Search

The genetic predisposition to lymphoma is not fully understood. We identified 13 lymphoma‐cancer families (2011–2021), in which 27 individuals developed lymphomas and 26 individuals had cancers. Notably, male is the predominant gender in lymphoma patients, whereas female is the predominant gender in cancer patients (p =.019; OR = 4.72, 95% CI, 1.30–14.33). We collected samples from 18 lymphoma patients, and detected germline variants through exome sequencing. We found that germline protein truncating variants (PTVs) were enriched in DNA repair and immune genes. Totally, we identified 31 heterozygous germline mutations (including 12 PTVs) of 25 DNA repair genes and 19 heterozygous germline variants (including 7 PTVs) of 14 immune genes. PTVs of ATM and PNKP were found in two families, respectively. We performed whole genome sequencing of diffuse large B cell lymphomas (DLBCLs), translocations at IGH locus and activation of oncogenes (BCL6 and MYC) were verified, and homologous recombination deficiency was detected. In DLBCLs with germline PTVs of ATM, deletion and insertion in CD58 were further revealed. Thus, in lymphoma‐cancer families, we identified germline defects of both DNA repair and immune genes in lymphoma patients. [ABSTRACT FROM AUTHOR]

Background: Patients with lymphoma and chronic hepatitis B virus infection need to be treated with both chemotherapy and nucleotide analogue (NA) therapy. However, dynamic changes in HBV DNA loads with increasing chemotherapy cycles are lacking. It is unknown whether HBV replication markers, namely, the quantitative hepatitis B core antibody (qAnti-HBc), HBV RNA, and the hepatitis B virus core-related antigen (HBcrAg), are also markers for predicting HBV reactivation (HBVr). Methods: From 29 June 2010 to 6 December 2021, the data of patients with single-site diffuse large B-cell lymphoma and HBV infection (HBsAg+ and HBsAg−/anti-HBc+) were collected from a hospital medical record system, retrospectively. Serum HBV DNA loads (using real-time fluorescent quantitative PCR tests), qAnti-HBc levels (using a newly developed chemiluminescent particle immunoassay), HBV RNA levels (using the simultaneous amplification testing method based on real-time fluorescence detection), and HBcrAg levels (using a Lumipulse G HBcrAg assay) were tested, and factors related to HBVr were analyzed. Results: Under NAs, the HBV DNA loads of 69 HBsAg+ lymphoma patients declined from 3.15 (2.13–4.73) lg IU/mL to 1.00 (1.00–1.75) lg IU/mL, and further declined to 1.00 (1.00–1.04) lg IU/mL at the end of a 24-month follow-up. The qAnti-HBc levels decreased gradually during chemotherapy in HBsAg+ lymphoma patients (F = 7.090, p = 0.009). The HBV RNA and HBcrAg levels remained stable. A multivariate analysis revealed that higher qAnti-HBc levels (1.97 ± 1.20 vs. 1.12 ± 0.84 lg IU/mL, OR = 6.369, [95% CI: 1.523–26.641], p = 0.011) and higher HBV RNA levels (1.00 ± 1.13 vs. 0.37 ± 0.80 lg copies/mL, OR = 3.299, [95% CI: 1.229–8.854], p = 0.018) were related to HBVr in HBsAg−/anti-HBc+ lymphoma patients. Conclusions: HBV DNA loads declined under NAs during chemotherapy in lymphoma patients. In HBsAg−/anti-HBc+ lymphoma patients, a higher level of baseline serum qAnti-HBc and HBV RNA levels can predict the likelihood of HBVr during chemotherapy. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, the different situations of identifying second primary malignant tumors (SPMTs) in lymphoma patients with synchronous solid tumors remain to be comprehensively investigated. Methods: We retrospectively collected information pertaining to lymphoma patients with synchronous solid tumors (diagnosed within 6 months) at Peking University Cancer Hospital & Institute between 2009 and 2019. The non‐parametric Aalen–Johansen estimator was applied to calculate cumulative incidence function in the competing risk model. Furthermore, propensity score‐matched analysis was performed to compare survival differences in lymphoma patients with or without synchronous solid tumors. Results: Thirty‐eight patients were enrolled. There were three situations of identifying SPMTs. First, in 15 patients (39.5%), SPMTs were identified before the initiation of any treatment. Among them, priority was given to anti‐lymphoma treatment in case of only three patients. Second, in 17 patients (44.7%), SPMTs were unexpectedly detected on surgical specimen assessment; of them, 13 received anti‐lymphoma treatment after surgery. Third, in six patients (15.8%), SPMTs were identified after the outset of treatment for the primary tumor; in this population, three of four patients with lymphoma switched toward the treatment plan for SPMTs. The 5‐year overall survival was 58.7%. The cumulative incidence function within 5 years was 26.6% for lymphoma and 14.7% for other solid tumors. The early identification of SPMTs was associated with better outcomes (p = 0.048). After balancing the baseline characteristics, no differences in survival were observed between lymphoma patients with and without synchronous solid tumors (p = 0.664). Conclusions: This is the first study to present the different situations of identifying SPMTs in lymphoma patients with synchronous solid tumors. In only <50% patients, SPMTs were identifiable at baseline. SPMT identification at different situations may make it difficult to choose the optimal therapeutic option, which may consequently impact patient survival. [ABSTRACT FROM AUTHOR]

