ALKHB5-demethylated lncRNA SNHG15 promotes myeloma tumorigenicity by increasing chromatin accessibility and recruiting H3K36me3 modifier SETD2.

Chromatin instability plays a crucial role in multiple myeloma (MM) relapse and progression, but its mechanism remains obscure. Here, we uncovered that m6A-demethylase ALKBH5 upregulated and stabilized long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15), which was elevated in MM and positively correlated with unfavorable clinical prognosis factors. ALKBH5-SNHG15 axis participated in viability and migration/invasion of myeloma cell lines and MM-xenografted SCID/NOD mice. Mechanically, ALKBH5 promoted the expression of trimethylated histone H3 at lysine 36 (H3K36me3) methyltransferase SETD2 through lncRNA SNHG15-mediated protein stability. ALKBH5-SNHG15 axis increased chromatin accessibility and altered the H3K36me3 enrichment at the gene body, which is responsible for transcription elongation. Our study suggested a novel epigenetically interaction of N6-methyladenosine (m6A) methylation, lncRNA SNHG15, and histone SETD2/H3K36me3 modifications in myeloma progression, indicating that ALKBH5 and lncRNA SNHG15 could serve as potential novel therapeutic targets for MM treatment.NEW & NOTEWORTHY To our knowledge, this study first demonstrated the prognostic significance and biological function of long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) in multiple myeloma (MM), and indicated a novel revelation on the effect of N6-methyladenosine (m6A)-regulated lncRNA on MM tumorigenicity. Moreover, the novel chromatin-regulatory mechanism of lncRNA by interacting with epigenetic modifiers including m6A demethylase ALKBH5 and H3K36me3 methyltransferase SETD2 in myeloma progression elucidated intricate mechanism of tumor pathogenesis.

Venetoclax combined with decitabine induced tumor lysis syndrome in a young patient with acute myeloid leukemia: a case report and literature review.

Venetoclax, in combination with hypomethylation agents (HMAs), is a novel treatment for leukemia patients with low chemotherapy tolerance. However, it has been reported to be a risk of causing tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL) and elderly acute myeloid leukemia (AML) patients. Here we report a rare case of a young adult AML patient who induced TLS after receiving a combination therapy of venetoclax with decitabine (DEC). A 36-year-old male patient presented with an unexplained fever and was diagnosed with AML-M5a. The patient was first treated with a combination of antibiotics, including voriconazole 300 mg Q12h. After the infection was relieved, he was treated with 100 mg venetoclax in combination with 75 mg/m 2 DEC. However, 12 h after the first treatment, he developed diarrhea, fatigue and other symptoms, and the laboratory results were consistent with the laboratory TLS. The patient stopped chemotherapy immediately, and TLS gradually improved after receiving rehydration, diuresis, dialysis and other treatments. Finally, the patient achieved complete remission. Based on the experience of this case and related studies, we recommend the prevention of TLS should not be limited to elderly patients taking venetoclax, and it is equally important in young patients. And reduce the dosage of venetoclax when using azole antifungal drugs.

Long noncoding RNA LINC01882 ameliorates aGVHD via skewing CD4+ T cell differentiation toward Treg cells.

Acute graft-versus-host disease (aGVHD) is a severe T cell-mediated immune response after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the molecular mechanisms remain to be elucidated and novel treatments are necessary to be developed. In the present study, we found that the expression of long noncoding RNA (lncRNA) LINC01882 decreased significantly in the peripheral blood CD4+ T lymphocytes of patients with aGVHD than non-aGVHD patients. In addition, lncRNA LINC01882 overexpression promoted Treg differentiation but exhibited no effects on Th17 percentages, while its knockdown resulted in opposite effects. Mechanistically, lncRNA LINC01882 could competitively bind with let-7b-5p to prevent the degradation of its target gene smad2, which acts as a promoter in Treg differentiation. Furthermore, the mice cotransplanted with LINC01882-overexpressed CD4+ T cells with PBMCs had a lower histological GVHD score and higher survival rate compared with control mice. In conclusion, our study discloses a novel LINC01882/let-7b-5p/smad2 pathway in the modulation of aGVHD and indicates that lncRNA LINC01882 could be a promising biomarker and therapeutic target for patients with aGVHD.

