Elevated Serum Lactate Dehydrogenase Research Articles

Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti-PD-1 Therapy.

Recent research indicates that gut microbiota may be vital in the advancement of melanoma. In this study, we found that melanoma patients exhibited a distinct gut mycobiota structure compared with healthy participants. Candida albicans, Candida dubliniensis, and Neurospora crassa were more abundant in samples from patients with melanoma, whereas Saccharomyces cerevisiae and Debaryomyces hansenii were less abundant. During anti-PD-1 treatment, the relative amount of Malassezia restricta and C. albicans increased. A higher level of Saccharomyces paradoxus was associated with a positive response to anti-PD-1 treatment, whereas a higher level of Tetrapisispora blattae was associated with a lack of clinical benefits. High levels of M. restricta and C. albicans, elevated serum lactate dehydrogenase, and being overweight were linked to increased risk of melanoma progression and poorer response to anti-PD-1 treatment. Thus, this study has revealed melanoma-associated mycobiome dysbiosis, characterized by altered fungal composition and fungi species associated with a higher risk of melanoma progression, identifying a role for the gut mycobiome in melanoma progression.

Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma

AbstractDiffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC−, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center–like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center–like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.

Comprehensive analysis of orbital lymphoma in a Turkish cohort: clinical characteristics, histological subtypes, treatment modalities, prognostic factors, and implications for management.

The study analysed the clinical characteristics, treatment approaches, and survival outcomes of 97 consecutive patients with orbital lymphoma (OL) over a 25-year period at. The median age of the patients was 57.6years, and 59.8% (n = 58) were male. Marginal zone lymphoma constitutes the most prevalent subtype, accounting for 67% of cases, whereas other common subtypes include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, and T-cell lymphomas. Unilateral involvement was observed in the majority of cases (72.3%). Common clinical presentations included mass (30.9%), swelling (26.8%), and epiphora (11.3%). Of the patients, 7.2% received rituximab alone, 14.4% received radiotherapy alone, 48.5% received chemotherapy, 27.8% received radiotherapy plus rituximab, 22.7% received radiotherapy plus chemotherapy, and 5.2% underwent surgery as the first-line treatment. During a median follow-up of 4.3years, 15.5% of patients experienced relapse or disease progression. The 5-year and 10-year progression-free survival rates were 84.1% and 79.1%, respectively. This study contributes to our understanding of OLs and provides a foundation for further investigations in this field. Male gender, presence of B symptoms, advanced stage, secondary orbital lymphoma, aggressive histological subtype, and elevated serum lactate dehydrogenase levels were associated with poorer (either inferior or worse) progression-free survival.

[Effect and mechanism of Poria cocos polysaccharides on myocardial cell apoptosis in rats with myocardial ischemia-reperfusion injury by regulating Rho-ROCK signaling pathway].

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1β(IL-1β) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1β and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1β and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.

