Impact of an antimicrobial stewardship programme on antibiotic utilization and resistance burden in patients with acute leukaemia: an 11-year longitudinal cohort study using interrupted time-series analysis.

BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), P = 0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, P < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, P = 0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all P < 0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.

Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML.

Given that there are only a few prospective studies with conflicting results, we investigated the prognostic value of multiparameter geriatric assessment (GA) domains on tolerance and outcomes after intensive chemotherapy in older adults with acute myeloid leukemia (AML). In all, 105 newly diagnosed patients with AML who were older than age 60 years and who received intensive chemotherapy consisting of cytarabine and idarubicin were enrolled prospectively. Pretreatment GA included evaluations for social and nutritional support, cognition, depression, distress, and physical function. The median age was 64 years (range, 60-75 years), and 93% had an Eastern Cooperative Oncology Group performance score <2. Between 32.4% and 69.5% of patients met the criteria for impairment for each domain of GA. Physical impairment by the Short Physical Performance Battery (SPPB) and cognitive dysfunction by the Mini-Mental State Examination in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Assessment Packet (MMSE-KC) were significantly associated with nonfatal toxicities, including grade 3 to 4 infections (SPPB, P = .024; MMSE-KC, P = .044), acute renal failure (SPPB, P = .013), and/or prolonged hospitalization (≥40 days) during induction chemotherapy (MMSE-KC, P = .005). Reduced physical function by SPPB and depressive symptoms by the Korean version of the short form of geriatric depression scales (SGDS-K) were significantly associated with inferior survival (SPPB, P = .027; SGDS-K, P = .048). Gait speed and sit-and-stand speed were the most powerful measurements for predicting survival outcomes. Notably, the addition of SPPB and SGDS-K, gait speed and SGDS-K, or sit-and-stand speed and SGDS-K significantly improved the power of existing survival prediction models. In conclusion, GA improved risk stratification for treatment decisions and may inform interventions to improve outcomes for older adults with AML. This study was registered at the Clinical Research Information Service as #KCT0002172.

Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Short term effect of intravenous treprostinil in term and preterm infants with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil. METHODS: This retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment. RESULTS: During the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil. CONCLUSION: Intravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.

Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients.

BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.

Distinguishing between DNA-Loaded Full and Empty Capsids of Adeno-Associated Virus with Atomic Force Microscopy Imaging.

Recently, miraculous therapy approaches involving adeno-associated virus (AAV) for incurable diseases such as spinal muscular atrophy and inherited retinal dysfunction have been introduced. Nonreplicative, nonpathogenic, low rates of chromosome insertional properties and the existence of neutralizing antibodies are main safety reasons why the FDA approved its use in gene delivery. To date, AAV production always results in a mixture of nontherapeutic (empty) and therapeutic (DNA-loaded) full capsids (10-98%). Such existence of empty viral particles inevitably increases viral doses to human. Thus, the rapid monitoring of empty capsids and reducing the empty-to-full ratio are critical in AAV science. However, transmission electron microscopy (TEM) is the primary tool for distinguishing between empty and full capsids, which creates a research bottleneck because of instrument accessibility and technical difficulty. Herein, we demonstrate that atomic force microscopy (AFM) can be an alternative tool to TEM. The simple, noncontact-mode imaging of AAV particles allows the distinct height difference between full capsids (∼22 nm) and empty capsids (∼16 nm). The sphere-to-ellipsoidal morphological distortion observed for empty AAV particles clearly distinguishes them from full AAV particles. Our study indicates that AFM imaging can be an extremely useful, quality-control tool in AAV particle monitoring, which is beneficial for the future development of AAV-based gene therapy.

