Treatment Of Lymphoma Patients Research Articles

Progression and application of circulating tumor DNA in lymphoma

Lymphomas are a highly heterogeneous group of tumors that are classified into several subtypes. The gold standard method for the molecular profiling of lymphoma is based on invasive lymph node or tissue biopsy. However, this method cannot accurately capture spatial tumor heterogeneity in each patient as well as systemic tumor invasion and tumor burden. Circulating tumor DNA (ctDNA) is an emerging and highly versatile biomarker that overcomes the basic limitations of imaging scanning and tissue biopsy; has the characteristics of being simple, rapid, and non-invasive; and has good specificity and high sensitivity. ctDNA testing has been applied to a variety of subtypes of lymphoma and has been used for somatic mutation genotyping, efficacy monitoring during treatment, detection of minimal residual disease, and the prediction of survival, which may help clinicians make better clinical decisions in the diagnosis and treatment of lymphoma patients. Furthermore, this study also aims to review the different methods of ctDNA analysis and describe the specific applications of ctDNA in different lymphoma subtypes.

Evolution of Radiation Fields from Involved Field to Involved Site—A Summary of the Current Guidelines by the International Lymphoma Radiation Oncology Group

Radiation therapy has been proven to be highly effective in the treatment of lymphoma. With increasing rates of long-term survival, the reduction in toxicity has gained importance. The evolving understanding of the diseases’ biology, as well as technical and conceptual advances, allows for a precise and individualized application of irradiation. Smaller treatment fields and safety margins make it possible to spare healthy neighbouring tissue (organs at risk). The International Lymphoma Radiation Oncology Group (ILROG) has developed several guidelines to optimize radiotherapy treatment in lymphoma patients. Since its introduction in 2013, involved site radiotherapy (ISRT) has been adopted as the standard of care in most treatment regimens in adult lymphoma. This article serves as a summary of the current ILROG guidelines, also considering contemporary developments and possible future directions.

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients

BackgroundChimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy.MethodWe searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated.ResultsWe analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06–0.39, I2 = 0.37%), 27% (95% CI 0.03–0.60, I2 = 60.43%) and 65% (95% CI 0.23–0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08–0.99, I2 = 85.20%), 47% (95% CI 0.14–0.81, I2 = 74.17%), 59% (95% CI 0.27–0.89, I2 = 60.23%), and 50% (95% CI 0.13–0.87, I2 = 73.89%), respectively.ConclusionCAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever.RegistrationThe protocol was registered in prospero, with the registration number CRD42022342647.

Comparative Efficacy and Safety of Beam and Team Conditioning Regimens for Autologous Stem Cell Transplantation in Lymphoma Patients

Conditioning regimens with high-dose chemotherapy and autologous stem cell transplantation (ASCT) are the mainstays of treatment in lymphoma patients. Although the most frequently used conditioning regimen is the BEAM regimen (Carmustine, Etoposide, Cytarabine, and Melphalan), and alternatives are also used in certain circumstances. The TEAM regimen (carmustine is substituted by the alkylating agent thiotepa) is one of these alternatives; however, data regarding the comparisons of efficacy and safety profiles of these 2 regimens is scarce. This study compared the outcomes of patients who received conditioning regimens with BEAM and TEAM and underwent an ASCT. This study was conducted as a retrospective assessment of 294 patient outcomes in terms of efficacy and safety. Adult patients with lymphoma diagnosis who received BEAM or TEAM conditioning regimens and underwent an ASCT between January 1, 2016 and December 31, 2019 were included in the analyses. A total of 294 patients (median age at ASCT: 50 years, males: 60.5%, diffuse large B-cell lymphoma: 35%) were included. Eighty patients (27.2%) received the TEAM regimen, and 214 (72.8%) received the BEAM regimen. Regarding safety profiles, the thrombocyte engraftment time was significantly higher in the TEAM group (P=.003) and fever of unknown etiology was significantly higher in the BEAM group (P=.042). Also, nausea was more in the TEAM group (P=.031). The complete remission rate was 57.5% and 70.3% in the TEAM and BEAM regimens, respectively. The overall mortality rate was 37.3% and not significantly different between the groups (43% and 35% in the TEAM and BEAM groups, P=.22) over a similar median follow-up of 1667 days (P=.28). The 3-year survival rate was 66% and 67% and the 5-year survival rate was 52% and 58% in the TEAM and BEAM regimens, respectively, without significant difference. To the best of our knowledge, this is one of the few studies in the literature that compared the TEAM and BEAM as conditioning regimens for ASCT in lymphoma patients. The 2 regimens may provide similar overall survival outcomes and have a comparable safety profile. Although the BEAM regimen may be associated with longer progression-free survival times, the difference may be covered by the similar survival after ASCT.

