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Antithymocytic globulin (ATG) and post-transplant cyclophosphamide (PTCy) are frequently used regimens for graft-versus-host disease (GVHD) prophylaxis. However, there is a lack of data about the difference in regulatory T-cell (Treg) subpopulations between these two regimens. Peripheral blood samples were collected on day +21 following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and the Treg subpopulations were analyzed using flow cytometry. The Treg populations were categorized into three distinct subgroups: naïve, effector, and non-suppressive. And we compared overall survival (OS), the cumulative incidence of acute and chronic GVHD, and the relapse rate between the ATG and PTCy groups. We enrolled 45 patients (28 in ATG, 17 in PTCy) in total. In the ATG group, 16 and 12 patients underwent human leukocyte antigen (HLA) matched-sibling donor and unrelated donor HSCT, respectively. In the PTCy group, 12 patients underwent haplo-identical HSCT, and 5 patients underwent HLA-matched unrelated donor HSCT. The cumulative incidence of Grade 2–4 acute GVHD was 18.3% in the ATG group compared to 38.1% in the PTCy group (p = 0.13), while severe chronic GVHD occurred in 19.4% of ATG patients and 41.7% of PTCy patients (p = 0.343). And OS and the relapse rate were not statistically different between the two groups. The conventional CD25+FOXP3+Treg count of CD4 + T cells was higher in the PTCy group than in the ATG group (p = 0.0020). The effector Treg subset was significantly higher in the PTCy group than in the ATG group (p = 0.0412). And the effector Treg cell count had an inverse correlation with the severity of acute GVHD (p = 0.0007). Effector Tregs may be used as a biomarker to predict the severity of acute GVHD after allo-HSCT.

Non-palpable, volumetric splenomegaly at diagnosis was evaluated using computed tomography in patients with essential thrombocythemia (ET) and prefibrotic/early primary myelofibrosis (pre-PMF) based on 2016 World Health Organization guidelines. Each patient’s spleen volume was adjusted for their age and body surface area. The degree of splenomegaly was classified as no, borderline volumetric, overt volumetric, or palpable splenomegaly. Seventy-six patients with ET (median age, 62.5 years) and 19 patients with pre-PMF (median age, 65 years) were followed up for a median of 2.4 years (range 0.1–17.6 years) and 4.2 years (range 0.2–19.6 years), respectively. Spleen volume was significantly greater in pre-PMF patients than in ET patients (377.9 ± 92.2 cm3 vs. 224.9 ± 115.2 cm3, P < 0.001). No, borderline volumetric, overt volumetric, and palpable splenomegaly were found in 42 (55.3%), 24 (31.6%), 10 (13.2%), and 0 (0%) patients with ET, respectively, and in 0 (0%), 8 (42.1%), 19 (52.6%), and 1 (5.2%) patient with pre-PMF, respectively (P < 0.001). Volumetric splenomegaly did not affect thrombosis-free survival in patients with ET or those with pre-PMF. This study indicates that all patients with pre-PMF present with splenomegaly, whereas half of the patients with ET have a normal-sized spleen at diagnosis.

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Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, complement-mediated hemolysis, frequently leading to debilitating clinical symptoms and life-threatening complications such as thromboembolism (TE). A retrospective analysis was performed on 301 patients from the South Korean National PNH Registry to describe disease burden and identify TE-associated risk factors. TE was identified in 18 % of patients and was associated with increased risk for mortality [odds ratio (OR), 6.85; P  < 0.001]. A multivariate analysis showed that PNH patients with elevated hemolysis [lactate dehydrogenase (LDH) levels ≥1.5 times the upper limit of normal (ULN)] at diagnosis were at significantly higher risk for TE than patients with LDH <1.5 × ULN (OR 7.0; P  = 0.013). The combination of LDH ≥1.5 × ULN with the clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria was associated with a greater increased risk for TE than elevated hemolysis or clinical symptoms alone. Continuous monitoring of these risk factors is critical for identifying PNH patients at risk for morbidities and mortality and allowing early intervention. (clinicaltrials.gov identifier: NCT01224483).

