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Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening blood disorder characterized by the formation of blood clots in small blood vessels. It is caused by antibodies targeting the A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13), which plays a role in cleaving von Willebrand factor. Most patients with iTTP have autoantibodies against specific domains of the ADAMTS13 protein, particularly the cysteine-rich and spacer domains. This study aimed to identify ADAMTS13 muteins that are resistant to autoantibodies and maintain their enzymatic activity. A panel of muteins was generated using rational and random mutagenesis methods and screened for autoantibody binding and ADAMTS13 activity. The selected muteins were assessed for pharmacodynamic biomarkers and pharmacokinetic profiles in the iTTP-mimic and wild-type mice, respectively. GC1126A was the most effective variant for escaping autoantibodies and had a longer half-life than the wild-type ADAMTS13 fragment (MDTCS). In the iTTP-mimic mouse model, GC1126A treatment significantly improved platelet counts, lactate dehydrogenase levels, and ADAMTS13 residual activity. In addition, GC1126A outperformed recombinant human wild-type ADAMTS13 (rh WT-ADAMTS13) and caplacizumab in terms of platelet recovery and sustained effectiveness. Results from the ex vivo study using plasma from patients with iTTP showed that GC1126A exhibited higher residual activity than rh WT-ADAMTS13, particularly in patients with high autoantibody titers. These findings suggest that GC1126A could be a promising new treatment option for patients with iTTP.

ABSTRACT Background The prognostic significance of extranodal sites in stage IV diffuse large B‐cell lymphoma (DLBCL) remains uncertain, making it challenging to select appropriate treatment strategies for individual patients. In this study, we aimed to evaluate the influence of different extranodal sites on prognosis in young patients with stage IV DLBCL who achieved complete remission (CR) following initial chemo‐immunotherapy and to explore the potential of autologous hematopoietic stem cell transplantation (ASCT) as a consolidation treatment for specific patient subgroups. Methods We retrospectively reviewed data from 119 patients with DLBCL aged

IntroductionMonomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, aggressive subtype of primary gastrointestinal T-cell lymphoma. Owing to the absence of symptoms characteristic of MEITL, diagnosis can be challenging, and the low response rate to conventional chemotherapy leads to an abysmal prognosis. This study aimed to define the clinicopathologic characteristics of MEITL in Korea, evaluate the clinical outcomes of intensive chemotherapy with and without hematopoietic stem cell transplantation (HSCT), and explore prognostic factors.MethodsThis single-center retrospective study examined the clinical data of 35 patients diagnosed with MEITL at Seoul St. Mary’s Hospital from May 2012 to May 2023.ResultsWe included 22 men and 13 women (median age: 59 years; range: 37–79 years). Many patients exhibited acute abdominal pain (n=23, 65.7%) related to bowel perforation (n=21, 60.0%). Most patients (30/35, 85.7%) underwent surgical intervention to diagnose MEITL, whereas only five were diagnosed via endoscopic evaluation. Of the 32 patients receiving first-line therapy, 4 died before assessment, 10 achieved a complete response (CR), 6 had a relapse, and 18 exhibited progressive disease (PD). Seven of 10 patients received upfront HSCT, either autologous (auto-HSCT, n=4) or allogeneic (allo-HSCT, n=3). All four patients on auto-HSCT died after relapse. All three patients who received allo-HSCT maintained a CR by the final follow-up. Three of 6 patients who relapsed and 13 of 18 exhibiting PD received salvage therapy; one patient on salvage auto-HSCT with cytokine-induced killer cell infusion has survived progression free. Salvage allo-HSCT was performed on 6 of 16 patients; among them, 2 achieved a CR, 2 died after relapse, and 2 died owing to septic shock while maintaining a CR. The remaining patients, who received salvage therapy without HSCT, mostly died owing to PD. The median overall survival was 12.1 months, and the median follow-up was 33.2 months. The 1- and 5-year overall survival was 50.9% and 13.3%, respectively.DiscussionMEITL is an aggressive disease resistant to conventional therapy. Therefore, intensive chemotherapy followed by upfront allo-HSCT should be considered upon diagnosis. These findings underscore the need for novel therapeutic strategies and further investigation into optimizing treatment protocols for MEITL.

