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Abstract This case report presents the successful management of relapsed/refractory (r/r) B‐cell acute lymphoblastic leukemia in a 54‐year‐old male post‐allogeneic hematopoietic cell transplantation. The combinatorial approach of sequential antibody treatment (Inotuzumab [InO] and Blinatumomab [Blina]) combined with three donor lymphocyte infusions (DLI) applications and cytoreductive chemotherapy‐induced sustained complete molecular remission as documented at the last follow‐up 30 months later. This case highlights the feasibility and potential synergistic efficacy of a Blina/DLI regimen and supports the hypothesis that T‐cell engagers could enhance the DLI effect. Furthermore, the co‐administration of InO, Blina, DLI, and cytoreductive chemotherapy was proven to be feasible without severe adverse events.

To achieve high-density tomato seedlings in a plant factory with artificial lighting, tomatoes (Solanum lycopersicum Mill. cv. "Zhongza NO.9") were used as the experimental material. This study expected to analyze the effects of light intensity (150, 200, 250, and 300 μmol·m−2·s−1) and light time (12 and 14 h), as well as daily light integral (DLI, 10.80, 12.60, and 12.96 mol·m−2·d−1) and sowing density (50, 72, and 105 holes per tray), on seedling quality. The results indicated that biomass accumulation, seedling quality, and energy use efficiency of seedlings significantly improved with an increase in DLI. At a DLI of 12.96 mol·m−2·d−1, seedlings sown at a density of 72 holes per tray exhibited comparable growth characteristics and biomass accumulation to those sown at 50 holes per tray. However, under lower DLIs, seedlings at 50 holes per tray displayed superior growth morphology and seedling quality compared to those at 72 holes per tray. This indicates that increasing the DLI can partially mitigate the negative effects of higher sowing density on seedling quality. Light use efficiency (LUE) and energy use efficiency (EUE) were not significantly different between seedlings at 72 and 105 holes per tray but were higher than those at 50 holes per tray. Therefore, optimizing parameters such as DLI and sowing density can effectively enhance the seedling quality, spatial use efficiency, and light use efficiency in industrial seedling production. Based on the results of this study, a DLI of 12.96 mol·m−2·d−1 (achieved with a light intensity of 300 μmol·m−2·s−1 and a light time of 12 h) and sowing density of 72 holes per tray are recommended for cultivating high-quality tomato seedlings while reducing energy consumption. [ABSTRACT FROM AUTHOR]

The expanding cannabis production sector faces economic challenges, intensified by freshwater scarcity in the main US production areas. Greenhouse cultivation harnesses sunlight to reduce production costs, yet the impact of greenhouse light levels on crucial production components, such as plant growth, branching, and water use efficiency (WUE), remains poorly understood. This study aimed to assess the effects of combined sunlight and supplemental lighting on the crop’s main production components and leaf gas exchange of Cannabis sativa ‘Suver Haze’ in the vegetative stage. Within a greenhouse, LED lighting provided at intensities of ~150, 300, 500, and 700 µmol m-2 s-1 (18-hour photoperiod), combined with solar radiation, resulted in average daily light integrals of 17.9, 29.8, 39.5, and 51.8 mol m-2 d-1. Increasing light levels linearly increased biomass, leaf area, and the number of branches per plant and square meter, with respective rates of 0.26 g, 32.5 cm², and 0.41 branches per mole of additional light. As anticipated, crop evapotranspiration increased by 1.8-fold with the increase in light intensity yet crop WUE improved by 1.6-fold when comparing the lowest and highest light treatments. Moreover, water requirements per unit of plant biomass decreased from 0.37 to 0.24 liters per gram when lighting increased from ~18 to 52 mol m-2 d-1, marking a 35% reduction in evapotranspiration. These results were supported by increments in leaf photosynthesis and WUE with light enhancement. Furthermore, our findings indicate that even 52 mol m-2 d-1 of supplemental lighting did not saturate any of the crop responses to light and can be economically viable for cannabis nurseries. In conclusion, light supplementation strongly enhanced photosynthesis and plant growth while increasing WUE. Additionally, a comprehensive discussion highlights the shared physiological mechanisms governing WUE in diverse plant species and their potential for water conservation under enhanced lighting conditions. [ABSTRACT FROM AUTHOR]

Aim: Ileorectal anastomosis (IRA) following total abdominal colectomy (TAC) allows for resortation of bowel continuity but prior studies have reported rates of anastomotic leak (AL) to be as high as 23%. We aimed to report rates of AL and complications in a large cohort of patients undergoing IRA. We hypothesized that AL rates were lower than previously reported and that selective use of diverting loop ileostomy (DLI) is associated with decreased AL rates. Method: Patients undergoing TAC or end‐ileostomy reversal with IRA, with or without DLI, between 1980 and 2021 were identified from a prospectively maintained institutional database and retrospectively analysed. Redo IRA cases were excluded. Short‐term (30‐day) surgical outcomes were collected using our database. AL was defined using a combination of imaging and, in the case of return to the operating room, intraoperative findings. Results: Of 823 patients in the study cohort, DLI was performed in 27% and performed more frequently for constipation and inflammatory bowel disease. The overall AL rate was 3% (1% and 4% in those with and without DLI, respectively) and diversion was found to be protective against leak (OR 0.28, 95% CI 0.08–0.94, p = 0.04). However, patients undergoing diversion had a higher overall rate of postoperative complications (51% vs. 36%, p < 0.001) including superficial wound infection, urinary tract infection, dehydration, blood transfusion and portomesenteric venous thrombosis (all p < 0.04). Conclusion: Our study represents the largest series of patients undergoing IRA reported to date and demonstrates an AL rate of 3%. While IRA appears to be a viable surgical option for diverse indications, our study underscores the importance of careful patient selection and thoughtful consideration of staging the anastomosis and temporary faecal diversion when necessary. [ABSTRACT FROM AUTHOR]