CAR T Cells and Their Immune Environment Synergize to Shape Distinct Immune Profiles in Response Versus Toxicity in B Cell Lymphoma Patients

Genetically engineered CD19-redirected chimeric antigen receptor T (CAR T) cells represent a breakthrough immunotherapy for B cell malignancies. However, response rates are variable and many patients face life-threatening side effects such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). The impact of the patient's immune landscape as a whole - consisting of CAR T cells and non-CAR T immune cells - on patients' outcome is largely unknown. Furthermore, reliable biomarkers to predict response and toxicity are lacking. To decode the crosstalk of CAR T cells and their circulating immune environment, we used longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided computational analysis of 47 peripheral blood samples from 19 lymphoma patients, together with 6 healthy controls. Patient samples were harvested one day before (day -1) up to 104 days after CAR T infusion. The generated immune map, based on 69 parameters and 2078 extracted immune features, was enriched with numerous clinical parameters from the lymphoma patients, including response and toxicity data of a follow-up period ≥ 315 days. When comparing healthy controls and B cell lymphoma patient samples at baseline (day -1 and day 0, pre-CAR T infusion), the two cohorts demonstrated distinct immune profiles, including a strong lymphodepletion and proportional expansion of the myeloid/ dendritic cell fraction in lymphoma patients. Furthermore, this translational proteomics approach revealed a lymphoma patient-specific, heterogeneous CAR T cell population (Figure 1). However, most of the identified 13 CAR T subsets, such as γδ T cells and CD4 T regulatory cells next to naive/effector/memory T cell populations, appeared in each sample. The temporal composition of the CAR+ T population varied, presenting an inverse relationship over time with a bias of CD8 CAR T cells at early timepoints and dominating CD4 CAR T subsets later on. When stratifying the overall immune profile at the time of CAR T cell expansion and toxicities (day 9 to 21), immune alterations associated with response to CAR T therapy (best overall response complete remission (CR)) were primarily found in the non-CAR T immune compartments, while CRS- and ICANS-associated signatures affected predominantly the CAR T population (Figure 2; deregulated immune features: p < 0.5 and wilcoxon effect size > 0.6). In particular, higher expression of TCF1 in CD8 CAR T cells and EOMES in CD8 T stem cell memory (Tscm) cells - suggestive for stem-like features that allow expansion/long-term persistence - and CD223 (LAG3) in CD4 CAR T cells marked the immune profile of CR patients. The interplay of CAR T and non-CAR T immune alterations was even more striking in toxicity: both CRS and ICANS were linked to a dysbalance in the CD226/TIGIT-axis with higher expression of the co-stimulatory receptor CD226 together with its regulator EOMES in CD4 and CD8 CAR T cells, whereas the co-inhibitory and competing receptor TIGIT demonstrated reduced levels in several CAR T subsets as well as CD8 T central memory and Tscm cells. In line with the latter result, lower expression of the immune checkpoint CTLA-4 was detected in both CAR positive and negative unconventional T cells, indicating immunopathological signatures in CRS and ICANS are based on imbalanced activating/inhibitory receptor profiles. Supportive for a pivotal role of the immune environment in CAR T treated patients, stratifying immune signatures associated with patient outcomes were already detected pre-CAR-T-infusion (Figure 2). Towards clinical translation, these altered signatures affecting the T, NK and myeloid/dendritic cell compartment are further investigated and could serve as potential biomarkers predicting patient outcome. In-depth immune profiling of CAR T treated lymphoma patients allowed us to ultimately define the CAR T specific immune landscape and uncovered a synergy of CAR T and surrounding immune cells in stratifying immune profiles. These results could serve to delineate CAR T-based therapeutic strategies targeting the immunopathologic cascade, aimed to enhance anti-cancer activity and confine toxicity. . Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Left Atrium Involvement in Lymphoma Patients: Single Center Observational Study

