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Background: Immune checkpoint blockade (ICB) therapy, including antibodies targeting the programmed cell death protein 1 (PD-1) pathway, has significantly prolonged the overall survival (OS) in patients with advanced cervical cancer (CC). ICB treatment affects both target cells and various components released by immune cells, which can be observed in peripheral blood. However, there has been limited research on the dynamics of peripheral blood immunophenotyping and its association with OS in CC patients receiving ICB therapy., Methods: Patients with persistent, recurrent, or metastatic CC treated with ICB were enrolled between December 2019 and September 2022. The dynamic changes in peripheral blood immune cells, immunoglobulins, and complement components were analyzed at baseline (within 30 days prior to the first ICB cycle) and after the second cycle of ICB treatment (4-6 weeks after the first ICB treatment). Associations of the baseline levels of peripheral blood immune cells, immunoglobulins, complement components with OS were analyzed using multivariable Cox regression analysis., Results: In this retrospective cohort study, 119 patients who received at least two cycles of ICB were included. Data on peripheral blood immune cells, immunoglobulins, and complement components were available for 70 of these patients. The percentages of suppressor T (Ts) cells and natural killer (NK) cells in peripheral blood increased significantly post-ICB treatment, whereas the Th/Ts ratio and IgM levels decreased. The percentages of cytotoxic T (Tc) cells, Ts cells, the Th/Ts ratio, and levels of IgM, IgA, C3, and C4 were significantly associated with the OS of patients. Furthermore, multivariable Cox regression analysis found that a high level of IgA was associated with poor OS of the patients (HR = 2.918; 95% CI, 1.081-7.877, P = 0.035)., Conclusion: Our study demonstrated the potential proliferation of peripheral blood anti-tumor T cells in some CC patients undergoing ICB therapy. The observed associations between peripheral blood immunophenotyping and OS suggest that these biomarkers might have potential as prognostic tools., Competing Interests: Declarations. Ethics approval and consent to participate: The study involving human participants was reviewed and approved by the Ethics Committee of Guangxi Medical University Cancer Hospital (KY2021331). All subjects gave written informed consent in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Although several different parameters of PET/CT were reported to be predictive of survival in DLBCL, the best parameter remains to be elucidated and whether it could improve the risk stratification of IPI in patients with DLBCL., Procedures: 262 DLBCL patients including in the training and validation cohort were retrospectively analyzed in this study., Results: Among different parameters, MTV was identified as the optimal prognostic parameter with a maximum area under the curve (AUC) of 0.652 ± 0.112 than TLG and SDmax (0.645 ± 0.113 and 0.600 ± 0.117, respectively). Patients with high MTV were associated with inferior PFS (p < 0.001 and p = 0.021, respectively) and OS (p < 0.001 and p < 0.001, respectively) in both the training and validation cohort. The multivariate analysis revealed that high MTV was an unfavorable factor for PFS (relative ratio [RR], 2.295; 95% confidence interval [CI], 1.457-3.615; p < 0.01) and OS (RR, 2.929; 95% CI 1.679-5.109; p < 0.01) independent of IPI., Conclusions: Further analysis showed MTV could improve the risk stratification of IPI for both PFS and OS (p < 0.01 and p < 0.01, respectively). In conclusion, our study suggests that MTV was an optimal prognostic parameter of PET/CT for survival and it could improve the risk stratification of IPI in DLBCL, which may help to guide treatment in clinical trial., Competing Interests: Declarations. Ethics approval: This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Approval was granted by the Ethics Committee of Nanfang Hospital, Southern Medical University (Ethics approval number: NFEC-202307-K13). Consent to participate: Not applicable. Competing interests: The authors declare no competing interests. The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic., Design: Retrospective cohort study between 2018 and 2021., Setting: The largest haematological centre in southern China., Results: A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p<0.001) and 0.27% versus 0.44% (p=0.027), respectively. The main isolates from Gram-negative or Gram-positive BSI and susceptibility profiles also changed. The 30-day mortality caused by BSI was lower during the pandemic (21.1% vs 14.3%, p=0.043). Multivariate analysis revealed that disease status, pulmonary infection and shock were independent predictors of 30-day mortality., Conclusion: Our data showed that the incidence of total and Gram-negative organisms BSI decreased, but Gram-positive BSI incidence increased in patients with HMs during the pandemic along with the changes of main isolates and susceptibility profiles. Although the 30-day mortality due to BSI was lower during the pandemic, the new infection prevention strategy should be considered for any future pandemics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Among hematological malignancies, multiple myeloma (MM) represents the leading indication of autologous hematopoietic stem cell transplantation (auto-HCT). Auto-HCT is predominantly performed with peripheral blood stem cells (PBSCs), and the mobilization and collection of PBSCs are essential steps for auto-HCT. Despite the improved success of conventional methods with the incorporation of novel agents for PBSC mobilization in MM, mobilization failure is still a concern. The current review comprehensively summarizes various mobilization strategies for mobilizing PBSCs in MM patients and the evolution of these strategies over time. Moreover, existing evidence substantiates that the mobilization regimen used may be an important determinant of graft content. However, limited data are available on the effects of graft characteristics in patient outcomes other than hematopoietic engraftment. In this review, we discussed the effect of graft characteristics on clinical outcomes, mobilization failure, factors predictive of poor mobilization, and potential mobilization regimens for such patients., (© 2023. The Author(s).)