Summary: To investigate the clinical characteristics and risk factors of specific human leukocyte antigen loss (HLA loss) in relapsed acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) patients after allogeneic haematopoietic stem cell transplantation (allo‐HSCT), and compare the responses of patients with HLA loss relapse with those without HLA loss (non‐HLA loss) to different treatment regimens. Clinical data of traceable patients with AML/MDS after myeloablative allo‐HSCT in our centre between January 2010 and June 2021, who experienced disease relapse after the transplantation, were collected. The patients were divided into the HLA loss relapse group and the non‐HLA loss relapsed group based on HLA loss gene test findings by next‐generation sequencing. The patients' median overall survival (OS) after the relapse were compared, and univariate and multivariate analyses were performed using the Kaplan–Meier survival curve and Cox proportional hazard model to explore the responses to different treatments after relapse. A total of 2359 patients were selected. Retrospective HLA gene loss gene detection was performed for the deoxyribonucleic acid in 179 relapsed patients, including 47 patients in the HLA loss group (27.2%), 126 patients in the non‐HLA loss group (72.8%) and 6 patients were excluded due to a lack of confirmed results. There was no significant statistical difference in the baseline characteristics of patients between the two groups, but as to transplantation‐related characteristics, the donor–recipient relationship and HLA mismatched loci were statistically different between the two groups (both p < 0.001). Multivariate Cox analysis showed that more HLA mismatched loci ≥3 (HR = 3.66; 95% CI: 1.61–8.31; p = 0.002), time (≤6 months) from HSCT to relapse (HR = 7.92; 95% CI: 3.35–18.74; p < 0.001) and donor chimerism (CD3) in bone marrow at relapse (HR = 1.02; 95% CI: 1.00–1.03; p = 0.036) were independent factors affecting HLA loss relapse. The ratio of negative conversion of FLT3‐ITD or CEBPA mutation was significantly lower in patients with post‐transplantation HLA loss relapse than in the non‐HLA loss group (0.0% vs. 45.5%, p = 0.003; 0.0% vs. 80.0%, p = 0.035), with none of the patients with FLT3‐ITD or CEBPA mutation turned negative in the HLA loss group. The number of gene mutations turned negative when relapse in the non‐HLA loss group was remarkably higher than that in the HLA loss group (p = 0.001). Using donor lymphocyte infusion (DLI) could not prolong OS for the HLA loss group (p = 0.42). Nevertheless, second transplantation had a significant positive impact on OS in the HLA loss group (p = 0.017), although only five patients in the HLA loss group underwent second transplantation. However, patients in the non‐HLA loss group using DLI had a relatively longer OS time than those without DLI (p = 0.017). Second transplantation could also prolong OS in the non‐HLA loss group, but the effect was not as significant as in the HLA loss group (p = 0.053). In summary, HLA loss detection is essential for patients with recurrence after transplantation, especially for those with more HLA mismatched loci and non‐sibling donor. Furthermore, the detection of HLA loss has a guiding role in choosing subsequent therapy when relapsed, as secondary transplantation is more suitable than DLI for those with HLA loss. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part of the curative basis underlying HSCT for hematologic malignancies relies upon induction of the graft versus leukemia (GVL) effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient, thereby maintaining remission. GVL is a clinically evident phenomenon; however, specific cell types responsible for inducing this effect and molecular mechanisms involved remain largely undefined. One of the best examples of GVL is observed after donor lymphocyte infusions (DLI), an established therapy for relapsed disease or incipient/anticipated relapse. DLI involves infusion of peripheral blood lymphocytes from the original HSCT donor into the recipient. Sustained remission can be observed in 20-80% of patients treated with DLI depending upon the underlying disease and the intrinsic burden of targeted cells. In this review, we will discuss current knowledge about mechanisms of GVL after DLI, experimental strategies for augmenting GVL by manipulation of DLI (e.g. neoantigen vaccination, specific cell type selection/depletion) and research outlook for improving DLI and cellular immunotherapies for hematologic malignancies through better molecular definition of the GVL effect. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting antibody-drug conjugate BrentuximabVedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable responses in relapsed/refractory (r/r) HL. However, patients with a history of allo-HSCT were frequently excluded from clinical trials due to concerns about the risk of graft-versus-host disease (GVHD). We report the clinical history of a patient with refractory classical HL who underwent two allo-HSCTs (first from matched unrelated and second from haploidentical donor) after relapsing on BV and nivolumab and for whom durable remission was finally obtained using BV-pembrolizumab combination for relapse after haploidentical HSCT. Such treatment was associated with the onset of GVHD after only two cycles which led to treatment discontinuation. However, the side effects were rapidly controlled, and after 2 years of follow-up, the patient is still in remission. Our data support the feasibility and efficacy of combining PD-1 blockade with BV to enhance the graft-versus-lymphoma effect after allo-HSCT. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with highly chemorefractory Hodgkin lymphoma (HL). The CD30-targeting antibody-drug conjugate Brentuximab-Vedotin (BV) and programmed cell death protein-1 (PD-1) blocking agents have demonstrated clinical activity with durable responses in relapsed/refractory (r/r) HL. However, patients with a history of allo-HSCT were frequently excluded from clinical trials due to concerns about the risk of graft-versus-host disease (GVHD). We report the clinical history of a patient with refractory classical HL who underwent two allo-HSCTs (first from matched unrelated and second from haploidentical donor) after relapsing on BV and nivolumab and for whom durable remission was finally obtained using BV-pembrolizumab combination for relapse after haploidentical HSCT. Such treatment was associated with the onset of GVHD after only two cycles which led to treatment discontinuation. However, the side effects were rapidly controlled, and after 2 years of follow-up, the patient is still in remission. Our data support the feasibility and efficacy of combining PD-1 blockade with BV to enhance the graft-versus-lymphoma effect after allo-HSCT.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many hematologic malignancies as well as non-malignant conditions. Part of the curative basis underlying HSCT for hematologic malignancies relies upon induction of the graft versus leukemia (GVL) effect in which donor immune cells recognize and eliminate residual malignant cells within the recipient, thereby maintaining remission. GVL is a clinically evident phenomenon; however, specific cell types responsible for inducing this effect and molecular mechanisms involved remain largely undefined. One of the best examples of GVL is observed after donor lymphocyte infusions (DLI), an established therapy for relapsed disease or incipient/anticipated relapse. DLI involves infusion of peripheral blood lymphocytes from the original HSCT donor into the recipient. Sustained remission can be observed in 20-80% of patients treated with DLI depending upon the underlying disease and the intrinsic burden of targeted cells. In this review, we will discuss current knowledge about mechanisms of GVL after DLI, experimental strategies for augmenting GVL by manipulation of DLI (e.g. neoantigen vaccination, specific cell type selection/depletion) and research outlook for improving DLI and cellular immunotherapies for hematologic malignancies through better molecular definition of the GVL effect.