Aim. To assess the structure and performance of left atrium (LA) before and after 3 cycles of anticancer treatment in lymphoma patients, as well as the incidences of supraventricular arrhythmia (SVA) and the levels of biomarkers of inflammation.Material and Methods. This is a prospective observational study of patients with confirmed diagnosis of lymphoma [n=23; 57% men; median age 52 (34;64) years], who had no prior polychemotherapy. The comparison group included persons without lymphoma [n=18; 50% men; median age 43 (37; 54) years] comparable with the main group in terms of sex, age and risk factors for cardiovascular diseases. Patients with lymphoma underwent 24h-ECG monitoring and advanced transthoracic echocardiography at baseline and after 3 cycles (within 3 months) of anticancer treatment. Biomarkers of inflammation were measured. The results were compared with the data of the comparison group.Results. In lymphoma patients, LA reservoir, conduit, and booster function were found to be impaired at baseline but were comparable with these in matched controls. After 3 cycles of anticancer treatment, a trend to reduction of LA booster and conduit strain was found. The proportion of those with SVA was significantly higher in lymphoma patients before chemotherapy compared to those after anti-cancer treatment or controls: 57% vs 10% and 33% respectively (p&lt;0.05). Lymphoma patients had a higher number of premature ventricular beats at baseline than after treatment or in control [183 (14;841) vs 38 (14;94) and 9 (4;38) respectively]. There were no associations found between the parameters of LA structure and function and SVA. Moderate positive correlation between ESR and supraventricular premature complexes was found (rS=0.44; p&lt;0.05). A positive correlation between LA contractile function and inflammatory biomarkers were revealed: LA active ejection fraction (LA EFact) and ESR (rS=0.42, p&lt;0.05); LA volume index and β-globulin (rS=0.43, p&lt;0.05); LA EFact and neuregulin-1β (rS=0.42, p&lt;0.05); LA expansion index and neuregulin-1β (rS=0.55, p&lt;0.05).Conclusions. In lymphoma patients, LA phasic strain parameters were impaired regardless of anticancer treatment. The associations between inflammatory biomarkers with SVA and parameters of LA performance were found.

P1225: SECONDARY PRIMARY MALIGNANCIES (SPM) AFTER HIGH-DOSE CHEMOTHERAPY (HDT) WITH AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) FOR LYMPHOMA: A DANISH NATIONWIDE COHORT STUDY

