Author Correction: Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling.

High-dose radiation activates caspases in tumor cells to produce abundant DNA fragments for DNA sensing in antigen-presenting cells, but the intrinsic DNA sensing in tumor cells after radiation is rather limited. Here we demonstrate that irradiated tumor cells hijack caspase 9 signaling to suppress intrinsic DNA sensing. Instead of apoptotic genomic DNA, tumor-derived mitochondrial DNA triggers intrinsic DNA sensing. Specifically, loss of mitochondrial DNA sensing in Casp9-/- tumors abolishes the enhanced therapeutic effect of radiation. We demonstrated that combining emricasan, a pan-caspase inhibitor, with radiation generates synergistic therapeutic effects. Moreover, loss of CASP9 signaling in tumor cells led to adaptive resistance by upregulating programmed death-ligand 1 (PD-L1) and resulted in tumor relapse. Additional anti-PD-L1 blockade can further overcome this acquired immune resistance. Therefore, combining radiation with a caspase inhibitor and anti-PD-L1 can effectively control tumors by sequentially blocking both intrinsic and extrinsic inhibitory signaling.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

Usefulness of magnetic resonance imaging characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in spinal cord.

AIM: The aim of this study was to determine the usefulness of magnetic resonance imaging (MRI) characteristics in discriminating H3 K27M-mutant gliomas from wildtype gliomas in the spinal cord. MATERIALS AND METHODS: Fifty-eight patients with spinal cord gliomas were enrolled in this study. The H3 K27 gene status was identified by Sanger sequencing or immunohistochemistry test of resection tumor specimens. The MR imaging characteristics were evaluated and compared between H3 K27M-mutant and wildtype gliomas using the χ2 test and the Mann-Whitney U test. RESULTS: Of 58 recruited patients, 23 (39.7%) were diagnosed with H3 K27M-mutant glioma. The H3 K27M-mutant gliomas were found to more likely occur in men compared with wildtype gliomas (87.0% vs. 42.9%, p = 0.001). On T2-weighted MR images, the signal-to-noise ratio (SNR) of H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (103.9 ± 72.0 vs. 168.9 ± 86.8, p < 0.001). Of 35 wildtype tumors, 60% showed well-defined margin but this feature was not found in all mutant tumors (p < 0.001). The SNR of tumors on contrast-enhanced T1-weighted images of the H3 K27M-mutant gliomas was significantly lower than that of wildtype gliomas (187.7 ± 160.4 vs. 295.1 ± 207.8, p = 0.006). Receiver operating-characteristic analysis revealed that area under curve (AUC) of combination of 1/SNR on T2-weighted images, 1/SNR on contrast-enhanced T1-weighted images, ill-defined margin, and sex reached 0.937 (95% CI, 0.873-1.000) in discriminating H3 K27M-mutant gliomas. CONCLUSIONS: The MR imaging characteristics are valuable in discriminating H3 K27M-mutant from wildtype gliomas in the spinal cord and the combination of these imaging features with sex had a high strength in this discrimination.

Perfluoroalkyl and polyfluoroalkyl substances and hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP), including gestational hypertension (GH) and preeclampsia (PE), cause significant morbidity and mortality among pregnant women. Several environmental toxins, particularly those that affect the normal function of the placenta and the endothelium, are emerging as potential risk factors for HDP. Among them, per- and polyfluoroalkyl substances (PFAS), widely used in a variety of commercial products, have been related to a variety of adverse health effects including HDP. This study was conducted by searching three databases for observational studies reporting associations between PFAS and HDP, all of which were published before December 2022. We used random-effects meta-analysis to calculate pooled risk estimates, and assessing each combination of exposure and outcome for quality and level of evidence. In total, 15 studies were included in the systematic review and meta-analysis. The results from meta-analyses showed that risk of PE was increased with exposure to PFOA (perfluorooctanoic acid) (RR = 1.39, 95% CI = 1.05, 1.85; N = 6 studies; exposure = 1 ln-unit increment; low certainty), PFOS (perfluorooctane sulfonate) (RR = 1.51, 95% CI = 1.23, 1.86; N = 6 studies; exposure = 1 ln-unit increment; moderate certainty), and PFHxS (perfluorohexane sulfonate) (RR = 1.39, 95% CI = 1.10, 1.76; N = 6 studies; exposure = 1 ln-unit increment; low certainty). PFOS was also associated with an increased risk of HDP (RR = 1.39, 95% CI = 1.10, 1.76; exposure = 1 ln-unit increment; low certainty). Exposure to legacy PFAS (PFOA, PFOS, PFHxS) is associated with an increased risk of PE, and PFOS is further associated with HDP. In view of the limitations of meta-analysis and quality of evidence, these findings should be interpreted with caution. Further research is required that assesses exposure to multiple PFAS in diverse and well-powered cohorts.

