Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Carcinogenic mechanisms of virus-associated lymphoma.

The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus to clarify the current status of basic information and recent advances in the development of virus-associated lymphomas.

Advances in the treatment of relapsed/refractory marginal zone lymphoma.

Marginal zone lymphoma (MZL) is the second most common subtype of inert B-cell non-Hodgkin's lymphoma, accounting for 5-15% of non-Hodgkin's lymphoma cases. Patients with MZL have a long survival period, with a median survival of >10 years, and patients treated with a combination of anti-CD20 monoclonal antibody can achieve an overall effective rate of 81%. However, 20% of patients with MZL show relapse or experience disease progression within 2 years, with a median survival of only 3-5 years. Currently, the treatment options for patients with relapsed/refractory (R/R) MZL are limited, underscoring the pressing need for novel therapeutic drugs. The advent of novel anti-CD20 monoclonal antibodies, small molecule kinase inhibitors, immunomodulators, and other therapeutic strategies has ushered in a new era in the treatment of R/R MZL. Our objective is to summarize the existing treatment strategies, including immunotherapy and the emergent targeted therapies, and to evaluate their effectiveness and safety in the management of R/R MZL. By doing so, we aim to provide a clear understanding of the therapeutic landscape for R/R MZL, and to guide future research directions toward improving the prognosis and quality of life for patients afflicted with this challenging disease.

Hepatitis B surface antigen positivity is associated with poor short- and long-term outcomes in patients with diffuse large B-cell lymphoma who received CHOP or R-CHOP.

Objective: The development of diffuse large B-cell lymphoma (DLBCL) is closely related to the host infection status. China is a highly endemic area for hepatitis B virus (HBV) infection. It is not clear whether HBV infection has a consistent effect on the prognostic implications of patients with DLBCL in different treatment settings. Materials and methods: We conducted a cohort study of 692 patients with DLBCL receiving three or more cycles of treatment with a CHOP or R-CHOP regimen from the First Hospital of Jilin University between July 2011 and July 2022. The patients were divided into two groups based on their hepatitis B surface antigen (HBsAg) status: HBsAg-positive (n = 84, 12.1%) and HBsAg-negative (n = 608, 87.9%) groups. Tumor specimens from 180 patients with primary DLBCL were collected for next-generation sequencing (NGS). Results: The HBsAg-positive group had more frequent abnormal liver function (P = 0.003), hypoalbuminemia (P < 0.001), incidence of > 2 extranodal organs (P = 0.011), and spleen involvement (P < 0.001) than the HBsAg-negative group. HBsAg-positive patients had lower complete response (CR) and overall response rates (ORR) rates (all the p values < 0.05), in either the CHOP group or R-CHOP group. Among patients receiving R-CHOP, the rates of disease progression within 12 and 24 months were higher in the HBsAg-positive group than in the HBsAg-negative group (P=0.018, P=0.029). However, no significant difference in disease progression was observed between HBsAg-positive and HBsAg-negative patients in the CHOP group(P > 0.05). HBsAg positivity (OS: HR [95% CI] = 2.511 [1.214-5.192], P = 0.013) was only associated with poorer OS in the CHOP group. Whereas in the R-CHOP group, HBsAg positivity was associated with both poorer OS and PFS (OS: HR [95% CI] = 1.672 [1.050-2.665], P = 0.030; PFS: HR [95% CI] = 1.536 [1.013-2.331], P = 0.043). Additionally, HBsAg-positive patients with DLBCL also had a higher prevalence of mutations in MYC, ATM, PTPN6, and epigenetically regulated genes. Conclusion: These findings suggest that HBsAg-positive DLBCL patients may represent a distinct subgroup with a poorer prognosis. The standard therapies may be insufficient and new therapeutic strategies should be developed based on a better understanding of the underlying mechanisms of chemoresistance.

Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Marriage of a Dual-Plasmonic Interface and Optical Microfiber for NIR-II Cancer Theranostics.

The use of light as a powerful tool for disease treatment has introduced a new era in tumor treatment and provided abundant opportunities for light-based tumor theranostics. This work reports a photothermal theranostic fiber integrating cancer detection and therapeutic functions. Its self-heating effect can be tuned at ultralow powers and used for self-heating detection and tumor ablation. The fiber, consisting of a dual-plasmonic nanointerface and an optical microfiber, can be used to distinguish cancer cells from normal cells, quantify cancer cells, perform hyperthermal ablation of cancer cells, and evaluate the ablation efficacy. Its cancer cell ablation rate reaches 89% in a single treatment. In vitro and in vivo studies reveal quick, deep-tissue photonic hyperthermia in the NIR-II window, which can markedly ablate tumors. The marriage of a dual-plasmonic nanointerface and an optical microfiber presents a novel paradigm in photothermal therapy, offering the potential to surmount the challenges posed by limited light penetration depth, nonspecific accumulation in normal tissues, and inadvertent damage in current methods. This work thus provides insight for the exploration of an integrated theranostic platform with simultaneous functions in cancer diagnostics, therapeutics, and postoperative monitoring for future practical applications.

