A safety study on ultra­high or moderate static magnetic fields combined with platycodin D against lung cancer.

Due to the serious side effects of chemotherapy drugs against lung cancer, and the antitumor properties and high safety of magnetic fields, the present study combined moderate or ultra-high intensity statics magnetic fields (SMFs) with platycodin D (PD) to explore the antitumor efficiency and biosafety. The antitumor effects of PD with or without moderate and ultra-high SMFs on A549 cells bearing mice were compared. Mouse body weight, food/water intake, hematology routine, blood biochemistry, tumor weight and tissues hematoxylin and eosin (H&E) staining were examined. Behavior was measured using the elevated plus maze, open field and vital signs tests. The combined targets of PD and SMFs were detected using RNA-sequencing (RNA-seq). The results showed that the antitumor effect of 22 Tesla (T) SMF group was 3.6-fold higher compared with that of the 2 mg/kg PD group (tumor growth inhibition=10.08%), while the antitumor effect of 150 mT SMF was only 1.56-fold higher compared with that of PD. Although PD reduced the food intake, there was no significant difference in body weight, water intake or food consumption among PD and SMF groups. Behavioral results indicated that PD ameliorated dysphoria in mice, but SMFs reduced this effect. However, no significant abnormalities were found in routine blood, blood biochemistry test, H&E staining or organ index, except renal index which was reduced by PD with or without SMFs. RNA-sequencing (RNA-seq) demonstrated that SMFs and PD synergistically targeted the expression of genes associated with tumor growth, inflammation and neurological disease. The present study showed the antitumor efficacy and biosafety of moderate or ultra-high SMF combined with PD, which exhibited only few side effects in the treatment of lung cancer, thus supporting further research for the clinical application of magnetic fields.

Synergistic Modulation between Non-thermal and Thermal Effects in Photothermal Catalysis based on Modified In2O3.

To promote the solar-energy cascade utilization, it is necessary to increase the thermal effect of irradiation in the catalytic reactions, while simultaneously augmenting the non-thermal effect, so as to fulfill photothermal coupling. Herein, the non-thermal and thermal effect of light radiation on the surface of In2O3-based catalysts are explored and enhanced by the modification of transition metals Fe and Cu. Optical characterizations combined with water-splitting experiments show that Fe doping greatly broadens the radiation response range and enhances the absorption intensity of semiconductors' intrinsic portion, and Cu doping facilitates the absorption of visible-infrared light. The concurrent incorporation of Fe and Cu offers synergistic benefits, resulting in improved radiation response range, carrier separation and migration, as well as higher photothermal temperature upon photoexcitation. Collectively, these advantages comprehensively enhance the photothermal synergistic water-splitting reactivity. The characterizations under variable temperature conditions have demonstrated that the reaction temperature exerts a significant influence on the process of radiation absorption and conversion, ultimately impacting the non-thermal effect. The results of DFT calculations have revealed that the increasing temperature directly impacts the chemical reaction by reducing the energy barrier associated with the rate-determining step. These findings shine new light on the fundamental mechanisms underlying non-thermal and thermal effect, while also imparting significant insights for photo-thermal-coupled catalyst designing.

A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera.

Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 µg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 µg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

Microbial source tracking identifies sources of contamination for a river flowing into the Yellow Sea.

The excessive input of nutrients into rivers can lead to contamination and eutrophication, which poses a threat to the health of aquatic ecosystems. It is crucial to identify the sources of contaminants to develop effective management plans for eutrophication. However, traditional methods for identifying pollution sources have been insufficient, making it difficult to manage river health effectively. High-throughput sequencing offers a novel method for microbial community source tracking, which can help identify dominant pollution sources in rivers. The Wanggang River was selected for study, as it has suffered accelerated eutrophication due to considerable nutrient input from riparian pollutants. The present study identified the dominant microbial communities in the Wanggang River basin, including Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, Verrucomicrobia, and Firmicutes. The Source Tracker machine-learning classification system was used to create source-specific microbial community fingerprints to determine the primary sources of contaminants in the basin, with agricultural fertilizer being identified as the main pollutant source. By identifying the microbial communities of potential pollution sources, the study determined the contributing pollutant sources in several major sections of the Wanggang River, including industry, urban land, pond culture, and livestock land. These findings can be used to improve the identification of pollution sources in specific environments and develop effective pollution management plans for polluted river water.