Acute lymphoblastic leukemia (ALL) is one of the most rapidly changing hematological malignancies with advanced understanding of the genetic landscape, detection methods of minimal residual disease (MRD), and the development of immunotherapeutic agents with good clinical outcomes. The annual incidence of adult ALL in Korea is 300–350 patients per year. The WHO classification of ALL was revised in 2022 to reflect the molecular cytogenetic features and suggest new adverse-risk subgroups, such as Ph-like ALL and ETP-ALL. We continue to use traditional adverse-risk features and cytogenetics, with MRD-directed post-remission therapy including allogeneic hematopoietic cell transplantation. However, with the introduction of novel agents, such as ponatinib, blinatumomab, and inotuzumab ozogamicin incorporated into frontline therapy, good MRD responses have been achieved, and overall survival outcomes are improving. Accordingly, some clinical trials have suggested a possible era of chemotherapy-free or transplantation-free approaches in the near future. Nevertheless, relapse of refractory ALL still occurs, and some poor ALL subtypes, such as Ph-like ALL and ETP-ALL, are unsolved problems for which novel agents and treatment strategies are needed. In this review, we summarize the currently applied diagnostic and therapeutic practices in the era of advanced genetic analysis and targeted immunotherapies in United States and Europe and introduce real-world Korean data.

Abstract To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.

Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease. We analyzed 78 patients with biopsy-confirmed hepatic GVHD (n = 38) or autoimmune liver disease (n = 40) between 2016 and 2021. The cholestatic variant was defined by an R-value < 2.0, based on the ratio of alanine aminotransferase to alkaline phosphatase. The primary outcome was the biochemical response at 4 (early) and 8–12 (late) weeks after corticosteroid treatment. In hepatic GVHD patients, the hepatitic variant (n = 19) showed greater CD3+ T-cell infiltration than the cholestatic variant (n = 19; p < 0.001). No significant differences were observed in the infiltration of CD20+, CD38+, or CD68+ cells. The hepatitic variant had significantly better early and late responses and higher liver-related event-free survival than the cholestatic variants (p < 0.05). Concerning autoimmune liver diseases, the autoimmune hepatitis (AIH) group had significantly more portal T-cell infiltration and better treatment responses than the primary biliary cholangitis (PBC) group. In conclusion, higher portal T-cell infiltration may be associated with better clinical outcomes in patients with hepatic GVHD. Additionally, this study highlights similarities in portal T-cell infiltration and treatment response patterns between AIH and the hepatitic variant, as well as PBC and the cholestatic variant.

Abstract Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p

IntroductionIntensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking.MethodsTherefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined.ResultsAll GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival.DiscussionThis study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.

Background: Blinatumomab showed a higher complete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Objectives: We tried to analyze the outcome of blinatumomab compared with the real-world historical data. We expected superior outcome of blinatumomab compared with historical conventional chemotherapy. Design: We conducted a retrospective study using real-world data in the Catholic Hematology Hospital. Methods: Total 197 consecutive cases of R/R BCP-ALL were treated with conventional chemotherapy ( n = 113) or blinatumomab, which was available since late 2016 ( n = 84). Patients who achieved CR underwent allo-HCT if donor was available. We conducted a propensity score–matched cohort analysis using 5 criteria of age, CR duration, cytogenetics, previous allo-HCT, and salvage lines between historical group and blinatumomab. Results: Each cohort consisted of 52 patients. In blinatumomab group, CR rate was higher (80.8% versus 53.8%, p = 0.006) and more patients proceeded to allo-HCT (80.8% versus 46.2%, p

BackgroundCastleman disease (CD), classified as unicentric CD (UCD) or multicentric CD (MCD), is a rare non-neoplastic lymphoproliferative disorder of unknown origin. Owing to its rarity, the clinical characteristics, therapeutic modalities, treatment outcomes, and prognostic factors related to UCD or MCD are not well defined.MethodWe retrospectively analyzed 88 patients with CD, including those with hyaline-vascular, plasma-cell, mixed type, hypervascular, and plasmablastic subtypes, for presenting symptoms, physical, laboratory, and radiologic findings, and treatment response in the Korean population.ResultsThe median patient age was 44 years (range: 18–84 years) with slight predominance of women (53.4%). UCD and MCD accounted for 38.6% (n=34) and 61.4% (n=54) of cases, respectively. Histopathologically, UCD patients were classified as 88.2% (n=30) hyaline-vascular and 11.8% (n=4) plasma cell types, whereas MCD patients were classified as 27.8% (n=15) hypervascular, 61.1% (n=33) plasma cell, 7.4% (n=4) mixed, and 3.7% (n=2) plasmablastic types. Twelve (13.6%) patients exhibited a poor performance status with an Eastern Cooperative Oncology Group score of 2. The most common presenting symptom was sustained fever, followed by fatigue, anorexia, peripheral edema, and weight loss. Furthermore, splenomegaly, pleural effusion, and ascites were observed to be associated with CD. Surgical resection and siltuximab were the preferred treatment modalities for UCD and MCD, respectively, with favorable symptomatic, laboratory, and radiologic outcomes and safety profiles. The overall survival was 90.2%, with no significant difference between the UCD and MCD groups (p=0.073), but progression-free survival was significantly poorer in the MCD group (p=0.001). Age ≥60 years and splenomegaly significantly affected the overall and progression-free survival rates.ConclusionPatients with UCD had favorable outcomes with surgical resection of a solitary mass, whereas in patients with MCD, old age and splenomegaly were identified as independent prognostic factors. Further well-designed prospective studies under advancing knowledge of the pathophysiology of MCD are warranted to establish suitable guidelines for the discontinuation or prolonging infusion intervals of siltuximab and treatment modalities for HHV-8 positive MCD patients or patients with siltuximab failure.