Effects of Traditional Chinese Medicine Five-Element Music Therapy Combined with Mirtazapine on Depression and Limb Function Recovery After Ischemic Stroke.

Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.

Mini-Review: The Diagnostic Methods of Tinea Capitis.

Tinea capitis is a widespread superficial fungal infection that affects children predominately. Microscopic examination and fungal culture are the conventional gold standards for diagnosis, but they are insensitive and time-consuming. In recent years, new diagnostic methods have been developed to facilitate the diagnosis and identification of causative pathogens. Trichoscopy examination showed high sensitivity and specificity for diagnosing tinea capitis with the characteristic signs of comma hairs, corkscrew hairs, bar code-like hairs and zigzag hairs. Reflectance confocal microscopy has also been used in the rapid diagnosis of tinea capitis in several studies. Molecular assays such as polymerase chain reaction and matrix-assisted desorption/ionization time to flight mass spectrometry are extensively utilized for rapid and accurate identification of the pathogens. Early diagnosis and treatment can aid in disease control and scarring reduction.

Visualizing the Entire Range of Noncovalent Interactions in Nanocrystalline Hybrid Materials Using 3D Electron Diffraction.

Noncovalent interactions are essential in the formation and properties of a diverse range of hybrid materials. However, reliably identifying the noncovalent interactions in nanocrystalline materials remains challenging using conventional methods such as X-ray diffraction and spectroscopy. Here, we demonstrate that accurate atomic positions including hydrogen atoms can be determined using three-dimensional electron diffraction (3D ED), from which the entire range of noncovalent interactions in a nanocrystalline aluminophosphate hybrid material SCM-34 are directly visualized. The protonation states of both the inorganic and organic components in SCM-34 are determined from the hydrogen positions. All noncovalent interactions, including hydrogen-bonding, electrostatic, π-π stacking, and van der Waals interactions, are unambiguously identified, which provides detailed insights into the formation of the material. The 3D ED data also allow us to distinguish different types of covalent bonds based on their bond lengths and to identify an elongated terminal P═O π-bond caused by noncovalent interactions. Our results show that 3D ED can be a powerful tool for resolving detailed noncovalent interactions in nanocrystalline materials. This can improve our understanding of hybrid systems and guide the development of novel functional materials.

All-trans retinoic acid increases the pathogenicity of the H9N2 influenza virus in mice.

BACKGROUND: The H9N2 virus can infect not only birds but also humans. The pathogenicity of H9N2 virus infection is determined by an excessive immune response in the lung. All-trans retinoic acid (ATRA), the active metabolite of vitamin A, plays an important regulatory role and has been widely used in the clinical practice. This study was aimed to investigate whether ATRA could regulate the immune response to H9N2 virus infection in the lungs of mice, thereby reducing the pathogenicity of the H9N2 virus in mice. METHODS: Mice were infected intranasally with H9N2 virus, and injected intraperitoneally with 0.2 mL of ATRA at low (1 mg/kg), medium (5 or 10 mg/kg), or high therapeutic dose (20 mg/kg), and toxic dose (40, 60, or 80 mg/kg), once per day for 10 days. Clinical signs, survival rates, and lung gross pathology were compared between the ATRA-treated H9N2-infected group, the ATRA group, and the H9N2-infected group, to investigate the effect of different doses of ATRA on the pathogenicity of H9N2 virus. Additionally, the viral load and cytokine concentration of lungs were measured at 3, 5, 7, and 9 days after infection, to investigate the potential mechanism of ATRA in affecting the pathogenicity of the H9N2 virus. Expression levels of cellular retinoic acid-binding protein 1 (CRABP1), cellular retinoic acid-binding protein 2 (CRABP2), and Retinoic acid-inducible gene-I (RIG-I) were detected using Western blotting. RESULTS: The ATRA-treated H9N2-infected mice showed more severe clinical signs compared with the H9N2-infected group. The medium and high therapeutic doses of ATRA reduced the survival rates, aggravated lung tissue damage, decreased the expression of interferon beta (IFN-ß), and increased the concentrations of interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and C-C motif chemokine ligand 2 (CCL2) in the lungs of the H9N2-infected mice. At the same time, the expression patterns of CRABP1, CRABP2, and RIG-I were changed in mice infected by H9N2 and treated with different concentrations of ATRA. CONCLUSIONS: Our findings suggest that the therapeutic dose of ATRA can increase the pathogenicity of the H9N2 virus. Therefore, the consequences of those infected by influenza virus would be more severe after ATRA treatment.