Validating the Systemic Inmmune-Inflamation Index (SII) As a Prognostic Biomarker of Overall Survival in Diffuse Large B-Cell Lymphoma: A Retrospective Analyses By the Gruppo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Introduction: Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common type of non-hodgkin´s lymphoma. Biologically, survival of neoplastic lymphoid cells depends on self-mediated mechanisms and the tumor microenvironment ( Steen CB,2021) leading to an inflammatory state. Although a better understanding of lymphoma biology has helped predict outcomes in DLBCL, modern tools such as next generation sequencing are not available in Latin America ( LATAM). The systemic immune-inflammation index (SII) is a score based on neutrophil, platelet, and lymphocyte counts that has proven to be useful in DLBCL ( ZanZan W, 2021 & Xiao-Bo,2021). Moreover, its variables can be easily evaluated at resource-limited healthcare setting. Thus, we aim to validate this new SII score in our LATAM DLBCL population. Methods. A retrospective analysis of patients aged ≥18 years with a new diagnosis of DLBCL between 2010 and 2018 were included. Data were obtained from 7 LATAM countries: Argentina, Colombia, Chile Mexico, Peru, Uruguay, and Venezuela. Clinical features including the international Prognostic Index (IPI) variables (i.e. age≥60 years, ECOG performance status ≥2, >1 site extranodal involvement, elevated serum LDH, and advanced clinical stage) and low serum albumin defined as <3.5mg/dL (divided in low 3.4-2.5mg/dL & very low <2.5mg/dL) were recorded. We calculated the neutrophil/lymphocyte ratio (NLR) and use the cut-off previously published by our group (Beltran&Villela,2020). The SII score was calculated using the following formula: (absolute neutrophil count x platelet count) divided by absolute lymphocyte count x100; The cut-off was calculated by the ROC method. Demographics characteristics are reported using descriptive statistics. Cox proportional-harzard regression model was used to evaluate parameters associated with OS curves estimated with the Kaplan-Meier (KM) method. Outcomes. A total of 1032 patients were identified of whom 1029 received standard dose RCHOP (n=862,84%), R-miniCHOP (43,4.17%), R-EPOCH (n=61,5.92%) and CHOP (n=63,6.12%) with a curative intent. A total of 992 patients had suffcient data for analysis. Median follow.up for all cohort was 45 months (IQR: 7 to 60). Median age at diagnosis was 63 years (58.4%, age ≥60;IQR: 50 to 73), 50% was female, 33% had ECOG ≥2, 22% extranodal involvement (EN) >1 sites, 48% elevated serum lactate dehydrogenase (LDH), 41% advanced stage (Stage III/IV). Patients with hypoalbuminemia (Low & very low) were 25% & 6%, respectively; NLR >4 was 14%. The median calculated SII score for the entire cohort was 1774 (IQR:523 to 1856) with a cut-off of >1636 (AUC 0.55[95%C.I. 0.53 to 0.59], p=0.004). The clinical characteristics of non-inflammation group [NIG,n=736,71.5%] (below cut-off) and inflammation group [IG,n=293,28.5%] (above cut-off) are presented in Table 1. ECOG ≥2; elevated serum LDH, advanced stage; low & very low albumin; and NLR >4 were assocated to de IG ( all of them p<0.0001). The KM for NIG and IG showed better OS for the NIG at 3 years (67% vs. 49%, p<0.0001). Table 2 shows the univariate and multivariate analysis of variables with independent influence on OS. All but EN involvement were independent factors to prognosticate OS with a Harrell´s C-Index of 0.73 (95% C.I. 0.69 to 0.76). Conclusions. In this large cohort of LATAM DLBCL patients, we were able to validate the SII score. We found the SII score was able to discriminate low from hogh risk DLBCL inflammatory groups. Moreover, these findings were coupled to the validation of other prognostic factors such as the IPI score, hypoalbuminemia, and high NLR.

Survival and CNS Relapse in Patients with CD5-Positive Diffuse Large B-Cell Lymphoma: A Multi-Institutional Observational Study in Japan