Background: Partial immunoparesis, which means at least two suppressed uninvolved immunoglobulins (Igs), had been reported to be associated with poor prognosis in patients with multiple myeloma (MM), but the impact on early infections remains unknown. The purpose of our study was to determine the prognostic implications of partial immunoparesis on early grade ≥3 infections in patients with MM., Methods: Herein we retrospectively analyzed the clinical data of 123 MM patients between 2012 and 2020 at Nanfang Hospital. All patients received bortezomib-based regimens. The relationship between early grade ≥3 infections and partial immunoparesis was investigated using Cox regression analysis., Results: Our data showed partial immunoapresis was found in 63% MM patients. Partial immunoparesis was significantly related to elevated beta-2-microglobulin (B2M), decreased estimated glomerular filtration rate (eGFR) and progressive international staging system (ISS) stage (P<0.05). Especially, univariate Cox regression analysis showed partial immunoparesis was significantly correlated with early grade ≥3 infections (P=0.003). Moreover, multivariate Cox regression analysis showed partial immunoparesis was an independent significant prognostic factor for early grade ≥3 infections [odds ratio (OR) =3.048; 95% confidence interval (CI): 1.429-6.504; P=0.004]. Furthermore, partial immunoapresis could improve the infection risk model built by Dumontet et al., Conclusions: Our study showed that partial immunoparesis could predict early infections in patients with MM, which may be used to identify the high risk patients for infections and guide strategies for infection prevention., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-1627). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

Introduction: Emerging evidence has revealed that long noncoding RNA (lncRNA) play important role in almost all kinds of human cancers. LINC00908 has been reported to be involved in the development of prostate cancer, colorectal cancer and gastric cancer which was functioned as an oncogene. However, the potential biology role and molecular mechanism of LINC00908 in diffuse large B-cell lymphoma are still unclear., Methods: LINC00908 and miR-671-5p expression were evaluated in DLBCL tissues and cell lines using RT-qPCR. CCK-8 and transwell assay were used to analyze the in vitro role of LINC00908 in DLBCL progression. The xenograft model was used to explore the in vivo role of LINC00908 in DLBCL growth. The physical interaction between LINC00908 and miR-671-5p was confirmed using bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down., Results: The expression of LINC00908 was markedly up-regulated in diffuse large B-cell lymphoma tissues and cell lines, and the decreased expression of LINC00908 significantly inhibited diffuse large B-cell lymphoma cell proliferation and invasion. Then, we revealed that LINC00908 directly interacted with miR-671-5p, which was down-regulated in diffuse large B-cell lymphoma cells and highly expressed with LINC00908 knockdown. Moreover, luciferase reporter assays and RNA immunoprecipitation (RIP) assay further proved that miR-671-5p is a direct target of LINC00908 in diffuse large B-cell lymphoma cells. Rescue experiments were also performed, and we confirmed that LINC00908 acts as an oncogene role in diffuse large B-cell lymphoma through miR-671-5p. Finally, the influence of LINC00908 silence significantly inhibited diffuse large B-cell lymphoma growth in vivo., Conclusion: LINC00908 promotes malignancy of diffuse large B-cell lymphoma through regulating miR-671-5p., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Zeng et al.)

Previous studies showed albumin at diagnosis could be used to predict outcome in patients with diffuse large B-cell lymphoma (DLBCL), but whether albumin could improve the international prognostic index (IPI) risk stratification remains unknown. Herein, we retrospectively analyzed 440 de novo DLBCL patients in this study. The cutoff value of albumin was 39.2 g/L. Patients with high serum albumin showed superior OS and PFS (p = 0.002 and p < 0.001, respectively). According to IPI, there were 163 patients (37.0%) in low-risk group, 107 (24.3%) in low-intermediate risk group, 114 (25.9%) in high-intermediate risk group and 56 (12.7%) in high-risk group. Further analysis showed high albumin could identify a subgroup of patients with extremely superior OS and PFS in low IPI risk patients (p = 0.022 and p = 0.034, respectively). Multivariate analysis revealed that high albumin was an independent prognostic factor for OS (relative ratio [RR] 0.122; 95% confidence interval [CI] 0.021-0.715, p = 0.020) and trend for PFS (RR 0.417; 95% CI 0.168-1.035, p = 0.059). In conclusion, our study suggests that albumin at diagnosis is a simple and effective prognostic factor in DLBCL patients, allowing the identification of a superior outcome subgroup in low-risk patients, which may help to guide treatment in clinical trial.

