A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant.

Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival. Methods: A single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy. Results: The median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021). Conclusions: Our study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.

Non-native Brachiaria humidicola with biological nitrification inhibition capacity stimulates in situ grassland N2O emissions.

Introduction: Brachiaria humidicola, a tropical grass, could release root exudates with biological nitrification inhibition (BNI) capacity and reduce soil nitrous oxide (N2O) emissions from grasslands. However, evidence of the reduction effect in situ in tropical grasslands in China is lacking. Methods: To evaluate the potential effects of B. humidicola on soil N2O emissions, a 2-year (2015-2017) field experiment was established in a Latosol and included eight treatments, consisting of two pastures, non-native B. humidicola and a native grass, Eremochloa ophiuroide, with four nitrogen (N) application rates. The annual urea application rates were 0, 150, 300, and 450 kg N ha-1. Results: The average 2-year E. ophiuroides biomass with and without N fertilization were 9.07-11.45 and 7.34 t ha-1, respectively, and corresponding values for B. humidicola increased to 31.97-39.07 and 29.54 t ha-1, respectively. The N-use efficiencies under E. ophiuroide and B. humidicola cultivation were 9.3-12.0 and 35.5-39.4%, respectively. Annual N2O emissions in the E. ophiuroides and B. humidicola fields were 1.37 and 2.83 kg N2O-N ha-1, respectively, under no N fertilization, and 1.54-3.46 and 4.30-7.19 kg N2O-N ha-1, respectively, under N fertilization. Discussions: According to the results, B. humidicola cultivation increased soil N2O emissions, especially under N fertilization. This is because B. humidicola exhibited the more effective stimulation effect on N2O production via denitrification primarily due to increased soil organic carbon and exudates than the inhibition effect on N2O production via autotrophic nitrification. Annual yield-scaled N2O emissions in the B. humidicola treatment were 93.02-183.12 mg N2O-N kg-1 biomass, which were significantly lower than those in the E. ophiuroides treatment. Overall, our results suggest that cultivation of the non-native grass, B. humidicola with BNI capacity, increased soil N2O emissions, while decreasing yield-scaled N2O emissions, when compared with native grass cultivation.

Gynecological complications in long-term survivors after allogeneic hematopoietic cell transplantation-a single-center real-life cross-sectional study.

Background and objectives: Hematopoietic stem cell transplantation (HCT) is a treatment for hematopoietic diseases. However, most cured female patients may suffer from premature ovarian insufficiency (POI) after HCT, which is mainly caused by the pre-HCT conditioning regimen. Hence, this study aims to explore the impact of HCT treatment on reproductive and ovarian functions in female survivors. Methods: A total of 55 female participants under the age of 40, who underwent HCT and met the inclusion criteria were enrolled. Data related to blood disease, menstruation, and fertility in the 3 years following HCT were collected. Results: The involved patients received transplantation at different age stages, ranging from 8 to 37. All patients, except those with aplastic anemia (AA; 5/55), received a myeloablative conditioning regimen, usually modified total body irradiation/cyclophosphamide (TBI/Cy; 25/55) or modified Busulfan/cyclophosphamide (Bu/Cy; 23/55). Among women (42/55) who menstruated before HCT, 16.67% (7/42) had a spontaneous menstrual relapse and 83.3% (35/42) had amenorrhea after HCT. 72.7% (40/55) could be regarded as having POI. This proportion included 100% (25/25) of women aged 21-40 at the time of HCT, 62.5% (15/24) of those aged 11-20, and 0% (0/6) of those ≤10 years old. Patients with AML were more likely to have POI (95.7%). Patients aged ≤10 years (0%) or 11-20 years (16.7%) at the time of HCT were less likely to have moderate to severe menopause than those 21-40 years old (44%). Conclusion: The prevalence of POI following HCT was high and POI was associated with age, conditioning regimen, and type of blood disease.

Comparisons of unmanipulated haploidentical donor, unrelated cord blood donor and matched unrelated donor hematopoietic stem cell transplantation in pediatric acquired severe aplastic anemia: a single center study.

We retrospectively analyzed the outcomes of 240 pediatric SAA patients who underwent unmanipulated alternative HSCT between September 2012 and November 2020 at our center. The incidence of GF (PGF + SGF) was higher in the UCBD cohort compared to the MUD and HID cohorts [(13.5% ± 6.5%) vs (0%), and (1.6% ± 5.3%), respectively, p = .0001]. The incidence of platelet engraftment within 180 days post-HSCT was lower in the UCBD cohort (82.4% ± 2.3%) compared to the HID group (96.2% ± 1.3%) and the MUD group (97.4% ± 0.5%) (p = .020). the median duration time for platelet engraftment in the UCBD cohort was 29 days, longer than in HID cohort 14 days and the MUD cohort 13 days (p = .005). UCBD cohort had a lower 3-year failure-free survival (FFS) (70.5% ± 8.4%) compared to the HID cohort (81.1% ± 4.3%) and the MUD cohort (92.5% ± 3.1%) (p = .030) and lower 3-year GVHD/relapse free survival (GRFS) (63.3% ± 9.5.4%) compared to the HID cohort (75.5% ± 6.8%) and MUD cohort (87.9% ± 4.5%) (p = .002). UCBD-HSCT had inferior FFS and GRFS compared to an HSCT with an HID or MUD in pediatric patients with acquired SAA. A UCBD-HSCT had a higher GF and lower incidence of platelet engraftment and longer platelet engraftment time.