To achieve high-density tomato seedlings in a plant factory with artificial lighting, tomatoes (Solanum lycopersicum Mill. cv. “Zhongza NO.9”) were used as the experimental material. This study expected to analyze the effects of light intensity (150, 200, 250, and 300 μmol·m−2·s−1) and light time (12 and 14 h), as well as daily light integral (DLI, 10.80, 12.60, and 12.96 mol·m−2·d−1) and sowing density (50, 72, and 105 holes per tray), on seedling quality. The results indicated that biomass accumulation, seedling quality, and energy use efficiency of seedlings significantly improved with an increase in DLI. At a DLI of 12.96 mol·m−2·d−1, seedlings sown at a density of 72 holes per tray exhibited comparable growth characteristics and biomass accumulation to those sown at 50 holes per tray. However, under lower DLIs, seedlings at 50 holes per tray displayed superior growth morphology and seedling quality compared to those at 72 holes per tray. This indicates that increasing the DLI can partially mitigate the negative effects of higher sowing density on seedling quality. Light use efficiency (LUE) and energy use efficiency (EUE) were not significantly different between seedlings at 72 and 105 holes per tray but were higher than those at 50 holes per tray. Therefore, optimizing parameters such as DLI and sowing density can effectively enhance the seedling quality, spatial use efficiency, and light use efficiency in industrial seedling production. Based on the results of this study, a DLI of 12.96 mol·m−2·d−1 (achieved with a light intensity of 300 μmol·m−2·s−1 and a light time of 12 h) and sowing density of 72 holes per tray are recommended for cultivating high-quality tomato seedlings while reducing energy consumption.

Light-emitting diodes (LEDs) have been widely used as light sources for plant production in plant factories with artificial lighting (PFALs), and light spectrum and light amount have great impacts on plant growth and development. With the expansion of the product list of PFALs, tomato production in PFALs has received attention, but studies on fruit quality influenced by artificial light are lacking. In this study, precisely modulated LED light sources based on white light combined with additional red, blue, and green lights were used to investigate the effects of light spectrum and daily light integral (DLI) on the main quality indicators and flavor substances of "Micro-Tom" tomato fruits. The highest sugar–acid ratio was obtained under the white light with addition of red light with high DLI and blue light with low DLI. The contents of β-carotene, lycopene, and lutein were significantly increased by higher DLI conditions except for under the blue light treatment, and the cross-interactions between the light spectrum and DLI were observed. The accumulation of the main flavor substances in tomato fruits was decreased by addition of green light with a high DLI and red light with a low DLI; notably, the percentage of 2-isobutylthiazole, which is associated with fresh tomato aroma, was decreased by green light. This study provides insights for improving tomato fruit quality and flavor by regulating light conditions in PFALs. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo–HCT relapse both as consolidative therapy and as a bridge to second transplant. [ABSTRACT FROM AUTHOR]

Introduction: Post‐transplant graft‐versus‐leukemia (GVL) effect has been shown to be an important determinant of a successful outcome following hematopoietic stem cell transplantation (HSCT) in children with acute leukemia. Patients and Methods: We performed a retrospective analysis of the children up to 18 years of age with acute leukemia who underwent HSCT between November 2002 and November 2018. GVL induction strategies included whole blood donor lymphocyte infusions (DLI) and/or lenalidomide. Results: A total of 134 children were included with engraftment in 125 children (93%). Acute graft‐versus‐host disease (GVHD) was documented in 85 (63%) children without any induction strategies. GVL induction strategies were employed in 19 children (14%); DLI (n = 12), Lenalidomide (n = 2), DLI + lenalidomide (n = 5). Among the 19, 12 children (63%) are alive without relapse; 6 children died of relapse (31%). Among the 6 who died of relapse despite induction strategies, 5/6 had ALL and one child had AML. GVL induction was effective in preventing relapse in 7/12 (58%) children with ALL and 5/6 (83%) children with AML. Relapse‐free survival in the cohort is 73/134 (55%) with a median follow‐up of 32 months. GVHD of any grade was significantly associated with a lower risk of relapse (p =.008). Median survival time was 160.3 days (range 132–187) in those with chronic GVHD versus 88.3 days (range 68–107) in those without (p value =.004). Conclusion: Pre‐emptive whole blood DLIs in graded aliquots, and lenalidomide are important tools for post HSCT GVL induction, which significantly impacts relapse‐free survival in childhood leukemia. [ABSTRACT FROM AUTHOR]

Patients with Myelodysplastic syndromes (MDS) have few therapy options for sustainable responses in the frontline setting, and even less after hypomethylating agent (HMA) failure in relapsed and refractory setting. The only potential cure is an allogeneic hematopoietic stem cell transplant which is an unrealistic option for the majority of MDS patients. Immunotherapy with checkpoint inhibition, CAR-T cells, and vaccine therapy few have shown promise in a variety cancer and have now been tested in patients with MDS. Most trials have focused on AML patients and included small numbers of MDS patients. Until now, a dedicated review of immunotherapy outcomes in MDS patients has been lacking. Thus, herein we review outcomes of MDS patients after immunotherapies on a variety of clinical trials reported to date.

Abstract Background Degenerative lumbar instability (DLI) is a common disease that causes low back pain (LBP) in clinic. It is difficult to completely recover from DLI, and it occurs repeatedly, which seriously affects the quality of life of patients. The epidemiological survey showed that 20–30% of low back pain was related to lumbar instability. Increasing evidence shows that seated lumbar rotation manipulation can effectively improve the clinical symptoms of patients with low back pain. The primary aim of this clinical trial is to observe the intervention effect of seated lumbar rotation manipulation on DLI patients. Method/design A total of 60 participants with DLI will be recruited and randomly allocated into the seated lumbar rotation manipulation group (the intervention group) or lumbar traction in supine position group (the control group) in this prospective, outcome assessor-blind, two-arm randomized controlled clinical trial. The treatment of the two groups lasted for 3 weeks, and the manipulation of the intervention group would be carried out once every other day, three times a week, a total of 9 times; the control group would be given lumbar traction once a day, five times a week, a total of 15 times. JOA (Japanese Orthopaedic Association) and VAS (Visual Analogue Scales) scores will be recorded as the primary outcomes before the treatment and at the 1st, 3rd, 5th, 8th, 10th, 12th, 15th, 17th, and 19th days after treatment and follow-up visit at the first, third, and sixth months. JOA efficacy evaluation standard will be used to evaluate the overall efficacy as the secondary outcomes. Discussion The results of this prospective, randomized controlled trial will provide a clinical evidence for the treatment of DLI with seated lumbar rotation manipulation. Trial registration Chinese Clinical Trial Registry ChiCTR2000032017 . Registered on 18 April 2020, Prospective registration.