The application of nanopore targeted sequencing in the diagnosis and antimicrobial treatment guidance of bloodstream infection of febrile neutropenia patients with hematologic disease.

Traditional microbiological methodology has limited sensitivity, detection range, and turnaround times in diagnosis of bloodstream infection in Febrile Neutropenia (FN) patients. A more rapid and sensitive detection technology is urgently needed. Here we used the newly developed Nanapore targeted sequencing (NTS) to diagnose the pathogens in blood samples. The diagnostic performance (sensitivity, specificity and turnaround time) of NTS detection of 202 blood samples from FN patients with hematologic disease was evaluated in comparison to blood culture and nested Polymerase Chain Reaction (PCR) followed by sanger sequence. The impact of NTS results on antibiotic treatment modification, the effectivity and mortality of the patients under the guidance of NTS results were assessed. The data showed that NTS had clinical sensitivity of 92.11%, clinical specificity of 78.41% compared with the blood culture and PCR combination. Importantly, the turnaround time for NTS was <24 h for all specimens, and the pre-report time within 6 h in emergency cases was possible in clinical practice. Among 118 NTS positive patients, 98.3% patients' antibiotic regimens were guided according to NTS results. There was no significant difference in effectivity and mortality rate between Antibiotic regimen switched according to NTS group and Antibiotic regimen covering pathogens detected by NTS group. Therefore, NTS could yield a higher sensitivity, specificity and shorter turnaround time for broad-spectrum pathogens identification in blood samples detection compared with traditional tests. It's also a good guidance in clinical targeted antibiotic treatment for FN patients with hematologic disease, thereby emerging as a promising technology for detecting infectious disease.

Salvage hematopoietic stem cell transplantation for patients with higher leukemia burden in relapsed or refractory acute myeloid leukemia: a ten-year study.

Patients with relapsed and refractory acute myeloid leukemia (R-R AML), especially those in non-remission (NR) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to optimize the entire allo-HSCT process for R-R AML patients and identify potential factors affecting clinical outcomes after HSCT, we retrospectively analyzed 44 adult patients with R-R AML who underwent salvage allo-HSCT while in NR or with concomitant extramedullary leukemia at the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2022. The 1-year and 2-year overall survival (OS) of the 44 patients were 55.3% (95% confidence interval [CI], 41.1%-74.3%) and 44.4% (95%CI, 30.2%-65.4%), respectively. The 1-year and 2-year cumulative incidence of relapse (CIR) were 39.4% (95%CI, 38.0%-40.7%) and 53.0% (95%CI, 51.0%-55.1%), respectively, and the 1-year and 2-year leukemia-free survival (LFS) were 37.8% (95%CI, 24.8%-57.7%) and 20.3% (95%CI, 9.1%-45.3%), respectively. The 100-day, 1-year and 2-year treatment-related mortality (TRM) was 13.8% (95%CI, 13.3%-14.4%), 22.8% (95%CI, 21.9%-23.7%) and 26.7% (95%CI, 25.5%-27.8%), respectively. Multivariate analysis revealed that patients who developed chronic graft-versus-host disease (cGVHD) after transplantation had lower relapse rate. Our analysis also indicated that patients with blast counts in bone marrow (BM) <20% and those with ≥20% had comparable clinical outcomes after allo-HSCT. In conclusion, our study demonstrated that R-R AML patients in NR or with concomitant extramedullary leukemia can benefit from allo-HSCT, regardless of leukemia burden at the time of transplantation. Patients who experience cGVHD after allo-HSCT may have lower relapse rate due to enhanced graft-versus-leukemia (GVL) effects, but cGVHD should be controlled at mild to moderate level to avoid life-threatening complications.

Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study.

The Phase 3 single-arm COMMODORE 3 study (ClinicalTrials.gov, NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor-naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every-4-weeks subcutaneous maintenance doses per weight-based tiered-dosing schedule. Co-primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15-58 years old) were enrolled; all received treatment. At primary analysis, both co-primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8-86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant (p < .0001). No adverse events led to treatment discontinuation. One treatment-unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every-4-weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor-naive patients with PNH.