Background: High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) have resulted in more long-term lymphoma survivors. However, HDT-ASCT is potentially associated with an increased risk of secondary primary malignancies (SPM) leading to loss of lifetime for these patients. Aims: To investigate the risk and types of SPM in lymphoma patients treated with HDT-ASCT compared to the risk of malignancies in a matched background population and to explore risk factors for SPM in HDT-ASCT treated lymphoma patients. Methods: In a nationwide matched cohort study, The Danish Lymphoma Register was used to identify all adult patients treated with HDT-ASCT in Denmark between 2001-2017 for diffuse large B-cell lymphoma, Hodgkin lymphoma, peripheral T-cell lymphoma, or mantle cell lymphoma, excluding patients with other prior cancers. Patients were matched in a ratio of 1:5 to cancer-free comparators from the Danish background population. Malignancies were identified in the Danish National Patient Register using ICD-10 codes and compared between the two groups using the Aalen-Johansen estimator, Cox regression, and incidence rate ratios (IRRs). Results: A total of 856 HDT-ASCT treated lymphoma patients and 4,280 matched comparators were followed for a median of 8 years. The cumulative risk of SPM with death as competing risk was higher for patients compared to comparators with risks at 5, 10, and 15 years of 8.9% [95% confidence interval 6.9;11.0], 16.3% [13.3;19.3], and 20.1% [16.1;24.2] for patients compared to 4.8% [4.1;5.5], 10.5% [9.3;11.7], and 16.6% [14.6;18.5] for comparators (Fig. 1a). The crude hazard ratio (HR) of SPM among patients vs comparators was 2.26 [1.83;2.79]. After adjusting for sex, educational level (low/high), chronic obstructive pulmonary disease (COPD), and alcohol-related diseases (neurological, mental, cardiovascular, or chronic use), the HR was 2.50 [2.02;3.10]. Compared to comparators, patients had increased rates of non-melanoma skin cancer (IRR 3.47 [2.18;5.38]) and myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) (IRR 35.32 [15.73; 94.26]) (Table 1). Rates of other malignancies (oral, gastrointestinal, respiratory, breast, female- or male genital, urinary, soft tissue, and melanoma) were similar between the two groups. The 15-year cumulative risk of MDS/AML was 4.6% [2.8;6.3] for patients (Fig. 1c) and the median overall survival following secondary MDS/AML was only 7 months. In comparison, median overall survival was 40 months in a sex- and age matched background population with newly diagnosed MDS/AML (Fig. 1d). Risk factors for SPM in lymphoma patients were older age (HR 1.06 [1.04;1.08] per year) and COPD (HR 3.15 [1.16;8.57]). Prior therapy (number of lines, intensive chemotherapy, radiotherapy), time since diagnosis, Ann Arbor stage, performance status, alcohol-related disease, and education were not associated with SPM. Table 1. - Rates of SPM per 1,000 person-years in lymphoma patients and matched comparators Comparators Patients SPM type Rate Rate IRR IRR 95% CI Overall 11.35 24.77 2.18 1.76; 2.18 Hematological 0.45 7.74 17.05 9.5; 32.16 MDS/AML 0.18 6.41 35.32 15.73; 94.26 MDS 0.12 3.98 32.89 12.27; 113.84 AML 0.06 2.43 40.19 10.79; 259.78 Non-melanoma skin cancer 1.79 6.19 3.47 2.18; 5.38 Image:Summary/Conclusion: Lymphoma patients treated with HDT-ASCT have an increased risk of SPM compared to a matched background population, especially for non-melanoma skin cancer and MDS/AML. Risk factors for SPM in patients were older age and COPD. These findings are important in the light of new potential treatment alternatives, such as CAR-T.

A phase Ib study of a PI3Kδ inhibitor Linperlisib in patients with relapsed or refractory peripheral T-cell lymphoma.

7531 Background: PI3Kδ inhibitors have been shown to have important roles in blocking mitogenic and survival signaling within the tumor cell and the tumor microenvironment and activate antilymphoma immune responses. Linperlisib is an oral highly selective small molecule inhibitor of PI3Kδ and has been demonstrated to be well-tolerated with a favorable PK profile in patients with lymphomas at the RP2D. This phase Ib study is evaluating the efficacy and safety of Linperlisib in relapsed or refractory peripheral T-cell lymphoma (PTCL), a highly aggressive malignancy with few treatment options for patients. Methods: Eligible PTCL patients who must have received at least 1 prior systemic conventional therapy were administrated Linperlisib 80mg orally once daily (RP2D) in 28 days cycle until disease progression, unacceptable toxicity, or withdrawal from the study. Tumor response was assessed by IWG 2007 criteria with CT performed every 2 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoint was toxicity assessed by NCI-CTCAE5.0. Results: As of February 2, 2021, 36 PTCL patients were enrolled in this exploratory trial. Most patients were stage III (38.2%) or IV (50%). Of the 27 evaluable patients to date, the PTCL histologies were PTCL-NOS (n=12), AITL (n=10), ALCL (n=3), NKTCL (n=1) and MEITL (n=1). 19 of the 27 evaluable patients had Investigator confirmed responses for a 70.4% ORR including 25.9% CR (7pt) and 44.4% PR (12pt). In the major subtypes, ORR was 50% (6/12) PTCL-NOS and 80% (8/10) AITL, respectively. A disease control rate of 100% was observed, and most responses occurred by first assessment at C2D28. One subject who had a CR at C2D28 is currently in cycle 9 and continuing on Linperlisib. 36 patients experienced at least 1 AE in the trial, with 95% of AEs ≤ grade 2. Consistent with previously treated lymphoma patients, no unexpected toxicities were observed. The most common TRAEs (≥10%) were neutrophil count decreased (55.6%), leukocyte count decreased (33.3%), hypertriglyceridemia (22.2%), aspartate aminotransferase increased (16.7%), hypercholesterolemia (16.7%), alanine aminotransferase increased (11.1%), creatinine increased (11.1%), rash (11.1%), thrombocyte count decreased (11.1%) and electrocardiogram T wave abnormal (11.1%). No AE grade 4 was observed. 6 patients (16.7%) experienced at least one SAE, in which 4 (11.1%) SAEs were considered to be drug-related, including neutrophil count and leukocyte count decreased (2.8%), gastritis (2.8%), and pneumonia (5.6%). Conclusions: The oral PI3Kd inhibitor Linperlisib had significant activity in patients with relapsed or refractory PTCL. Toxicities with Linperlisib therapy were generally tolerable and manageable. Further efficacy and safety is being evaluated. Clinical trial information: NCT04108325.