Light-emitting diodes (LEDs) have been widely used as light sources for plant production in plant factories with artificial lighting (PFALs), and light spectrum and light amount have great impacts on plant growth and development. With the expansion of the product list of PFALs, tomato production in PFALs has received attention, but studies on fruit quality influenced by artificial light are lacking. In this study, precisely modulated LED light sources based on white light combined with additional red, blue, and green lights were used to investigate the effects of light spectrum and daily light integral (DLI) on the main quality indicators and flavor substances of “Micro-Tom” tomato fruits. The highest sugar–acid ratio was obtained under the white light with addition of red light with high DLI and blue light with low DLI. The contents of β-carotene, lycopene, and lutein were significantly increased by higher DLI conditions except for under the blue light treatment, and the cross-interactions between the light spectrum and DLI were observed. The accumulation of the main flavor substances in tomato fruits was decreased by addition of green light with a high DLI and red light with a low DLI; notably, the percentage of 2-isobutylthiazole, which is associated with fresh tomato aroma, was decreased by green light. This study provides insights for improving tomato fruit quality and flavor by regulating light conditions in PFALs.

Our objective was to characterize the growth, physiological responses, fruit yield, and quality of tomato (Solanum lycopersicum L.) plants grown under different daily light integrals (DLIs) and photoperiods. In experiment I, nine compact tomato cultivars were grown indoors using broadband white light-emitting diode (LED) fixtures. Plants were grown under low (10.4 mol·m−2·d−1) and high (18.4 mol·m−2·d−1) DLIs with 12 and 16 h photoperiods, respectively, and two intermediate DLIs of 13.8 mol·m−2·d−1 with either 12 or 16 h photoperiods. In experiment II, three compact tomato cultivars were grown under the same low DLI with either 8 or 12 h photoperiods, and the same high DLI with either 12 or 16 h photoperiods. Generally, higher DLIs decreased plant growth and increased the fruit yield. Changing the DLI delivery strategy by adjusting the photoperiod and photosynthetic photon flux density (PPFD) did not have major effects on the growth, yield, and fruit quality of the compact tomato plants evaluated in this study, even though net photosynthesis increased under higher PPFDs in experiment II. Although several cultivars were affected by intumescence, only two cultivars showed treatment responses, for which the severity was generally higher in lower PPFDs using the same DLI. [ABSTRACT FROM AUTHOR]

Prophylactic donor lymphocyte infusions (DLI) are part of the sequential FLAMSA‐reduced intensity conditioning (RIC) regimen to cure high risk myeloid neoplasia with allogeneic hematopoietic stem cell transplantation (HSCT). Although DLI themselves carry significant risks, their prophylactic use has not been analyzed in a time‐dependent manner. One hundred and fourteen patients underwent FLAMSA‐RIC HSCT between 2013 and 2020. Next to Kaplan‐Meier estimation of overall, disease‐free, and graft‐versus‐host relapse‐free survival (OS, DFS, GRFS), cumulative incidences of relapse and death in remission were calculated in a competing risk model. Additionally, the contribution of prophylactic and preemptive DLI as time‐dependent covariates was assessed using a time‐varying model toward DFS (Simon‐Makuch method, Mantel‐Byar test). At 2 years, OS was 45.2% [95% CI 36.7–55.7%], DFS 31.8% [95% CI 24–42.2%] and GRFS 11.3 [95% CI 6.5–19.8]. Neither prophylactic nor preemptive DLI showed a significant influence on DFS when considered time‐dependent covariates (Mantel‐Byar, p =.3). This was further corroborated in competing risk analysis with DLI as time‐dependent covariates. Both prophylactic and preemptive DLI miss significance in their impact on survival within a high‐risk cohort in a time‐varying model. Controlled trials to address the impact of postgrafting immunotherapy approaches are needed. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.

Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated. [ABSTRACT FROM AUTHOR]

Cryopreserved cellular products, as parts of hematopoietic progenitor cell (HPC) transplants, mononuclear cell reinjections for donor lymphocyte infusion or extracorporeal photopheresis, can be washed before being reinjected into the patient or infused directly, depending on local practices. The aim of washing is to reduce the incidence and severity of adverse reactions (ARs) due to the dimethyl sulfoxide (DMSO) used as a cryoprotective agent and other factors, such as dead cell debris. At the authors' cell therapy laboratory (CTL) in Poitiers, France, as in 76% of Etablissement Français du Sang (EFS) CTLs, all cryopreserved products undergo thawing in a water bath followed by washing with the COBE 2991. As this device will soon cease to be available, an alternative process needs to be assessed. The authors compared two closed systems: the authors' semi-automatic system using the traditional centrifugation method (COBE 2991) and an automated device using spinning membrane filtration (Lovo). A total of 72 HPC bags available for research were used. The authors first performed a paired comparison, processing one or two HPC bags washed by each device. A second study was carried out to compare two different washing solutions generally used by EFS CTLs along with variable storage conditions. Finally, the authors studied the efficiency of the Lovo with three or four thawed bags. The main parameters studied were viable CD34+ cell recovery and viability, CD3+ cell recovery, stability up to 6 h after washing, DMSO elimination and center feasibility. The Lovo device showed better CD34+ cell recovery compared with the COBE 2991 while maintaining CD34+ viability and stability over 6 h. Moreover, Lovo efficiency seemed to be independent of the number of thawed bags processed and washing solution used in the authors' study. CD3+ cell recovery met the authors' internal specifications (cell recovery >50%), with similar results seen when processing with either the COBE 2991 or Lovo. Additionally, on average, 97% of DMSO was removed after washing with Lovo, minimizing the risk of ARs. The storage conditions post-processing indicated preferred storage conditions of 7 ± 3°C. Finally, if processing time seemed shorter using COBE 2991 for one bag washed, the Lovo device required only one staff member regardless of the number of HPC bags processed. The Lovo device seems to provide an opportunity to standardize HPC processing, ensuring patient safety, with, on average, 97% of DMSO removed, while improving recovery of cells of interest and maintaining viability over time in case of delayed transplant. The Lovo device consequently seems to be a serious alternative to the COBE 2991. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI "preemptively," in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML. [ABSTRACT FROM AUTHOR]