Non-native plant invasion can accelerate global climate change by increasing wetland methane and terrestrial nitrous oxide emissions.

Approximately 17% of the land worldwide is considered highly vulnerable to non-native plant invasion, which can dramatically alter nutrient cycles and influence greenhouse gas (GHG) emissions in terrestrial and wetland ecosystems. However, a systematic investigation of the impact of non-native plant invasion on GHG dynamics at a global scale has not yet been conducted, making it impossible to predict the exact biological feedback of non-native plant invasion to global climate change. Here, we compiled 273 paired observational cases from 94 peer-reviewed articles to evaluate the effects of plant invasion on GHG emissions and to identify the associated key drivers. Non-native plant invasion significantly increased methane (CH4 ) emissions from 129 kg CH4 ha-1  year-1 in natural wetlands to 217 kg CH4 ha-1  year-1 in invaded wetlands. Plant invasion showed a significant tendency to increase CH4 uptakes from 2.95 to 3.64 kg CH4 ha-1  year-1 in terrestrial ecosystems. Invasive plant species also significantly increased nitrous oxide (N2 O) emissions in grasslands from an average of 0.76 kg N2 O ha-1  year-1 in native sites to 1.35 kg N2 O ha-1  year-1 but did not affect N2 O emissions in forests or wetlands. Soil organic carbon, mean annual air temperature (MAT), and nitrogenous deposition (N_DEP) were the key factors responsible for the changes in wetland CH4 emissions due to plant invasion. The responses of terrestrial CH4 uptake rates to plant invasion were mainly driven by MAT, soil NH4 + , and soil moisture. Soil NO3 - , mean annual precipitation, and N_DEP affected terrestrial N2 O emissions in response to plant invasion. Our meta-analysis not only sheds light on the stimulatory effects of plant invasion on GHG emissions from wetland and terrestrial ecosystems but also improves our current understanding of the mechanisms underlying the responses of GHG emissions to plant invasion.

Long-Term Compost Amendment Spurs Cellulose Decomposition by Driving Shifts in Fungal Community Composition and Promoting Fungal Diversity and Phylogenetic Relatedness.

Cellulose is the most abundant polysaccharide in plant biomass and an important precursor of soil organic matter formation. Fungi play a key role in carbon cycling dynamics because they tend to decompose recalcitrant materials. Here, we applied [12C]cellulose and [13C]cellulose to distinguish the effects of application of compost, nitrogen-phosphorus-potassium (NPK) fertilizer, and no fertilizer (control) for 27 years upon cellulose decomposition via RNA-based stable isotope probing (RNA-SIP). The loss ratio of added cellulose C in compost soil was 67.6 to 106.7% higher than in NPK and control soils during their 20-day incubation. Dothideomycetes (mainly members of the genus Cryptococcus) dominated cellulose utilization in compost soil, whereas the copiotrophic Sordariomycetes were more abundant in NPK and unfertilized soils. Compared with NPK and control soils, compost application increased the diversity of 13C-assimilating fungi. The 13C-labeled fungal communities in compost soil were more phylogenetically clustered and exhibited greater species relatedness than those in NPK and control soils, perhaps because of stringent filtering of narrow-spectrum organic resources and biological invasion originating from added compost. These changes led to an augmented decomposition capacity of fungal species for cellulose-rich substrates and reduced cellulose C sequestration efficiency. The RNA-SIP technique is more sensitive to responses of fungi to altered soil resource availability than DNA-SIP. Overall, long-term compost application modified fungal community composition and promoted fungal diversity and phylogenetic relatedness, accelerating the decomposition of substrate cellulose in soil. This work also highlights the RNA-SIP technique's value for comprehensively assessing the contributions of active fungi to the substrate decomposition process. IMPORTANCE Cellulose is a very rich component in plant biomass and an important precursor of soil organic matter formation. Fungal communities are known to be important drivers of organic carbon accumulation in arable soils. However, current understanding of responses of fungal species to cellulose amendment and the contributions of active fungi to substrate decomposition process is still very superficial. Here, we established a [13C]cellulose microcosm experiment with soils subjected to long-term application of compost, nitrogen-phosphorus-potassium (NPK) fertilizer, and no fertilizer (control). The novel 13C-RNA-SIP technique with subsequent high-throughput sequencing was used to investigate the linkages between active fungal taxa and cellulose decomposition. Our study demonstrated that Dothideomycetes dominated cellulose utilization in compost soil, whereas the copiotrophic Sordariomycetes were more enriched in both NPK and unfertilized soils. We also found that the compost amendment promoted fungal diversity and phylogenetic relatedness and strengthened the decomposition capacity of fungi for cellulose-rich substrates by enhancing synergistic interactions, thereby reducing cellulose C sequestration efficiency. Overall, our research has implications for our understanding of the role of active fungi in cellulose C transformation in soils undergoing different types of long-term nutrient management.

