Adult Lymphoma Patients Research Articles

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

At-Home Care Versus Total Hospital Care Model for Autologous Stem Cell Transplantation in Adult Lymphoma Patients: A Pilot Case-Control Study.

Lymphoma is the second most prevalent cancer treated with autologous stem cell transplantation (ASCT). Additional resources are required to enhance the provision of care for these patients. To explore the complications and economic costs of home versus hospital care models for ASCT in patients diagnosed with lymphoma and to describe the experience of home care patients. This was an observational pilot case-control study with 1:1 matching, in which all patients assisted at home were included. Data were obtained by reviewing medical records and data from the hospital's financial and resource management service. The IEXPAC scale version 11 + 4 was used to assess the care process experience as perceived by home care patients. The study included 34 patients, in which there was a significant decrease in neutropenic fever, both in frequency and duration (P = .001 and P < .001, respectively), in mucositis days (P = .038), and the rate of red cell concentrate transfusion (P < .001); however, there was a longer neutrophil recovery time (P = .044) in home care versus hospitalized patients. The overall cost was higher in the hospital care model (P = .001). Home care patients obtained high scores on the perceived experience of the care process scale. The home ASCT model is associated with fewer complications, shorter hospital stays, and more significant cost savings. The experience of the home care process was rated satisfactorily. This study provides evidence for a model that offers high-quality care and a comfortable experience for ASCT patients. Preparing more nurses for this home care model is imperative.

Cisplatin as a Viable and Secure Alternative to Carmustine in BEAM-Based Conditioning for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma

BackgroundHigh-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment for relapsed/refractory lymphoma patients. Yet, the widespread use of BEAM is hindered by carmustine accessibility. This study evaluates the efficacy and safety of PEAM (Cisplatin, Etoposide, Cytarabine, and Melphalan) versus BEAM in auto-HSCT for Hodgkin (HL) and non-Hodgkin lymphoma (NHL) patients. MethodsWe conducted a retrospective single-center study of adult lymphoma patients who received PEAM or BEAM pretransplant conditioning between January 2004 to December 2022, comparing efficacy and safety outcomes. ResultsAmong 143 patients (median age of 33 years, 58% males), 55 had HL, and 88 had NHL. The overall response rate (ORR) was 86.7% for PEAM and 72.3% for BEAM, and the relapse rate (RR) was lower for PEAM than BEAM (22.9% vs 45.6%). Median time to relapse (TTR) and overall survival (OS) were not reached for either group. PEAM exhibited a shorter time to both neutrophil (NE) and platelet (PE) engraftment compared to BEAM (10 vs 12 days), with a more tolerable gastrointestinal (GI) toxicity profile. ConclusionsBoth BEAM and PEAM showed similar outcomes, demonstrating comparable efficacy in terms of ORR, TTR, and OS for both HL and NHL patients. However, PEAM-conditioning was associated with a shorter time to engraftment and fewer GI adverse events.

Thrombosis risk prediction in lymphoma patients: A multi-institutional, retrospective model development and validation study.

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients.

Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013–2017: A Population-Based Cohort Study

Introduction: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013–December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. Methods: A retrospective, descriptive study of consecutive cases was conducted at Qatar’s NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. Results: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36–95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. Conclusions: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar’s immigration patterns.

Brentuximab Vedotin Combined with Chemotherapy in the Treatment of Pediatric Patients with R/R Hodgkin Lymphoma: Results of a Real World Setting Study