Background: Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML. Methods: We compared AML patients who received IC ( n = 89) to those who received a VEN in combination with hypomethylating agents or low dose cytarabine (VEN combination) ( n = 54) as their first- or second-line salvage after failing anthracycline-containing intensive chemotherapy. Results: The median age was 49 years, and significantly more patients in the VEN combination group were in their second salvage and had received prior stem cell transplantation (SCT). Overall response rates including CR, CRi, and MLFS were comparable (44.0% for IC vs. 59.3% for VEN combination, p = 0.081), but VEN combination group compared to IC group tended to show lower treatment related mortality. The rate of bridging to SCT was the same (68.5%), but the percentage of SCT at blast clearance was significantly higher in the VEN-combined group (62.3% vs. 86.5%, p = 0.010). After median follow-up periods of 22.5 (IC) and 11.3 months (VEN combination), the median overall survival was 8.9 (95% CI, 5.4-12.4) and 12.4 months (95% CI, 9.5-15.2) ( p = 0.724), respectively. Conclusion: VEN combination provides a comparable anti-leukemic response and survival to salvage IC, and provide a bridge to SCT with better disease control in medically-fit patients with R/R AML.

Background: Cord blood transplantation (CBT) has been reported as an acceptable option with comparable outcomes to conventional donors in adults with acute lymphoblastic leukemia (ALL). We aimed to analyze the long-term CBT outcomes and risk factors for early and long-term mortalities. Methods: Between 2006 and 2020, 112 patients (median age: 35 years; 62 Ph-negative ALL and 50 Ph-positive ALL) were treated with double CBT. Conditioning regimen consisted of total body irradiation (12 Gy) plus cytarabine (9.0 g/m 2 ) plus fludarabine (150 mg/ m 2 ), and graft-versus-host disease (GVHD) prophylaxis was attempted by administering tacrolimus plus mycophenolate mofetil. Results: The median time for neutrophil and platelet recovery was 25 days (range: 5–59 days) and 34 days (range: 7–185 days), respectively. The cumulative incidence of acute GVHD at 1 year was 43.8%, and the incidence of acute GVHD with grades III–IV was 8.9%. The overall cumulative incidence of chronic GVHD was 22.0%, and the incidence of moderate to severe chronic GVHD was 8.5%. After a median follow-up of 60.1 months (range: 5.7–181.3 months), the 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) were 15.9% and 28.5% (9.7% and 27.2% for CR1), respectively, and the 5-year overall survival (OS) was 57.9% (66.5% for CR1). In multivariate analysis of 88 patients receiving double CBT in CR1, delayed CR1 was related to high CIR, and age older than 40 years was associated with high NRM and early mortality. Unexpectedly, Ph-positive ALL with MRD had a higher NRM and early mortality than Ph-negative ALL and Ph-positive ALL without MRD subgroups, possibly due to delayed neutrophil and platelet recovery. Conclusion: Our data suggest that double CBT for adult ALL in CR1 has a greater benefit in younger patients and in patients with Ph-positive ALL without MRD or Ph-negative ALL.

The relationship between housing and stock prices has traditionally been positive and stable. However, prior research suggests this relationship can vary significantly under certain economic conditions. For instance, Yoon (2018) identified a typical business cycle between housing and stock prices in the U.S. and U.K. during oil shocks, the IT bubble collapse, and the 2008 financial crisis. This study examines whether such standard asymmetric behaviour exists across G7 countries using the FIML Markov-switching model developed by Yoon and Nawrot (2022). Our findings indicate that housing and stock prices exhibit a shared business cycle during major economic disruptions, such as oil shocks, the global financial crisis, and the COVID-19 pandemic. Notably, these periods are characterised by heightened volatility in both markets. Conversely, no significant co-movement between housing and stock prices is observed during normal economic periods. These results underscore the importance of considering asymmetric relationships in analysing the interconnected dynamics of housing and stock markets, particularly during financial instability. [ABSTRACT FROM AUTHOR]

This article discusses a scientific study conducted in 2010 by Alastruey-Izquierdo et al. The study focuses on the antifungal susceptibility profile of human-pathogenic species of Lichtheimia, a genus of fungi. The study aims to determine the minimum inhibitory concentrations of antifungal agents for these fungi. The article references a technical note by the Subcommittee on Antifungal Susceptibility Testing of the ESCMID in 2008, which provides a method for determining these concentrations. The study's findings and methodology can be explored further by accessing the full article. [Extracted from the article]