The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.

Palbociclib promotes the antitumor activity of Venetoclax plus Azacitidine against acute myeloid leukemia.

Around 70 % of patients diagnosed with acute myeloid leukemia (AML) survive less than 5 years due to drug resistance and disease relapse. Consequently, improved clinical treatments are urgently needed. Some but not all AML patients benefit from the combination of the BCL-2 inhibitor Venetoclax with the hypomethylation agent Azacitidine. Here we investigated the utility of employing the cyclin dependent kinase (CDK6) inhibitor Palbociclib to improve the efficacy of Venetoclax/Azacitidine combination therapy. Our analysis of publicly available RNA sequencing datasets showed CDK6 was highly expressed in the major acute forms of leukemia including AML. Consistently, using qPCR and flow cytometry we found that CDK6 was overexpressed in bone marrow mononuclear cells from AML patients compared to healthy controls. Subsequent in vitro testing of Palbociclib, Venetoclax and Azacitidine, alone and in combination against CDK6-overexpressing AML cells lines THP-1 and KG-1 and primary AML cells showed that the Palbociclib/Venetoclax/Azacitidine combination improved treatment efficacy compared to Venetoclax/Azacitidine treatment alone. Additional investigations in a subcutaneous KG-1 mouse model showed similarly the three-drug combination produced the most significant reductions in tumor load together with the least amount of spleen infiltration. We established Palbociclib functioned in combination with Venetoclax/Azacitidine by increasing the rates of apoptosis in AML cells. Further investigations revealed that Palbociclib does not affect BCL-2 activity but downregulated the anti-apoptotic proteins MCL-1 and BCL-XL, making AML cells more sensitive to Venetoclax/Azacitidine treatment. Our results propose that the Palbociclib/Venetoclax/Azacitidine regimen warrants further preclinical research for clinical application in AML patients.

The Distribution of DOM in the Wanggang River Flowing into the East China Sea.

Dissolved organic matter (DOM) is a central component in the biogeochemical cycles of marine and terrestrial carbon pools, and its structural features greatly impact the function and behavior of ecosystems. In this study, the Wanggang River, which is a seagoing river that passes through Yancheng City, was selected as the research object. Three-dimensional (3D) fluorescence spectral data and UV−visible spectral data were used for component identification and source analysis of DOM based on the PARAFAC model. The results showed that the DOM content of the Wanggang River during the dry season was significantly higher than during the wet season; the DOM content increased gradually from the upper to lower reaches; the proportion of terrigenous components was higher during the wet season than during the dry. UV−Vis spectral data a280 and a355 indicated that the relative concentrations of protein-like components in the DOM of the Wanggang River were higher than those of humic-like components, and the ratio of aromatic substances in the DOM of the Wanggang River water was higher during the wet season. The DOM in the Wanggang River was dominated by protein-like components (>60%), and the protein-like components were dominated by tryptophan proteins (>40%). This study showed that the temporal and spatial distributions of DOM in rivers can be accurately determined using 3D fluorescence spectroscopy combined with the PARAFAC model. This provides useful insight into the biogeochemical process of DOM in rivers of coastal areas.

Cytokine release syndrome and relevant factors of CD19 targeted chimeric antigen receptor T cell therapy in relapsed/refractory B cell hematological malignancies.