Multimodal image translation via deep learning inference model trained in video domain.

BACKGROUND: Current medical image translation is implemented in the image domain. Considering the medical image acquisition is essentially a temporally continuous process, we attempt to develop a novel image translation framework via deep learning trained in video domain for generating synthesized computed tomography (CT) images from cone-beam computed tomography (CBCT) images. METHODS: For a proof-of-concept demonstration, CBCT and CT images from 100 patients were collected to demonstrate the feasibility and reliability of the proposed framework. The CBCT and CT images were further registered as paired samples and used as the input data for the supervised model training. A vid2vid framework based on the conditional GAN network, with carefully-designed generators, discriminators and a new spatio-temporal learning objective, was applied to realize the CBCT-CT image translation in the video domain. Four evaluation metrics, including mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross-correlation (NCC), and structural similarity (SSIM), were calculated on all the real and synthetic CT images from 10 new testing patients to illustrate the model performance. RESULTS: The average values for four evaluation metrics, including MAE, PSNR, NCC, and SSIM, are 23.27 ± 5.53, 32.67 ± 1.98, 0.99 ± 0.0059, and 0.97 ± 0.028, respectively. Most of the pixel-wise hounsfield units value differences between real and synthetic CT images are within 50. The synthetic CT images have great agreement with the real CT images and the image quality is improved with lower noise and artifacts compared with CBCT images. CONCLUSIONS: We developed a deep-learning-based approach to perform the medical image translation problem in the video domain. Although the feasibility and reliability of the proposed framework were demonstrated by CBCT-CT image translation, it can be easily extended to other types of medical images. The current results illustrate that it is a very promising method that may pave a new path for medical image translation research.

Increased Pulmonary Pneumococcal Clearance after Resolution of H9N2 Avian Influenza Virus Infection in Mice.

H9N2 avian influenza virus has been continuously circulating among poultry and can infect mammals, indicating that this virus is a potential pandemic strain. During influenza pandemics, secondary bacterial (particularly pneumococcal) pneumonia usually contributes to excessive mortality. In the present study, we observed the dynamic effect of H9N2 virus infection on host defense against secondary pneumococcal infection in mice. BALB/c mice were intranasally inoculated with 1.2 × 105 PFU of H9N2 virus followed by 1 × 106 CFU of Streptococcus pneumoniae at 7, 14, or 28 days post-H9N2 infection (dpi). The bacterial load, histopathology, body weight, and survival were assessed after pneumococcal infection. Our results showed that H9N2 virus infection had no significant impact on host resistance to secondary pneumococcal infection at 7 dpi. However, H9N2 virus infection increased pulmonary pneumococcal clearance and reduced pneumococcal pneumonia-induced morbidity after secondary pneumococcal infection at 14 or 28 dpi, as reflected by significantly decreased bacterial loads, markedly alleviated pulmonary histopathological changes, and significantly reduced weight loss in mice infected with H9N2 virus followed by S. pneumoniae compared with mice infected only with S. pneumoniae Further, the significantly decreased bacterial loads were observed when mice were previously infected with a high dose (1.2 × 106 PFU) of H9N2 virus. Also, similar to the results obtained in BALB/c mice, improvement in pulmonary pneumococcal clearance was observed in C57BL/6 mice. Overall, our results showed that pulmonary pneumococcal clearance is improved after resolution of H9N2 virus infection in mice.

Strong and Robust Electrochemical Artificial Muscles by Ionic-Liquid-in-Nanofiber-Sheathed Carbon Nanotube Yarns.