Background: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is usually characterized by activated B-cell type, poor prognosis, and frequent central nervous system (CNS) relapse. A sandwich therapy of dose-adjusted (DA)-EPOCH-R combined with high-dose methotrexate (HD-MTX) (DA-EPOCH-R/HD-MTX) showed excellent efficacy in a phase II study for newly diagnosed stage II-IV CD5+ DLBCL, including 2-year (yr) overall survival (OS), progression-free survival (PFS), and CNS relapse rates of 89%, 79%, and 9%, respectively (Miyazaki K, et al. Haematologica, 2020). It has been introduced in practice in Japan; however, the current status of treatment and the prognosis in patients with CD5+ DLBCL are unclear. Methods: We retrospectively analyzed the prognosis and CNS relapse rate of consecutive patients with untreated CD5+ DLBCL who were diagnosed at 30 hospitals in Japan from January 2016 to December 2021. Patients who were diagnosed with double-/triple-hit lymphoma, those with CNS involvement at diagnosis, and those who had not received any anthracycline-containing chemotherapy with rituximab (R-chemo) were excluded. We identified risk factors for OS using Cox proportional hazards method. The outcomes in the stage II-IV patients who received DA-EPOCH-R/HD-MTX were compared with those of the phase II study. To evaluate the efficacy of CNS prophylaxis, we divided patients into four groups: HD-MTX alone, intrathecal administration of MTX alone (IT MTX), both HD-MTX and IT MTX (HD/IT MTX), and no CNS prophylaxis. Results: Among the413 enrolled patients, 20 were excluded due to ineligible diagnosis or insufficient clinical information, 18 had CNS involvement at diagnosis, and 27 did not receive R-chemo. As a result, 348 patients were eligible and showed the following features: median age, 71 yrs (range, 23-92); male sex, 54%; stage II-IV, 90%; stage III or IV, 73%; ECOG performance status (PS) > 1, 30%; > 1 extranodal site, 42%; elevated serum lactate dehydrogenase (sLDH) level, 71%; high-intermediate or high International Prognostic Index (IPI), 63%; high CNS-IPI, 41%; and B symptoms, 29%. According to Hans's criteria, the nongerminal center B-cell type accounted for 67% of the 276 cases examined. Among the 348 patients, 62 (18%) received DA-EPOCH-R/HD-MTX, and 286 (82%) were treated with other R-chemo, such as R-CHOP (n = 254). The median age was 63.5 yrs (range, 29-75) in the DA-EPOCH-R/HD-MTX group and 72 yrs (range, 23-92) in the other R-chemo group. The DA-EPOCH-R/HD-MTX group included significantly more patients aged ≤ 60 yrs ( P < 0.001), although it tended to have more patients with ECOG PS > 1 than the other R-chemo group ( P = 0.069). Patients who received IT MTX made up 16% of the DA-EPOCH-R/HD-MTX group and 31% in the other R-chemo group. HD-MTX was used in 100% of patients in the DA-EPOCH-R/HD-MTX group and 17% of patients in the other R-chemo group. Details of CNS prophylaxis were HD-MTX alone in 84 patients (24%), IT MTX alone in 70 (20%), both HD/IT MTX in 28 (8%), and no CNS prophylaxis in 166 (48%). At a median follow-up of 43 months, the 2-yr OS, PFS, and CNS relapse rates of patients with stage II-IV disease in the DA-EPOCH-R/HD-MTX group were 87% (95% CI, 73-94%), 78% (95% CI, 63-87%), and 7.3% (95% CI, 2.8-18.2%), respectively. There were no significant differences in OS or PFS between stage I and stage II-IV patients in the DA-EPOCH-R/HD-MTX group. In all 348 patients with stage I-IV, both the OS ( P = 0.044) and PFS ( P = 0.043) in the DA-EPOCH-R/HD-MTX group were longer than those in the other R-chemo group. The 2-yr OS in these groups were 89% and 78%, and their 2-yr PFS were 78% and 64%, respectively. Multivariate analysis identified elevated sLDH ( P = 0.005), > 1 extranodal involvement ( P < 0.001), no IT MTX ( P = 0.005), and no DA-EPOCH-R/HD-MTX ( P = 0.005) as independent risk factors for OS. The 2-yr CNS relapse rate was 6.5% in the DA-EPOCH-R/HD-MTX group (n = 4) and 10.0% in the other R-chemo group. There were no significant differences in the CNS relapse rate between the two groups ( P = 0.54). The 2-yr CNS relapse rates of HD-MTX, IT MTX alone, both HD/IT MTX, and no prophylaxis were 9.8%, 9.1%, 3.7% (n = 1), and 10.3%, respectively. Conclusions: Our results confirmed favorable survival in the phase II study of DA-EPOCH-R/HD-MTX in clinical settings. DA-EPOCH-R/HD-MTX and IT MTX were associated with longer OS of patients with CD5+ DLBCL in our study cohort, warranting further investigation.

Updated Results of a Prospective Study: Rituximab and Lenalidomide Plus Chidamide (RLC) for Patients with Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma

Introduction Angioimmunoblastic T-cell lymphoma (AITL) is the second most common subtype of peripheral T-cell lymphoma (PTCL). The therapeutic effect of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), the most common first-line chemotherapy regimen, is not satisfactory, and most patients experience relapse or disease progression. The 5-year progression-free survival (PFS) of AITL is 13%-23%, and 5-year overall survival (OS) is 33%-36%. The benzamide histone deacetylase inhibitor (HDACi) Chidamide and lenalidomide (a second-generation immunomodulatory compound) are both approved for the treatment of relapsed or refractory PTCL in China. About 70%-100% of the AITL patients have EBV infection, which may cause abnormal immune functions in hosts. EBV infects immunocytes such as B cells, T cells, and natural killer cells, and it impairs immune functions that can clear neoplastic cells from the body. Rituximab may eradicate EBV-B cells and activated B cells and may prevent the progression to AITL. When combined with rituximab, lenalidomide augmented antibody-dependent cell-mediated cytotoxicity by enhancing NK cells, which overcomes rituximab resistance in lymphoma patients. In this prospective phase II study, the efficacy and safety of a new regimen consisting of rituximab, lenalidomide and chidamide has been evaluated in relapsed/refractory AITL patients. We have reported the preliminary results (2022 ASH, poster 1600), and now we update the data of this study. Methods Patients with relapsed/refractory AITL after at least first-line chemotherapy were treated with up to 6 cycles of a rituximab and lenalidomide plus chidamide (RLC) regimen every 3 weeks. The initial dose of each drug has been reported. The primary endpoint of the study was PFS. The secondary endpoints included overall response rate (ORR), OS, and adverse events (AEs). Results Between Aug 2019 and May 2023, 24 patients with relapsed/refractory AITL were enrolled. The characteristics of these patients are listed in table 1. On enrollment, 16 (66.7%) patients had received 1st-line chemotherapy, 7 (29.1%) patients had received 2nd-line chemotherapy, and 1 (4.2%) patient had received 3rd-line chemotherapy. The median age was 63 years (range 43-78) and 9 (37.5%) patients were female. Fifteen (62.5%) patients had B symptoms, including weight loss in 3 (12.5%) cases, night sweat in 1 (4.2%) case and fever in 11 (45.8%) cases. Sixteen (66.7%) patients had elevated serum lactate dehydrogenase (LDH), and 21 (87.5%) patients had IPI score≥2. All patients had completed RLC treatment for at least 1 cycle and underwent imaging assessment. The ORR was 75% (18/24) with a complete remission (CR) rate of 20.8% (5/24), and 13 (54.2%) patients achieved partial remission (PR). While 1 (4.2%) patient achieved stable disease (SD) and 5 (20.8%) patients achieved progressive disease (PD). Two patients received autologous hematopoietic stem cell transplantation as consolidation treatment after achieving CR from RLC chemotherapy. With a median follow-up of 9.7 months, 9 patients had died. The median PFS was 10.8 months (95% confidence interval <CI>, 9.0 to 12.6 months), but the median OS was not reached. No patient presented with Grade 5 AE. The most frequent all-grade hematological toxicity included leucopenia (35.7%, 5/14), followed by anemia (21.4%, 3/14) and thrombocytopenia (41.7%, 10/24). Other common toxicities included infusion reaction (16.7%, 4/24), skin rash (20.8%, 5/24), pulmonary pneumonia (41.7%, 10/24), and nausea (12.5%, 3/24). Dose reduction was performed in 8 patients. The exploratory analysis of possible prognostic factors by mass spectrum flow are undergoing. Conclusions The updated results of this prospective study confirmed the good response rate and manageable toxicity of rituximab and lenalidomide plus chidamide (RLC) regimen. This combination may be a promising regimen in patients with relapsed/refractory AITL.

Clinical and Molecular Features of Patients with Double/Triple Hit Large B-Cell Lymphoma

Background: High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) is a recently defined category in the latest revision of the World Health Organization (WHO) classification, which comprises approximately 5-15% of newly diagnosed DLBCL. This subtype of lymphoma poses numerous challenges from diagnosis to treatment of patients. On the one hand, diagnosis of HGBL-DH/TH requires the accomplishment of fluorescent in-situ hybridization (FISH) to identify the translocations of MYC(8q24) and BCL2(18q21) or/and BCL6(3q27), with no consensus being reached regarding the most applicable population for FISH tests due to high cost and low prevalence. On the other hand, HGBL-DH/TH displays aggressive features, including a high incidence of advanced disease at diagnosis, and inferior efficacy to standard-induced chemical immunotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Despite several treatment strategies including intensified protocols and hematopoietic cell transplantation (HCT) have been explored, there is no standard regimen to improve outcomes for HGBL patients, and participation in clinical trials is encouraged. Aims: This study aims to investigate the clinical characteristics and prognostic outcomes of HGBL-DH/TH patients, and performed genomic and transcriptomic analyses to link the oncogenic mutations and tumor microenvironment alterations to different DLBCL subgroups. Method:In this study, 107 patients with newly diagnosed HGBL-DH/TH were analyzed. Histological diagnoses were established according to the WHO classification. These HGBL-DH/THs were termed DHL-BCL2 (MYC and BCL2 translocation), DHL-BCL6 (MYC and BCL6 translocation), and THL in our study. DNA sequencing was carried out on 95 patients, for detection of genetic aberrations. Results: Patients with DHL-BCL2 (n=44) and THL (n=15) have similar clinical features, including elevated serum lactate dehydrogenase (LDH), increased proportion of double expression (DE) as well as increased prevalence of non-GCB subtype compared to those with DHL-BCL6 (n=48). With the median follow-up time of 19.3 months (2.5-114.2 months), patients in the DHL-BCL2 and THL group had dismal survival (2-year PFS: 49.3% and 34.2%; 2-year OS: 64.0% and 55.6%) when compared with those in the DHL-BCL6 group (2-year PFS: 63.5%; 2-year OS: 89.3%) (Figure A). Moreover, intensive chemoimmunotherapy or combination with novel targeted agents seemed to improve outcomes in patients with DHL/THL compared with those who received a standard R-CHOP regime. The use of autologous stem cell transplant (ASCT) did not yield a significant improvement in survival for patients who achieved remission after receiving first-line R-DA-EDOCH therapy. However, it is worth noting that there was a trend towards prolonging progression-free survival (PFS) and overall survival (OS) in patients who achieve complete remission (CR) through RCHOP-based treatment and undergo ASCT (Figure B). Compared to DHL-BCL6, the primary genetic lesions in DHL-BCL2 and THL were alterations associating epigenetic regulators like EZH2 and CREBBP, while the primary genetic lesions in DHL-BCL6 were alterations associating cellular differentiation and transcription factors like BTG2, PTPN6, CD70, and BCL6. Correlatively, the EZB genotype was more frequently observed in patients with DHL-BCL2 and THL, while the BN2 genotype was more frequently observed in patients with DHL-BCL6. Conclusion: DHL-BCL2/THL exhibits similar clinical characteristics, prognostic outcomes, and molecular features that set it apart from DHL-BCL6. This implies the need for testing novel agents or therapeutic strategies to expedite treatment development for patients with DHL-BCL2/THL.

