Background:Current treatment options for patients with squamous non-small cell lung cancer (sqNSCLC) include immune checkpoint inhibitors combined with chemotherapy, monotherapy with immune therapy, and platinum-based doublet chemotherapy, among others. However, there is still a lack of systematic comparisons regarding the relative efficacy and safety of these regimens. This study aims to comprehensively assess the clinical benefits [such as overall survival (OS), progression-free survival (PFS)] and adverse event rates across different treatment strategies via a network meta-analysis, providing evidence-based guidance for individualized treatment decisions in sqNSCLC patients. Methods:We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to May 3, 2025 for eligible randomized controlled trials (RCTs). The primary outcome measures were PFS and OS; secondary outcomes included objective response rate (ORR) and grade ≥3 treatment-related adverse events (≥3 TRAEs). A network meta-analysis was carried out using Stata 16.0 and R 4.4.0. Results:A total of 32 RCTs, involving 9,652 participants, were included. This study analyzed 18 different treatment strategies. The network meta-analysis showed that for PFS, paclitaxel-based doublet chemotherapy combined with programmed cell death-1 and programmed death-ligand 1 [PD-(L)1] checkpoint inhibitors [surface under the cumulative ranking curve (SUCRA): 96.52%] and gemcitabine-based doublet chemotherapy combined with PD-(L)1 checkpoint inhibitors (SUCRA: 85.16%) were the most effective. For OS, paclitaxel-based doublet chemotherapy combined with a Toll-like receptor-2 agonist (CADI-05) (SUCRA: 92.11%), paclitaxel-based doublet chemotherapy combined with PD-(L)1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors (SUCRA: 89.65%), and paclitaxel-based doublet chemotherapy combined with PD-(L)1 checkpoint inhibitors (SUCRA: 83.58%) were the top three choices. The combination of paclitaxel-based doublet chemotherapy with PD-(L)1 checkpoint inhibitors (SUCRA: 87.00%) was associated with the best improvement in ORR. Conclusions:For first-line treatment of sqNSCLC, the current evidence supports the use of paclitaxel-based doublet chemotherapy combined with PD-(L)1 checkpoint inhibitors as one of the preferred treatment options. However, more high-quality trials are needed to confirm these findings.

Despite advances with JAK and ROCK inhibitors, durable responses in chronic GVHD (cGVHD) remain challenging. For patients with advanced, multi-refractory disease, simultaneously targeting multiple pathways may be necessary. Building on preclinical synergy between JAK and ROCK inhibition, we evaluated the combination of belumosudil and ruxolitinib in a multicenter, retrospective study of 57 ruxolitinib-refractory cGVHD patients. The cohort had high-risk features, with 63.2% having severe NIH-grade disease and 66.7% receiving ≥ 5 prior lines of therapy.The primary endpoint was the 3-month overall response rate (ORR). At a median follow-up of 170 days, the ORR was 59.6%, with a best overall response of 75.4%. Notably, in patients with lung involvement (63.2%), 83.3% achieved symptom-based responses, versus 3.7% FEV1 improvement. The 12-month failure-free survival rate was 94.5%, and 86.4% of patients achieved a corticosteroid reduction. The regimen demonstrated a favorable safety profile, with only 5.3% grade ≥ 3 pneumonia and no treatment-related discontinuations or severe hematologic toxicities.These results confirm the clinically meaningful efficacy and safety of dual JAK/ROCK inhibition in this heavily pretreated population. These findings support the mechanistic rationale for concurrent pathway inhibition and warrant prospective validation in randomized controlled trials.