Background: Degenerative lumbar instability (DLI) is a common disease that causes low back pain (LBP) in clinic. It is difficult to completely recover from DLI, and it occurs repeatedly, which seriously affects the quality of life of patients. The epidemiological survey showed that 20-30% of low back pain was related to lumbar instability. Increasing evidence shows that seated lumbar rotation manipulation can effectively improve the clinical symptoms of patients with low back pain. The primary aim of this clinical trial is to observe the intervention effect of seated lumbar rotation manipulation on DLI patients.Method/design: A total of 60 participants with DLI will be recruited and randomly allocated into the seated lumbar rotation manipulation group (the intervention group) or lumbar traction in supine position group (the control group) in this prospective, outcome assessor-blind, two-arm randomized controlled clinical trial. The treatment of the two groups lasted for 3 weeks, and the manipulation of the intervention group would be carried out once every other day, three times a week, a total of 9 times; the control group would be given lumbar traction once a day, five times a week, a total of 15 times. JOA (Japanese Orthopaedic Association) and VAS (Visual Analogue Scales) scores will be recorded as the primary outcomes before the treatment and at the 1st, 3rd, 5th, 8th, 10th, 12th, 15th, 17th, and 19th days after treatment and follow-up visit at the first, third, and sixth months. JOA efficacy evaluation standard will be used to evaluate the overall efficacy as the secondary outcomes.Discussion: The results of this prospective, randomized controlled trial will provide a clinical evidence for the treatment of DLI with seated lumbar rotation manipulation.Trial Registration: Chinese Clinical Trial Registry ChiCTR2000032017 . Registered on 18 April 2020, Prospective registration. [ABSTRACT FROM AUTHOR]

Air temperature and light conditions are important factors not only to produce high quality seedlings but also to promote energy efficiency in a plant factory with artificial lighting. In this study, we conducted two experiments in order to investigate the favorable conditions of air temperature, light intensity and photoperiod for the production of cucumber scions and rootstocks in a plant factory with artificial lighting. Cucumber scions and rootstocks were cultivated in two combined treatments: the combination of three different levels of difference between the day and night temperature (DIF), 25/20, 26/18 and 27/16 ◦C and five different light intensity conditions of photosynthetic photon flux, 50, 100, 150, 200 and 250 µmol·m−2 ·s −1 was set for the first experiment, and the combination of three different photoperiod conditions, 12, 16 and 20 h·d −1 and five different light intensity conditions, 50, 100, 150, 200 and 250 µmol·m−2 ·s −1 was set for the second experiment. In the air temperature and light intensity treatments, the hypocotyl elongation of cucumber scions and rootstocks was affected more largely by light intensity than DIF. The highest DIF treatment (27/16 ◦C) affected negatively on the accumulation of dry mass. On the contrary, the smallest DIF treatment (25/20 ◦C) was favorable for seedling growth due to lesser stress by rapid change of air temperature between photo- and dark-period. In the photoperiod and light intensity treatments, an increased DLI (daily light integral) promoted the growth of scions and rootstocks. Under the same DLI condition, the growth of scions and rootstocks increased with increasing photoperiod and decreasing light intensity. In both of experiments, while the dry weight increased with increasing the light intensity, the light use efficiencies were reduced by increasing the light intensity. Considering the growth and quality of seedlings and energy efficiency, the optimal environment conditions were represented by 25/20 ◦C of air temperature, 150 µmol·m−2 ·s −1 of light intensity and 16 h·d −1 of photoperiod. [ABSTRACT FROM AUTHOR]

Our objective was to characterize the growth, physiological responses, fruit yield, and quality of tomato (Solanum lycopersicum L.) plants grown under different daily light integrals (DLIs) and photoperiods. In experiment I, nine compact tomato cultivars were grown indoors using broadband white light-emitting diode (LED) fixtures. Plants were grown under low (10.4 mol·m−2·d−1) and high (18.4 mol·m−2·d−1) DLIs with 12 and 16 h photoperiods, respectively, and two intermediate DLIs of 13.8 mol·m−2·d−1 with either 12 or 16 h photoperiods. In experiment II, three compact tomato cultivars were grown under the same low DLI with either 8 or 12 h photoperiods, and the same high DLI with either 12 or 16 h photoperiods. Generally, higher DLIs decreased plant growth and increased the fruit yield. Changing the DLI delivery strategy by adjusting the photoperiod and photosynthetic photon flux density (PPFD) did not have major effects on the growth, yield, and fruit quality of the compact tomato plants evaluated in this study, even though net photosynthesis increased under higher PPFDs in experiment II. Although several cultivars were affected by intumescence, only two cultivars showed treatment responses, for which the severity was generally higher in lower PPFDs using the same DLI.

Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine (n = 13) or decitabine (n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1-19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRDneg, 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients (p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) (n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months (p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit. [ABSTRACT FROM AUTHOR]

Prognosis in patients with post allogeneic HCT-early relapse of acute myeloid leukemia (<6 months post HCT) is dismal and response to salvage treatment is < 20%. In addition, majority of patients at this early point are unable to withstand intensive salvage chemotherapy. We hypothesized that the combination of donor lymphocyte infusion (DLI) and venetoclax may result in increased response in this difficult to treat patient group. We retrospectively analyzed 22 patients from February 2017–December 2019, who were given the Venetoclax/DLI combination. Median age was 65 (43–75) years. There were no cases of tumor lysis syndrome. Microbiology documented infections occurred in 8 patients (36%). Majority were able to tolerate the protocol without admissions. Acute GVHD was observed in 4 (18%) patients and cGVHD was observed in 6 (27%) patients. Overall response was observed in 11 (50%) patients (CR, n = 4; CRi, n = 1; CRp, n = 4; MLFS n = 2). Median time to response was 28 (18–67) days and median cycles of venetoclax 2 [1–8] and duration of response were 135 (31–564) days. Median survival was 6.1 months (95% CI.73–11.4). Cox regression model for survival showed decreased WBC at relapse, GVHD and better performance status were associated with better survival. These results may endorse the hypothesis that enhancing alloreactivity combined with venetoclax is safe and efficacious and should be further investigated in prospective trials. [ABSTRACT FROM AUTHOR]

This case report presents the successful management of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia in a 54-year-old male post-allogeneic hematopoietic cell transplantation. The combinatorial approach of sequential antibody treatment (Inotuzumab [InO] and Blinatumomab [Blina]) combined with three donor lymphocyte infusions (DLI) applications and cytoreductive chemotherapy-induced sustained complete molecular remission as documented at the last follow-up 30 months later. This case highlights the feasibility and potential synergistic efficacy of a Blina/DLI regimen and supports the hypothesis that T-cell engagers could enhance the DLI effect. Furthermore, the co-administration of InO, Blina, DLI, and cytoreductive chemotherapy was proven to be feasible without severe adverse events., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

