FLT3-ITD, NPM1 mutations and CEBPa using samples obtained at diagnosis, which therefore did not affect the therapeutic decisions. Among 235 patients who had achieved CR1, 152 relapsed, and 52% of them achieved second CR. The rate of achieving second CR was significantly higher (85%) in those with dmCEBPa. Patients with FLT3-ITD had significantly worse OS after relapse than those without (19% vs 41%, p = 0.002), while OS was comparable between patients with and without NPM1 mutations (37% vs 34%, p = 0.309). Patients with dmCEBPa had improved OS than those without (61% vs 32%, p = 0.006). By multivariate analysis, FLT3-ITD was independently associated with worse OS after relapse [hazard ratio (HR) 1.99, 95% CI 1.27–3.12, p = 0.003], and dmCEBPa with improved OS (HR 0.40, 95% CI 0.17–0.93, p = 0.033). Our data show that screening for these mutations at diagnosis is useful for facilitating effective therapeutic decision-making even after relapse. [ABSTRACT FROM AUTHOR]

This phase I study was designed for graft-versus-host disease (GVHD) prophylaxis including bortezomib in allogeneic hematopoietic cell transplantation (allo-HCT) from human leukocyte antigen (HLA)-mismatched unrelated donors in Japanese patients. Patients were administered bortezomib on days 1, 4, and 7, with short-term methotrexate and tacrolimus. Three bortezomib dose levels were prepared (1.0, 1.3, and 1.5 mg/m2). A dose of 1.3 mg/m2 was planned for administration to the initial six patients, and was adjusted if dose-limiting toxicity developed. Five of six patients enrolled for the initial dose had bone marrow donors. Two cases had single-antigen and single-allele mismatches; four had single-antigen mismatch at the A, B, C, and/or DRB1 loci in the GVH direction. All patients achieved neutrophil engraftment and complete donor chimerism. Three patients developed grade II acute GVHD, and none developed grade III-IV GVHD or any dose-limiting toxicity attributable to bortezomib by day 100. Two patients developed late-onset acute GVHD, and two developed chronic GVHD, but all cases were manageable. All patients were alive without relapse after a median follow-up period of 52 months. The optimal dose of bortezomib was determined to be 1.3 mg/m2. Prophylaxis against GVHD using a regimen including bortezomib thus seems feasible for HLA-mismatched unrelated allo-HCT. [ABSTRACT FROM AUTHOR]

The abundance index used in a tuned virtual population analysis (VPA) is usually assumed to be proportional to actual abundance. However, the actual abundance and abundance index do not always have a linear relationship. Such nonlinearity can cause biases in abundance estimates as well as retrospective biases arising from systematic differences in abundance estimates when more data are successively added. Severe retrospective biases can damage the reliability of stock assessments. In this study, we use an approach to estimate an additional parameter that controls the nonlinearity in a tuned VPA. A performance test using simulated data revealed that the tuned VPA was able to accurately estimate the nonlinearity parameter and thus yielded less biased abundance estimates and smaller retrospective biases. We also found that estimating the nonlinearity parameters was effective even under other model misspecification scenarios, such as disregarding historical increases in catchability and time-varying natural mortality. Moreover, we applied this approach to some Japanese fish stocks and evaluated its validity. We found that estimating the nonlinearity parameters in the tuned VPA enhances the reliability of fisheries stock assessments. [ABSTRACT FROM AUTHOR]

Dear Editor, We have read with great interest the report by Wang et al. [[1]] regarding autologous hematopoietic stem cell transplantation (ASCT) following polatuzumab vedotin combined with rituximab-bendamustine (Pola-BR) for relapsed diffuse large B-cell lymphoma (rDLBCL) to improve its prognosis. Pola-BR may be used increasingly frequently in the future as a preceding therapy for patients scheduled to undergo CAR-T therapy or allogeneic transplantation. [Extracted from the article]

Limited access to aquatic populations hinders estimation of their status and establishment of effective management measures. We propose a modified surplus production model to cope with this problem. The model provides population parameters and biological reference points from a time series of annual accessible abundance data. Simulation tests showed that the model provided biological reference point estimates with little bias when sufficiently long time series were available. Even for short time series, we could obtain nearly unbiased estimates by providing information on the exploitation rate at the maximum sustainable yield ( F ). As an application, we fit the modified surplus production model to 7-year accessible biomass estimates of a local population of Japanese spiky sea cucumber Apostichopus japonicus using a Bayesian approach. The results indicated that the stock in the area studied was likely to have experienced recent overfishing and had a high probability of being overfished in the future. [ABSTRACT FROM AUTHOR]

Purpose: Although a few prospective studies have addressed the question as to which biomarker of infection in adult patients with febrile neutropenia (FN) is superior, procalcitonin (PCT) or C-reactive protein (CRP), the results have been inconsistent and inconclusive. This was possibly due to the poor sensitivity of previous PCT tests that have a functional sensitivity of 0.5 ng/ml. Methods: Between November 2010 and February 2012, we prospectively compared the diagnostic utility of serum high-sensitivity (hs) PCT (lower limit of detection, 0.02 ng/ml) and CRP levels for detecting bacterial infection in patients with FN. Serum was collected within 72 h after the onset of FN in patients with hematological disorders. Results: Seventy-five febrile episodes were evaluable. The areas under the receiver operating characteristic curves for life-threatening infection defined as septic shock and bacteremia caused by non-coagulase negative staphylococcus were 0.824 (95 % CI 0.711-0.937; P = 0.001) for hsPCT and 0.673 (0.505-0.842; P = 0.068) for CRP, respectively. In contrast, CRP, but not hsPCT, tended to increase significantly with the clinical severity, as indicated by the diagnostic classification ( P = 0.002 for trend). Conclusions: The serum hsPCT test may be more useful than the serum CRP test in the detection of life-threatening infection at an early phase after the onset of FN. In contrast, the serum CRP test may be more useful in diagnosing the severity of infection. However, neither of these tests was able to differentiate the cause of FN with a low probability of fatal outcome. [ABSTRACT FROM AUTHOR]