Viable Bifidobacterium tablets for the prevention of chemotherapy-/radiation-induced mucositis in patients undergoing haematopoietic stem cell transplantation.

PURPOSE: Mucositis is a frequent and severe complication in haematopoietic stem cell transplantation (HSCT). The effectiveness of probiotics in mucositis has been indicated by several clinical trials, but the results are still controversial. To date, studies on the influence of probiotics in HSCT are limited. Therefore, we conducted this retrospective study to evaluate the impact of viable Bifidobacterium tablets on the incidence and duration of chemotherapy-/radiation-induced mucositis in patients undergoing HSCT. METHODS: Clinical data of 278 patients who underwent HSCT between May 2020 and November 2021 were retrospectively analysed. They were divided into a control group (138) and a probiotic group (140) according to whether they took viable Bifidobacterium tablets. First, we analysed the baseline data of the two groups. Then, we compared the incidence, severity and duration of mucositis between the two groups by using Mann-Whitney U test, chi-square test and Fisher's exact test according to the type of data. In order to exclude the influence of confounding factors, we further evaluated the efficacy of oral probiotics in preventing oral mucositis by Binary logistic regression analysis. RESULTS: The use of viable Bifidobacterium tablets markedly reduced the incidence of oral mucositis (OM) (62.9% vs. 81.2%, p = 0.001) and mainly reduced the incidence of grades 1-2 OM (74.6% vs. 58.6%, p = 0.005). There was no significant difference in the incidence of severe (grades 3-4) OM between the two groups (6.5% vs. 4.3%, p = 0.409). The median duration of OM was shorter in the probiotic group (10 vs. 12 days, p = 0.037). The incidence and duration of diarrhoea did not differ between the two groups. Moreover, the use of viable Bifidobacterium tablets had no influence on engraftment. CONCLUSIONS: Our results suggested that viable Bifidobacterium tablets could effectively reduce the incidence of grades 1-2 OM and duration of OM during the transplant process without affecting the outcome of HSCT.

Comparable long-term outcomes between upfront haploidentical and identical sibling donor transplant in aplastic anemia: a national registry-based study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for severe aplastic anemia (SAA), and transplantation from identical sibling donors (ISD) has been recommended as a first-line treatment. Haploidentical donor (HID) transplantation for SAA has made great advances; thus, an increased role of HID-SCT in SAA should be considered. We performed a national registry-based analysis comparing long-term outcomes in the upfront HID or upfront ISD SCT setting. A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival and failure-free survival were 87.1±2.5% and 89.3±3.7% (P=0.173) and 86.5±2.6% versus 88.1±3.8% (P=0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft-versus-host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year time points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. These data suggest that haploidentical transplant can be considered a potential therapeutic option in the upfront setting for SAA patients in the absence of an HLA-identical related or unrelated donor.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease.

The optimal conditioning regimen of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients with minimal residual disease (MRD) remains controversial. We studied the results in 98 high-risk acute leukemia patients transplanted with idarubicin (IDA)-intensified conditioning regimens between 2012 January and 2017 January. Among these patients, 31 (31.6%) had more than 5% marrow blasts at time of transplantation and 67 patients were in morphologic remission: MRD negative status at time of conditioning was achieved in 39 patients (39.8%), whereas 28 (28.6%) remained carriers of any other positive MRD level in the bone marrow. Three-year relapse estimates of patients with MRD-positive remission was 22.0%, which was remarkably lower than patients with active disease (45.4%, P = .027) but approximate to that of patients in MRD-negative remission (15.5%, P = .522). There were no significant differences in terms of 3-year estimated overall survival (OS) and disease-free survival (DFS) between MRD-positive remission and MRD-negative remission groups (71.4% versus 79.1% [P = .562] and 67.9% versus 76.9% [P = .634], respectively). Moreover, the estimated rates of 3-year OS and DFS of patients in MRD-positive remission were significantly better than those in patients with active disease (71.4% versus 41.9% [P = .033] and 67.9% versus 38.7% [P = .037], respectively). These data indicate that IDA-intensified conditioning allo-HSCT could overcome the negative prognostic impact of MRD.

Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial.

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD- CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD- CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD- CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease.

Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD.

Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study.

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes.

Nuclear Matrix-associated Protein SMAR1 Attenuated Acute Graft-versus-host Disease by Targeting JAK-STAT Signaling in CD4 + T Cells.

BACKGROUND: Acute graft-versus-host disease (aGVHD) mediated by alloreactive T cells remains a serious and life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). The contribution of the different CD4 + T helper cell subtypes to the pathogenesis and regulation of aGVHD is a central point in current research. The specialized effector subsets of T cells that differentiate from naive T cells into mature cells are closely related to scaffold/matrix-associated region-1-binding protein (SMAR1). However, the role of SMAR1 in aGVHD is unclear. METHODS: Peripheral blood was collected from the patients with or without aGVHD after allo-HCT. The differences in CD4 + T cells transduced with the SMAR1 lentivirus vector and empty vector were analyzed. A humanized aGVHD mouse model was constructed to evaluate the function of SMAR1 in aGVHD. RESULTS: The expression of SMAR1 was significantly reduced in the CD4 + T cells from aGVHD patients and related to the occurrence of aGVHD. SMAR1 overexpression in human CD4 + T cells regulated CD4 + T-cell subsets differentiation and inflammatory cytokines secretion and inhibited the Janus kinase/signal transducer and activator of transcription pathway. Moreover, SMAR1 changed chromatin accessibility landscapes and affected the binding motifs of key transcription factors regulating T cells. Additionally, upregulation of SMAR1 expression in CD4 + T cells improved the survival and pathology in a humanized aGVHD mouse model. CONCLUSIONS: Our results showed that upregulation of SMAR1 regulated the CD4 + T-cell subpopulation and cytokines secretion and improved survival in a humanized aGVHD mouse model by alleviating inflammation. This study provides a promising therapeutic target for aGVHD.

Case report: nanopore targeted sequencing in the diagnosis of invasive pulmonary Aspergillus infection in a patient with acute promyelocytic leukemia.

Invasive pulmonary aspergillosis (IPA) is an infectious disease with a high mortality rate due to diagnostic difficulties associated with the lack of a typical clinical presentation and the inadequacy of the available laboratory testing methods. Nanopore targeted sequencing (NTS) is an alternative method of broad-based pathogen discovery, associated with rapid turnaround and high accuracy. This case report presents a patient with IPA and acute promyelocytic leukemia, diagnosed using the NTS method, which detected Aspergillus flavus in the patient's blood and pleural fluid. The patient was treated effectively with antifungal therapy. Early diagnosis of IPA improved long-term patient prognosis and quality of life.

Nanopore-Targeted Sequencing Improves the Diagnosis and Treatment of Patients with Serious Infections.

Serious infections are characterized by rapid progression, poor prognosis, and difficulty in diagnosis. Recently, a new technique known as nanopore-targeted sequencing (NTS) was developed that facilitates the rapid and accurate detection of pathogenic microorganisms and is extremely suitable for patients with serious infections. The aim of our study was to evaluate the clinical application of NTS in the diagnosis and treatment of patients with serious infections. We developed an NTS technology that could detect microorganisms within a 6-h window based on the amplification of the 16S rRNA gene of bacteria, the internal transcribed spacer region of fungi, and the rpoB gene of Mycobacterium. The NTS detection results were compared with those of blood cultures and anal swabs from 50 patients with blood diseases suffering serious infections. The patient's condition before and after NTS was compared. The response rate and the infection-related mortality after the adjustment of antibiotics based on NTS were calculated. The positivity rate of pathogens was highest in NTS (90%), followed by blood culture (32.6%) and anal swabs (14.6%). After adjusting antibiotics for bacteria and fungi detected by NTS, the patients' condition improved significantly. Moreover, the response rate of anti-infective treatment based on NTS was 93.02% (40/43), and infection-related mortality was reduced to 0. NTS is an effective method to identify pathogens in the blood specimens of patients with serious infections and can guide anti-infection treatment and reduce infection-related mortality. IMPORTANCE We introduce the application of NTS in blood samples of patients with serious infections and expound the efficiency and accuracy of NTS in detecting pathogenic microorganisms. Our work builds on the considerable interest of the scientific community in the management of serious infection. This issue is becoming more pressing, especially since the incidence of blood diseases is increasing year by year and hematopoietic stem cell transplantation (HSCT) has been widely used in benign and malignant blood diseases in recent years. The infection progression of these patients is faster, and the study further demonstrates the effectiveness of NTS in guiding the diagnosis and treatment of patients with severe infections. We firmly believe that this method will guide clinicians to adjust anti-infection strategies and bring significant benefits to patients, and our study will have implications for the future clinical application of NTS in all kinds of patients with serious infections.