Background: There is no consensus regarding the risk stratification scores for elderly patients with diffuse large B-cell lymphoma (DLBCL). We aimed to compare the prognostic predictive ability of the current clinical scoring indices in DLBCL elderly patients treated with the R-CODP regimen (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone). Methods: We retrospectively collected the data of elderly DLBCL patients who received the R-CODP regimen as the first-line treatment. The efficacy of the regimen was evaluated. The Akaike information criteria (AIC), concordance index (C-index), and integrated discrimination improvement (IDI) were used to assess the fitness and prognostic performance of the current clinical prognostic indices. Results: In the total of 158 patients enrolled, the median follow-up time was 6.7 years (95% CI: 6.3– 7.9), and the 5-year OS was 52.8% (95% CI: 45.5%– 61.2%). The International Prognostic Index (IPI), National Comprehensive Cancer Network-IPI (NCCN-IPI), and Elderly International Prognostic Index (E-IPI) were all significantly associated with OS (P < 0.001 for all). However, no significance was observed in 5-year OS in the low- vs low-intermediate-risk groups for IPI (P = 0.377), NCCN-IPI (P = 0.238), and E-IPI (P = 0.080). Compared with the IPI and NCCN-IPI, the E-IPI had the lowest AIC value of 747.5 and the highest C-index of 0.692. For predicting 5-year mortality, the E-IPI showed better performance (AUC: 0.715 for E-IPI vs 0.676 for IPI, P = 0.036), with the IDI of 6.29% (95% CI: 3.71%-8.88%, P < 0.001) and 4.80% (95% CI: 1.32%-8.28%, P = 0.007) compared to the IPI and NCCN-IPI, respectively. Conclusion: The E-IPI might be a better prognostic prediction model in Chinese DLBCL generics treated with R-CODP for predicting 5-year mortality. However, the IPI, NCCN-IPI, and E-IPI did not seem to be able to distinguish patients with a favorable prognosis well. [ABSTRACT FROM AUTHOR]

Lymphoma is a malignant disease that threatens human health and imposes a significant burden on the society burden; however, there are limited accurate mortality data on lymphoma in China. The present study aimed to analyse lymphoma-associated mortality at the national and provincial levels in mainland China. Mortality data of lymphoma was extracted from the disease surveillance system of the Chinese Center for Disease Control and Prevention. Mortality was represented by the number of deaths, crude mortality rate, and age-standardized mortality rate. Temporal trends in mortality rates were examined using the fitting joinpoint models. Lymphoma accounted for 31,225 deaths in 2020, of which 1,838 and 29,387 were due to Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), respectively. The age-standardized mortality rate per 100,000 population was 1.76 for lymphoma, 0.10 for HL, and 1.66 for NHL. The mortality rate increased with age, reaching a peak in the age group of 80–84 years for HL and over 85 years for NHL. Moreover, the death risk due to lymphoma was approximately 1.5–2 times greater in males than in females in all age groups. The mortality rate was higher in eastern China than in central and western China, indicating a heterogeneous distribution at the provincial level. During 2013–2020, the mortality rate of lymphoma decreased by 1.85% (−22.94% for HL and −0.14% for NHL). In conclusion, the mortality of lymphoma varied by sex, age, and regions, which highlighted the need of establish differentiated strategy for disease control and prevention. [ABSTRACT FROM AUTHOR]