INTRODUCTION: Hodgkin Lymphoma (HL) is a familiar malignant lymphoma of the lymphatic system that accounts for 10% of all lymphoma diagnoses and 5% of lymphoma-related deaths. According to statistics, the incidence of HL in children and adolescents (0-19 years old) in China is about 1.78/million, and an average of 569 new cases are estimated annually from 2019 to 2021 . Brentuximab vedotin (BV) is an antibody-drug conjugates (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Most of the data on the efficacy and safety of BV came from prospective and retrospective studies in adults or foreign children, and there are insufficient data in Chinese children. The purpose of this study is to explore the efficacy and safety of BV Combined with chemotherapy in Chinese pediatric patients with refractory and/or relapsed Hodgkin's lymphoma. METHODS: Retrospective analysis of clinical data of 9 children with refractory and/or relapsed Hodgkin's lymphoma from October 2021 to May 2023 at Beijing Children's Hospital, Capital Medical University. Patients were classified according to: clinical stage(Ann Arbor stage), huge tumor, huge tumor in the mediastinum, symptoms of B, and whether multiple lymph nodes were involved. Among them, the low-risk group was IA, ⅡA without giant tumor. The middle risk group was IB and ⅢA without huge tumor. High-risk groups were patients with stage ⅡB, ⅢB, Ⅳ or (each stage) with large tumors, or children with &amp;gt; 4 lymph node regions. All patients received BV in combination with chemotherapy for at least 2 cycles, and patients were assessed for remission response according to the Revised Response Criteria for Malignant Lymphoma at the end of every 2 cycles and followed up until July 20, 2023. RESULTS: Totally 32 cycles of chemotherapy were recorded, including 36 doses of BV administration(Table 1). The overall response rate of the children after 2 cycles of treatment was 100%, and the complete response rate was 88.89%. After remission, 2 cases (P1, P2) were treated with BV single drug 1.8mg/kg, Q3W for 6 months, and 3 cases (P3, P4, P7) were treated with radiotherapy. Two patients (P5, P6) received sequential chemotherapy, and two patients (P8, P9) were followed by programmed cell death 1(PD-1) antibody maintenance treatment for 6 months. After receiving PD-1 antibody for 6 months, 1 patient (P9) was transferred to BV monotherapy for maintenance, with 18 times planned. 2 cases (P1, P2) were then treated with autologous stem cell transplantation. None of the children developed disease progression during treatment. All patients successfully completed all planned dosage of BV, and serious adverse events were dominated by grade 3 or higher hematocrit, none of which interfered with normal treatment. Interpretation. BV had demonstrated the better efficacy and tolerable safety profile in the treatment of refractory and/or relapsed Hodgkin's lymphoma in children. CONCLUSIONS: BV has been approved by National Medical Products Administration in China since 2020, the clinical cases are mostly from adult lymphoma patients, and children data of in China is rare. In this study, we retrospectively reviewed and analyzed the data of BV combined chemotherapy in the treatment of refractory and relapsed Hodgkin lymphoma from single center, and found that the treatment response was rapid, continuousand safe. However, this study is a single-center retrospective study with a small sample size So We are conducting a prospective study of BV in first-line Hodgkin lymphoma children patients in China and aiming to generate more data for this specific population.

Adolescent and young adult Hodgkin lymphoma patients at risk for subcutaneous fat gain during early cancer treatment: a brief report

Computed tomography scans were assessed for subcutaneous fat area and density at thoracic vertebra 4 in 65 adolescent and young adult (AYA) patients with Hodgkin lymphoma. Subcutaneous fat was quantified over 3 timepoints; (1) baseline, (2) end of initial anthracycline treatment (EOT) and (3) 1 year. Fat area increased at EOT (62.3 ± 5.4 cm/m2 vs 53.5 ± 5.0 cm/m2, p < 0.01) and 1 year (65.8 ± 5.6 cm/m2 vs 53.5 ± 5.0 cm/m2, p < 0.01) compared to baseline. Fat density significantly decreased at EOT (-91.2 ± 1.4 HU vs −86.5 ± 1.4 HU, p < 0.01) and at 1 year (-90.3 ± 1.6 HU vs −86.5 ± 1.4 HU, p = 0.01) compared to baseline. Female, radiation receiving, and anthracycline dosage >250mg/m2subgroups experienced significant fat gain (p < 0.05 for all). Female AYA Hodgkin lymphoma patients receiving radiation, and/or high-dose anthracyclines may be at higher risk of subcutaneous fat gain during therapy.

Disparities in care and outcomes for adolescent and young adult lymphoma patients.

Though survival outcomes among adolescents and young adults (AYAs) with lymphoma have improved over the last three decades, socially vulnerable populations including non-White, low-income, and publicly insured groups continue to trail behind on survival curves. These disparities, while likely the result of both biological and non-biological factors, can be largely attributed to inequities in care over the full cancer continuum. Nationally representative studies have demonstrated that from diagnosis through therapy and into long-term survivorship, socially vulnerable AYAs with lymphoma face barriers to care that impact their short and long-term survival. Thus, improving outcomes for all AYAs with lymphoma requires dedicated study to understand, and then address the unique challenges faced by non-White and low-income lymphoma populations within this age group.