Cytogenetic and molecular characteristics and outcomes of adult patients with early T-cell precursor acute lymphoblastic leukemia.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently identified high-risk subgroup of T-cell ALL in children. However, there have been conflicting reports and limited data have been reported in adult patients. We retrospectively analyzed the cytogenetic and molecular characteristics and long-term survival outcomes of adult patients with ETP-ALL versus non-ETP-ALL. We analyzed 58 patients (median age, 35 years [range, 18-76 years]) with newly diagnosed T-cell ALL who received a uniform remission induction and consolidation chemotherapy with suitable samples for genetic analyses. If a donor was available, all patients were recommended allogeneic hematopoietic cell transplantation (allo-HCT) for post-remission therapy. Out of 58 patients, 21 (36.2%) had ETP-ALL. Patients with ETP-ALL were older and had a higher proportion of complex karyotype than non-ETP-ALL. Additionally, more DNMT3A mutations were detected in ETP-ALL, whereas FBXW7 mutations and CDKN2A/CDKN2B deletions were found nearly exclusively in non-ETP-ALL. The overall complete remission (CR) rates were not different between ETP-ALL (95.2%) and non-ETP-ALL (81.1%) and subsequent allo-HCT proceeding rates in CR1 were 61.9% for ETP-ALL and 43.2% for non-ETP-ALL, respectively. The overall prognosis of patients with T-ALL was poor that estimated 5-year overall survival (OS) was 33.3% for ETP-ALL and 29.5% for non-ETP-ALL. In a subgroup analysis of patients treated with allo-HCT in CR1 (n = 29), 5-year OS was 53.8% for ETP-ALL and 55.4% for non-ETP-ALL. Our data showed molecular characteristics of ETP-ALL and non-ETP-ALL and revealed that intensive chemotherapy followed by allo-HCT for post-remission therapy can contribute to preserved survival outcome of adult patients with ETP-ALL.

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial.

BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Enhancement of galactose uptake for bioethanol production from Eucheuma denticulatum hydrolysate using galactose-adapted yeasts.

Eucheuma denticulatum is a red macroalgae with a high carbohydrate content. The fermentable sugars from E. denticulatum were obtained through sequential thermal acid hydrolysis, enzymatic saccharification, and detoxification. Thermal acid hydrolysis of E. denticulatum was optimized under the condition of 10% (w/v) slurry content and 300 mM HNO3 at 121 â„ƒ for 90 min. The maximum monosaccharide concentration after thermal acid hydrolysis was 31.0 g/L with an efficiency (ETAH) of 44.7%. By further enzymatic hydrolysis of pretreated biomass solution under 20 U/mL Cellic CTec2 at 50 â„ƒ and 160 rpm for 72 h, the maximum monosaccharide concentration reached 79.9 g/L with an efficiency of 66.2% (ES). To remove 5-hydroxymethylfurfural (5-HMF), a fermentation inhibitor, absorption using 2% activated carbon was performed for 2 min. Ethanol fermentation was performed using wild-type and high galactose-adapted strains of Saccharomyces cerevisiae, Kluyveromyces marxianus, and Candida lusitaniae. As a result, galactose-adapted strains showed higher ethanol production than wild-type strains. Especially, the fermentation result by adaptively evolved S. cerevisiae produced the highest ethanol of 37.6 g/L and with YEtOH of 0.48 g/g. Moreover, the transcript level of MIG1 in the galactose-adapted strain was slightly lower than that in the wild-type strain. The application of adaptive evolution of microorganisms was efficient for bioethanol production.

Five-day versus 7-day treatment regimen with azacitidine in lower risk myelodysplastic syndrome: A phase 2, multicenter, randomized trial.