The FLAMSA reduced intensity (RIC) concept, also known as "sequential therapy", is a conceptual platform for the treatment of leukemia separated in several parts: induction therapy, a sequence of antileukemic and immunosuppressive conditioning for allogeneic stem cell transplantation, and immune restitution supported by donor lymphocyte transfusions. The antileukemic part consists of fludarabine, cytosine arabinoside, and amsacrine (FLAMSA); non-cross reactive agents like fludarabine and amsacrine have been successfully used in cases of refractoriness and relapse. Immunosuppressive conditioning and transplantation follow after only 3 days of rest. This way, the toxicity of allogeneic transplantation could be reduced and the anti-leukemia effects by using allogeneic immune cells could be optimized. This review summarizes available data on efficacy and toxicity of this approach. Further, possible strategies for improvements are discussed in order to provide better chances for elderly and frail patients and patients with advanced and high-risk disease. Among others, several new agents are available that target molecular changes of leukemia for induction of remission and allow for bridging the time after transplantation until adoptive immunotherapy becomes safe and effective. [ABSTRACT FROM AUTHOR]

Opinion Statement: Cellular immunotherapy has been rapidly evolving and increasingly utilized in the management of relapsed and refractory lymphoma. CD19-specific chimeric antigen receptor T cells (CARTs) have achieved impressive results in pivotal clinical trials. Although CART development continues, these products have fundamental limitations that may make them less desirable in particular settings. For example, CARTs can only target cell surface antigens and thus are incapable of targeting intracellular tumor-associated proteins. In contrast to CARTs, conventional T cell receptors (TCR) allow T cells to target any cellular antigen, including intracellular proteins, since they interact with peptides presented by MHC I and II molecules. T cells recognizing EBV antigens through native TCRs have been successfully employed for treatment and prophylaxis of EBV-associated lymphomas, including post-transplant lymphoproliferative disorder. Currently, transgenic TCR-transduced T cells targeting nonviral tumor antigens remain experimental but, if successful, could become an invaluable cellular therapy option. Because the manufacturing process of autologous T cell products, including CARTs and other tumor-specific T cells, takes several weeks, patients often need bridging therapy to maintain disease control, which may be challenging. Novel cellular platforms, such as genetically modified NK and NKT cells, may be amenable to allogeneic use and thus may allow production as a readily available, "off-the-shelf" product. As cellular therapies beyond CART continue to grow, available therapeutic options for relapsed and refractory lymphoma patients are expected to expand further. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting graft-vs.-leukemia (GVL) effects. However, sufficient tumor control cannot be established in all patients and occurrence of graft-vs.-host disease (GVHD) prevents further dose escalation. Previous data indicate that invariant natural killer T (iNKT) cells promote anti-tumor immunity without exacerbating GVHD. In the present study we investigated lysis of leukemic blasts through iNKT cells from donor-derived lymphocytes for leukemia control and found that iNKT cells constitute about 0.12% of cryopreserved donor T cells. Therefore, we established a 2-week cell culture protocol allowing for a robust expansion of iNKT cells from cryopreserved DLIs (DLI-iNKTs) that can be used for further preclinical and clinical applications. Such DLI-iNKTs efficiently lysed leukemia cell lines and primary patient AML blasts ex vivo in a dose- and CD1d-dependent manner. Furthermore, expression of CD1d on target cells was required to release proinflammatory cytokines and proapoptotic effector molecules. Our results suggest that iNKT cells from donor-derived lymphocytes are involved in anti-tumor immunity after allo-HCT and therefore may reduce the risk of relapse and improve progression-free and overall survival.

This study was conducted to determine the effects of daily light integral (DLI) levels with different photoperiods and light intensities on the growth and flowering initiation of Phalaenopsis plants. Five-month-old Phalaenopsis Queen Beer 'Mantefon' plants were treated with combinations of three photoperiods [8/16 (day/night, short day, SD), 12/12 (medium day, MD), and 16/8 h (long day, LD)] and three light intensities in the range of photosynthetically active radiation of 50, 100, and 200 μmol·m−2·s−1, resulting in DLI levels ranging from 1.44 to 11.52 mol·m−2·d−1 with warm-white LEDs at 28°C during the vegetative period. Additionally, 12-month-old plants were treated with combinations of three photoperiods [8/16 (day/night, SD), 8 + 8/8 (day-extension (DE); an extension with 10 μmol·m−2·s−1 for 8 h right after the SD), and 16/8 h (LD)] and three light intensities (75, 150, and 300 μmol·m−2·s−1), resulting in DLI levels ranging from 2.16 to 17.28 mol·m−2·d−1, at 20°C during the forcing period for flowering. During the vegetative period, plants showed a tendency of overgrowth in leaves, via the formation of long and narrow leaves, as the light intensity decreased, irrespective of the photoperiod. The number of new leaves, total leaf area, and shoot and root dry weights increased with increasing photoperiod and light intensity, implying an increase in the amount of light energy. During the forcing period, photoperiodic effects on flowering initiation were not observed, while increasing the light intensity increased the number of inflorescences and accelerated spiking. The DLI showed higher correlation coefficients with growth and flowering initiation characteristics than those of the photoperiod or light intensity alone. New leaf emergence, biomass accumulation, and spiking were enhanced as DLI levels increased, although these positive effects were gradually saturated. These findings indicated that the DLI is a major factor in the growth and flowering initiation of Phalaenopsis plants and increasing DLI levels can promote growth or flowering initiation of these plants. These findings will be useful in controlling light conditions to maximize the growth rate and shorten the cultivation time in Phalaenopsis cultivation. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting graft-vs.-leukemia (GVL) effects. However, sufficient tumor control cannot be established in all patients and occurrence of graft-vs.-host disease (GVHD) prevents further dose escalation. Previous data indicate that invariant natural killer T (iNKT) cells promote anti-tumor immunity without exacerbating GVHD. In the present study we investigated lysis of leukemic blasts through iNKT cells from donor-derived lymphocytes for leukemia control and found that iNKT cells constitute about 0.12% of cryopreserved donor T cells. Therefore, we established a 2-week cell culture protocol allowing for a robust expansion of iNKT cells from cryopreserved DLIs (DLI-iNKTs) that can be used for further preclinical and clinical applications. Such DLI-iNKTs efficiently lysed leukemia cell lines and primary patient AML blasts ex vivo in a dose- and CD1d-dependent manner. Furthermore, expression of CD1d on target cells was required to release proinflammatory cytokines and proapoptotic effector molecules. Our results suggest that iNKT cells from donor-derived lymphocytes are involved in anti-tumor immunity after allo-HCT and therefore may reduce the risk of relapse and improve progression-free and overall survival. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (aHSCT) cures a considerable number of patients with myeloid malignancies, but relapse is the most frequent cause of death. We retrospectively studied relapse rate, kinetics, treatment, and outcome after first aHSCT in 446 patients during a 13-year period. Relapse occurred in 167 patients after a median of 4.6 months (116 hematologic (HR), 38 molecular (MR), and 13 extramedullary relapses (XR)). Median survival after relapse was 8.4 months and 2-year overall survival was 25%. Regarding survival after relapse, type (MR/HR/XR) and timepoint of relapse ( 12 months), age ( 50), diagnosis (MDS/AML and sAML), and remission status at transplant (CR and untreated MDS vs. refractory disease) were relevant in univariate analyses, in multivariate analyses timepoint, and type of relapse, age, and diagnosis. One hundred fifty-six patients were treated, most frequently with hypomethylating agents (HMA, n = 109) or intensive chemotherapy (n = 12). Donor lymphocyte infusion (DLI) was administered to 99 patients. Second aHSCT was performed in three patients as first and in 21 as higher salvage treatment. A complete remission (CR) was achieved in 46 patients (30%). Among CR patients, 65% had received HMA and DLI. Median survival of patients achieving CR was 105 months and 2-year overall survival was 80%. We conclude that with HMA and DLI or second aHSCT, a substantial number of patients, who relapse after aHSCT, can re-achieve remission and long-term survival. Techniques to further improve the detection of minimal residual disease are urgently needed because early treatment of MR results in significantly better survival. [ABSTRACT FROM AUTHOR]