B-cell prolymphocytic leukemia with P53 abnormalities successfully treated with bendamustine and rituximab: a report of three cases.

Background: B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell tumor with an aggressive clinical course and poor prognosis. It is characterized by prominent splenomegaly and prolymphocytes exceeding 55% of the lymphoid cells in the blood. Purine analog-based chemo-immunotherapy is the first-line therapy for B-PLL. Owing to its rarity, there are few reports on the efficacy of bendamustine and rituximab (BR) regimen. Our study presents three cases of BR being effective in the treatment of B-PLL and provides experience for clinical treatment. Case Description: This report describes the cases of three male patients (median age: 66 years old) who initially presented with abdominal discomfort. Physical examinations and imaging revealed splenomegaly, while a peripheral blood (PB) smear revealed a prolymphocyte count exceeding 70% of the lymphoid cells. Therefore, the three patients were diagnosed with B-PLL. Further molecular detection showed that they harbored P53 abnormalities (17p deletion/TP53 mutation) associated with resistance to conventional chemotherapies. In addition, one of the patients had a highly complex karyotype and multiple gene mutations. All patients underwent four cycles of BR, and two of them received two further cycles of rituximab monotherapy. Ultimately, the patients achieved a complete response (CR) that lasted for 25, 33, and 34 months, respectively, with a median follow-up time of 34 months. The adverse events of the BR mainly included a grade 3 haematological toxicities. Also, the treatment was well-tolerated. Conclusions: This case series suggests that BR regimen is promising for bringing deep remission to patients with B-PLL. Prospective trials are still required for further elucidation.

HBV-associated DLBCL of poor prognosis: advance in pathogenesis, immunity and therapy.

Advanced studies have shown a biological correlation between hepatitis B virus (HBV) and B-cell lymphoma, especially diffuse large B-cell lymphoma (DLBCL). Patients with DLBCL infected with HBV (HBV-associated DLBCL) are clinically characterized by an advanced clinical stage, poor response to front-line immunochemotherapy regimens, and worse clinical prognosis. HBV-associated DLBCL often exhibits abnormal activation of the nuclear factor kappa B pathway as well as mutations in oncogenes, including Myc and BCL-6. Currently, there is no consensus on any specific and effective treatment for HBV-associated DLBCL. Therefore, in this review, we comprehensively and mechanistically analyzed the natural history of HBV infection and immunity, including HBV-mediated oncogenes, immune escape, epigenetic alterations, dysregulated signaling pathways, and potential therapeutic approaches for HBV-associated DLBCL. We hope that an improved understanding of the biology of HBV-associated DLBCL would lead to the development of novel therapeutic approaches, enhance the number of effective clinical trials, and improve the prognosis of this disease.

Compact optical fiber photoacoustic gas sensor with integrated multi-pass cell.

Optical fiber acoustic sensors with miniature size and high sensitivity are attractive to develop compact photoacoustic spectroscopy. Here, a compact photoacoustic gas sensor was demonstrated by utilizing a diaphragm-based fiber-optic Fabry-Perot cavity as both the acoustic sensor and the multipass cell. A nanoscale graphite film was used as the flexible diaphragm to increase the acoustic sensitivity of the Fabry-Perot cavity and the cavity inner surface was coated with highly-reflective Au film to form a multipass cell for amplification of the photoacoustic signal. With a laser power of 20 mW at 1532.8 nm, the sensor demonstrated a low detection limit of ∼ 50 ppb for C2H2 gas with an integration time of ∼ 100 s. The optical fiber photoacoustic gas sensor with a millimeter-scale diameter and ppb-level detection limit is promising for trace gas sensing in various areas including industrial process and environmental monitoring.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

Clinical features and prognosis of double primary malignant neoplasms in patients with non-hodgkin lymphoma.