Objective: This study aimed to investigate the recurrence patterns of diffuse large B-cell lymphoma (DLBCL) and assess the significance of clinical manifestation consistency at the time of recurrence.Methods: A total of 141 patients who were newly diagnosed with DLBCL between January 2015 and October 2024 and who initially achieved complete remission but eventually developed relapsed disease during follow-up were retrospectively identified, their recurrence circumstances were assessed, and their clinical manifestations at diagnosis and recurrence were compared. The timing of recurrence was categorized as within 1 year of postchemotherapy or later.Results: A total of 113 (80.1%) patients presented with clinical manifestations leading to the diagnosis of recurrence. A total of 87 (61.7%) patients presented similar clinical manifestations at recurrence to those observed during initial diagnosis. Importantly, for patients who relapsed within 1 year of chemotherapy, those with inconsistent manifestations at recurrence had significantly poorer prognoses and lower survival rates (complete remission (CR) rate, 7.4%; 1-year overall survival (OS), 37.5%; 1-year progression-free survival (PFS), 18.5%) than those with consistent manifestations (CR rate, 20.8%; 1-year OS, 34.0%; 1-year PFS, 22.6%; PFS, p = 0.046; OS, p = 0.049). In contrast, for patients whose recurrence occurred more than 1 year postchemotherapy, consistent manifestations were associated with better survival outcomes (CR rate, 44.1%; 1-year OS, 61.8%; 1-year PFS, 52.9%).Conclusion: The timing of recurrence and the consistency of clinical manifestations are important factors influencing the prognosis of DLBCL. Specifically, early recurrence with inconsistent manifestations is associated with worse outcomes, whereas recurrence with consistent manifestations 1 year postchemotherapy is correlated with an improved prognosis.

BACKGROUND:The optimal regimens for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain uncertain. METHODS:The authors conducted a multicenter phase 2 trial to evaluate the novel venetoclax, fludarabine, and melphalan (VFM) regimen in patients with AML or MDS aged 50 years and older. The VFM regimen consisted of venetoclax (400 mg daily on days -8 to -2), fludarabine (30 mg/m2 daily on days -7 to - 3), and melphalan (120-140 mg/m2 daily on day -2). RESULTS:Sixty patients (median age, 58 years; age range, 51-66 years) received the novel VFM conditioning regimen. The 2-year disease-free survival (DFS) rate was 75.0% (95% confidence interval [CI], 64.8%-86.8%), which was the primary end point. Two-year rates of overall survival, graft-versus-host disease (GVHD)-free and recurrence-free survival, nonrelapse mortality, and relapse were 78.3% (95% CI, 68.6%-89.5%), 61.6% (95% CI, 50.5%-75.3%), 13.3% (95% CI, 6.1%-23.3%), and 11.7% (95% CI, 5.1%-21.3%), respectively. Treatment-related grade 2-3 nonhematologic adverse events occurred in 58% of patients, with no grade 4-5 nonhematologic toxicities. The cumulative incidence of grade 2-4 and grade 3-4 acute GVHD at day 100 was 5.0% (95% CI, 1.3%-12.7%) and 1.7% (95% CI, 0.1%-7.9%), respectively. The 2-year cumulative incidence of moderate-to-severe chronic GVHD was 16.7% (95% CI, 8.5%-27.3%). CONCLUSIONS:These findings support the feasibility of incorporating venetoclax into a fludarabine and melphalan conditioning regimen in older adults with AML/MDS. Notably, the low rates of GVHD and relapse associated with this venetoclax-based conditioning regimen support further study of this platform [ClinicalTrials.gov Identifier: NCT05084027].

Objective:This study aimed to investigate the anatomic patterns and outcomes of first relapse in patients with diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Between January 2015 and October 2024, a total of 1,047 newly diagnosed patients were evaluated, of which 139 patients who initially achieved complete remission (CR) but subsequently experienced relapse during follow-up were included in the analysis. Histological and imaging data were reviewed to determine the involvement of nodal regions, extranodal locations, and Waldeyer’s Ring at the time of relapse. Results: Our findings indicated that 112 patients (80.4%) presented with clinical manifestations that led to the diagnosis of recurrence. Two-thirds of patients relapsed within 18 months, and 85% within two years, with a median time to relapse of 9 months. Notably, 43.2% of patients experienced a change in the anatomic site of recurrence, which correlated with poorer clinical outcomes. The overall CR rate after relapse was 36.7% for those relapsing at previously involved sites, compared to just 10.0% for those with new site relapses. Higher CR rates were also observed in patients with relapses at previously involved sites from Waldeyer’s Ring (50% CR; 8 of 16) and extranodal lymphomas (40% CR; 8 of 20), compared to those relapsing at new sites (P=0.019 and P=0.006, respectively). Overall survival(OS) was significantly lower in patients with relapses at new sites (23.0 ± 4.2 months) compared to those at previously involved sites (41.8 ± 6.1 months). Kaplan-Meier analysis revealed significant differences in OS and progression-free survival(PFS) based on the site of relapse (P=0.043 and P=0.004, respectively). Patients experiencing relapses at new sites, particularly involving Waldeyer’s Ring and extranodal origins, had significantly poorer outcomes, with two-year OS rates of 16.7% and 8.3%, respectively (P=0.032 and P=0.006). Conclusions: Relapsed DLBCL tends to primarily affect previously involved sites, especially in patients with nodal origins. Recurrences at new sites are associated with poor outcomes, particularly when the initial anatomic sites were Waldeyer’s Ring and extranodal.