To address the lack of a suitable electrolyte that supports the stable operation of the electrochemical yarn muscles in air, an ionic-liquid-in-nanofibers sheathed carbon nanotube (CNT) yarn muscle is prepared. The nanofibers serve as a separator to avoid the short-circuiting of the yarns and a reservoir for ionic liquid. The ionic-liquid-in-nanofiber-sheathed yarn muscles are strong, providing an isometric stress of 10.8 MPa (about 31 times the skeletal muscles). The yarn muscles are highly robust, which can reversibly contract stably at such conditions as being knotted, wide-range humidity (30 to 90 RH%) and temperature (25 to 70 °C), and long-term cycling and storage in air. By utilizing the accumulated isometric stress, the yarn muscles achieve a high contraction rate of 36.3% s-1 . The yarn muscles are tightly bundled to lift heavy weights and grasp objects. These unique features can make the strong and robust yarn muscles as a desirable actuation component for robotic devices.

The active GLP-1 analogue liraglutide alleviates H9N2 influenza virus-induced acute lung injury in mice.

Influenza virus is responsible for significant morbidity and mortality worldwide. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the major cause of death in influenza virus infected patients. Recent studies indicated that active glucagon like peptide-1 (GLP-1) encoded by glucagon (GCG) gene exerts anti-inflammatory functions. The aim of this study was to determine the potential role of active GLP-1 in H9N2 influenza virus-induced ALI/ARDS in mice. First, we uncovered that GCG mRNA expression levels and GCG precursor protein levels were significantly increased, but total GLP-1 and active GLP-1 levels were decreased in the lungs of H9N2-infected mice. Next, liraglutide, an active GLP-1 analogue, was used to treat infected mice and to observe its effects on H9N2 virus-induced ALI. Liraglutide treatment ameliorated the declined body weight, decreased food intake and mortality observed in infected mice. It also alleviated the severity of lung injury, including lowering lung index, decreasing inflammatory cell infiltration and lowing total protein levels in bronchoalveolar lavage fluid (BALF). In addition, liraglutide did not influence viral titers in infected lungs, but decreased the levels of interleukin-1ß, interleukin-6 and tumor necrosis factor-α in BALF. These results indicated that liraglutide alleviated H9N2 virus-induced ALI in mice most likely due to lower levels of pro-inflammatory cytokines.

Comparative study of micro-transplantation from HLA fully mismatched unrelated and partly matched related donors in acute myeloid leukemia.

Micro-transplantation (MST) by chemotherapy, combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (GPBSC) infusion, from an HLA partial matched related donor has shown some encouraging effective therapy for acute myeloid leukemia (AML). However, the outcome of human leukocyte antigen (HLA) fully mismatched unrelated donor-derived MST in such patients is still unknown. In the present study, we compared the efficacy of HLA fully mismatched unrelated donor-derived MST, and partly matched related donor-derived MST, in AML of 126 patients from two centers in China, These patients, aged 16 to 65 years, were given three or four courses of MST, which consisted of a high dosage cytarabine followed by GPBSC from unrelated donor or related donor. There was a statistically significant difference in 3-year leukemia-free survival (LFS) and 3-year overall survival (OS) between the unrelated and the related group. The non-treatment-related mortality (NRM) rates of patients, and other adverse complications, were no different in the two groups. In conclusion, unrelated donor-derived MST is believed to be a safe treatment, with efficacy similar to or higher than related donor-derived MST. This result provides support for the potential of MST for expanding the donor selection. However, the specific mechanism of action needs further study.

All-in-One Bifunctional Oxygen Electrode Films for Flexible Zn-Air Batteries.