Cyclin D1-Positive Expression Associated with Prognostic Significance and Clinicopathological Characteristics By Paving the Way for Proliferation in Diffuse Large B-Cell Lymphomas

Introduction: Cyclin D1 protein expression in lymphocytes is commonly associated with mantle cell lymphoma. However, it has rarely been reported in patients with diffuse large B-cell leukemia (DLBCL), particularly in Asia where studies on cyclin D1 expression in DLBCL are limited and often small. Furthermore, the clinical implications of cyclin D1 expression in Asia remain unclear. Methods: In this study, a total of 815 patients diagnosed with DLBCL and treated with R-CHOP or R-CHOP-like regimens over a five-year period were reviewed. The authors conducted clinical, immunohistochemical, and genetic analyses, with a specific focus on cyclin D1. Immunohistochemistry was used to identify cyclin D1-positive patients, and fluorescence in situ hybridization was employed to assess cyclin D1 gene (CCND1) rearrangements. A comparison was made between DLBCL patients with and without cyclin D1 expression in terms of clinical, immunohistochemical, and genetic features. Results: Among the DLBCL patients, 16 individuals (2.61%) exhibited cyclin D1 expression without CCND1 gene rearrangements. Cyclin D1-positive DLBCLs were observed in patients with a median age of 58.88 ± 4.07 years, with 93.75% of them classified as stage IV. The majority of cyclin D1-positive patients (81.25%) displayed elevated serum lactate dehydrogenase (LDH) levels and advanced international prognostic index (IPI) scores. Additionally, all cases exhibited a proliferation rate exceeding 80%, and a significant proportion (93.75%) demonstrated MYC expression. Cyclin D1-positive DLBCLs were associated with elevated LDH levels, higher IPI scores, advanced stage, increased Ki-67 proliferation, and MYC expression (p<0.05). However, no significant differences were observed in other clinical characteristics and immunohistochemical features. Patients with cyclin D1 expression experienced shorter progression-free survival (PFS) and overall survival (OS) compared to cyclin D1-negative patients (p<0.05). Next-generation sequencing (NGS) was performed to explore the molecular mechanisms underlying cyclin D1-positive DLBCL. Among the top 50 gene alterations identified, all samples exhibited BRD9 and NOTCH2NL gene mutations, while gene alterations in the PI3K/AKT signaling pathways were evident in cyclin D1-positive DLBCLs. Furthermore, a more pronounced variation in the MTOR gene was observed between cyclin D1-positive and negative patients. Notably, DLBCL patients with cyclin D1 expression frequently exhibited CDKN2A and CDKN2B gene deletions, known to regulate the cell cycle transition from G1 to S phase in tumors. Conclusion: Cyclin D1-positive DLBCL patients exhibited aggressive clinical behavior and inferior survival outcomes compared to DLBCL patients without cyclin D1 expression. NGS studies revealed a potential association between cyclin D1 expression and abnormal cell cycle transition and AKT pathway activation. These findings support the existence of a diagnostically challenging “gray zone” of DLBCL associated with cyclin D1 expression.

High-dose chemotherapy with transplantation of autologous hematopoietic stem cells in the first line of follicular lymphoma therapy