ALL-476 Correlation of CT Chest Findings With Bronchoalveolar Fluid (BAL) Analysis in Adolescent and Adult Leukemia and Lymphoma Patients With Febrile Neutropenia

ALL-476 Correlation of CT Chest Findings With Bronchoalveolar Fluid (BAL) Analysis in Adolescent and Adult Leukemia and Lymphoma Patients With Febrile Neutropenia

Guideline Concordance of Treatment and Outcomes Among Adult Non-Hodgkin Lymphoma Patients in Sub-Saharan Africa: A Multinational, Population-Based Cohort.

Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.

The β-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 axis promotes adult T-cell lymphoblastic lymphoma progression and chemoresistance

BackgroundHigh-intensity chemotherapy regimens are often used in adult T-cell lymphoblastic lymphoma (T-LBL) patients. Nevertheless, the response rate remains unsatisfactory due to emergence of chemoresistance. Growing evidence has shown that long non-coding RNAs (lncRNAs) are involved in tumor progression and chemoresistance. Herein, we investigated the potential role of lncRNAs in T-LBLs.MethodsRNAseq was used to screen and identify candidate lncRNAs associated with T-LBL progression and chemoresistance. Luciferase reporter assay was used to examine the binding of miR-371b-5p to the 3’UTR of Smad2 and LEF1, and the binding of TCF-4/LEF1 to the promoter of LINC00183. Chromatin immunoprecipitation assay was undertaken to analyze the connection between LEF1 and the LINC00183 promoter region. RNA immunoprecipitation assays were used to explore the mechanism whereby LINC00183 regulated miR-371b-5p. MTT and flow cytometry assays were used to measure apoptosis of T-LBL cells.ResultsLINC00183 was upregulated in T-LBL progression and chemoresistant tissues in both the Sun Yat-sen University Cancer Center dataset and the First Affiliated Hospital of Anhui Medical University dataset. High expression of LINC00183 was correlated with poorer overall survival and progression-free survival of T-LBL patients compared to those with low expression of LINC00183. Furthermore, miR-371b-5p was negatively regulated by LINC00183. In vivo and in vitro assays showed that LINC00183-mediated T-LBL chemoresistance depended on miR-371b-5p expression. The direct binding of miR-371b-5p to Smad2 and LEF1 was verified by luciferase assays. It was shown that TCF4/LEF1 could bind to the LINC00183 promoter site and increase its transcript level. Downregulation of miR-371b-5p led to increased expression of Smad2/LEF1, and in turn increased LINC00183 expression. Additionally, phospho-Smad2 promotes nuclear translocation of β-catenin, LINC00183 downregulation decreased chemoresistance induced by β-catenin and TGF-β1 in T-LBL cells.ConclusionWe unraveled a β-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 feedback loop that promotes T-LBL progression and chemoresistance, indicating that LINC00183 may serve as a potential therapeutic target in T-LBLs.

Translation and Validation of the Chichewa Pediatric Patient-Reported Outcome CTCAE Tool to Measure Treatment-Related Adverse Events Among Adolescent and Young Adult Lymphoma Patients in Malawi (TH114B)

Translation and Validation of the Chichewa Pediatric Patient-Reported Outcome CTCAE Tool to Measure Treatment-Related Adverse Events Among Adolescent and Young Adult Lymphoma Patients in Malawi (TH114B)

Hepatitis B and C infections among lymphoma patients: a national study in the Republic of Moldova

Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent common infections that are presumably associated with various types of lymphoma and specific clinical features. However, conclusive data are lacking and results from different regional studies are conflicting. Hence, a national study was performed in order to investigate potential associations between hepatitis infections and lymphoma in the Republic of Moldova. Data were collected from newly diagnosed adult lymphoma patients from January 2020 to January 2022. Patients who were not tested for HBsAg and anti-HCV and those with an undetermined lymphoma subtype diagnosis were excluded from the study. Subjects with and without viral hepatitis were then evaluated on the basis of clinical and pathological characteristics. One hundred and twenty-nine lymphoma patients were included in the study; 15 (11.6%) patients were diagnosed with hepatitis B, 21 (16.3%) patients with hepatitis C, and 1 (0.78%) patient was positive for both. The majority of hepatitis patients were over 60 years old (62.2%), presented with stage III or IV (81%), had normal lactate dehydrogenase (58.3%) and 0 or 1 extranodal sites (78.4%). The most common lymphoma subtypes were diffuse large B-cell lymphoma (64.9%) and marginal zone lymphoma (8.1%). We did not find any statistically significant differences between infected and uninfected lymphoma patients in regards to clinical features, specific lymphoma subtypes, and presence and location of extranodal involvement. Presence of hepatitis B or C virus infections is not associated with specific clinical and pathological features in Moldovan lymphoma patients.