Heat Shock Proteins in Lymphoma Immunotherapy.

Immunotherapy harnessing the host immune system for tumor destruction revolutionized oncology research and advanced treatment strategies for lymphoma patients. Lymphoma is a heterogeneous group of cancer, where the central roles in pathogenesis play immune evasion and dysregulation of multiple signaling pathways. Immunotherapy-based approaches such as engineered T cells (CAR T), immune checkpoint modulators and NK cell-based therapies are now in the frontline of lymphoma research. Even though emerging immunotherapies showed promising results in treating lymphoma patients, low efficacy and on-target/off-tumor toxicity are of a major concern. To address that issue it is suggested to look into the emerging role of heat shock proteins. Heat shock proteins (HSPs) showed to be highly expressed in lymphoma cells. HSPs are known for their abilities to modulate immune responses and inhibit apoptosis, which made their successful entry into cancer clinical trials. Here, we explore the role of HSPs in Hodgkin and Non-Hodgkin lymphoma and their involvement in CAR T therapy, checkpoint blockade and NK cell- based therapies. Understanding the role of HSPs in lymphoma pathogenesis and the ways how HSPs may enhance anti-tumor responses, may help in the development of more effective, specific and safe immunotherapy.

Results of a completely outpatient autologous stem cell transplant program for lymphoma patients receiving reduced-intensity conditioning

Autologous stem cell transplantation (ASCT) is commonly an in-patient procedure. However, outpatient ASCT grows as a cost-effective and feasible option for patients with lymphoma and reports assessing it after reduced-intensity conditioning (RIC) are sparse. We report the outcome of 102 patients with lymphoma who underwent ASCT on a full outpatient basis in a single-center transplant program between 2010 and 2020. Forty-two percent of the cohort required transfusion support, 36.3% experienced a neutropenic fever episode, 25.5% mucositis, and 9.8% developed severe infection. At a median time of 5 days (range 1–28), only 22.5% of the cohort required admission within the first 100 days after the autograft, median length of hospital stay was 0 days (range 0–14) and neutropenic fever was the most common reason for hospitalization. Non-relapse mortality at 1 year was 5%. ASCT in a completely outpatient setting is feasible, safe, and highly effective to treat lymphoma patients.

Targeting N-myristoylation for therapy of B-cell lymphomas

Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for membrane targeting and cell signaling. Because cancer cells often have increased N-myristoyltransferase (NMT) expression, NMTs were proposed as anti-cancer targets. To systematically investigate this, we performed robotic cancer cell line screens and discovered a marked sensitivity of hematological cancer cell lines, including B-cell lymphomas, to the potent pan-NMT inhibitor PCLX-001. PCLX-001 treatment impacts the global myristoylation of lymphoma cell proteins and inhibits early B-cell receptor (BCR) signaling events critical for survival. In addition to abrogating myristoylation of Src family kinases, PCLX-001 also promotes their degradation and, unexpectedly, that of numerous non-myristoylated BCR effectors including c-Myc, NFκB and P-ERK, leading to cancer cell death in vitro and in xenograft models. Because some treated lymphoma patients experience relapse and die, targeting B-cell lymphomas with a NMT inhibitor potentially provides an additional much needed treatment option for lymphoma.