   Introduction. The follicular lymphoma (FL) is the most common indolent lymphatic tumor with high sensitivity to immunochemotherapy un most cases. Although overall survival (OS) is generally long, the disease is characterized by multiple relapses. High-dose chemotherapy (HDCT) with transplantation of autologous hematopoietic stem cells (auto-HSCT) is used for recurrent FL.   Aim: to evaluate the efficacy and safety of HDCT with aHSCT in the first line of FL therapy; identify risk factors for disease progression and refractoriness.   Material and methods. A prospective single-center study (conducted from May 2015 to January 2023) included 35 patients aged 18–65 years (median 43) with PL 1–3A grade t(14;18)+ with stages III–IV or stage II with bulky, having at least one criterion for the need to start therapy (according to GELF). Patients were treated according to the FL-2015 protocol: 4 R-CHOP, 2 R-DHAP and BeEAM with auto-HSCT. The primary endpoint was the rate of overall response (OR) and/or complete remission (CR) at the end of chemotherapy. Secondary end points were 3-year survival rates: OS, relapse-free survival (RFS), progression-free survival (PFS), and event-free survival (EFS). Minimal residual disease (MRD) in blood and/or bone marrow was assessed by PCR based on immunoglobulin heavy chain (IGH) gene rearrangements and/or BCL2::IGH rearrangements. Statistical analysis (by intent to treat) was performed on January 12, 2023.   Results. 86 % of patients had stage IV tumor and 79 % had 3–5 FLIPI factors. After the end of treatment, OR and PR were 90 % and 90 %, the incidence of POD24 was 3 %. After the end of induction (4 courses of R-CHOP), MRD-negativity was achieved in 77 % and 53 % of patients as determined by PCR-IGH and BCL2::IGH. After the full completion of the FL-2015 protocol, MRD was not detected in 96 % of patients (according to PCR-IGH). Three-year overall survival, disease-free survival, progression-free survival and event-free survival were respectively: 90 %, 90 %, 95 % and 85 % (with the same standarderror of 9 %) at a median follow-up (by inverse Kaplan-Meier estimate) of 19 months (range: from 1 to 91 months) There were no deaths due to early toxicity within 100 days of auto-HSCT. Prognostically unfavorable independent statistically significant (р < 0.01; Wald test; hazard ratio > 1) predictors of progression and refractoriness according to the results of multivariate analysis using the Fine-Grey competing risk model (р = 0.052 for the model) were: bone marrow disease, ECOG high risk, patient age > 50 years, stage 4 disease, elevated serum lactate dehydrogenase and B-symptoms.   Conclusion. The use of HDCT with auto-HSCT in the first line in patients with FL is highly effective and can significantly reduce the incidence of POD24 and early mortality from the tumor. The study is ongoing.

Comparative analysis of clinicopathologic characteristics and prognosis between nasal and nonnasal extranodal NK/T-cell lymphoma.

The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the underlying features responsible for these differences are not well clarified especially in the era of asparaginase therapy. In total, 1007 newly diagnosed ENKTL patients from 11 medical centers were included in this study. Clinicopathologic characteristics and survival data were collected. The chi-squared test and Kruskal-Wallis test were utilized for the comparison of different groups. Univariable and multivariable Cox proportional hazards models were used to screen prognostic factors. Overall, 869 (86.3%) patients were nasal forms. Compared to patients with nasal ENKTL, nonnasal patients were at more advanced stages and had poor performance status, bone marrow involvement, elevated serum lactate dehydrogenase (LDH), and CD56-negative status (p < 0.05). The 5-year overall survival (OS) for nasal and nonnasal patients were 65.6% and 45.0%, respectively. The OS of nasal forms patients were superior to nonnasal patients, especially in Eastern Cooperative Oncology Group performance status (ECOG PS) (≥2), advanced stage, KPI (HIR/HR), IPI (HIR/HR), PINK (HR), and high EBV DNA load groups. In patients treated with pegaspargase/L-asparaginase-based regimens, the OS of nasal patients was better than that of nonnasal patients. After adjusting the covariates of age, stage, ECOG PS score, LDH, B symptoms, and BM involvement, results showed that the nonnasal site was associated with poor survival of ENKTL. The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.

Relationship between serum lactate dehydrogenase levels and prognosis in patients infected with omicron and delta variants of COVID-19: A cross-sectional study

Determining the prognosis of COVID-19 is crucial for understanding disease trends and developing effective treatment strategies, particularly for severe cases. However, there is currently insufficient evidence regarding the role of lactate dehydrogenase (LDH) in COVID-19 and its prognostic implications. This retrospective cross-sectional study analyzed data from all patients hospitalized at Urmia Imam Khomeini Hospital between September 2021 and March 2023 with a diagnosis of COVID-19 involving the Delta and Omicron variants. Patient information, including age, sex, duration of hospitalization, admission to the intensive care unit (ICU), strain type, and outcomes, was extracted. Exclusion criteria encompassed myocardial infarction, lung, liver, blood, skeletal muscle diseases, injury, neoplasm, pancreatitis, pregnancy, poisoning, unwillingness to participate in the study, and the use of ascorbic acid. A total of 609 patients with an average age of 54.80 years were included in this study. Among these patients, 56.3% were female, and the mortality rate was 20.7%. The serum LDH levels were significantly higher in patients who succumbed to the disease (P < 0.001), those requiring ICU admission (P < 0.001), and female patients (P = 0.02) compared to other groups. Furthermore, the LDH serum levels exhibited a strong significant correlation with the duration of hospitalization (r = −0.11, P = 0.007). The results revealed that there is a difference in the mean serum LDH levels between deceased patients and discharged patients (P < 0.001). The findings indicate that elevated serum LDH levels are associated with increased mortality, prolonged hospitalization, ICU admission, and infection with the Delta variant of COVID-19.