Purpose: Copanlisib, a pan-PI3K inhibitor, has previously shown clinical efficacy and a tolerable safety profile in patients with indolent non-Hodgkin lymphoma. However, the pharmacokinetics, safety, tolerability, and efficacy of copanlisib in Chinese patients have not been reported. Methods: This was a single-arm, open-label, phase I study of copanlisib in Chinese patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). Patients received a single intravenous 60 mg infusion of copanlisib over 1 h on days 1, 8, and 15 of a 28-day cycle, with 1 week of rest. Safety was monitored throughout the study, and plasma copanlisib levels were measured for pharmacokinetic analysis. Tumor response was determined by independent central radiologic review. Results: Sixteen patients were enrolled and 13 were treated with 60 mg of copanlisib for a median of 15.0 weeks. With a Cmax of 566 μg/L and a AUC (0–24) of 1880 μg·h/L following single intravenous infusion, the pharmacokinetic parameters of copanlisib were consistent with that in previous studies, and no accumulation in plasma was observed. Treatment-emergent adverse events were reported for all 13 patients, the most common of which were hyperglycemia (100.0%), hypertension (76.9%), decreased neutrophil count (76.9%), and decreased white blood cell count (69.2%). Seven out of 12 evaluated patients achieved partial response, resulting in an overall response rate of 58.3% Conclusions: Copanlisib was well tolerated in Chinese patients with relapsed or refractory iNHL at the dose of 60 mg and demonstrated encouraging disease control, thus warranting further clinical investigation. Clinical trial registration number: NCT03498430 (April 13, 2018). [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma (AITL) is a unique sub-type of peripheral T-cell lymphoma (PTCL). We aimed to evaluate treatment programs and prognostic factors of 121 newly diagnosed patients with AITL in China from January 2001 to December 2018. The median age was 58 years with male predominance. Bone marrow involvement appeared in only 8.3% of patients, which was different from the previously published literature. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) were 29.7% and 44.0%, respectively. Univariate and multivariate analyses showed that involvement of >5 nodal areas, age and Beta-2 microglubulin were highly predictive of OS but only the involvement of fewer than five nodal areas was significant for PFS. We identified a novel prognostic model including the three factors that may be applied in clinical practice and offer an alternative to IPI and PIT. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs. [ABSTRACT FROM AUTHOR]

Little is known regarding the outcome of lymphoma patients undergoing autologous hematopoietic stem cell transplantation (AHSCT) using inadequate hematopoietic stem cell (HSC) doses. Fifty-six patients were enrolled in the study, and the cohort was subdivided into two groups according to the infusion dose: < 1 × 106/kg (poor HSC group) and 1–2 × 106/kg (unfavorable HSC group). Compared with the unfavorable group, the poor HSC group had a longer median time to neutrophil (13 vs. 11 days, p =.007) and platelet engraftment (17 vs. 13 days, p =.024). CD34+ cell infusion dose of < 1 × 106/kg was the only risk factor for neutrophil and platelet engraftment. The expected 3-year progression-free survival and overall survival rates for the whole cohort were 53% and 66%, and no statistical difference was observed between two groups. In conclusion, inadequate HSC infusion dose did not negatively impact AHSCT patient survival but significantly prolonged the time to hematopoietic engraftment. [ABSTRACT FROM AUTHOR]