BACKGROUND: Low-dose azacitidine (AZA) regimens, primarily 5-day AZA, have been used in lower risk myelodysplastic syndrome (LrMDS) but they have yet to be directly compared to the standard 7-day, uninterrupted dosing schedule. METHOD: In this phase 2, multicenter, randomized trial, 55 patients with adult LrMDS (low and intermediate-1 risk by international prognostic scoring system [IPSS]) were randomly assigned and received either 5-day (n = 26) or 7-day (n = 29) AZA between March 2012 and August 2020. The trial was stopped prematurely because of the slow accrual of patients. The primary end point was the overall response rate (ORR) of the 5-day AZA as compared to that of the 7-day regimen. RESULTS: Median patient age was 59 years, and IPSS intermediate-1 risk comprised the majority (81.8%). The median number of cycles in both arms was six. In the ITT subset (n = 53), in each of the 5-day and 7-day arms, the ORR of 48.0% and 39.3%, hematologic improvement of 44.0% and 39.3%, and RBC transfusion independence of 35.3% and 40.0% were observed respectively, and none of these findings were significantly different between the two arms. A cytogenetic response rate was significantly higher in the 7-day arm (8.3% and 53.8%, p = .027). Survival and adverse events were similar between the groups, although gastrointestinal toxicities, grade ≥3 thrombocytopenia, and febrile neutropenia were less frequent in the 5-day arm. CONCLUSION: The 5-day AZA in LrMDS showed comparable efficacy to a 7-day regimen in terms of similar overall response and other outcomes, despite significantly higher rates of cytogenetic responses in the 7-day regimen. LAY SUMMARY: Azacitidine (75 mg/m2 /day for 7 consecutive days per 28-day cycle) has shown survival benefit in patients with higher risk myelodysplastic syndrome (MDS). Although the use of azacitidine is less-well studied for lower risk MDS, it is generally accepted as a feasible option for lower risk MDS (LrMDS).

Splenectomy Outcomes in Relapsed or Refractory Immune Thrombocytopenia according to First-Line Intravenous Immunoglobulin Response.

OBJECTIVES: Although splenectomy has long been second-line option for immune thrombocytopenia (ITP) patients, an indicator that reliably predicts the efficacy of splenectomy is still being explored. We investigated the treatment outcomes of splenectomy as a second-line therapy for relapsed/refractory ITP according to first-line intravenous immunoglobulin (IVIG) responses. METHODS: Fifty-two adult patients treated with splenectomy as second-line therapy for ITP between 2009 and 2019 were included, and they were classified according to first-line IVIG responses (no response to IVIG: nonresponders; only transient IVIG response shorter than 4 weeks: poor responders; IVIG response for a longer period; stable responders). The efficacy of splenectomy was analyzed in the three subgroups. RESULTS: Of the 52 patients, 10 were IVIG nonresponders, 34 were poor responders, and the remaining 8 were stable responders. Response to splenectomy was observed in 50.0% of IVIG nonresponders, 94.1% of poor responders, and 100% of stable responders (p = 0.0030). Among the 45 patients who responded to splenectomy, 51.1% relapsed subsequently, and a significantly lower relapse rate was noted in the stable IVIG responders (12.5%, p = 0.0220) than in nonresponders (60.0%) and poor responders (59.4%). CONCLUSIONS: First-line IVIG response is indicated as a useful predictive factor for response to splenectomy.

Infectious events after endoscopic procedures in patients with neutropenia and hematologic diseases.

BACKGROUND: Few studies evaluated the post-endoscopic adverse events in patients with neutropenia. We investigated the development of infectious events after endoscopic procedures in neutropenic patients with hematologic diseases. METHODS: Patients with neutropenia and hematologic diseases who underwent endoscopic procedures were enrolled. Neutropenia was defined as an absolute neutrophil count < 1500 cells/mm3 and its severity was subdivided as mild, moderate (< 1000 cells/mm3), and severe (< 500 cells/mm3). Infectious events were defined as fever or bacteremia within 7 days after endoscopy. We assessed the development and risk factors of infectious events after endoscopic procedures. RESULTS: We identified 528 procedures in 479 patients (51.0 ± 1.0 years). Antibiotics were used in 455 (95.0%) cases within 3 days of endoscopy. Infectious events were observed in 154 patients (32.2%): 22.9% in mild, 29.5% in moderate, and 43.1% in severe neutropenia. Fever developed in 147 cases (30.7%). Among patients with blood culture studies (n = 267), bacteremia was found in 22 cases (8.2%). In univariate analysis, patients with myelodysplastic syndrome, poor performance status, severe neutropenia, non-use of immunosuppressive drugs, and without history of hematopoietic stem cell transplantation and colony-stimulating factor use were positively correlated with infectious events. Poor performance status was the strongest factor for the development of infectious events in multivariate analysis (OR 10.3; 95% CI 4.4-23.3; P < 0.01). CONCLUSIONS: Procedural invasiveness and severity of neutropenia did not appear to affect infectious events after endoscopic procedure with the use of antibiotics. Neutropenic patients who have poor performance status require careful evaluation for appropriate indications of endoscopic evaluation.