OBJECTIVES AND METHODS: We reviewed the outcomes of 77 episodes of CD19 CAR-T therapy in 67 patients with B cell hematological malignancies from October 2016 to January 2020. Factors related to the grade of cytokine release syndrome (CRS) were explored by multivariate analysis, nonparametric test was conducted to explore the correlation between CRS and response. Kaplan-Meier curves were used to indicate survival profiles, and the correlation between CRS and survival was determined by the log-rank test. RESULTS: The rate of complete remission (CR) was 74.0% (57/77). CRS of any grade occurred in 68 of 77 episodes (grade 1: 32.5%, grade 2: 24.7%, grade 3: 22.1%, grade 4: 6.5%, grade 5: 2.6%). Patients with a history of transplantation had less severe CRS, and dose escalation-based infusion reduced the severity of CRS. Severe CRS was related to a higher CR rate but had no significant impact on event-free survival (EFS), relapse-free survival (RFS), or overall survival (OS). CONCLUSION: As a common adverse reaction of CAR-T therapy, the severity of CRS can be alleviated by dose escalation infusion, a history of transplantation was correlated with less severe CRS. Severe CRS was related to better response but was unrelated to long-term survival.

ECSIT inhibits cell death to increase tumor progression and metastasis via p53 in human breast cancer.

Background: Currently, breast cancer has surpassed lung cancer as the most common cancer and the molecular mechanism involved in tumor initiation and metastasis was unclear. Therefore, it is necessary to advance our understanding of tumor progression and metastasis and find out new targets. An evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is involved in the innate immune response and has been shown as tumor suppressors by downregulating nuclear factor-kappa B (NF-κB) pathway. However, the role of ECSIT in the progression and metastasis of human breast cancer remains unknown. Methods: We overexpressed ECSIT by transfection of a eukaryotic expression plasmid and constructed a breast cancer cell line with stable knockdown of ECSIT by short hairpin RNA. And we silenced p53 through small interfering RNA. In vivo, we replicated a xenograft mouse model in nude mice. The effects on the proliferation, viability, migration and invasion were studied by 5-ethynyl-2-deoxyuridine, cell counting Kit-8, wound healing and invasion assays. Propidium iodide/Hoechst 33342 staining and cleaved-caspase-3 staining were used to verify cell death. Western blot, immunohistochemistry (IHC) and histological analyses were used to explore the regulatory mechanism of tumor changes. Results: We reported the association of ECSIT with human breast cancer. In vitro assays demonstrated that ECSIT promoted MDA-MB-231 cell proliferation (by 66.15%), migration and invasion (by 58.29%). Knockdown of ECSIT significantly decreased cell proliferation (by 38.33%), viability, migration and invasion (by 62.37%), and increased cell death (by 41.1%). The in vivo results further confirmed that knockdown of ECSIT depressed tumorigenicity (by 29.46%) and metastasis (by 76.19%). Mechanistic investigations indicated that silencing of ECSIT could decrease the expression of p65 (by 46.05%), a subunit of NF-κB, and increase p53 protein expression in nuclei (by 89.53%). Moreover, we demonstrated that knockdown of p53 abolished the protection against cell death, which indicated that ECSIT might be involved in breast cancer progression through a p53-dependent pathway. Conclusions: Our studies provide new insight into the mechanisms underlying the role of ECSIT as well as a novel target for human breast cancer, and the development of novel ECSIT inhibitors is important for the management of TNBC.

Impact of Consolidative Unrelated Cord Blood Transplantation on Clinical Outcomes of Patients With Relapsed/Refractory Acute B Lymphoblastic Leukemia Entering Remission Following CD19 Chimeric Antigen Receptor T Cells.