Anthracycline-related cardiotoxicity is an important dose-limiting toxicity for Hodgkin lymphoma (HL) treatment. This study aimed to assess the efficacy and safety of pegylated liposomal doxorubicin (PLD) for HL treatment. Patients with newly diagnosed HL treated with at least two cycles of PLD-containing chemotherapy were retrospectively analyzed. The dosing and scheduling of the PLD-containing regimen (the PBVD regimen) were as follows: PLD 25 mg/m2, vincristine 1.4 mg/m2 (maximum dose of 2 mg), bleomycin 10 mg/m2, and dacarbazine 375 mg/m2 at days l and 15, repeated every 28 days. Forty-six HL patients were analyzed. The median age was 41.5 years (range 12–77 years), with a male/female ratio of 0.9:1. Fourteen (30%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status score > 1, and 32 (70%) had a history of cardiovascular disease (CVD) or related risk factors. The median chemotherapy cycle number with the PBVD regimen was 6 (range, 2–8). The overall response rate (ORR) was 91% for the whole cohort; 35 (76%) patients achieved complete remission (CR), and 7 (15%) achieved partial remission. The efficacy of the PBVD regimen was similar in patients with or without CVD or related risk factors (ORR 93% vs. 91%, P = 1.00; CR 86% vs. 72%, P = 0.46). With a median follow-up of 28.5 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 70% and 82%, respectively, for the whole cohort. The differences in the PFS and OS rates between the groups with or without CVD or related risk factors were not significant. Cardiotoxicity was observed in 6 (13%) patients. All adverse events were grades 1–2. The PBVD regimen is an effective chemotherapy option with tolerable toxicity, and it could be a substitute in HL patients who cannot be treated with conventional doxorubicin, especially those with CVD or related risk factors. [ABSTRACT FROM AUTHOR]

Background: The treatment outcomes and prognosis of lymphoma are affected by various factors such as hospital types. This study was to describe the temporal trend in the survival of lymphoma in an academic center in China. Methods: A total of 3840 consecutive patients with lymphoma diagnosed between 1996 and 2015 were reviewed. Eighty patients were excluded, and finally, 3760 patients were analyzed in this study. The cohort was divided into four groups according to calendar periods at diagnosis: 1996‐2000, 2001‐2005, 2006‐2010, and 2010‐2015. The overall survival (OS) rates among the four groups were compared. Results: The 5‐ and 10‐year OS for the whole cohort were 62% and 52%, respectively. The 5‐year OS of patient with classic Hodgkin lymphoma (cHL), mature B‐cell lymphoma (BCL), and peripheral T‐cell lymphoma (PTCL) were 79%, 63%, and 50%, respectively. Among mature BCL, the 5‐year OS was highest in follicular lymphoma (77.8%), followed by Burkitt lymphoma (76.5%), marginal zone lymphoma (74.1%), diffuse large B‐cell lymphoma (61.5%), small lymphocytic lymphoma/chronic lymphocytic leukemia (55.1%), and mantle cell lymphoma (44.3%). Among PTCL, the 5‐year OS was highest in ALK+anaplastic large cell lymphoma (79.0%), followed by ALK−anaplastic large cell lymphoma (63.1%), natural killer/T‐cell lymphoma (57.7%), angioimmunoblastic T‐cell lymphoma (34.9%, and peripheral T‐cell lymphoma not otherwise specified (27.6%). Significant improvement in the survival of lymphoma was observed, with the 5‐year OS increasing from 48% in 1996‐2000 to 65% in 2011‐2015 (P <.001). The 5‐year OS of patients with cHL, mature BCL, and PTCL changed from 55%, 49%, and 41% in 1996‐2000 to 79%, 65%, and 51% in 2011‐2015, respectively (P values were.014,.002, and.592, respectively). Conclusion: The survival of most types of lymphoma such as cHL and mature BCL, rather than PTCL, was improved significantly during the past two decades. [ABSTRACT FROM AUTHOR]

While combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) cures most patients with diffuse large B-cell lymphoma (DLBCL), those with high-risk international prognostic index disease have inferior survival. Enzastaurin as a potent inhibitor of PKC-β and PI3K/AKT pathway suppressor has been tested in many clinical trials including two key studies in DLBCL: Phase III maintenance study (Preventing Relapse in Lymphoma Using Daily Enzastaurin [PRELUDE]) and a first-line Phase II study (S028). DNA extracted from PRELUDE patients' blood samples was retrospectively genotyped identifying a novel genetic biomarker, DGM1 that showed high correlation with response to enzastaurin. A similar finding observed in the S028 study suggested that addition of enzastaurin to R-CHOP may significantly improve outcomes as frontline therapy for high-risk DGM1 positive DLBCL patients. ENGINE is a global, multicenter, placebo-controlled and randomized study to compare the effect of R-CHOP/enzastaurin as frontline treatment in high-risk DLBCL patients. The primary end point for this study is overall survival in patients who are DGM1 positive. Clinical Trial Registration Identifier: NCT03263026. [ABSTRACT FROM AUTHOR]

Background: The accurate information about lymphoma burden at national and provincial levels remains unknown in China. Methods: Following the general analytical strategy used in GBD 2016, the age-, sex-, and province-specific incidence, mortality, and prevalence of lymphoma in China were analyzed. Trends in the incidence, mortality, prevalence, and disability-adjusted life years (DALYs) due to Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) were assessed from 2006 to 2016. Results: It was estimated that there were 75,400 new cases and 40,500 deaths of lymphoma in 2016 in China, of which 6900 new cases and 2900 deaths were due to HL, while 68,500 new cases and 37,600 deaths were due to NHL. The age-standardized incidence rate (ASIR), mortality rate (ASMR), and prevalence rate (ASPR) per 100,000 were 0.46, 0.19, and 1.75 for HL, and 4.29, 2.45, and 14.9 for NHL, respectively. An upward trend with age in incidence and mortality was observed. Males had higher incidence and mortality rates than females in all age groups. Sociodemographic index had a correlation with the ASIR (r = 0.75), ASMR (r = − 0.74), ASPR (r = 0.84), and age-standardized DALYs (r = − 0.75) of HL, as well as with the ASIR (r = 0.80), ASPR (r = 0.83), and age-standardized DALYs (r = − 0.33) of NHL. From 2006 to 2016, the age-standardized DALYs of HL decreased significantly, while the age-standardized DALYs of NHL increased from 2006 to 2013 and remained stable from 2013 to 2016. Conclusions: The burden of lymphoma in China showed unexpected patterns varied by sex, age, and provinces, with an increased trend of NHL and a decreased trend of HL from 2006 to 2016. [ABSTRACT FROM AUTHOR]

Background: There is a dearth of accurate information about patterns of mortality of lymphoid neoplasms and temporal trends in China. In this nationwide mortality study, we aimed to assess the mortality of lymphoma and myeloma in 2017 and the changes in the trend from 2004 to 2016. Methods: Death certificate data obtained from the Chinese Center for Disease Control and Prevention's disease surveillance points system (CDC-DSP) and population data from the National Bureau of Statistics of China were used in this study. We described the mortality of lymphoma and myeloma in 2017 by age group, sex, residence, and region and evaluated the temporal trend from 2004 to 2016 using joinpoint regression. Results: An estimated 52,000 deaths associated with lymphoma and myeloma occurred in 2017. The age-standardized mortality rate China (ASMRC) and age-standardized mortality rate worldwide (ASMRW) per 100,000 were 3.74 and 2.60, respectively. Males had higher ASMRC than females (4.54 vs. 2.91 per 100,000). The ASMRC in urban areas was significantly higher than that in rural areas (4.35 vs. 3.47 per 100,000). The age-specific mortality rate showed an upward trend with age and reached a maximum in the age group of over 85 years. In terms of regional variation, Eastern China had the highest mortality rate (3.43/100,000), followed by Central China (3.10/100,000) and Western China (3.02/100,000). The mortality rates of lymphoma and myeloma increased annually by 4.5% during the period 2004–2016, with a significant rapid upward trend in rural areas since 2007. Conclusions: The mortality of lymphoma and myeloma increased in China from 2004 to 2017. The rapid increase in disease burden in rural areas highlights new challenges for disease prevention and control strategies. [ABSTRACT FROM AUTHOR]