Higher prevalence of rotavirus infection among out-born newborns transferred to a regional neonatal intensive care unit in Korea.

BACKGROUND: Rotavirus is one of important pathogens which require infection control in nurseries and neonatal intensive care unit (NICU). METHOD: We retrospectively reviewed 1,135 out-born newborns who were transferred to a regional tertiary NICU of Chungbuk National University Hospital between January 2012 and December 2016. We assessed the clinical characteristics of newborns based on the results of rotavirus surveillance tests. The prevalence of rotavirus was evaluated according to the year, month, and season. RESULTS: Among the 1,135 infants, 213 (18.8%) had positive results in the rotavirus surveillance test. The rotavirus positive group had a significantly higher gestational age, birth weight, and Apgar score. They also had a significantly higher rate of postpartum care centers when compared to the rotavirus negative group (45.5% vs. 12.6%, P < 0.001). Notably, the prevalence of rotavirus was significantly increased from 3.2 to 33.8% when infants were hospitalized 48 h after birth (P < 0.001). During the study period, there were no significant differences in the annual, monthly, or seasonal prevalence of rotavirus infection. CONCLUSION AND DISCUSSION: These findings suggest that more active screening for rotavirus infection is necessary, especially for out-born newborns admitted to NICUs 48 h after birth or hospitalized after using postpartum care centers in Korea.

Haploidentical vs matched unrelated donor transplantation for acute myeloid leukemia in remission: A prospective comparative study.

Despite comparable outcomes of haploidentical transplants (Haplo-HSCT) with HLA-matched unrelated transplants (MUD-HSCT) in retrospective comparisons, few studies have prospectively compared Haplo-HSCT with MUD-HSCT in AML. Here, we prospectively compared the outcomes of Haplo-HSCT with MUD-HSCT for AML in remission (n = 110) to prove non-inferiority of overall survival in Haplo-HSCT. Both groups were well balanced in factors related to biological features of AML and measurable residual disease (MRD) status by Wilms' tumor gene 1 (WT1) assay. A unique, reduced-toxicity preparative regimen was used for Haplo-HSCT, whereas mostly-myeloablative regimen was for MUD-HSCT. Both groups showed similar patterns of neutrophil and platelet recovery, whereas delayed T-cell reconstitution in Haplo-HSCT was found compared with MUD-HSCT. No significant differences were found in acute or chronic graft-vs-host-disease (GVHD) and post-transplant infectious events with an exception of EBV or CMV infection, which occurred more frequently in Haplo-HSCT. After a median follow-up of 47 months, no significant differences in overall survival (65% vs 54%, P = .146), disease-free survival (67% vs 53%, P = .142), relapse (20% vs 21%, P = .858), non-relapse mortality (14% vs 26%, P = .103), or GVHD-free/relapse-free survival (54% vs 41%, P = .138) were observed for Haplo-HSCT vs MUD-HSCT. In multivariate analysis, WT1 expression before transplantation independently predicted relapse, resulting in inferior survival. Separate analysis of unenrolled patients (n = 110) who were excluded or refused to participate in this study showed consistent results with enrolled patients. This prospective study demonstrated the non-inferiority of Haplo-HSCT to MUD-HSCT for AML in remission, and validated the role of WT1 quantification as an MRD marker (ClinicalTrial.gov identifier: NCT01751997).

Low-dose thymoglobulin for prevention of chronic graft-versus-host disease in transplantation from an HLA-matched sibling donor.