To investigate the clinical features, survival, and prognostic factors of patients with double primary malignant neoplasms (DPMNs) comprising non-Hodgkin lymphoma (NHL) and malignant solid tumors. Of the 2352 patients diagnosed with NHL, 105 (4.46%) patients were diagnosed with DPMNs, 42 (40.0%) had NHL first (the NHL-first group) and 63 (60.0%) had solid tumor first (the ST-first group). Females were more frequent in the ST-first group, and the interval time between the two tumors was longer. More NHLs in early stages and originating from extranodal sites were observed in the NHL-first group. Male, age ≥ 55 years at diagnosis of the first tumor, interval time <60 months, NHL diagnosed first, NHL arising from an extranodal site, DPMNs without breast cancer, and no surgery for the first primary tumor were associated with poorer overall survival (OS). Interval time <60 months and NHL diagnosed first were independent risk factors that affected the prognosis of patients with DPMNs. Therefore, careful monitoring and follow-up are especially important for these patients. 50.5% (53/105) of patients with DPMNs did not receive chemotherapy or radiotherapy prior to the diagnosis of the second tumor. We further compared the baseline characteristics of diffuse large B-cell lymphoma(DLBCL) patients with and without solid tumors, the former had a higher proportion of extranodal DLBCL, suggesting that extranodal DLBCL is more likely to develop solid tumors than nodal DLBCL.

Etoposide, dexamethasone, and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma: A randomized phase III study.

Methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). We explored the efficacy and safety of reduced-intensity, non-intravenous etoposide, dexamethasone, and pegaspargase (ESA) with sandwiched radiotherapy. This multicenter, randomized, phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China. Patients were randomly assigned (1:1) to receive ESA (pegaspargase 2,500 IU/m2 intramuscularly on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2-4) or MESA (methotrexate 1 g/m2 intravenously on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2-4, and pegaspargase 2,500 IU/m2 intramuscularly on day 5) regimen (four cycles), combined with sandwiched radiotherapy. The primary endpoint was overall response rate (ORR). The non-inferiority margin was -10.0%. From March 16, 2016, to July 17, 2020, 256 patients underwent randomization, and 248 (ESA [n = 125] or MESA [n = 123]) made up the modified intention-to-treat population. The ORR was 88.8% (95% confidence interval [CI], 81.9-93.7) for ESA with sandwiched radiotherapy and 86.2% (95% CI, 78.8-91.7) for MESA with sandwiched radiotherapy, with an absolute rate difference of 2.6% (95% CI, -5.6-10.9), meeting the non-inferiority criteria. Per-protocol and sensitivity analysis supported this result. Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma.

BACKGROUND: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed. METHODS: The gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated. RESULTS: In human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages. CONCLUSION: S1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis.

Second primary malignancies in non-Hodgkin lymphoma: epidemiology and risk factors.

With the advancements in therapeutics for non-Hodgkin lymphoma (NHL), the long-term survival of patients with NHL has markedly increased. Second primary malignancies (SPMs) have become an increasingly relevant long-term concern for NHL survivors. The etiology of SPMs is multifactorial and involves multiple steps. Germline alterations, immune dysregulation, and clonal hematopoiesis contribute to the accumulation of intrinsic adverse factors, and external factors such as lifestyle; exposure to infectious factors; and late effects of radiotherapy, chemotherapy, high-dose therapy, and autologous hematopoietic stem cell transplantation further increase SPM risk. Therapy-related myeloid neoplasms (t-MNs) are a devastating complication of cytotoxic chemotherapeutic agents. However, as targeted therapies begin to replace cytotoxic chemotherapy, the incidence of t-MNs is likely to decline, particularly for indolent B-cell NHL.

Mechanism of action and therapeutic targeting of CD30 molecule in lymphomas.

At present, the treatment of lymphoma has entered the era of precision medicine, and CD30, as a transmembrane protein, has become an important marker to help the diagnosis and formulation of treatment plans for lymphomas. This protein is widely expressed in various types of lymphomas and can play a role through nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and other pathways, and ultimately lead to the up-regulation of CD30 expression to give tumor cells a survival advantage. Brentuximab vedotin (BV), as an antibody-drug conjugate (ADC) targeting CD30, is one of the first new drugs to significantly improve survival in patients with CD30+lymphomas. However, the biological function of CD30 has not been fully elucidated. Therefore, this review highlights the CD30-mediated tumor-promoting mechanisms and the molecular factors that regulate CD30 expression. We hope that a better understanding of CD30 biology will provide new insights into clinical treatment and improve the survival and quality of life of lymphoma patients.

Dysregulation of FBW7 in malignant lymphoproliferative disorders.

The ubiquitin-proteasome system (UPS) is involved in various aspects of cell processes, including cell proliferation, differentiation, and cell cycle progression. F-box and WD repeat domain-containing protein 7 (FBW7), as a key component of UPS proteins and a critical tumor suppressor in human cancers, controls proteasome-mediated degradation by ubiquitinating oncoproteins such as c-Myc, Mcl-1, cyclin E, and Notch. It also plays a role in the development of various cancers, including solid and hematological malignancies, such as T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma. This comprehensive review emphasizes the functions, substrates, and expression of FBW7 in malignant lymphoproliferative disorders.