Mutations of internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) contribute to poor prognosis in cytogenetically normal acute myeloid leukemia (CN-AML). Chemotherapy has limited effect, while allogeneic hematopoietic stem cell transplantation (allo-HSCT) plus sorafenib maintenance is a promising protocol to improve their therapeutic outcome. However, the prognostic significance of FLT3-ITD mutant status remains controversial. To investigate this, we detected FLT3-ITD mutant ratio (high and low) and length (long and short) in enrolled 184 CN-AML patients without NPM1 mutation, and evaluated their impact on complete remission (CR), overall survival (OS), relapse-free survival (RFS) and relapse risk (RR) after chemotherapy or allo-HSCT plus sorafenib maintenance. Our studies showed that FLT3-ITD mutation had negative impact on chemotherapeutic response, OS and RFS in CN-AML patients. There was no significant difference in CR rate between high and low ratio, or long and short length. Increasing ITD mutant ratio and length were associated with decreasing OS, and long length had shorter RFS and higher RR than the short after chemotherapy. Allo-HSCT plus sorafenib maintenance was an effective strategy to improve RFS and decrease relapse probability in FLT3-ITD AML patients, and benefited to these regardless of mutant ratio, and those with long length instead of the short.

Adult T-cell leukemia lymphoma (ATLL) is a rare T cell neoplasm that is endemic in Japanese, Caribbean, and Latin American populations. Most North American ATLL patients are of Caribbean descent and are characterized by high rates of chemo-refractory disease and worse prognosis compared with Japanese ATLL. To determine genomic differences between these 2 cohorts, we performed targeted exon sequencing on 30 North American ATLL patients and compared the results with the Japanese ATLL cases. Although the frequency of TP53 mutations was comparable, the mutation frequency in epigenetic and histone modifying genes (57%) was significantly higher, whereas the mutation frequency in JAK/STAT and T-cell receptor/NF-κB pathway genes was significantly lower. The most common type of epigenetic mutation is that affecting EP300 (20%). As a category, epigenetic mutations were associated with adverse prognosis. Dissimilarities with the Japanese cases were also revealed by RNA sequencing analysis of 9 primary patient samples. ATLL samples with a mutated EP300 gene have decreased total and acetyl p53 protein and a transcriptional signature reminiscent of p53-mutated cancers. Most importantly, decitabine has highly selective single-agent activity in the EP300-mutated ATLL samples, suggesting that decitabine treatment induces a synthetic lethal phenotype in EP300-mutated ATLL cells. In conclusion, we demonstrate that North American ATLL has a distinct genomic landscape that is characterized by frequent epigenetic mutations that are targetable preclinically with DNA methyltransferase inhibitors., (© 2018 by The American Society of Hematology.)

Prognostic nutritional index (PNI), based on serum albumin concentration and the absolute peripheral lymphocyte count, has been used to predict survival in various tumors. Whether PNI can predict prognosis in patients with diffuse large B-cell lymphoma (DLBCL) remains unknown. We retrospectively analyzed 253 patients with newly diagnosed DLBCL in the present study. The PNI was calculated as: albumin (g/L) + 5 × total lymphocyte count × 10(9)/L. All patients were divided in low and high groups according to the analysis of receiver operating characteristic (ROC) curve. Low PNI was associated with more unfavorable clinical features (p < 0.05). Patients with low PNI tended to have worse event-free survival (EFS) and overall survival (OS) (EFS, p = 0.001; OS, p < 0.001). For patients treated with R-CHOP, PNI proved to be predictive for survival (EFS, p = 0.001; OS, p < 0.001), while no significant effect was found in DLBCL patients who received CHOP chemotherapy (EFS, p = 0.496; OS, p = 0.125). Multivariate analysis showed that low PNI is an independent adverse predictor of OS and EFS, especially in DLBCL patients treated with R-CHOP. In conclusion, this study suggests that PNI is an effective prognostic factor in DLBCL patients treated with R-CHOP.