BackgroundEsophageal cancer (EC) is associated with a high morbidity and mortality rate. Immunotherapy has demonstrated effective antitumor activity in patients with EC, making it imperative to investigate easily accessible prognostic factors. Consequently, we conducted a meta-analysis to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in EC patients treated with immunotherapy.MethodsThe literature search was conducted across three databases: PubMed, Embase, and Web of Science. The primary deadline for literature retrieval was July 2024. Hazard ratio (HR) with a 95% confidence interval (CI) was utilized to assess the association between NLR or PLR and overall survival (OS) as well as progression-free survival (PFS). Statistical analysis was performed using Review Manager version 5.4 and STATA version 15.0.ResultsThe meta-analysis included a total of 16 studies involving 1,481 patients. The results indicated a significant correlation between high pretreatment NLR and poor PFS (HR=1.76, 95%CI:1.38-2.25, p<0.001) as well as poor OS (HR=2.61,95%CI:1.86-3.67, p<0.001). Subgroup analyses based on tumor stage revealed that the association between elevated NLR and poor PFS was only observed in advanced EC patients. Regarding PLR, an increased PLR was found to be indicative of inferior PFS (HR=1.44, 95%CI: 1.20-1.72, p<0.001) and OS (HR=1.72,95%CI:1.08-2.74, p=0.020). However, the sensitivity analyses suggested that the observed increase in PLR lack robustness in terms of its impact on inferior OS.ConclusionElevated NLR and PLR are associated with inferior PFS and OS in EC patients receiving immunotherapy. These findings suggest that NLR and PLR levels hold promise as prognostic biomarkers in clinical practice, offering valuable guidance for personalized immunotherapy strategies.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42024596737.

PURPOSE:Pegylated liposomal doxorubicin (PLD) has emerged as an effective therapeutic option for diffuse large B-cell lymphoma (DLBCL). While demonstrating an improved safety profile compared to conventional doxorubicin, PLD has been associated with a potentially elevated risk of Pneumocystis jirovecii pneumonia (PJP), warranting clinical vigilance. This study aimed to evaluate the association between PLD administtion and PJP development in patients with diffuse large B-cell lymphoma (DLBCL). METHODS:We conducted a comparative analysis of 43 chemotherapy-treated DLBCL patients with PJP versus 195 contemporaneous DLBCL controls without PJP. The evaluation included PLD administration patterns and covariate-adjusted risk assessments. FINGDINGS:The analysis revealed significant differences between PJP cases and controls. Patients who developed PJP were more likely to have received PLD-containing chemotherapy regimens (p = 0.001) and less likely to have received TMP-SMX prophylaxis (p = 0.001). The majority of PJP cases (51.2%) occurred after 3-4 chemotherapy cycles, with an 18.6% case-fatality rate (n = 8). Multivariable logistic regression identified 2 independent predictors, PLD-containing regimen (OR: 3.2, 95% CI: 1.5-6.8; P = 0.003) as a risk factor; TMP-SMX prophylaxis (OR: 0.4, 95% CI: 0.2-0.8; P = 0.003) as a protective factor. Notably, baseline characteristics including demographic parameters, disease stage, ECOG performance status, LDH levels, and IPI scores showed no significant intergroup differences (all P > 0.05). IMPLICATIONS:These findings demonstrate a clinically significant association between PLD-containing regimens and PJP development in DLBCL patients. Regular clinical and radiographic monitoring for PJP symptoms should be implemented and PJP prophylaxis should be strongly considered for all patients receiving PLD-based therapy.