This study used a delta-lognormal model to analyze monthly catches of age-0 Pacific bluefin tuna by the troll fishery. The model included fixed effects of month, area, and month-area interaction, and random effects of port, year and port-year interaction. The catch patterns by month and area predicted by the statistical model (standardized catch) revealed that main fishing grounds along the Tsushima Warm Current generally shifted from north to south as the season turned from autumn to winter. In contrast, the standardized catch along the Kuroshio Current did not show such clear spatiotemporal patterns. The standardized catch along the Tsushima Warm Current is significantly associated with average monthly sea surface temperatures in the fishing grounds and consistent with migration routes revealed by tagging experiments in previous studies. These associations indicate the spatiotemporal catch pattern in the Tsushima Warm Current region partly reflects seasonal migration. Knowledge of the possible associations among fish migration, environmental factors and spatiotemporal distribution of the catch will contribute to future management of this species. [ABSTRACT FROM AUTHOR]

The article presents a research related to quantifying resource selection in animal ecology. It notes that the autocorrelation of data in ecological researches causes difficulties for most standard statistical procedures of resource selection. Accordingly, a mixed-effects model is developed to estimate resource selection functions from the data. It states that the model applied the expectation-maximization (EM) algorithm by proposing a Monte Carlo EM algorithm with Gibbs sampling.

The management of Japanese domestic fisheries for small cetaceans has been based on a traditional approach that involves only the best set of assumptions and data. However, uncertainty, which is pervasive and inevitable for most fisheries resources, often leads the traditional approach to serious failure. Here is presented the basic framework of a simulation-based approach with a simple Bayesian method that is applicable to Japanese fisheries for small cetaceans. For illustration, the simulation model was applied to Dall's porpoise data in order to investigate the robustness of several management procedures against uncertainty. The simulation showed that the current management procedure, based on only the best values, could fail to manage the stocks at a considerably high probability. However, the use of the conservative management procedure, potential biological removal, permits the sustainable harvesting of Dall's porpoise for at least 100 years into the future, even under uncertainty. In conjunction with a firm structure for implementation of management procedures, the spread of simulation-based approaches will quickly enable successful sustainable management of small cetaceans. [ABSTRACT FROM AUTHOR]

Population sizes of long-diving marine mammals can be estimated with minimal bias using line transect sampling techniques in conjunction with data on surfacing/diving, even though the detection probability on the trackline is considerably less than 1. Using a simulation, it was investigated whether population sizes can be accurately estimated when only the mean cue production rate, without information on surfacing/diving patterns, is available. In addition, a new model that incorporates information on surfacing/diving patterns into the estimation procedure was developed. The simulation showed that the new model can provide less biased abundance estimates, whereas neglecting surfacing/diving patterns can result in serious underestimates of abundance, in particular for long-diving animals. [ABSTRACT FROM AUTHOR]

Long-diving marine mammals, such as sperm whales and Baird's beaked whales are frequently missed in line transect sampling even though they are on the trackline. The methods so far developed to estimate the proportion of animals missed on the trackline are complicated or sensitive to model assumptions. A simpler model is developed in the present study. The model requires an estimate of mean surfacing rate that is independent of the line transect survey and does not require any complicated survey design and non-robust parameters, such as scan rate of the binoculars of observers. In addition, it can flexibly take account of systematic heterogeneity using covariates. The abundance is estimated using the Horvitz-Thompson estimator. The simulation test showed that the proposed method is promising. [ABSTRACT FROM AUTHOR]

Two cases of serous surface carcinoma of the peritoneum (SSCP) are discussed. The first patient was a 48-year-old Japanese woman with abdominal pain and fullness. The second patient was a 66-year-old Japanese woman with abdominal fullness. In both patients, laparotomy revealed many tumor nodules on the peritoneal surface. However, the ovaries, the uterus, and other intraperitoneal organs were free from tumors. The serum levels of CA125 were excessively elevated. The tumor cells were arranged in a papillotubular pattern. Mitoses were frequent. Diastaseresistant PAS-positive, and hyaluronidase-resistant alcian blue-positive materials were observed. In immunohistochemistry, the tumor cells showed positive reactions for cytokeratin, EMA, CA125, and HBME-1, and, in contrast, negative reactions for CEA, thrombomodulin, vimentin, and HHF35. In analysis for Ber-EP4, all tumor cells of case 1 were negative, and a few tumor cells of case 2 were positive. Ultrastructurally, hobnail-shaped tumor cells rested on a continuous basal lamina. Each cell was attached to short desmosomes. Microvilli were slender, straight, and short, and some had core rootlets. Many primary lysosomes were aggregated in the basal portion of the cytoplasm. A few well-differentiated ciliated cells were present. These two cases were diagnosed as SSCP. [ABSTRACT FROM AUTHOR]

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