Background: While chimeric antigen receptor (CAR)-T cell therapy is becoming widely used in hematological malignancies with remarkable remission rate, their high recurrence remains an obstacle to overcome. The role of consolidative transplantation following CAR-T cell-mediated remission remains controversial. We conducted a retrospective study to explore whether bridging to unrelated cord blood transplantation (UCBT) could improve the prognosis of patients entering remission after CAR-T therapy with different characteristics through subgroup analyses. Methods: We reviewed 53 patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) successfully infused with CD19 CAR-T cells and achieved complete remission (CR). In this study, 25 patients received consolidative UCBT (UCBT group) and 28 patients did not accept any intervention until relapse (non-UCBT group). Subgroup analysis on prognosis was then performed according to gender, age, number of previous relapses, tumor burden, presence of poor prognostic markers, and structure of CAR. Results: Compared with the non-UCBT group, patients who underwent consolidative UCBT had better median event-free survival (EFS; 12.3 months vs. 6.2 months; P = 0.035) and relapse-free survival (RFS; 22.3 months vs. 7.2 months; P = 0.046), while no significant difference was found in overall survival (OS; 30.8 months vs. 15.3 months; P = 0.118). Subsequent multivariate analysis revealed that bridging to UCBT was a protective factor for RFS (P = 0.048) but had no significant effect on EFS (P = 0.205) or OS (P = 0.541). In the subgroup analysis, UCBT has an added benefit in patients with specific characteristics. Patients who experienced ≥2 relapses or with sustained non-remission (NR) showed better RFS (P = 0.025) after UCBT. Better EFS was seen in patients with poor prognostic markers (P = 0.027). In the subgroup with pre-infusion minimal residual disease (MRD) ≥5% or with extramedullary disease (EMD), UCBT significantly prolonged EFS (P = 0.009), RFS (P = 0.017), and OS (P = 0.026). Patients with occurrence of acute graft-versus-host disease (aGVHD) appeared to have a longer duration of remission (P = 0.007). Conclusion: Consolidative UCBT can, to some extent, improve clinical outcomes of patients with R/R B-ALL entering remission following CD19 CAR-T therapy, especially in patients with more recurrences before treatment, patients with poor prognostic markers, and patients with a higher tumor burden. The occurrence of aGVHD after UCBT was associated with better RFS.

Elaborated Reaction Pathway of Photothermal Catalytic CO2 Conversion with H2 O on Gallium Oxide-Decorated and -Defective Surfaces.

Ga2 O3 -decorated and -defective surface models based on anatase TiO2 have been established. The thermodynamic reaction pathways, including protonation, deoxygenation and hydroxylation steps, during CO2 conversion with H2 O to C1 products were calculated. The calculation results demonstrate that a Ga2 O3 cocatalyst enhances the selective adsorption of CO2 and slightly weakens the competitive adsorption of H2 O. The promotion effect of Ga2 O3 on the subsequent reaction depends on the availability of protons and electrons. Free-energy calculations revealed that the basic functional site generated by Ga2 O3 not only suppresses the back reaction of the OH group after H2 O directly provides protons but also maintains the surface defect oxygen vacancy (VO ), which promotes the reaction thermodynamics but tends to be consumed in the process. Additionally, Ga2 O3 decoration promotes VO formation, and the coexistence of Ga2 O3 and VO further decreases the reaction rate-determining step energy barrier, promoting C1 production.

Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked ß-N-Acetylglucosamine Strategy.

Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. Our strategy comprises the introduction of simple O-linked ß-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. After folding, the O-GlcNAc groups can be efficiently removed using O-GlcNAcase (OGA) to afford the correctly folded proteins. Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation.

Clinical outcome of cord blood transplantation for nine children with juvenile myelomonocytic leukemia receiving fludarabine-busulfan-cyclophosphamide-based conditioning.

BACKGROUND: Juvenile myelomonocytic leukemia (JMML) is a rare hematological malignancy in young children and can only be cured through the allogeneic stem cell transplantation. PROCEDURE: We have retrospectively analyzed the outcomes of nine children with JMML after unrelated cord blood transplantation (UCBT). RESULTS: Eight patients who have received a myeloablative conditioning regimen of fludarabine (FLU), busulfan (BU), and cyclophosphamide (CY) have gotten engraftment. None of the nine patients has relapsed following initial UCBT. Six patients are still alive and in complete remission after UCBT with a median observation time of 43 months (range: 10-80 months). CONCLUSIONS: This study shows that UCBT with FLU-BU-CY conditioning regimen can represent a suitable option for children with JMML.