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the impact of courses of intermediate-dose cytarabine (ID-Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell transplantation (auto-HSCT)., Methods: 90 patients with de novo AML undergoing auto-HSCT between August 1999 and November 2012 were enrolled. All patients received the mobilization regimen of cytarabine and etoposide chemotherapy in combination with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Stem cell apheresis was scheduled when blood leukocyte count recovered greater than 4.0 × 10⁹/L or the proportion of CD34⁺ cells greater than 1% in peripheral blood. The impact of ID-Ara-C courses on the mobilization efficiency was analyzed retrospectively., Results: According to the ID-Ara-C courses, patients were divided into group A (<2 courses), B (2 courses), and C (>2 courses). The median doses of CD34⁺ cells (×10⁶/kg) in three groups were 4.7, 2.7, 2.3, respectively (P=0.003). Of the available 87 patients who could be evaluated, 61 (70.1%) cases had CD34⁺ cells greater than 2.0 × 10⁶/kg, and 26 (29.9%) cases less than 2.0 × 10⁶/kg. Of the 26 patients without satisfactory mobilization efficiency, 7 (15.2%) were in group A, 10 (47.6%) in group B, and 9 (45.0%) in group C (χ²=10.05, P=0.007). In addition, patients with satisfactory mobilization efficiency (CD34⁺ cells ≥ 2.0×10⁶/kg) in groups C needed more times of collection, more volume of blood processed, and even high-dose and longer course of rhG-CSF (P<0.05). In univariate analysis. The ID-Ara-C courses and the cumulative dose were significant correlate with mobilization efficiency. In multivariate analysis, the ID-Ara-C courses was an independent correlation factor for mobilization efficiency (odd ratio=0.623, 95% confidence interval=0.418-0.926, P=0.019). The sex, age, cytogenetic risk, the standard chemotherapy courses did not correlate with mobilization efficiency., Conclusion: The number of ID-Ara-C courses was independent factor for the mobilization efficiency and should be taken seriously in AML patients with auto-HSCT.

Objective: To evaluate the long-term clinical efficacy and safety of nilotinib in the treatment of chronic myelogenous leukemia (CML) patients with imatinib resistance or intolerance., Methods: Twenty-six CML patients with imatinib resistance or intolerance received nilotinib treatment at the dose of 400 mg once or twice daily. The patients were followed up for nearly 5 years with regular monitoring of the hematologic, cytogenetic and molecular biological markers and recording of the clinical manifestations and biochemical indicators to evaluate the therapeutic effect and adverse events., Results: The median duration of nilotinib therapy was 17 (1-56) months, and the patients were follow up for a median of 51 months. At the last follow-up, 16 (61.5%) patients achieved a complete hematologic response, 13 (50.0%) achieved a major cytogenetic response, 9 (34.6%) achieved a complete cytogenetic response, and 7 (26.9%) achieved a major molecular response accumulatively. Nonhematologic adverse events were mostly of grade l or 2. The most common adverse effects possibly related to nilotinib were increased bilirubin (69.2%) and rash (57.7%). Grade 3 or 4 hematologic adverse events included thrombocytopenia (53.8%), neutropenia (26.9%) and anemia (19.2%). The patients in chronic and remission phase had better efficacy and fewer hematological side effects than those in advanced phase., Conclusion: Nilotinib is an effective and safe treatment option for imatinib-resistant or -intolerant CML patients, especially for those in chronic and remission phase.

Ridge waveguide 1.3 mum GaInNAs lasers were fabricated from high quality double quantum well material grown by molecular beam epitaxy. Short cavity (250 mum) lasers have low threshold currents and small temperature dependencies of threshold current and slope efficiency, with a characteristic temperature of the threshold current as high as 200 K. The temperature stability allows for uncooled 2.5 Gb/s operation up to temperatures as high as 110 degrees C with a constant modulation voltage and only the bias current adjusted for constant average output power. Under these conditions, an extinction ratio larger than 6 dB and a spectral rms-width smaller than 2 nm are obtained.

Objective: To explore the association between chimerism, minimal residual disease (MRD) and relapse after sex-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemia., Methods: Fifty-seven patients with leukemia received allogeneic hematopoietic stem cell grafts from HLA-matched or partially matched, but sex-mismatched donors. Chimeric status and MRD were detected by dual-color interphase fluorescence in situ hybridization (I-FISH) using X/Y sex chromosome centromere DNA probe and bcr/abl dual fusion DNA probe, respectively, at different time points after transplantation. SPSS software was used to analyse the correlation between chimeric status, MRD and relapse., Results: In comparison with karyotype analysis, I-FISH was of higher sensitivity in detecting sex chromosome and bcr/abl fusion gene. Chimeric status was negatively correlated with MRD (r=-0.9690, P<0.01). In the early times of transplantation (within 3 months), mixed chimerism had higher relapse rate than did complete chimerism. Chimeric status and MRD were correlated with leukemic relapse (r=-8240, P<0.01; r=-0.9040, P<0.01). The decrease in chimeric status occurred before leukemic relapse in hematology., Conclusion: I-FISH is a more specific and sensitive test for monitoring MRD after transplantation. The clinical value of sex chromosome is identical to that of the special tumor gene for monitoring MRD after transplantation. Chimeric status is negatively correlated with MRD. Chimeric status and MRD are associated with leukemic relapse. The decrease in chimeric status is considered a mark of leukemic relapse after transplantation.