A multicenter investigation and analysis on anemia in lymphoma patients in Shanghai

目的研究淋巴瘤患者贫血的发生情况、影响因素及其对疗效的影响。方法对上海地区4所综合性医院2017年1月至2018年6月住院的501例淋巴瘤患者进行6个月随访，统计分析贫血相关临床资料。结果501例淋巴瘤患者中178例（35.5%）伴有贫血；初治淋巴瘤289例，其中贫血患者99例（34.3%）；调查过程中新发贫血136例（42.1%）；整个调查过程，贫血患病率达62.7%。单因素分析结果显示：初治淋巴瘤患者贫血发生与年龄、病理类型、有无骨髓浸润、国际预后指数（IPI）评分及Ann Arbor分期相关；初治淋巴瘤伴有贫血的患者较无贫血患者疗效差。多因素分析结果显示：IPI评分3~5分（P<0.001，OR=4.230，95%CI 2.339~7.650）及化疗（P<0.001，OR=11.049，95%CI 5.149~23.711）是新发贫血的独立危险因素，患者的体能状态评分（PS评分）与贫血显著相关。结论淋巴瘤患者贫血发病率及患病率高，贫血的发生与严重程度与淋巴瘤患者疗效及体能状态密切相关。

Improving T cell functionality for adoptive T cell therapy in metastatic colorectal cancer

Abstract Adoptive T cell therapy in solid tumors such as colorectal cancers are challenging due the low frequency of tumor infiltrating T cells and high molecular tumor heterogeneity. In this study, we are proposing to address this issue by developing a novel technology to expand patient tumor specific T cells ex-vivo, using patient’s matched tumor and PBMCs. Published data from our group shows T cells isolated from heavily treated lymphoma patients when treated with inhibitors of PI3K delta (idelalisib) and vasoactive intestinal peptide (VIPhyb) signaling results in decreased levels of senescent T cells and increased persistence in-vivo in NSG mice. Additionally, we have demonstrated that tumor membrane vesicles (TMVs) prepared from human tumor cells decorated with IL-12 and B7-1 (decorated TMVs), stimulate expansion of tumor antigen specific T cells with increased IFN gamma release. This study thus combines both strategies to obtain tumor antigen specific T cells with enhanced anti-tumor activity and in-vivo persistence. Preliminary data was generated with PBMCs obtained from consented colon cancer patients expanded with decorated TMVs with/without VIPhyb and idelalisib. Results showed that on day 14 of T cell expansion, T cells expanded with decorated TMVs + VIPhyb + idelalisib resulted in significantly increased number of IFN gamma secreting CD8+ T cells (25% of T cells), when compared to T cells treated with decorated TMVs without VIPhyb and idelalisib (13% of T cells). On the other hand, in the absence of decorated TMVs, there were less IFN gamma secreting T cells, both in the CD4 and CD8 compartment. Further experiments are underway to test the persistence and efficacy of the expanded T cells in PDX mice with matched human colon cancer.

Germinal center-derived lymphomas: The darkest side of humoral immunity.

SummaryOne of the unusual features of germinal center (GC) B cells is that they manifest many hallmarks of cancer cells. Accordingly, most B‐cell neoplasms originate from the GC reaction, and characteristically display abundant point mutations, structural genomic lesions, and clonal diversity from the genetic and epigenetic standpoints. The dominant biological theme of GC‐derived lymphomas is mutation of genes involved in epigenetic regulation and immune receptor signaling, which come into play at critical transitional stages of the GC reaction. Hence, mechanistic studies of these mutations reveal fundamental insight into the biology of the normal and malignant GC B cell. The BCL6 transcription factor plays a central role in establishing the GC phenotype in B cells, and most lymphomas are dependent on BCL6 to maintain survival, proliferation, and perhaps immune evasion. Many lymphoma mutations have the commonality of enhancing the oncogenic functions of BCL6, or overcoming some of its tumor suppressive effects. Herein, we discuss how unique features of the GC reaction create vulnerabilities that select for particular lymphoma mutations. We examine the interplay between epigenetic programming, metabolism, signaling, and immune regulatory mechanisms in lymphoma, and discuss how these are leading to novel precision therapy strategies to treat lymphoma patients.