Long telomeres at baseline and male sex are main determinants of telomere loss following chemotherapy exposure in lymphoma patients.

Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1year from CHT completion. Median age was 59yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n=27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p<0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (<51years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.

Anti-spike antibody response to the COVID vaccine in lymphoma patients.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

Elevated CCL22 and sIL2Rα Levels Precede the Diagnosis of Young Adult Classical Hodgkin Lymphoma: A Nested Case-Control Study from the DoD Serum Repository

Background: Young adult classical Hodgkin lymphoma (YAcHL) patients have immune abnormalities that persist long after cure. It is difficult to assess whether manifestations are present prior to diagnosis because the cancer is rare and occurs in the late teens and twenties, and therefore cohort studies are generally impractical. We conducted a nested case-control study in the Department of Defense (DoD) Serum Repository, a repository of samples from active duty U.S. military service members, to determine whether levels of serum biomarkers of Th1, Th2 and innate immunity predicted risk of YAcHL. Active duty service members are an ideal population for a prospective study because they are the age group at risk for this subgroup of cHL patients and blood samples are collected upon entry into military service. Methods: Cases were identified by the ICD-9 CM code 201, diagnosed from 1990-1999. Two unaffected controls were matched to each case by age (within 1 year), sex, race/ethnicity, number of samples in the repository and blood draw date (within 1 month). Subjects with HIV or a prior cancer (other than non-melanoma skin cancer) were excluded. CCL22 and sIL2Rα (reflecting Th2 immunity), sCD163 (reflecting innate immunity from macrophages), and CXCL9 and CXCL10 (reflecting Th1 immunity) were measured from the earliest sample in 103 cases and 206 controls with pre-diagnosis serum samples archived in the DoD Serum Repository. Most participants (>96%) had detectable levels of CCL22, sCD163 and sIL2Rα. We compared cases and controls using multivariable conditional logistic regression to estimate the effect of the biomarker levels (in tertiles) on risk of YAcHL, in two main strata: within 3 years of diagnosis and from 3-6 years prior to diagnosis. The middle tertile was considered the reference group. There was a high proportion of undetectable values for CXCL9 (57.6%) and CXCL10 (11.6%), thus these were dichotomized into detectable vs. undetectable levels for multivariable conditional logistic regression. Stratified analyses were also conducted examining the biomarkers by Epstein-Barr virus (EBV) status and histology. Results: The median age at diagnosis was 25 years (IQR: 22-31 years) and 90% were male. The race/ethnicity distribution was: 75% non-Hispanic white, 12% Black, 11% Hispanic white, 2% Other/unknown. The number of pre-diagnostic blood draws ranged from 1 (38%) to 5 (3%). The distribution of histology was 65% nodular sclerosis (NS), 13% mixed cellularity and 22% other histology; 74% were EBV-negative, 22% EBV-positive and 4% undetermined. The highest relative to the middle tertile of CCL22 and sIL2Ra levels were strongly associated with YAcHL risk 0-3 years prior to diagnosis (ORCCL22=5.35, 95% CI=1.93, 14.85; ORsIL2Rα=5.37; 95% CI=2.06,14.00) but not 3-6 years prior to diagnosis (ORCCL22=1.18, 95% CI=0.49,2.84; ORsIL2Rα=1.43; 95% CI=0.59,3.45) (Figure 1). These associations were present for EBV-negative and nodular sclerosis (NS) YAcHL, but not EBV-positive or other histological subtypes. The lowest tertile of sCD163 relative to the middle tertile was associated with an inverse risk 0-3 years prior to diagnosis (ORCD163= 0.31, 95% CI=0.12,0.78). Detectable relative to undetectable levels of CXCL10 was associated with an increased risk of the EBV-negative subtype (ORCXCL10 EBV-= 2.93, 95%CI= 1.01-8.44) only. When cytokine levels were examined in a single model, the associations remained significant although attenuated. Conclusions: Risk of YAcHL was associated with elevated CCL22 and sIL2Rα levels within 3 years before cHL diagnosis, reflecting a disease, rather than an etiological effect. The stronger association within EBV-negative, NS cHL is consistent with the Th2 pattern observed in these subtypes in young adults. CCL22 in particular is correlated with TARC, a known predictor of YAHL. There may be a role for some Th2 cytokines as early diagnostic biomarkers. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Research in Africa: Collaborative Project between Senegal and France to Improve the Diagnosis and Therapeutic Management of Adult Lymphoma Patients