As a promising energy-storage device, rechargeable Zn-air batteries have attracted considerable interests. Herein, a bifunctional oxygen electrode film prepared by adhering NiCo2 O4 nanosheets to a nitrogen and oxygen dual-doped carbon nanotubes film in a large scale is reported. The resulting self-supporting film electrode is multifunctional, which integrates a porous conducting structure for air diffusion and charge transfer, high-performance catalysts for oxygen reduction and evolution, and novel structural flexibility. The composite film demonstrates excellent oxygen reduction/evolution reaction catalytic activities with low Tafel slopes (50 mV dec-1 for oxygen reduction reaction; 92 mV dec-1 for oxygen evolution reaction). Without any additional current collector, gas diffusion layer, or binder, the obtained bifunctional film performs as an "all-in-one" air electrode in a Zn-air battery. A 50-cm-long cable-shaped Zn-air battery based on such a film air electrode exhibits high operating potentials (≈1.2 V at 0.25 mA cm-2 ), low charging-discharging overpotentials (≈0.7 V), and stable cycling performance. Moreover, the flexible cable Zn-air batteries show excellent stability under different deformation conditions. The proposed concept of constructing scalable, all-in-one, freestanding, and flexible air electrodes would pave the way to develop next-generation wearable and portable energy-storage devices.

Large-Stroke Electrochemical Carbon Nanotube/Graphene Hybrid Yarn Muscles.

Artificial muscles are reported in which reduced graphene oxide (rGO) is trapped in the helical corridors of a carbon nanotube (CNT) yarn. When electrochemically driven in aqueous electrolytes, these coiled CNT/rGO yarn muscles can contract by 8.1%, which is over six times that of the previous results for CNT yarn muscles driven in an inorganic electrolyte (1.3%). They can contract to provide a final stress of over 14 MPa, which is about 40 times that of natural muscles. The hybrid yarn muscle shows a unique catch state, in which 95% of the contraction is retained for 1000 s following charging and subsequent disconnection from the power supply. Hence, they are unlike thermal muscles and natural muscles, which need to consume energy to maintain contraction. Additionally, these muscles can be reversibly cycled while lifting heavy loads.

Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Mediates Ubiquitination-Dependent STAT3 Activation upon Salmonella enterica Serovar Typhimurium Infection.

Salmonella enterica serovar Typhimurium can inject effector proteins into host cells via type III secretion systems (T3SSs). These effector proteins modulate a variety of host transcriptional responses to facilitate bacterial growth and survival. Here we show that infection of host cells with S Typhimurium specifically induces the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). This TRAF6 ubiquitination is triggered by the Salmonella pathogenicity island 1 (SPI-1) T3SS effectors SopB and SopE2. We also demonstrate that TRAF6 is involved in the SopB/SopE2-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a signaling event conducive to the intracellular growth of S Typhimurium. Specifically, TRAF6 mediates lysine-63 ubiquitination within the Src homology 2 (SH2) domain of STAT3, which is an essential step for STAT3 membrane recruitment and subsequent phosphorylation in response to S Typhimurium infection. TRAF6 ubiquitination participates in STAT3 phosphorylation rather than serving as only a hallmark of E3 ubiquitin ligase activation. Our results reveal a novel strategy in which S Typhimurium T3SS effectors broaden their functions through the activation of host proteins in a ubiquitination-dependent manner to manipulate host cells into becoming a Salmonella-friendly zone.

A novel antibody targeting sequence 31-35 in amyloid ß protein attenuates Alzheimer's disease-related neuronal damage.

Amyloid ß protein (Aß) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aß molecule is an effective active center responsible for Aß neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid ß protein, and investigated the neuroprotection of the anti-Aß31-35 antibody against Aß1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats. The results showed that the anti-Aß31-35 antibody almost equally bound to both Aß31-35 and Aß1-42 , and pretreatment with the antibody dose-dependently prevented Aß1-42 -induced cytotoxicity on cultured primary cortical neurons. In behavioral study, intracerebroventricular (i.c.v.) injection of anti-Aß31-35 antibody efficiently attenuated Aß1-42 -induced impairments in spatial learning and memory of rats. In vivo electrophysiological experiments further indicated that Aß1-42 -induced suppression of hippocampal synaptic plasticity was effectively reversed by the antibody. These results demonstrated that the sequence 31-35 of Aß may be a new therapeutic target, and the anti-Aß31-35 antibody could be a novel immunotheraputic approach for the treatment of AD. © 2016 Wiley Periodicals, Inc.

The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group.

This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3, respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %, significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P < 0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05), but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC transplantation with MRD and MUD had similar outcome in leukemia which is better than that with HID. RIC transplantation with HID had lower relapsed with higher TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with MRD and MUD had similar outcomes in leukemia and they were better than those with HID. RIC transplantation with HID had a lower relapse rate but higher TRM and GVHD rates, particularly in cases of advanced leukemia.