BackgroundSeveral head-to-head meta-analyses have compared the efficacy and safety of different first-line treatments in patients with EGFR mutation-positive (M+) advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC). However, there is a lack of comprehensive evaluation encompassing multiple treatment strategies. Our objective is to conduct a network meta-analysis that includes various treatment modalities, enabling both direct and indirect comparisons for a more thorough assessment.MethodsWe conducted a search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception until May 8, 2024, to identify eligible randomized controlled trials (RCTs). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary outcomes included objective response rate (ORR) and grade 3 or higher adverse events (≥3AEs). Stata 15.0 and R 4.3.2 software were utilized for the network meta-analysis.ResultsA total of 30 RCTs, comprising 8654 participants, were included. The study encompassed the following 19 treatments: Chemotherapy; Afatinib; Afatinib + Cetuximab; Apatinib + Gefitinib; Befotertinib; Cetuximab + Chemotherapy; Erlotinib; Erlotinib + Bevacizumab; Erlotinib + Chemotherapy; Gefitinib; Gefitinib + Chemotherapy; Gefitinib + Olaparib; Icotinib; Icotinib + Chemotherapy; Lazertinib; Naquotinib; Osimertinib; Osimertinib + Bevacizumab; Osimertinib + Chemotherapy. The network meta-analysis results indicated that, in terms of PFS, Osimertinib + Chemotherapy (SUCRAs: 93.4%) and Osimertinib (SUCRAs: 84.61%) were the most effective. Regarding OS, Lazertinib (SUCRAs: 89.72%), Gefitinib (SUCRAs: 72.07%), and Osimertinib + Chemotherapy (SUCRAs: 70.74%) emerged as the top three options. Afatinib (SUCRAs: 92.27%) was associated with the best ORR improvement. For ≥3AEs, Afatinib (SUCRAs: 74.93%) and Osimertinib (SUCRAs: 69.42%) were likely the best choices.ConclusionCurrent evidence suggests that, considering both survival and safety, Osimertinib stands out as the preferred first-line treatment for untreated EGFR M + advanced or metastatic nsq-NSCLC. Notably, the combination of Osimertinib with chemotherapy demonstrated superior survival benefits. However, due to the limitations in the number and quality of included studies, these conclusions await further validation through more high-quality research.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024562981, identifier CRD42024562981.

Background Chronic graft-versus-host disease (cGVHD) remains a leading cause of non-relapse mortality post-allogeneic hematopoietic stem cell transplantation (allo-HSCT), with 30-50% of patients developing steroid-refractory disease. Despite advances with JAK inhibitors (ruxolitinib) and ROCK2 inhibitors (belumosudil) in cGVHD, long-lasting responses remain uncommon, a significant number of patients need next immunosuppressive therapies. Refractory cases demand personalized, multi-targeted approaches. Preclinical data suggest synergistic effects through dual JAK/ROCK pathway inhibition, potentially addressing fibrotic and Th17-mediated resistance mechanisms. While clinical data on this specific combination are limited, whether the combined belumosudil and ruxolitinib improves efficacy without safety concerns. Methods We conducted a retrospective multicenter study to investigate the safety and efficacy of belumosudil and ruxolitinib combination in the treatment of ruxolitinib refractory cGVHD. Eligibility required progression or suboptimal response after ≥3 months of ruxolitinib, more than 2 prior lines of treatment. Primary endpoints was 3 months overall response rate (ORR). Best of response (BOR), Failure-free survival (FFS), adverse events (AEs), change in Lee Symptom Scale (LSS) summary score, duration of response (DOR) and change in CS dose were secondary end points. Results A total of 42 patients at median 42 (17-68) years were enrolled, 61.9% (n=26/42) had severe NIH-grade cGVHD, and 61.9% (n=26/42) had ≥4 organs involved. The cohort was heavily pretreated, with 52.4% (n=22/42) having received ≥5 prior lines of therapy (LOTs). Lung involvement occurred in 57.1% (n=24/42) (23.8% with lung score 3). The median time from transplantation to cGVHD diagnosis was 217 days (68-743). Median time from ruxolitinib initiation to combination therapy was 303 days (69–2471). At median follow-up of 178 days (57–577), ORR was 54.8% (n=23/42) (95%CI 39.8–67.0), with BOR reaching 76.2% (n=32/42) (95%CI 60.0–87.1). Patients achieved responses at a median of 48 days (21-112) after starting combination treatment. Subgroup analyses revealed that ORR was 53.9% (n=14/26) in severe cGVHD and 63.6% (n=14/22) in ≥5 prior LOTs. Lung cGVHD showed 87.5% (PR:58.3%; CR:29.2%) symptom-based ORR and 12.5% (PR:12.5%) FEV1%-based ORR. Ocular cGVHD demonstrated higher sensitivity to therapy (ORR 45.5% [18.2% CR + 27.3% PR]) than joint/fascia disease (36.0% ORR [12.0% CR + 24.0% PR]). FFS was 92.5% (82.3–100.0) at 12 months. CS doses were reduced in 90% of patients (median reduction 70.8%). The safety analysis revealed leukocytopenia as the most common hematologic adverse event, occurring in 7.2% of patients (n=3/42). Infectious complications included pneumonia in 14.3% of cases (n=6/42), with grade ≥3 events observed in 4.8% (n=2/42). Notably, no treatment-related discontinuations or grade ≥4 hematologic toxicities were reported. The combination was well tolerated with preserved immune reconstitution and improved LSS. Clinically meaningful improvement (≥7-point reduction) in LSS summary scores was achieved by 19.1% of patients (8/42) at 3 months. Responders demonstrated significantly greater LSS improvement compared to non-responders. Conclusion The belumosudil and ruxolitinib combination demonstrated clinically meaningful efficacy in ruxolitinib-refractory cGVHD. High response rates (ORR 54.8%, best ORR 76.2%), durable disease control (12-month FFS 92.5%), and significant CS reduction (median 70.8% dose decrease) were achieved without severe toxicity (grade ≥3 infections: 4.8%; no treatment discontinuations). These findings support the mechanistic rationale for concurrent JAK/ROCK inhibition and warrant prospective validation.