Clinical Significance of Detecting the Erythrocyte Life Expectancy in Patients with Malignant Lymphoma Complicated with Anemia

To investigate the clinical value of erythrocyte life span in the diagnosis and treatment of lymphoma patients with anemia. The clinical data of 45 patients with lymphoma diagnosed by Department of Hematology in Beijing Union Hospital from January 2017 to June 2017 were collected. The life of erythrocytes was detected by alveolar gas CO test. The incidence of anemia in patients with malignant lymphoma was 46.7%, 40.0% of patients displayed the shorting of blood cell life and the hemolytic status existed in 15.56% of patients. The incidence of anemia was 47.1% in patients with DLBCL. Patients with B symptoms, bone marrow involvement, splenomegaly or LDH increase often accompanied with anemia, but only the splenomegaly and LDH level were significantly negatively correlated with red blood cell life; there was a significant difference in the effects of CHOP ± R regimen and other chemotherapy regimens (R+MINE/FC/SMILE/GDP) on patients with anemia and erythrocyte life span. The incidence of anemia in patients with lymphoma is high, red cell damage or shortened life may be involved in the mechanism of anemia, the use of a strong chemotherapy regimen can significantly shorten the red blood cell life of patients and aggravates anemia.

Oncologist volume and outcomes in older adults diagnosed with diffuse large B cell lymphoma

Although provider-level volume is frequently associated with outcomes in cancers requiring complex surgeries, whether similar relations exist for cancers treated primarily with systemic therapy is unknown. Using a population-based cohort analysis of older adults diagnosed with diffuse large B cell lymphoma (DLBCL) during the years 2004-2011, we evaluated the association between oncologist volume and 4 clinical outcomes (receipt of any chemotherapy, receipt of an anthracycline-containing or equivalent regimen, early hospitalization, and overall survival). Our primary explanatory variable was lymphoma treatment volume, defined as the number of patients with newly diagnosed lymphoma for which an oncologist initiated therapy during a 12-month look-back period from each incident DLBCL case. We identified 8247 Medicare beneficiaries who were newly diagnosed with DLBCL. Chemotherapy was administered to 6202 (75.2%) beneficiaries, and 71.4% of cytotoxic regimens contained an anthracycline. Beneficiaries who were treated by higher-volume oncologists had increased odds of receiving chemotherapy (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.24-1.70; P <.001) and of receiving an anthracycline-containing regimen (aOR, 1.26; 95% CI, 1.06-1.50; P = .009). Receiving care from a higher-volume provider was also associated with decreased hospitalization (aOR, 0.80; 95% CI, 0.69-0.95; P = .007) and improved survival (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92; P < .001). In older adults diagnosed with DLBCL, receiving care from a provider with more experience treating lymphoma patients was associated with receipt of guideline-adherent therapy, reduced hospitalizations, and improved survival. Clinical volume may be an important factor in providing high-quality cancer care in the modern era.

Renewed interest for low‐dose radiation therapy in follicular lymphomas: From biology to clinical applications

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoproliferative disorders. Treatment strategies for FL may include several therapeutic choices, ranging from a "watchful waiting" approach to stem cell transplantation, mostly depending on staging, age, risk factors, and disease burden at diagnosis. The high radiosensitivity of FL compared with other solid tumors has been known since the beginning of radiotherapy treatment in lymphoma patients. Doses of 24 to 40Gy were considered appropriate in first line curative treatment for localized disease (stages I-II), but several publications investigating low-dose radiotherapy (LDRT) of 4Gy (2×2Gy) reported an overall response rate surprisingly high. Due to its high local efficacy and negligible toxicity, LDRT might be offered to both early and advanced stage FL patients in combination with new agents, at diagnosis or after several lines of systemic therapy. The aim of this review is to summarize and discuss the current knowledge on LDRT for FL and its potential application in a curative setting in combination with new drugs for both early and advanced disease.