Highlights • CTLA4Ig primed DLI is a novel approach for immunotherapy that results in in vivo proliferation of CD56dim16+ NK cells with donor KIR phenotype and upregulation of CD86 expression. • Attenuation of disease progression was associated with NK B haplotype donor and early proliferation of CD56dim16+ NK cells post-transplant with lower expression of NKG2A. • Progression-free survival of 75% was achieved in advanced leukemia with acute GVHD and NRM of 6.7% and 4.5%, suggesting that this approach exploits the GVL effect of NK cells with attenuation of early T cell–mediated alloreactivity. Abstract CTLA4Ig attenuates T cell activation by co-stimulation blockade, but natural killer (NK) cells are not only resistant to CTLA4Ig, they also may demonstrate better antileukemia effect in the presence of CTLA4Ig. To explore this phenomenon we used sequential CTLA4Ig primed donor lymphocyte infusion (DLI) after post-transplant cyclophosphamide–based haploidentical transplantation. Thirty patients (CTLA4Ig-DLI group) with advanced leukemia received CTLA4Ig on day –1 and subsequently on days +7, +21, and +35, followed 12hours later by DLI of 1 to 10 × 106 CD3+ T cells/kg containing.1 to 3.27 × 106/kg CD56+ NK cells, with low dose cyclosporine for 60days. The incidences of acute graft-versus-host disease (GVHD), chronic GVHD and nonrelapse mortality (NRM) were 6.7%, 21%, and 4.5 %, respectively, with disease progression of 23.3% and overall survival of 79% at 18 months. Patients without disease progression had a significant early surge in CD56dimCD16+NK cells with lower NKG2A expression. CTLA4Ig primed DLI was associated with an upregulation of CD86 in mature NK cells that was not witnessed with CTLA4Ig administration alone. Thus, CTLA4Ig primed DLI resulted in early proliferation of mature NK cells with cytotoxic potential enabling early institution of adoptive immunotherapy to mitigate the risk of relapse in advanced leukemia with reduced GVHD and NRM. Graphical Abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Summary: Strategies for relapse prevention after allogeneic transplantation in acute leukaemia are warranted. A registry‐based matched‐pair analysis evaluated the efficacy of prophylactic donor lymphocyte infusion (proDLI). Adults receiving proDLI in complete remission (CR) and controls were pair‐matched for age, diagnosis, cytogenetics, stage, donor, gender, conditioning and T‐cell depletion. Eighty‐nine pairs were identified (median follow‐up: 6.9 years). Within the entire cohort, no difference was observed. However, among patients with high‐risk acute myeloid leukaemia (AML) (unfavourable cytogenetics and/or transplanted beyond first CR), proDLI recipients had improved overall survival (69.8% vs. 40.2% in controls, P = 0.027). ProDLI has moderate efficacy, but can contribute to improved outcome in high‐risk AML. [ABSTRACT FROM AUTHOR]

Treatment options for patients with adult T cell leukemia/lymphoma (ATLL) who have relapsed disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are limited. To clarify which patients with ATLL are likely to benefit from these treatment options and to define patient populations for novel treatments, we performed a nationwide retrospective analysis of 252 Japanese patients who had relapsed ATLL after allo-HSCT. Some long-term survivors remained after tapering and withdrawal of immunosuppressive agents. Thirty-six patients who received donor lymphocyte infusion had a better overall survival (OS) in comparison to those who did not [hazard ratio (HR), 0.63; 95% confidence interval (CI), 0.43-0.93; P = .02], suggesting the efficacy of a graft-versus-ATLL (GvATLL) effect even after relapse. Multivariate analysis demonstrated that skin lesions at initial relapse of ATLL were independently associated with higher OS (HR, 0.41; 95% CI, 0.22-0.74; P = .003), indicating that the skin is a susceptible target organ of GvATLL. This study suggested that enhancement of a GvATLL effect is a potential therapeutic option for relapsed disease after allo-HSCT. Further investigations of incorporation of immune-based approaches with new molecular target drugs into the therapeutic options of patients with ATLL before and after transplantation are warranted. [ABSTRACT FROM AUTHOR]