Background Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common prophylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD. Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from January 2019 to February 2023. Results Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p  = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group ( p  < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p  < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p  < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p  = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p  = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p  = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group ( p  = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: To evaluate the role of the cardiopulmonary exercise test (CPET) with comorbidity index as a predictor of overall survival (OS) and non-relapse mortality (NRM) in patients with hematological malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). Methods: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent HLA-matched donor-HSCT at Chungnam National University Hospital (Daejeon, South Korea) between January 2014 and December 2020. Maximal oxygen consumption (VO2max) was classified using the recommendations of the Mayo Clinic database. Results: Of 72 patients, 38 (52.8%) had VO2max values lower than the 25th percentile (VO2max ≤ 25th) of an age- and sex-matched normal population. Patients with VO2max ≤ 25th had no significant differences both OS and NRM (30 month OS 29.8% vs 41%, P = .328; and 30 month NRM 16% vs 3.3%, P = .222), compared with other patients. VO2max ≤ 25th was assigned a weight of 1 when added to the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) to form a composite comorbidity/CPET index (HCT-CI/CPET). Patients with HCT-CI/CPET scores of 0 to 1 demonstrated significantly better OS and NRM than did patients with HCT-CI/CPET scores ≥2 [median OS not reached vs 6 months, P < .001 and 30 month NRM 7.4% vs 33.3%, P = .006]. An HCT-CI/CPET score ≥2 was the only adverse risk factor for NRM on multivariate analysis [hazard ratio (HR) of NRM 10.36 (95% CI 1.486-2.25, P = .018)]. Conclusion: The composite HCT-CI/CPET score can predict the survival and mortality of patients with hematological malignancies who undergo allogeneic HSCT.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in patients with hematologic malignancies. To better understand the mechanisms underlying early relapse (ER), we comprehensively explored the expression of inhibitory receptors (IRs) in bone marrow (BM) T cells at differentiation stage and examined transcriptional differences. Among the evaluated IRs, TIM3 was significantly upregulated in CD3 + T cells of patients with ER compared to patients with complete remission (CR). Notably, double-negative T (DNT) cells, a unique subset with MHC-independent cytotoxic potential, constituted a high proportion of BM T cells and expressed increased TIM3 expression in ER patients. Moreover, regulatory T cells (Tregs) showed elevated TIM3 levels, contributing to an immunosuppressive microenvironment after allo-HSCT. Transcriptomic analysis revealed downregulation of cytotoxic granules and effector genes in DNT cells from ER patients. Functional assays demonstrated that TIM3 blockade with sabatolimab restored T cell cytotoxicity, leading to enhanced leukemia cell apoptosis in ER patients. These findings highlight TIM3 as a critical regulator of T cell exhaustion and immune suppression in patients with ER and provide a rationale for the therapeutic use of TIM3 blockade in preventing and treating relapses after allo-HSCT.

Although renal dysfunction at the time of diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is a risk factor for mortality, subsequent renal events can occur. The objective of this study was to identify clinical implication of renal dysfunction occurring during the disease course in PNH patients. One hundred one patients with a granulocyte clone size of > 10% were enrolled. Renal events were observed in 55 (54.5%) patients during a median follow-up of 94.2 months. Median time to first renal event from diagnosis of PNH was 79.3 months. Thromboembolism (TE) event and recurrent TE events were observed in 25 (24.8%) and 8 (7.9%) patients, respectively. The rate of recurrent TE was significantly higher in patients with renal events ≥ 2 compared with that in patients with renal event ≤ 1 (18.8% vs. 2.9%; P = 0.012). The rate of recurrent TE was significantly higher in patients with chronic kidney disease (CKD) + acute kidney disease (AKD) compared with the rest of the patients (27.3% vs. 5.6%; P = 0.040). CKD+AKD was the only independent risk factor for OS in multivariate analysis (hazard ratio 7.95, 95% CI 1.24–51.15, P = 0.029). Therefore, close monitoring of renal events in PNH patients during the entire clinical course is essential.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with post-transplant cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflammatory biomarkers, and reconstitution of various T cell populations. Of 35 patients, 4 developed LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

The clinical significance of ADAMTS13 activity for response to treatment, mortality rate, recurrence, and prognosis is unclear. Therefore, we investigated the characteristics of severe ADAMTS13 deficiency and evaluated its prognostic features in Thrombotic thrombocytopenic purpura (TTP). The Korean TTP Registry includes 66 patients from 13 teaching hospitals in Korea who received the diagnosis of TTP from January 2005 to December 2008. Blood samples obtained upon admission were sent for ADAMTS13 analysis (multimer analysis by sodium dodecyl sulfate electrophoresis) to a central laboratory along with patient clinical information. Patients with severe ADAMTS13 deficiency had lower serum creatinine levels ( P  = 0.001) than patients with non-severe ADAMTS13 deficiency. Although severe ADAMTS13 deficiency was associated with better response rate (75 vs. 53%, P  = 0.145), remission rate (81 vs. 61%, P  = 0.209), and mortality rate (19 vs. 31%, P  = 0.508) than non-severe ADAMTS13 deficiency, treatment outcomes did not differ significantly between groups. After adjusting for clinical and laboratory features, multivariate analysis did not reveal any independent risk factors for TTP-associated mortality. Patients with severe ADAMTS13 deficiency had lower serum creatinine levels at presentation, but severe ADAMTS13 activity deficiency at TTP diagnosis does not appear to have prognostic significance.