Photothermal Chemistry Based on Solar Energy: From Synergistic Effects to Practical Applications.

With the development of society, energy shortage and environmental problems have become more and more outstanding. Solar energy is a clean and sustainable energy resource, potentially driving energy conversion and environmental remediation reactions. Thus, solar-driven chemistry is an attractive way to solve the two problems. Photothermal chemistry (PTC) is developed to achieve full-spectral utilization of the solar radiation and drive chemical reactions more efficiently under relatively mild conditions. In this review, the mechanisms of PTC are summarized from the aspects of thermal and non-thermal effects, and then the interaction and synergy between these two effects are sorted out. In this paper, distinguishing and quantifying these two effects is discussed to understand PTC processes better and to design PTC catalysts more methodically. However, PTC is still a little far away from practical. Herein, several key points, which must be considered when pushing ahead with the engineering application of PTC, are proposed, along with some workable suggestions on the practical application. This review provides a unique perspective on PTC, focusing on the synergistic effects and pointing out a possible direction for practical application.

Four alternative splicing transcripts of intracellular copper/zinc superoxide dismutase 1 in Oxya chinensis.

In this study, we obtained four alternative splicing transcripts of intracellular copper/zinc superoxide dismutase 1 (icCuZnSOD1) in Oxya chinensis. OcicCuZnSOD1a has all common characteristics of CuZnSOD family and is a canonical CuZnSOD. OcicCuZnSOD1b is missing a Zn binding site. OcicCuZnSOD1c lacks Zn ion and is a Cu-only SOD. OcicCuZnSOD1d is missing a CuZnSOD conserved sequence and lacks the E-loop, a conserved disulfide bond, and an active site arginine. OcicCuZnSOD1a was the most heat-resistant and OcicCuZnSOD1c was the most unstable at high temperatures above 55 °C. They were stable at a wide pH range, especially in alkaline conditions. The four variants expressed at the throughout developmental stages and had various tissue expression patterns. OcicCuZnSOD1a and OcicCuZnSOD1d were significantly induced by 8.79 mM CuCl2 and OcicCuZnSOD1b was significantly up-regulated by 14.67 mM CuCl2. OcicCuZnSOD1a was significantly inhibited by 19.13 mM ZnSO4 while OcicCuZnSOD1d were significantly induced by 22.61 mM ZnSO4. Disc diffusion assay showed that the four isoforms of OcicCuZnSOD1 made the killing zones smaller surrounding the CdCl2-soaked filter discs. However, the reduction ratios of OcicCuZnSOD1a were the highest. These results implied that the four transcripts played roles in defense against CdCl2-induced oxidative stress while OcicCuZnSOD1a had stronger antioxidant capacity.

Incidence and risk factors of late-onset hemorrhagic cystitis after single umbilical cord blood transplantation with myeloablative conditioning regimen.

OBJECTIVE: To explore the incidence and risk factors of late-onset hemorrhagic cystitis (LOHC) in patients undergoing single umbilical cord blood transplantation for hematological malignancies. METHODS: Clinical data from 234 patients who consecutively underwent single UCBT using a myeloablative conditioning regimen without antithymocyte globulin in our center were retrospectively analyzed. RESULTS: In total, 64 (27.4%) patients developed LOHC with a median onset time of 40.5 (range 8-154) days, and 15 (6.4%) patients gradually developed grade III-IV LOHC. The incidence of LOHC was marginally higher in adults (31.0%) than in children (23.7%) (p = 0.248). HLA matching ≤ 6/8 (HR = 2.624, 95% CI 1.112-6.191, p = 0.028) was an independent risk factor for LOHC. The overall survival of LOHC patients (59.8%, 95% CI 61.7-85.5%) was significantly lower than that of patients without LOHC (86.8%, 95% CI 79.6-91.6%) at 130 days post transplantation (p = 0.036). CONCLUSION: Patients with less well-matched grafts have a higher incidence of LOHC. Inherent deficiencies in immunity in the context of HLA disparity and more intense pharmacologic immunosuppression after severe acute graft-versus-host disease may contribute to viral activation. Prevention and treatment of LOHC have the potential to prolong long-term survival.