Optical-resolution functional gastrointestinal photoacoustic endoscopy based on optical heterodyne detection of ultrasound.

Photoacoustic endoscopy shows promise in the detection of gastrointestinal cancer, inflammation, and other lesions. High-resolution endoscopic imaging of the hemodynamic response necessitates a small-sized, high-sensitivity ultrasound sensor. Here, we utilize a laser ultrasound sensor to develop a miniaturized, optical-resolution photoacoustic endoscope. The sensor can boost the acoustic response by a gain factor of ωo/Ω (the frequency ratio of the signal light and measured ultrasound) by measuring the acoustically induced optical phase change. As a result, we achieve a noise-equivalent pressure density (NEPD) below 1.5 mPa·Hz-1/2 over the measured range of 5 to 25 MHz. The heterodyne phase detection using dual-frequency laser beams of the sensor can offer resistance to thermal drift and vibrational perturbations. The endoscope is used to in vivo image a rat rectum and visualize the oxygen saturation changes during acute inflammation, which can hardly be observed with other imaging modalities.

Epigenetic regulation of cutaneous T-cell lymphoma is mediated by dysregulated lncRNA MALAT1 through modulation of tumor microenvironment.

Cutaneous T-Cell Lymphoma (CTCL) is a rare non-Hodgkin lymphoma marked by migration of T-lymphocytes to the skin. It has many subtypes some of which are aggressive with documented metastasis. We investigated a possible role of lncRNA MALAT1 in CTCL cells because of its documented involvement in cancer metastasis. A screening of MALAT1 in CTCL patients revealed its elevated levels in the patients, compared to healthy individuals. For our investigation, we employed HH and H9 CTCL cells and silenced MALAT1 to understand the MALAT1 mediated functions. Such silencing of MALAT1 resulted in reversal of EMT and inhibition of cancer stem cell phenotype, along with reduced cell growth and proliferation. EMT reversal was established through increased E-cadherin and reduced N-cadherin while inhibition of cancer stem cell phenotype was evident through reduced Sox2 and Nanog. CTCL patients had higher circulating levels of IL-6, IL-8, IL-10, TGFß, PGE2 and MMP7 which are factors released by tumor-associated macrophages in tumor microenvironment. MALAT1 sponged miR-124 as this tumor suppressive miRNA was de-repressed upon MALAT1 silencing. Moreover, downregulation of miR-124 attenuated MALAT1 silencing effects. Our study provides a rationale for further studies focused on an evaluation of MALAT1-miR-124 in CTCL progression.

Improving the prognostic ability of PET/CT SUVmax to identify follicular lymphoma with early treatment failure.

Follicular lymphoma (FL) has a high degree of heterogeneity both clinically and molecularly. Early treatment failure (ETF), progression or relapse within 24 months of frontline immunochemotherapy is associated with a poor prognosis in FL. However, the clinical utility of ETF at diagnosis is limited. The maximum standardized uptake value (SUVmax) is a metabolic parameter for positron emission tomography/computed tomography (PET/CT); nevertheless, the relationship between SUVmax and ETF remains unclear. Thus, identifying early biomarkers that incorporate SUVmax and other clinical correlative variables could be helpful in identifying patients at high risk of ETF. A nomogram consisted of three independent variables, including SUVmax ≥ 12, beta-2 microglobulin > 3 mg/L, and Ki67 > 40%, was established to predict ETF in 127 patients with grade 1, 2, or 3a FL from the First Hospital of Jilin University (training cohort) and was validated using data from the Duke University Medical Center (validation cohort, n=95). The nomogram demonstrated prognostic accuracy in predicting ETF (sensitivity 70.8% and specificity 83.5% in the training cohort; sensitivity 84.2% and specificity 68.4% in the validation cohort). The patients were stratified into three groups: low-, intermediate-, and high-risk. In the training cohort, the corresponding 5-year progression-free survival (PFS) rates were 81.7%, 73.4%, and 34.9%, and the 5-year overall survival (OS) rates were 97.4%, 87.4%, and 62.3%, respectively. In the validation cohort, the 5-year PFS rates were 77.7%, 52.9%, and 34.8%, and the 5-year OS rates were 96.4%, 94.1%, and 73.7%, respectively. This was the first study to use a nomogram with SUVmax to predict ETF in FL to identify a subset of patients who might benefit from individualized targeted therapy.