The unexpensive and readily available biomarkers for CRS grading and prognosis assessment in CAR-T therapy are currently lacking. This study included 27 patients with relapsed/refractory MM who were treated with CAR-T cells. Our results suggest that ALP levels after CAR-T therapy could serve as a suitable biomarker for monitoring CAR-T cell proliferation, CRS grading, and prognosis in patients with MM.Background: The inexpensive and readily available biomarkers for cytokine release syndrome (CRS) grading and prognosis assessment in chimeric antigen receptor (CAR)-T therapy are currently lacking. This study examined the significance of alkaline phosphatase (ALP) after CAR-T therapy in patients with relapsed/refractory multiple myeloma (MM). Methods: This cohort study included 27 patients with relapsed/refractory MM who were treated with CAR-T cells between December 2017 and October 2021. Patients were classified into 2 groups: normal ALP group (peak ALP < 125 U/L, n = 10) and high ALP group (peak ALP >=;125 U/L, n = 17). Results: Within 1 month of CAR-T cell infusion, the incidence of ALP increases was 63%. We found that ALP levels began to rise in the second week, peaked in the third and fourth weeks, and began to decline in the second month. Moreover, the ALP levels in previous chemotherapy-responsive period were significantly lower than those after CAR-T therapy. Statistical analysis found that patients with increased ALP exhibited higher alanine aminotransferase and aspartate aminotransferase levels, higher and longer CAR-T cell proliferation, more serious CRS, higher cytokine and ferritin levels, and higher initial response rates. In addition, the duration of ALP increase was parallel to the duration of CAR-T expansion. Multivariable Cox-regression analysis showed that peak ALP was the independent predictor for progression-free survival (PFS) (HR = 0.029, 95% CI: 0.002-0.369). Conclusions: Our results suggest that the ALP levels after CAR-T therapy could serve as a suitable biomarker for monitoring CAR-T cell proliferation, CRS grading, and prognosis in patients with MM.