Despite the proven efficacy of anti-T-cell or antithymocyte globulin (ATG) for chronic graft-versus-host disease (GVHD) prevention in transplantation from an unrelated donor, dosing protocols and the effects of ATG on relapse and infection remain controversial. In the setting of transplantation from an HLA-matched sibling (MSD-T), few randomized studies have been conducted. We conducted a prospective, single-center, open-label, randomized study of low-dose thymoglobulin (2.5 mg/kg) for chronic GVHD prevention. A total of 120 patients with acute leukemia were randomly assigned in a 1:1 ratio. After a median follow-up of 27 months, the cumulative incidence of chronic GVHD in the ATG and non-ATG groups was 25.0% and 65.4% (p < 0.001), respectively. The ATG group had an increased relapse rate compared with the non-ATG-group (20.0% vs. 9.3%; p = 0.055), with risks that differed according to cytogenetic subgroup (high-risk, 29.6% vs. 9.3%, p = 0.042; non-high-risk, 12.2% vs. 9.2%, p = 0.596). Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group (46.7% vs. 19.4%; p = 0.070), and the difference was significant in a cytogenetic non-high-risk subgroup (45.5% vs. 0%; p = 0.038). No differences were observed in other survival outcomes. Improved physical components in quality-of-life scores were observed in the ATG group at 12 months after transplantation. A higher rate of Epstein-Barr virus reactivation was observed in the ATG group (21.8% vs. 5.1%; p = 0.013), whereas no between-group differences for other complications. In conclusion, the low-dose thymoglobulin effectively prevented chronic GVHD in MSD-T, resulting in improvement in quality-of-life and cGRFS, whereas the necessity of caution for high-risk acute leukemia.

Extrauterine growth restriction in extremely preterm infants based on the Intergrowth-21st Project Preterm Postnatal Follow-up Study growth charts and the Fenton growth charts.

Growth charts are essential for monitoring the postnatal growth of preterm infants. The preterm postnatal follow-up study (PPFS) of the Intergrowth-21st Project provides new growth standards based on a longitudinal study. This study was conducted to investigate the prevalence of extrautrine growth restriction (EUGR) and the associated factors of EUGR in preterm infants, using the PPFS charts and the Fenton charts. Data of 1,356 infants with gestational age (GA) less than 28 weeks from the Korean Neonatal Network were analysed. The prevalence of small for gestational age (SGA) of weight and length was higher with the Intergrowth charts than with the Fenton charts. EUGR in weight and length was more prevalent when using the Fenton charts. Multivariate analysis showed that low GA, high birthweight z score, male, treated patent ductus arteriosus (PDA), necrotizing enterocolitis, intraventricular haemorrhage and duration of parenteral nutrition (PN) were associated with EUGR in weight by the Intergrowth charts. High birthweight z score, treated PDA and PN duration were associated with EUGR defined by the Fenton charts.Conclusion: Compared to the Fenton charts, SGA was more defined and EUGR was less prevalent in extremely low gestational infants, while EUGR defined by the Intergrowth charts categorized infants with adverse clinical courses more elaborately. What is Known: • Preterm infants are at risk of postnatal growth restriction (PGR), although optimal postnatal growth is important for the long-term outcomes. • Growth charts are essential tools to monitor the postnatal growth of preterm infants. What is New: • PGR of weight and length were less defined with the Intergrowth charts than the Fenton charts. • PGR defined by the Intergrowth preterm postnatal follow-up study (PPFS) chart categorized preterm infants with morbidities more elaborately than the Fenton charts.

Comparison of Myeloablative (CyTBI, BuCy) versus Reduced-Intensity (FluBu2TBI400) Peripheral Blood Stem Cell Transplantation in Acute Myeloid Leukemia Patients with Pretransplant Low WT1 Expression.