Elevated serum lactate dehydrogenase to albumin ratio is a useful poor prognostic predictor of nivolumab in patients with non-small cell lung cancer.

This study aimed to evaluate the prognostic significance of the LDH-to-albumin ratio (LAR) in patients with non-small cell lung cancer (NSCLC) receiving nivolumab monotherapy. We comprehensively analyzed the associations between LAR and clinical parameters, progression-free survival (PFS), and overall survival (OS) to identify reliable biomarkers for treatment selection. A total of 144 patients with metastatic NSCLC treated with nivolumab were included. Patient characteristics, including demographic data, smoking history, albumin, lactate dehydrogenase (LDH) levels, and LAR were recorded. Univariate and multivariate analyses were conducted to determine the associations between these factors and PFS/OS. The LAR cut-off value was determined using receiver-operating characteristics (ROC) curve analysis. The median overall survival was 14.2 months, and the median progression-free survival was 5.28 months. Univariate analysis showed that smoking, ECOG performance score, brain metastasis, PD-L1 level, nivolumab treatment line, albumin, hemoglobin, LDH levels, platelet count, monocyte count, lymphocyte count, and LAR were associated with PFS. In the multivariate analysis, only LAR remained significantly associated with PFS. For overall survival, smoking, ECOG performance score, albumin level, LDH level, platelet count, monocyte count, lymphocyte count, brain metastasis, LAR, nivolumab treatment line, and PD-L1 level were significant in the univariate analysis. Albumin level, ECOG performance score, and LAR were independently associated with overall survival in the multivariate analysis. The LAR, reflecting tumor burden, tumor hypoxia, immune response, nutritional status, and systemic inflammation, emerged as a potential prognostic biomarker in NSCLC receiving nivolumab monotherapy. This study highlights the importance of considering multiple factors in treatment decisions and supports the need for personalized approaches in NSCLC immunotherapy. Further research is needed to validate the utility of LAR as a predictive biomarker in this patient population.

Acute bilateral renal infarction after left upper pulmonary lobectomy: a case report

BackgroundLeft upper lobectomy (LUL) is considered a risk factor for thrombus formation in the pulmonary vein stump compared with other lobectomies, and it occurs in 11.7–13.5% of cases. Although cerebral infarction after LUL has been reported in many articles, reports of bilateral renal infarction after lobectomy are rare.Case presentationA 70-year-old male patient was admitted to our hospital with a diagnosis of lung cancer. The nodule’s diameter was 2.5 cm on computed tomography, and it was diagnosed as a non-small cell lung carcinoma by a bronchoscopic biopsy. The clinical stage was cT1c N0M0 (c-stageIA3). The patient underwent thoracoscopic LUL and systemic lymph node dissection. No complications were observed during the operation, and the immediate postoperative period was uneventful until postoperative day 3. On postoperative day 4, he experienced fever, abdominal pain, and nausea, which spontaneously resolved. Laboratory data showed an elevated white blood cell count, and elevated serum lactate dehydrogenase and creatinine concentrations. Contrast-enhanced computed tomography from the thorax to the pelvic cavity showed a partial defect of the bilateral kidneys. We diagnosed the patient with bilateral renal infarction. ConclusionsBilateral renal infarction after lobectomy is a rare and serious condition, which should be diagnosed as early as possible. Since all cases of reported renal infarctions occurred after LUL, special attention should be paid to postoperative management after performing LUL.

POSTER: AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

POSTER: AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

Efficacy of induction chemotherapy in lymph node-positive stage III nasopharyngeal carcinoma and identification of beneficiaries based on clinical features: A propensity score matching analysis

PurposeTo investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). MethodsIn total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. ResultsAfter 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2–3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0–1 CNN. For patients with grade 0–1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). ConclusionAdding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0–1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan.