Background The incidence of Pneumocystis jirovecii pneumonia (PCP) has been increasing in patients with hematologic malignancies due to the use of glucocorticoid therapy and immunosuppressive medication. The reports of PCP in non-Hodgkin’s lymphoma (NHL) after rituximab-based chemotherapy are still rare. We reported a case series of PCP in NHL to show the clinical features and prognosis in those patients. Methods We conducted a retrospective review of 15 NHL patients who developed PCP after rituximab-based chemotherapy during June 30, 2014 to June 1, 2020. We analyzed the laboratory and radiographic findings for those patients through descriptive statistics analysis. Results The study revealed that PCP in NHL patients was complicated by chemotherapy after about 4 courses (range, 2 to 6 courses). Most patients had a standard lymphocyte count before treatment, and 14 of 15 patients (93.3%) had lymphopenia at the time of diagnosis of PCP. In addition to typical symptoms such as fever and dyspnea at the diagnosis of PCP, most patients had abnormal laboratory indexes such as marked elevations of C-reactive protein (CRP) and lactic dehydrogenase (LDH) both before and at the time of diagnosis. The (1,3)-β-D-glucan test was also revealed as a sensitive index for PCP. Bilateral ground-glass opacity was detected in 14 cases through computed tomography (CT) scans. Positive results of microbiological testing were observed in 7 cases; sputum culture was positive in 3 and next-generation sequencing (NGS) was positive in 3 of these 7 patients, and the other case was positive in both sputum culture and NGS. Patients received high-dose trimethoprim/sulfamethoxazole (TMP/SMZ), caspofungin, and steroids as the treatment for PCP. Ventilatory support was required by 3 patients, so they were admitted to the intensive care unit (ICU), and 1 patient died from PCP. Conclusions Dynamic monitoring of CRP, LDH, and (1,3)-β-D-glucan test during the treatment of NHL may have a predictive value for the diagnosis of PCP. Additionally, we should use NGS as a rapid and sensitive method for the early diagnosis of PCP. When patients are classified as ‘probable PCP’, early and effective treatment has obvious significance to improve the prognosis.

目的 探讨团体心理治疗对血液科保护性隔离患者不同阶段心理健康状况的影响.方法 2018年7月至2019年12月层流洁净病房保护性隔离患者,选取症状自评量表(SCL-90)测评结果呈阳性患者112例,按照进入层流洁净病房的顺序间隔分配为团辅组和对照组,团辅组在隔离期间参与团体心理治疗,2次/周,对照组仅接受常规心理护理;采用医学行为量表进行基线及干预后测评.结果 隔离开始团辅组和对照组SDS、SAS、SCL-90、PSQI、GSES量表评分差异无统计学意义(P>0.05).隔离中期团辅组SDS、SAS量表评分低于对照组(P<0.01);SCL-90、PSQI和GSES量表评分优于对照组(P<0.05).隔离后期团辅组SDS、SAS、SCL-90、PSQI、GSES量表评分和患者满意度调查表评分均明显优于对照组,差异有统计学意义(P<0.01).结论 团体心理治疗可以提高血液科保护性隔离患者的心理健康水平.

Cytokine release syndrome (CRS) is the most common on-target toxicity of chimeric antigen receptor (CAR) T cell therapy. However, the prognostic significance of CRS has not been well elucidated. The aim of our study was to evaluate the association between CRS and efficacy after anti-CD19 CAR-T therapy in a retrospective cohort of 22 patients with relapsed/refractory B cell hematological malignancies. The complete remission (CR) rates after CAR-T therapy were 68%, and median value for progression-free survival (PFS) was 6.8 months. Eight of 22 (36.4%) patients showed ≥ grade 2 CRS. Statistical analysis found that patients with ≥ grade 2 CRS had higher CR rates and longer PFS than those with < grade 2 CRS. Moreover, bridging hematopoietic stem cell transplantation was another independent predictor for PFS. These data suggested that appropriate CRS may be beneficial to the efficacy of CAR-T therapy. The Clinical Trial Registration number is NCT03110640, NCT03302403.

BACKGROUND:Iron overload, which is common in patients with haematological disorders, is known to have a suppressive effect on haematogenesis. However, the mechanism for this effect is still unclear. The antioxidant curcumin has been reported to protect against iron overload-induced bone marrow damage through an as-yet-unknown mechanism.METHODS:We established iron overload cell and mouse models. Mitochondrial reactive oxygen species (mROS) levels, autophagy levels and the SIRT3/SOD2 pathway were examined in the models and in the bone marrow of patients with iron overload.RESULTS:Iron overload was shown to depress haematogenesis and induce mitochondrion-derived superoxide anion-dependent autophagic cell death. Iron loading decreased SIRT3 protein expression, promoted an increase in SOD2, and led to the elevation of mROS. Overexpression of SIRT3 reversed these effects. Curcumin treatment ameliorated peripheral blood cells generation, enhanced SIRT3 activity, decreased SOD2 acetylation, inhibited mROS production, and suppressed iron loading-induced autophagy.CONCLUSIONS:Our results suggest that curcumin exerts a protective effect on bone marrow by reducing mROS-stimulated autophagic cell death in a manner dependent on the SIRT3/SOD2 pathway.