Background: Little is known about Non-Hodgkin Lymphoma (NHL) in Africa except for the high incidence of Burkitt lymphoma in children and the high association with HIV in Eastern Africa but not Western Africa. Difficulties including low access to health care, use of cytopuncture instead of nodal biopsy, cost of drugs and absence of supportive care lead to poor prognosis for NHL patients (pts) (overall response rate (ORR) <30%) (Diop et al., Bull Soc Patho Exo 2004). Meaningful lymphoma research cannot be conducted without accurate diagnosis (Naresh et al., Br J Hematol 2011). The Senegal Government has built a national anti-cancer program, focusing on prevention and improvement of diagnosis and treatment. A prospective single arm non-randomized phase 2 clinical trial was thus designed for adult pts with newly diagnosed diffuse large B-cell lymphoma (DLBCL) at Dakar (Senegal) University Hospital (DUH), in collaboration with Nancy (France) University Hospital (NUH). Methods: Histological results of suspected lymphoma in pts likely to be included in this trial are reported here. Only non-HIV adult patients were enrolled. A first histological study was performed in the pathology department of DUH. This included biopsies that were submitted to apposition before embedding. Hematoxylin and eosin staining was performed as well as immunohistochemistry (IHC). The panel used allowed to examine the expression of the following antigens: CD20, CD79a, CD3, CD5, CD23, cyclin D1, CD30, Bcl2, CD10 and Ki67. Biopsies were reviewed via an international telepathology platform using the i-Path software and retrospectively, in NUH Pathology department, by sending paraffin-embedded blocks on site. Findings: Between July 2018 and May 2022, 70 pts admitted with a clinical presentation suggestive of NHL were evaluated with a surgical biopsy, 31 of whom being confirmed with a diagnosis of DLBCL or equivalent as T-cell/histiocyte-rich large B cell LBCL, and thus eligible for the therapeutic trial. Median age of the 70 pts was 42 years old (18-70) and 32% were female. Other hematological diagnoses were Hodgkin lymphoma, small B-cell lymphoma, T-cell lymphoma, unclassed lymphoma and histiocytosis. There was no Burkitt lymphoma. Non-hematological diagnoses were achieved for 14 pts: lipoma, tuberculosis, reactive adenitis or metastasis of solid neoplasia. In nearly half of all cases, diagnosis was obtained without IHC, notably due to non-hematological diagnoses. In nearly half of all cases, the diagnosis was obtained without IHC. When IHC was used, CD20 and CD3 were mainly used to establish the diagnosis. The median time to obtain pathology results was 31 days. Thirty-one cases were diagnosed with the help of I-Path. Currently, 17 biopsies have been reviewed at NUH with diagnosis concordance in 71% of cases. The 5 inconsistent diagnoses were 2 NHL ultimately classified as adenocarcinoma, 1 reactive adenitis being in fact DLBCL and 2 T-cell/histiocyte-rich LBCL diagnosed as respectively DLBCL and small B-cell lymphoma. Interpretation: This is a large cohort of consecutive surgical biopsies performed in Senegal for lymphoma suspicion, showing the distribution of lymphoma in Western Africa and more interestingly, demonstrating that an accurate diagnosis is possible locally. The current hindrances in lymphoma diagnosis include basing treatment decisions on fine needle aspiration cytology in a large proportion of cases, poor quality histology or complete lack of IHC in cases where biopsies are performed, limited number of hematopathologists and lack of discussion between hematopathologists. In this study, systematic surgical biopsy, homogenous IHC staining procedures, electronic interaction between hematopathologists and retrospective review of biopsies have contributed to a huge improvement of the quality of diagnosis.

Role of Radiation Therapy in Mortality among Adolescents and Young Adults with Lymphoma: Differences According to Cause of Death.