Study to Determine Correlation of Elevated Serum Creatine Kinase-Muscle Brain Fraction (CK-MB) and Lactate Dehydrogenase (LDH) Levels with Asphyxia Neonatorum and Severity of Hypoxic Ischaemic Encephalopathy

Background: Asphyxia Neonatorum is a significant contributor to neonatal mortality and morbidity. Its burden in resource-poor countries prompts the development of investigative modalities that offers accuracy and affordability. Objective: To determine that serum CK-MB and LDH estimation could be markers of Asphyxia neonatorum, and the elevated levels directly correlate with the grade of severity of Hypoxic Ischemic Encephalopathy (HIE) as defined by Levine. Methods: In this single-center, non-interventional study, we included 100 asphyxiated neonates from level III NICU in the case group, and 100 apparently healthy neonates from the post-natal ward admitted over 18 months at RCSM Government Medical College and CPR Hospital, Kolhapur. 100 healthy neonates were the control group. Results: The median 8-hr serum CK-MB in the case group was 74 U/L and in the control group as 63.5 U/L with P&lt;0.001. Whereas the median serum LDH level in the case group was 597 U/L and the control group was 383.5 U/L with P&lt;0.001. Raised LDH (cut off 580 U/L) had 100% specificity, while CK-MB (cut off 92.6 U/L) had 100% specificity for asphyxia. Amongst the neonates with HIE (n=60), 56% had raised CK-MB (cut off 92.6) and 80% had raised LDH (cut off 580 U/L). 100% of neonates with HIE Grade III (n=9) had elevated CK-MB and LDH levels. Conclusion: The present study concluded that CK-MB and LDH as biochemical markers can be utilitarian in the diagnosis of perinatal asphyxia.

[Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning].

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Treatments and outcomes of patients with localized extranodal NK/T-cell lymphoma (ENKL) diagnosed between 2014 and 2021: A cooperative study in Japan.

7565 Background: A previous cooperative study of patients (pts) with ENKL who were diagnosed between 2000 and 2013 in 31 institutes in Japan reported that the most common first-line treatment for localized ENKL was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%). The 2-year (yr) overall survival (OS) and progression-free survival (PFS) of pts with localized ENKL were 78% and 68%, respectively (JCO 2017). RT-DeVIC has been included as a preferred regimen of combined modality therapy in the NCCN guidelines. The treatments and outcomes of pts with localized ENKL in recent clinical practice are unknown. Methods: We conducted a cooperative study (NKEA-Next; UMIN000046300) by hemato-oncologists and radiation oncologists of pts with ENKL who were diagnosed between 2014 and 2021 in 45 institutes in Japan. The results were compared with those from the 2000-2013 cohort (JCO 2017). The primary endpoint was OS of pts with ENKL who received next-generation treatment in 2014-2021 at participating institutes. We analyzed the data of localized ENKL. Results: Of 351 pts in the 2014-2021 cohort, 235 (67%) had localized ENKL. First-line therapy was RT-DeVIC in 185 (79%) pts, sequential chemoradiotherapy in 17, RT alone in 15 pts, and chemotherapy alone in 12 pts. Six pts received no treatment due to poor performance status (PS). Only two pts (1%) received anthracycline-containing regimens. With a median follow-up of 3.4 yrs, the 2-yr OS and PFS of localized ENKL were 83% and 75%, respectively. Pts treated with RT-DeVIC showed the following clinical features: median age, 58 yrs (range, 13-82); age &gt; 60 yrs, 45%; stage IIE, 34%; B symptoms present, 27%; elevated serum lactate dehydrogenase, 23%; ECOG PS 2, 4%; and soluble interleukin-2 receptor (sIL-2R) level &gt; upper limit of normal (ULN), 31% (57/183). The complete response rate was 88% among the 179 pts who were evaluated for response. The 2-yr OS and PFS of RT-DeVIC were 87% and 79%, respectively. There was no treatment-related death due to RT-DeVIC. G3/4 mucositis was recorded in 32% (G3, n = 59; G4, n = 0). G3/4 febrile neutropenia occurred in 18% (G3, n = 32; G4, n = 2). sIL-2R &gt; ULN was associated with worse OS ( P &lt; 0.01). In comparison with pts with localized disease in the 2000-2013 cohort, pts in the 2014-2021 cohort received RT-DeVIC more frequently ( P &lt; .001). There was no significant difference in OS ( P = 0.24) or PFS ( P = 0.10) between the two cohorts. Conclusions: RT-DeVIC was more frequently used for first-line treatment of localized ENKL, and its efficacy has been maintained, with 87% 2-yr OS in recent clinical practice in Japan, providing further evidence of RT-DeVIC as a preferred first-line regimen for localized ENKL. No obvious improvement in OS and a reduction in G3 mucositis were observed, suggesting that more efficacious and less toxic regimens need to be introduced.