The aim of this study was to evaluate the efficacy and toxicity of high-dose rituximab (HD-R) in combination with autologous stem cell transplantation (auto-SCT) in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). There were 22 patients in the HD-R group, to whom rituximab was administered during stem cell mobilization (375 mg/m2 1 day before and 7 days after chemotherapy) and after transplantation (1000 mg/m2 on days +1 and +8). In the control group, the procedure was the same as that in the HD-R group but without rituximab. We observed the safety, tolerability, adverse effects and immune reconstitution of HD-R therapy. The log-rank test, univariate analysis and multivariate Cox regression analysis were used to evaluate the effect of HD-R on survival. In total, 22 relapsed or refractory DLBCL patients were treated with HD-R. No dose-limiting toxicities were observed except for CD19+ B cell reconstruction in the first 6 months after SCT. There were 20 relapsed or refractory DLBCL patients in the control group. The 3-year progression-free survival (PFS) and overall survival (OS) greatly improved in the HD-R group compared to that in the control group (63.8% vs. 35.0%, P = 0.028 and 80.1% vs. 50.0%, P = 0.035, respectively). The univariate and multivariate analyses demonstrated that HD-R and the time to relapse were independent prognostic factors for OS and PFS. HD-R in combination with auto-SCT is a feasible and promising treatment for patients with relapsed or refractory DLBCL. El objetivo de este estudio fue evaluar la eficacia y la toxicidad de la combinación de altas dosis de rituximab (HD-R) y el trasplante de células madre autólogas (auto-SCT) en pacientes con linfoma B difuso de células grandes (LBDCG) en recaída o refractario. El grupo HD-R incluyó 22 pacientes a quienes se les administró rituximab durante la movilización de células madre (375 mg/m2 un día antes y 7 días después de la quimioterapia) y tras el trasplante (1000 mg/m2 los días +1 y +8). En el grupo control, el procedimiento fue el mismo que en el grupo HD-R, aunque sin rituximab. Observamos la seguridad, la tolerabilidad, los efectos adversos y la reconstitución inmune de la terapia HD-R. Utilizamos la prueba log-rank, el análisis univariante y el análisis de regresión de Cox multivariante para evaluar el efecto de HD-R en la supervivencia. En total, 22 pacientes de LBDCG en recaída o refractario fueron tratados con HD-R. No se observaron toxicidades limitantes de dosis excepto para la reconstrucción de células CD19+ B en los primeros 6 meses tras SCT. El grupo control incluyó 20 pacientes de LBDCG en recaída o refractario. La supervivencia libre de progresión (SLP) a 3 años y la supervivencia general (SG) mejoró significativamente en el grupo HD-R en comparación con el grupo control (63,8 vs. 35%; p = 0,028 y el 80,1 vs. 50%; p = 0,035, respectivamente). Los análisis univariante y multivariante demostraron que HD-R y tiempo de recaída eran factores pronósticos independientes para SG y SLP. La combinación de HD-R y auto-SCT es un tratamiento factible y prometedor para pacientes con LBDCG en recaída o refractario.