To investigate the influence of supplemental lighting intensity on the production (i.e., rate of flower development, flower quality, and yield) of cut gerbera during Canada’s supplemental lighting season (November to March), trials were carried out at a research greenhouse. Five supplemental light emitting diode (LED) light intensity (LI) treatments provided canopy-level photosynthetic photon flux densities (PPFD) ranging from 41 to 180 µmol m−2 s−1. With a 12-h photoperiod, the treatments provided 1.76 to 7.72 mol m−2 d−1 of supplemental light. Two cultivars of cut gerbera (Gerbera jamesonii H. Bolus ex Hook.f) were used to evaluate vegetative growth and flower production. Plugs of ‘Ultima’ were assessed for vegetative growth and rate of flower development. There were minor LI treatment effects on number of leaves and chlorophyll content index and flowers from plants under the highest versus the lowest LI matured 10% faster. Reproductively mature ‘Panama’ plants were assessed for flower yield and quality. ‘Panama’ flowers from the highest LI treatment had shorter stems than the three lowest LI treatments, and flowers from the middle LI treatment had larger diameter than the other treatments. Flowers from the lowest LI treatment had lower fresh mass than the three highest LI treatments. There were linear relationships between LI and numbers of flowers harvested, with the highest LI treatment producing 10.3 and 7.0 more total and marketable flowers per plant than the lowest LI treatment. In general, increasing levels of supplemental light had only minor effects on vegetative growth (young plants) and size and quality of harvested flowers (mature plants), but flowers from plants grown under higher LIs were more numerous and matured faster.

Supplemental light (SL) is a technique used to increase horticulture yield, especially in northern countries, where the Daily Light Integral (DLI) is a limiting factor during fall and winter, and which could also be used to obtain higher tomato yield at the Mediterranean latitude. In this study, three tomato hybrid (F1) cultivars were grown for year-round production in a commercial semi-closed glasshouse in Southern Italy: two of the cherry fruit-type (‘Juanita’ and ‘Sorentyno’) and one mini plum fruit-type (‘Solarino’). From 120 to 243 days after transplant, light-emitting diode (LED) toplights were used as SL, with a photoperiod of 18 h. The main climatic parameters inside and outside the glasshouse were recorded, and tomato plants’ development and yield were examined. Plants grown with LEDs had longer stems as compared to control treatment (9.53 vs. 8.79 m), a higher stem thickness and yielded more trusses. On average, the yield was 21.7% higher with LEDs. ‘Sorentyno’ was the cultivar with the highest cumulated productivity when it was grown under SL. However, the cultivar with best light use efficiency under LEDs was ‘Solarino’. Therefore, supplemental LED from mid-December until March enhanced tomato growth and yield, opening a favorable scenario for large-scale application of this technology also in the Mediterranean area.

Insufficient exposure to light in the winter may result in a longer production periods and lower quality of seedlings in greenhouses for plug growers. Supplementary artificial lighting to plug seedlings may be one solution to this problem. The objective of this study was to assess the effects of the duration of the supplementary light on the growth and development of two watermelon cultivars, ‘Speed’ and ‘Sambok Honey’ grafted onto ‘RS-Dongjanggun’ bottle gourd rootstocks (Lagenaria siceraria Stanld). Seedlings were grown for 10 days in a glasshouse with an average daily natural light intensity of 340 μmol·m−2·s−1 photosynthetic photon flux density (PPFD) and daily supplementary lighting of 8, 12 or 16 h from mixed LEDs (W1R2B1, chip ratio of white:red:blue = 1:2:1) at a light intensity of 100 μmol·m−2·s−1 PPFD, a group without supplementary light was set as the control (CK). The culture environment in a glasshouse had 25/15 °C day/night temperatures, an 85 ± 5% relative humidity, and a natural photoperiod of 8 h. The results showed that all the growth and development parameters of seedlings grown with supplementary light were significantly greater than those without supplementary light (CK). The 12 and 16 h supplementary light resulted in greater growth and development parameters than the 8 h supplementary light did. The same trend was also found with the indexes that reflect the quality of the seedlings, such as the dry weight ratio of the shoot and root, total biomass, dry weight to height ratio of scions, and specific leaf weight. The 12 h and 16 h light supplements resulted in greater Dickson’s quality indexes compared to the 8 h supplementary light, and the 12 h supplementary light showed the greatest use efficiency of the supplementary light. 16 h of daily supplementary light significantly increased the H2O2 content and the antioxidant enzyme activities in seedlings compared to the other treatments. This indicated that 16 h of supplementary light led to certain stresses in watermelon seedlings. In conclusion, considering the energy consumption, 12 h of supplementary light was the most efficient in improving the quality of the two cultivars of grafted watermelon plug seedlings.

A greenhouse study was undertaken to investigate whether light-emitting diode (LED) technology can be used to replace high-pressure sodium (HPS) lighting for cut gerbera production during Canada's traditional supplemental lighting (SL) season (November to March). The study was carried out at the University of Guelph's research greenhouse, using concurrent replications of SL treatments within the same growing environment. LED (85% red, 15% blue) and HPS treatment plots were set up to provide equal amounts of supplemental photosynthetically active radiation (PAR) at bench level. This setup was used to assess the production of three cultivars of cut gerbera (Gerbera jamesonii H. Bolus ex Hook.f): Acapulco, Heatwave, and Terra Saffier. There were no treatment differences in SL intensity, with average SL photosynthetic photon flux density (PPFD) and daily light integral (DLI) of 55.9 κmol·m-2·s-1 and 2.3 mol·m-2·d-1, respectively. Flowers harvested from the LED treatment had a 1.9% larger flower diameter in 'Acapulco'; 4.2% shorter and 3.8% longer stems in 'Heatwave' and 'Terra Saffier', respectively; and 7.7% and 8.6% higher fresh weights for 'Acapulco' and 'Terra Saffier', respectively, compared with flowers harvested from the HPS treatment. There were no differences in accumulated total or marketable flower harvests for any of the cultivars. The vase life of 'Acapulco' flowers grown under the LED treatment was 2.7 d longer than those grown under the HPS treatment, but there were no SL treatment effects on water uptake for any of the cultivars during the vase life trials. There were no SL treatment effects on specific leaf area for any of the cultivars. There were only minimal treatment differences in leaf, soil, and air temperatures. Cut gerbera crops grown with under LED SL had equivalent or better production and crop quality metrics compared with crops grown under HPS SL. [ABSTRACT FROM AUTHOR]

Stem cell transplant in India has been seeing a steady progressive growth over the last decade. Thirty abstracts related to various aspects of bone marrow transplant were presented in the annual conference of Indian Society of Hematology and Transfusion medicine in 2018. All abstracts which were published were reviewed. They were categorized into autologous transplants, allogeneic transplants, lab aspects and supportive care. They have been summarized to provide a snapshot of the data presented. These data are likely to encourage to start or enhance transplant activity at other centers. [ABSTRACT FROM AUTHOR]