Fungal key players of cellulose utilization: Microbial networks in aggregates of long-term fertilized soils disentangled using 13C-DNA-stable isotope probing.

Long-term compost application accelerates organic carbon (C) accumulation and macroaggregate formation in soil. Stable aggregates and high soil organic C (SOC) content are supposed to increase microbiota activity and promote transformation of litter compounds (i.e., cellulose) into SOC. Here, we used 13C-DNA-stable isotope probing with subsequent high-throughput sequencing to characterize fungal succession and co-occurrence trends during 13C-cellulose decomposition in aggregate size classes in soils subjected to no fertilizer (control), nitrogen-phosphorus­potassium (NPK) fertilizers, and compost (Compost) application for 27 years. Ascomycota (mostly saprotrophic fungi) were always highly competitive for cellulose in all aggregate size classes at the early stages of cellulose decomposition (20 days). Compost-treated soil was enriched with Ascomycota compared to the control soil, wherein Sordariomycetes, the majority, strongly dominated the cellulose utilization (13C incorporation in DNA). 13C-labeled fungal communities converged in the Compost soil, with lower abundance and diversity compared with the NPK and control soils. Such convergence led to greater cellulose decomposition, indicating that compost amendment increased the capacity of a few dominant fungal taxa to decompose litter. Compost soil had more 13C-labeled fungal decomposers in microaggregates and lower fungal decomposers in macroaggregates when compared with the levels in the NPK and control soils. This implies that compost application facilitates fungal colonization towards smaller aggregates. Fungal interactions were reinforced in microaggregates (<250 µm), with more positive associations than those in macroaggregates (>250 µm), indicating greater fungal synergism for recalcitrant resource utilization in microaggregates. The keystone taxa in the co-occurrence networks were not related to cellulose decomposition in microaggregates, but did in macroaggregates. The findings advance a process-based understanding of cellulose utilization by fungal key players based on C and energy availability and the regulation of microbial activity at the aggregate level.

Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study.

Introduction: We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1). Methods: We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021. Results: The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT. Conclusions: Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Combined biochar and double inhibitor application offsets NH3 and N2O emissions and mitigates N leaching in paddy fields.

The effects of combined biochar and double inhibitor application on gaseous nitrogen (N; nitrous oxide [N2O] and ammonia [NH3]) emissions and N leaching in paddy soils remain unclear. We investigated the effects of biochar application at different rates and double inhibitor application (hydroquinone [HQ] and dicyandiamide [DCD]) on NH3 and N2O emissions, N leaching, as well as rice yield in a paddy field, with eight treatments, including conventional urea N application at 280 kg N ha-1 (CN); reduced N application at 240 kg N ha-1 (RN); RN + 7.5 t ha-1 biochar (RNB1); RN + 15 t ha-1 biochar (RNB2); RN + HQ + DCD (RNI); RNB1 + HQ + DCD (RNIB1); RNB2 + HQ + DCD (RNIB2); and a control without N fertilizer. When compared with N leaching under RN, biochar application reduced total N leaching by 26.9-34.8% but stimulated NH3 emissions by 13.2-27.1%, mainly because of enhanced floodwater and soil NH4+-N concentrations and pH, and increased N2O emission by 7.7-21.2%, potentially due to increased soil NO3--N concentrations. Urease and nitrification inhibitor addition decreased NH3 and N2O emissions, and total N leaching by 20.1%, 21.5%, and 22.1%, respectively. Compared with RN, combined biochar (7.5 t ha-1) and double inhibitor application decreased NH3 and N2O emissions, with reductions of 24.3% and 14.6%, respectively, and reduced total N leaching by up to 45.4%. Biochar application alone or combined with double inhibitors enhanced N use efficiency from 26.2% (RN) to 44.7% (RNIB2). Conversely, double inhibitor application alone or combined with biochar enhanced rice yield and reduced yield-scaled N2O emissions. Our results suggest that double inhibitor application alone or combined with 7.5 t ha-1 biochar is an effective practice to mitigate NH3 and N2O emission and N leaching in paddy fields.