目的 构建与实践异基因造血干细胞移植后患者异型输血工作模式.方法 对温州市某三级甲等医院血液科2015年-2017年993例异型输血病例进行回顾性分析,成立异型输血工作小组,2018年3月-8月根据异型输血的特点,在变革同型输血工作模式的基础上,细化异型输血的步骤,构建阶段式异型输血护理工作流程,在血液科病房中实施,每周根据反馈改进,直至完善.结果 异基因造血干细胞移植后患者异型输血工作模式构建与实践后,配送错误、医嘱错误和输血反应的发生例数均明显减少,差异均具有统计学意义(均P＜0.05).结论 异基因造血干细胞移植后患者异型输血工作模式安全高效,不仅提高了护理工作效率,还防止了护理差错的发生,是针对异型输血的有效模式,可为临床护理实践提供借鉴.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only available curative treatment for patients with β-thalassemia major (β-TM). However, the problem of finding a suitable sibling donor with well-matched human leukocyte antigens is still a major obstacle to curing these patients. With the progress in high-resolution HLA typing technology and supportive care, outcomes after allogeneic HSCT from an HLA well-matched unrelated donor (UD) now approach those of well-matched sibling donors. However, UD HSCT is hampered by an increased risk of graft-versus-host disease and transplant-related mortality. Here we report the outcome of transplantation in patients with β-TM using a novel WZ-14-TM transplant protocol, based on cyclophosphamide, intravenous busulfan, fludarabine, and antithymocyte globulin, in our center. Forty-eight patients between 2 and 11 years of age with β-TM received HLA well-matched UD peripheral blood stem cell transplantation following the WZ-14-TM protocol. All of the transplanted patients achieved donor engraftment. The incidences of grade II to IV acute and chronic graft-versus-host disease were 8.3% and 8.3%, respectively. The overall survival and thalassemia-free survival rates were both 100%. This encouraging result suggests that the WZ-14-TM protocol is a feasible and safe conditioning regime for patients with β-TM undergoing UD HSCT.

目的 探讨伏立康唑、伊曲康唑和氟康唑分别预防血液病患者中性粒细胞缺乏(粒缺)期侵袭性真菌感染(IFI)的疗效性及安全性.方法 回顾性分析2010 ～2016年笔者医院收治的380例血液病患者在粒缺期用伏立康唑、伊曲康唑和氟康唑预防侵袭性真菌感染,观察IFI的发生率和药物不良反应情况.结果 伏立康唑组(n=114)的IFI发生率为7.0％,明显低于非伏立康唑组(n=266)的真菌感染率15.4％,差异有统计学意义(P =0.038).伏立康唑组和非伏立康唑组的总不良事件(AE)发生率分别为13.2％和23.3％,差异有统计学意义(P =0.034).而且Kaplan-Meier分析显示,伏立康唑组IFIs的累积发生率低于非伏立康唑组,差异有统计学意义(P =0.045).结论 伏立康唑用于恶性血液病粒缺期患者侵袭性真菌感染的预防,有较好的疗效及安全性.

MicroRNAs (miRs) have been demonstrated to perform important roles in normal hematopoiesis and leukemogenesis. Accumulating evidence suggests that miR-10a and miR-10b may behave as novel oncogenes or tumor suppressors in human cancer. The present study reported the function of the miR-10 family in myeloid differentiation and acute myeloid leukemia (AML). The levels of miR-10a/b expression were increased in AML cases compared with normal controls, particularly in M1, M2 and M3 subtypes. The levels of miR-10a/b expression were also upregulated in patients with nucleophosmin-mutated AML and AML patients with t(8;21) and t(9;11), compared with the normal control. In addition, the role of miR-10a/b in regulating myeloid differentiation and leukemogenesis was investigated. The results indicated that miR-10a/b expression was able to promote the proliferation of human promyelocytic leukemia cells, while suppressing the granulocytic and monocytic differentiation of the leukemia cells. These findings suggested that abnormal high expression of miR-10a/b may result in unlimited proliferation of immature blood progenitors and repression of mature blood cell differentiation and maturation, thus leading to the occurrence of AML. miR-10a/b may be developed as novel therapeutic targets for the treatment of AML.

It is generally believed that there is correlation between cancer prognosis and pretreatment PLR and NLR. However, there are limited data about their role in diffuse large B cell lymphoma (DLBCL). This study aims to determine the prognostic value of pretreatment PLR and NLR for patients who have DLBCL. The associations between clinical characteristics and NLR and PLR were evaluated among 182 DLBCL patients from January 2005 to June 2016. The optimal cutoff values for high PLR (⩾150) and NLR (⩾2.32) in prognosis prediction were determined. The effect of NLR and PLR on survival was evaluated through multivariate Cox regression analysis, univariate analysis, and log-rank test. According to the evaluation results, patients with high NLR and PLR had significantly shorter OS (P=0.026 and P=0.035) and PFS (P=0.024 and P=0.022) compared with those who have low PLR and NLR. On multivariate analyses, IPI>2, elevated LDH, and PLR⩾2.32 were prognostic factors for OS and PFS in DLBCL patients. Therefore, we demonstrated that high PLR and NLR predicted adverse prognostic factors in DLBCL patients.