Outcomes of Adolescents and Young Adults Compared with Children with Acute Leukemia after Single-Unit Unrelated Cord Blood Transplantation Using Myeloablative Conditioning without Antithymocyte Globulin.

BACKGROUND: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain. METHODS: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG). RESULTS: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. The 30-day cumulative incidence of neutrophil engraftment was similar between AYAs and children, but children had faster rates of neutrophil and platelet recovery than AYAs. The median time to neutrophil engraftment was earlier in children than in AYAs (AYAs, 19 days, 95% confidence interval [CI] 17.3-21.7; children, 16 days, 95% CI 13.1-19.5, p = 0.00003). The incidence of platelet recovery on day 120 was higher in children than in AYAs (AYAs, 80%, 95% CI 71-81%; children, 88%, 95% CI 82-92%, p = 0.037). CD34+ cell dose was the only independent factor influencing both neutrophil and platelet recovery. The cumulative incidence of NRM at 2 years was higher among AYAs than among children (AYAs, 27.5%, 95% CI 20-37%; children, 15%, 95% CI 10-21%, p = 0.008). Conditioning regimen was an independent factor influencing NRM. With respect to immune reconstitution, natural killer cell counts quickly recovered to normal levels 1-month post-CBT in both children and AYAs. CD8+ T-cell counts were higher in children than in AYAs at 1 and 3 months post-CBT. CD4+ T-cell counts were similar in both children and AYAs after CBT. CONCLUSION: AYAs with acute leukemia have outcomes of single-unit CBT using MAC without ATG that are as good as those of children. Thus, single-unit CBT using modified MAC without ATG is an acceptable choice for both AYAs and children who do not have a suitable donor.

Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival.

This is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1-2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4-89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89-37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0-83.6%), which was significantly higher than the 10% (95% CI, 5.72-35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0-46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8-98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0-41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2-76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

Decitabine prior to salvaged cord blood transplantation for acute myeloid leukaemia/myelodysplastic syndrome not in remission.

WHAT IS KNOWN AND OBJECTIVE: Many refractory/relapsed haematological malignancies, in non-remission state, still have poor prognosis even after allogeneic haematopoietic stem cell transplantation. Recently, decitabine or umbilical cord blood transplantation (UCBT) seemed to be effective in these patients. However, few studies have added decitabine to myeloablative conditioning regimens for UCBT in patients with haematological malignancies not in remission. Therefore, the objective was to evaluate the clinical outcomes of patients with refractory/relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) using decitabine as part of a myeloablative conditioning regimen prior to salvaged unrelated UCBT at our centre. METHODS: We enrolled 20 consecutive patients with refractory/relapsed AML/MDS between 2013 and 2018. All patients were in non-remission state before transplantation. All transplants were performed with decitabine as part of the myeloablative conditioning regimen, which was decitabine + fludarabine/busulfan/cyclophosphamide. RESULTS AND DISCUSSION: All patients achieved neutrophil and platelet engraftment. Incidence of grade III/IV acute graft-vs-host disease (GVHD) was 20.0%, which was also decreased compared to non-decitabine group (P = .025). The median follow-up time after UCBT was 29 months (range 14-64 months). The 2-year probability of GVHD-free relapse-free survival (GRFS) was higher in the decitabine group. Univariate showed that the decitabine group was associated with a higher GRFS than the non-decitabine group. The estimated probability of overall survival and relapse was 55% and 20.0%, respectively. WHAT IS NEW AND CONCLUSIONS: Our results suggest that addition of decitabine as part of the myeloablative conditioning regimen prior to UCBT for refractory/relapsed AML/MDS in patients who are not in remission is safe and might be an effective treatment option.