P103 Crosslinking immunogenetics to pharmacogenetics: Fc[formula omitted]RIIIa polymorphism predicts response to Rituximab therapy in mantle cell lymphoma

Aim Mantle cell lymphoma (MCL) and Diffuse large B cell lymphoma (DLBCL) are the most aggressive forms of B-cell lymphoma. Rituximab, a monoclonal anti-CD20 antibody is extensively used as a part of the frontline R-CHOP therapy for treatment of B-cell lymphoma. Rituximab triggers lymphoma cell killing through NK cell mediated antibody dependent cellular cytotoxicity (ADCC). The binding of Rituximab to Fc γ RIIIa during ADCC is influenced by Fc γ RIIIa (158 V/F; Valine to Phenylalanine) polymorphism, where −158 V allele has a high affinity for antibody binding. In the present investigation, we assessed the influence of Fc γ RIIIa 158 V/F polymorphism on the overall survival of MCL and DLBCL patients treated with R-CHOP therapy. Methods A total of 146 R-CHOP treated lymphoma patients (MCL = 42; DLBCL = 104) were accrued. Genotyping of Fc γ RIIIa −158 V/F polymorphism was performed on DNA extracted from diagnostic specimens by resequencing of PCR amplified regions using Sanger’s method. Survival analysis was performed using multivariate cox proportional hazards model. Results MCL patients carrying Fc γ RIIIa ‘V’ genotypes (VV/VF) had significantly better overall survival after R-CHOP therapy in comparison to MCL patients carrying FF genotypes (HR = 0.45, 95% CI = .55–1.1, Fig. 1). However, no correlation was observed in DLBCL patients treated with R-CHOP therapy. Conclusion Fc γ RIIIa −158 V allele (VV/VF genotypes) are predictive of survival of Mantle cell lymphoma patients receiving Rituximab (R-CHOP) therapy. The findings may lead to improved selection of lymphoma patients who will benefit from Rituximab therapy. Download : Download high-res image (150KB) Download : Download full-size image

PET/CT in initial staging and therapy response assessment of lymphoma

ObjectiveTo detect accuracy of PET/CT in the initial staging, response during the course and end of treatment in lymphoma patients compared to contrast CT. Materials and methodsWe studied 50 patients divided into 3 groups with pathologically proven lymphoma with a mean age=27. All patients performed CT and PET/CT for initial staging, during the course of chemotherapy and at the end of treatment. ResultsPET/CT and CECT were agreeable in 75% of cases. 61% during treatment and41% agreement at the end of treatment. ConclusionPET/CT proved higher sensitivity and specificity over CECT. The major strength of PET/CT over CECT was its higher ability for detection of extra-nodal sites of lymphoma and excluding active disease in residual nodal mass lesions on follow-up.

CT perfusion in evaluation of post therapy cervical lymphoma

ObjectiveCompare CT perfusion between responders and non-responders in patients with residual cervical nodes after lymphoma treatment. Subjects and methodsTwenty-seven patients with treated pathologically proved lymphoma were included in this prospective study, divided into two groups: responders (n. 15) and non-responders to treatment (n. 12). Blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability (PS) were determined using CT perfusion. Lymph nodes sizes were measured (short axis). ResultsBF, BV and PS were significantly higher in non-responders group [93.3 (65.3–111) ml/min/100g, 6.3 (5.2–8) ml/100g and 18.9 (14.5–25.1) ml/min/100g respectively] as compared to responders group [54 (43.8–77.5) ml/min/100g, 4.1 (2.2–4.8) ml/100g and 9.4 (7.5–14.5) ml/min/100g respectively], [p 0.019, 0.004 and 0.004 respectively]. MTT had a trend to be low in non-responders group, but did not reach statistical significance (p 0.305). Cutoff value for BF, BV and PS was 59.5 ml/min/100g, 3.6ml/100g and 11.1ml/min/100g respectively, 92% sensitivity for the three parameters and specificity 67%, 47% and 73% respectively. Lymph node sizes had no relation to the perfusion parameter values. ConclusionCT perfusion is a functional imaging tool with promising results in differentiating between responders and non-responders in treated lymphoma patients, using BF, BV and PS.