Relapse is a major concern with reduced-intensity conditioning. We analyzed 257 patients with acute myeloid leukemia (AML) who received allogeneic stem cell transplantation (SCT) and fulfilled the following criteria: intermediate- or poor-risk disease by National Comprehensive Cancer Network guidelines (2017, version 3), in first complete remission (CR1) at SCT, received either myeloablative conditioning (MAC; busulfan plus cyclophosphamide or cyclophosphamide plus total body irradiation) or reduced-intensity conditioning (RIC; FluBu2TBI400) peripheral blood SCT from 8/8 matched sibling or unrelated donor, and having bone marrow Wilms tumor gene 1 (WT1) expression results before transplant. We and other groups serially published a predictive value for pretransplant WT1 expression in patients with AML to identify patients at higher risk of relapse. Among the total 257 patients, 191 (74.3%) and 66 (25.7%) patients received MAC and RIC transplants, respectively. WT1 ≥250 copies/104ABL was defined as WT1high. WT1high before SCT was found to be an independent prognostic factor for inferior overall survival (OS), disease-free survival (DFS), and higher cumulative incidence of relapse (CIR). There were 201 patients with WT1 low expression based upon pretransplant analysis. There was no significant difference in OS, DFS, CIR, and nonrelapse mortality between MAC and RIC patients. To conclude, post-transplant survival or relapse was not different by conditioning intensity in AML CR1 patients whose WT1 level was below 250 copies per 104ABL at transplantation.

Outcomes of Haploidentical Stem Cell Transplantation using Total Body Irradiation (600 cGy) and Fludarabine with Antithymocyte Globulin in Adult Patients with Severe Aplastic Anemia: A Prospective Phase II Study.

The aim of this study was to verify the feasibility of rabbit antithymocyte globulin (ATG; 5 mg/kg) in combination with 600 cGy of fractionated total body irradiation (fTBI; 3 doses of 200 cGy) and fludarabine (Flu; 150 mg/m2) as a conditioning regimen for haploidentical stem cell transplantation from a related mismatched donor (haplo-SCT) in adult patients with severe aplastic anemia (SAA). We analyzed 47 consecutive patients who underwent haplo-SCT, including 24 patients from our previous pilot report. The median age was 36.0 years (range, 17 to 61 years), and 25 patients (53%) were very severe aplastic anemia (VSAA) at transplantation. All patients achieved primary engraftment. The cumulative incidence of grade ≥II acute graft-versus-host disease (GVHD) and chronic moderate or greater GVHD was 27.7% at 100 days and 13.5% at 3 years, respectively. With a median follow-up of 32.3 months, the 3-year probability of overall survival and failure-free survival was 91.0% and 88.6%, respectively. The 3-year GVHD- and failure-free survival (GFFS) was 71.6%. Offspring donor and lower comorbidity index were independent factors correlated with higher GFFS in multivariate analysis. In conclusion, the outcomes of haplo-SCT with fTBI 600 cGy/Flu/ATG-5 indicate that haplo-SCT can be an effective alternative option when a fully matched donor is not available or a patient with VSAA needs an urgent transplantation.

Hyper-N-glycosylated SAMD14 and neurabin-I as driver autoantigens of primary central nervous system lymphoma.

To address the role of chronic antigenic stimulation in primary central nervous system lymphoma (PCNSL), we searched for autoantigens and identified sterile α-motif domain containing protein 14 (SAMD14) and neural tissue-specific F-actin binding protein I (neurabin-I) as autoantigenic targets of the B-cell receptors (BCRs) from 8/12 PCNSLs. In the respective cases, SAMD14 and neurabin-I were atypically hyper-N-glycosylated (SAMD14 at ASN339 and neurabin-I at ASN1277), explaining their autoimmunogenicity. SAMD14 and neurabin-I induced BCR pathway activation and proliferation of aggressive lymphoma cell lines transfected with SAMD14- and neurabin-I-reactive BCRs. Moreover, the BCR binding epitope of neurabin-I conjugated to truncated Pseudomonas exotoxin-killed lymphoma cells expressing the respective BCRs. These results support the role of chronic antigenic stimulation by posttranslationally modified central nervous system (CNS) driver autoantigens in the pathogenesis of PCNSL, serve as an explanation for their CNS tropism, and provide the basis for a novel specific treatment approach.