How to improve the outcomes of elderly acute myeloid leukemia patients through allogeneic hematopoietic stem cell transplantation.

In recent years, with the gradual advancement of haploidentical transplantation technology, the availability of donors has increased significantly, along with the widespread use of reduced-intensity conditioning and the improvement of nursing techniques, giving more elderly acute myeloid leukemia (AML) patients the chance to receive allogeneic hematopoietic stem cell transplantation. We have summarized the classic and recently proposed pre-transplant assessment methods and assessed the various sources of donors, conditioning regimens, and post-transplant complication management based on the outcomes of large-scale clinical studies for elderly AML patients.

Comparison of efficacies of haploidentical transplantation and matched sibling donor transplantation in treating T-cell lymphoblastic lymphoma.

OBJECTIVE: To investigate the differences in efficacy and safety between haploidentical donor hematopoietic stem cell transplantation (HID-HSCT) and matched sibling donor HSCT (MSD-HSCT) in patients with T-cell lymphoblastic lymphoma (T-LBL). METHODS: In this retrospective analysis, we enrolled 38 patients who had undergone allogeneic HSCT at our institution between 2013 and 2021. The study participants included 28 patients who underwent HID-HSCT and 10 patients who underwent MSD-HSCT. We compared the patient characteristics and treatment effectiveness and safety between the two groups and evaluated potential prognostic variables for patients with T-LBL. RESULTS: The median follow-up durations in the HID-HSCT and MSD-HSCT groups were 23.5 (range: 4-111) and 28.5 (range: 13-56) months, respectively. All patients showed full-donor chimerism after hematopoietic stem cell transplantation (HSCT). Except for two patients in the HID-HSCT cohort who developed poor graft function, all patients showed neutrophil and platelet engraftments after HSCT. The cumulative incidences of grades III-IV acute graft-versus-host disease were 37.5% and 28.57% in the HID-HSCT and MSD-HSCT groups, respectively (p = 0.84). The cumulative incidences of limited (34.13% vs. 28.57%, p = 0.82) and extensive (31.22% vs. 37.50%, p = 0.53) chronic graft-versus-host disease did not differ between the two cohorts. In the HID-HSCT and MSD-HSCT cohorts, the estimated 2-year overall survival rates were 70.3% (95% confidence interval [CI]: 54.9%-90.0%) and 56.2% (95% CI: 31.6%-100%), respectively (p = 1.00), and the estimated 2-year progression-free survival (PFS) rates were 48.5% (95% CI: 32.8%-71.6%) and 48.0% (95% CI: 24.6%-93.8%), respectively (p = 0.94). Furthermore, the Cox proportional-hazards model showed that a positive positron emission tomography/computed tomography (PET/CT) status before HSCT in patients who had completed chemotherapy was an independent risk factor for PFS in the multivariate analysis (p = 0.0367). CONCLUSION: This study showed that HID-HSCT had comparable effectiveness and safety to MSD-HSCT in treating T-LBL. HID-HSCT could serve as an alternate treatment option for T-LBL in patients without an eligible identical donor. Achievement of the PET/CT-negative status before HSCT may contribute to better survival.