Simple SummaryDespite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. However, the most current research studying the association between RT and outcome is based only on groups of lymphoma patients and is not compared with the general population, which could more accurately reveal the impact of RT on outcomes. This population-based analysis showed that after adjusting for potential confounders, RT administration is associated with a low risk of cause-specific mortality, including death due to the original diagnosis, second malignant neoplasms (SMNs), and noncancer causes, among AYA patients with lymphoma. This analysis may play a guiding role in the design of future lymphoma studies and the formulation of healthcare policies regarding the widespread use of RT, especially for AYA survivors.Background: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. Few long-term follow-up studies have examined the association between RT and outcomes. Methods: Lymphoma patients aged 15–39 years were identified in the Surveillance, Epidemiology and End Results (SEER) database from 1992 to 2016. Mortality was assessed by comparing those with and without RT using the Fine–Gray competing risk model. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with the general U.S. population. Results: In total, 29,686 patients were included; 10,708 (36.07%) received RT. Cause-specific mortality was compared between patients with and without RT while considering other competing events, including death due to index cancer, second malignant neoplasms (SMNs), and noncancer causes. Patients with RT had a lower probability of death and crude 5-year cumulative incidence of death. Moreover, there were significantly lower SMRs in patients with RT than in patients without RT. Differences between the two groups were greatest for mortality due to hematological malignancies and infections. Additionally, in the RT cohort, the SMR for index-cancer-related death was highest in the first year after diagnosis and gradually decreased. Hematological malignancies and infections were the most common specific SMN and noncancer causes of death, respectively. Conclusions: RT did not increase mortality from index cancer, SMNs, or noncancer causes in AYA patients with lymphoid malignancies. The current analysis may serve as a reference for healthcare providers monitoring RT application for AYA lymphoid malignancy survivors.

ABCL-400 Adult Burkitt Lymphoma: An Institutional Experience With Uniform DA-EPOCH-R Protocol

DA-EPOCH-R (dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab) is one of the standard chemotherapeutic regimens for Burkitt lymphoma. This study aimed to evaluate the safety and efficacy of DA-EPOCH-R in adult Burkitt lymphoma in an Indian context. This retrospective study included 16 patients with adult Burkitt lymphoma who received uniform DA-EPOCH-R protocol, intrathecal methotrexate with each cycle, and GCSF prophylaxis in the Department of Medical Oncology at All India Institute of Medical Sciences, New Delhi, India, from May 1, 2013, to December 2021. Sixteen patients were included in this study. The median age was 35 (21-65) years with a male:female ratio of 3:1. The stage distribution was I/II in 4 cases (25%) and III/IV in 12 cases (75%). Poor performance status (ECOG>2) was observed in 9 cases (56.25%). One case was HIV-positive, and 13 cases (81.2%) were high risk. CSF cytology was negative in all cases at baseline, and 5 cases had bone marrow involvement. Low albumin (serum albumin <3.5 g/dL) was seen in 6/16 cases (37.5%). After the median 5 cycles (range 3-6) of chemotherapy, the overall response was 93.7%, and 81.25% of patients achieved complete response. The maximum dose intensity was level 3 in 6 patients, level 2 in 9 patients, and level 1 in 1 patient. There were no treatment-related deaths. The most common hematological toxicities (grade 3-4) were neutropenia in 3 patients, thrombocytopenia in 1 patient, and anemia in 2 patients. Febrile neutropenia was observed in 2 patients. Infections, thrombosis, and Grade 3 peripheral neuropathy were documented in 4, 2, and 1 cases, respectively. In our study, 2-year event-free survival and overall survival were 75.4% and 83%, respectively, with a median follow-up period of 27 months. DA-EPOCH-R is an effective and safe protocol even in high-risk adult Burkitt lymphoma patients.

Apheresis for chimeric antigen receptor T-cell production in adult lymphoma patients.

To date, in-depth analysis of leukapheresis products as starting material for CAR T-cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients. Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program. Apheresis success was defined as meeting a target total nucleated cell (TNC) count of ≥2 × 109 , a CD3-positive lymphocyte count of ≥1 × 109 and an overall viability of ≥70% in the lymphapheresis product. Twenty-three patients (age 37-77 years) and 24 apheresis runs were evaluated. The median CD3-positive lymphocyte count in peripheral blood at the beginning of apheresis was 565 cells/μl (range: 70-1345 cells/μl). Circulating lymphoma cells were detected in one patient prior to apheresis. Target criteria were met in 21 of 23 patients. The median TNC count in the apheresate was 11.2 × 109 (range: 2.9 × 109 -47.4 × 109 ). The median CD3-positive lymphocyte count in the apheresate was 2.55 × 109 (range: 0.370 × 109 -6.915 × 109 ), which resulted in a median collection efficiency for CD3-positive lymphocytes of 63.7% (range: 9.56%-93.6%). No adverse events associated with the apheresis process were observed. Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3-positive lymphocytes for CAR T-cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre-emptive lymphocyte collection in DLBCL-NOS patients intended to undergo treatment with Tisagenlecleucel.