International Prognosis Index Research Articles

Benefit of consolidative radiation in patients with extranodal limited-stage diffuse large B-cell lymphoma: a multicenter retrospective study in China.

Approximately 40% of limited-stage (stage I and II) diffuse large B-cell lymphoma (LS-DLBCL) presents with extranodal disease. Extranodal LS-DLBCL may have significant biological differences and associated with worse outcomes than nodal disease. Although rituximab based chemoimmunotherapy is standard of first-line treatment, the role of consolidative radiotherapy (RT) in this particular subgroup is controversial. In this multicenter retrospective study, we evaluated the survival benefit of consolidative RT in patients diagnosed with extranodal LS-DLBCL and received rituximab-based chemoimmunotherapy with or without consolidative RT. A total of 328 patients were included, 129 patients (39.3%) received chemoimmunotherapy and consolidative RT, and 199 patients (60.7%) received chemoimmunotherapy alone. With a median follow-up of 5.1 years (range, 0.3-14.8 years), 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 75.4% and 83.9%, respectively. In multivariate analyses, the addition of consolidative RT was associated with superior OS (P = 0.004) and PFS (P = 0.005). High stage-modified International Prognosis Index (SM-IPI) risk predicted worse OS (P = 0.001) and PFS (P = 0.005). Also, propensity score-matched analyses showed RT improved both OS (hazard ratio [HR] 0.228, 95% confidence index [CI] 0.111-0.467, P < 0.001) and PFS (HR 0.308, 95% CI 0.167-0.566, P < 0.001). Among patients who achieved CR, 49 patients (16.6%) developed disease relapse, of which 30.6% relapsed at local sites. Consolidative RT significantly reduced relapse risk (P = 0.002). Our results demonstrated that consolidative RT significantly improved outcomes in patients with extranodal LS-DLBCL in the rituximab era.

Lymphoma relapse 1 year or later after immunochemotherapy in DLBCL patients: clinical features and outcome

Despite great advances in treatment, 30–40% of patients with DLBCL undergo relapses. Patients with a relapse within 1 year or beyond have a distinct outcome. Few clinical characteristics and survival data in the Chinese population have been published. We aimed to define the incidence and clinical features of DLBCL patients with very early relapse after front-line immunochemotherapy who may benefit greatly from the emerging chimeric antigen receptor T-cell therapy. Data of 564 DLBCL patients were analyzed. Among the 413 patients achieving a first complete remission, 59 underwent relapses: 32 patients (54.2%) relapsed within 1 year, and 27 patients (46.8%) relapsed 1 year or more. Patients relapsing within 1 year, in comparison with the other group, showed an inferior risk profile at diagnosis: elevated lactate dehydrogenase level (P = 0.002), high Eastern Cooperative Oncology Group performance score (P = 0.02), and high international prognosis index (P = 0.004). As expected, a worse overall survival was observed in the early relapse group. Multivariate analysis for OS showed that relapse within 1 year was an independent parameter for reduced overall survival (HR 0.241, P = 0.002).

Efficacy and Safety of Selinexor-Based Combination Therapy in CNS Lymphoma: A Retrospective Experience

Introduction ： Primary central nervous system lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma (DLBCL) with distinct clinical and biological features, characterized by an aggressive course and poor prognosis. Patients with relapsed/refractory (R/R) disease have an unmet medical need due to a median overall survival (OS) of only 6.8 months. Novel therapies are urgently required for patients with R/R CNSL. In June 2020, the U.S. Food and Drug Administration granted accelerated approval to selinexor for the treatment of adult patients with R/R DLBCL. Selinexor has demonstrated central nervous system (CNS) penetration and activity in secondary CNS lymphoma (SCNSL) patients. Thus, we conducted a retrospective review of PCNSL/SCNSL cases treated with a selinexor-based regimen to preliminarily evaluate its effectiveness and safety. Methods: We retrospectively analyzed the medical records of 13 patients with CNSL who received selinexor-based combination therapy between June 2021 and June 2023 at three research centers in China. Among these cases, 2 were previously untreated, and 11 were relapsed or refractory patients. All patients had histopathologically confirmed DLBCL at the time of initial diagnosis. Data collection included baseline characteristics, treatment efficacy and safety evaluation. Results: A total of 13 patients (10 PCNSL and 3 SCNSL) were included in the study, with a median age of 62 years (range, 28-73), including three male patients. The median international extranodal lymphoma study group (IELSG) score for PCNSL cases was 3 (range, 1-3). The median International Prognosis Index (IPI) score for the three systemic DLBCL cases was 5 (range, 3-5), and three cases were at Ann Arbor stage IV. Among the patients, 11 had relapsed or refractory disease with a median of 2 prior treatments (range, 1-4), and 10 of them were refractory to previous treatments. The main patient characteristics, responses, and toxicities of the selinexor-based combination regimen are summarized in Table 1. Figure 1 presents the response of all evaluable patients. The overall response rate (ORR) of the patients was 84.6% (11 /13), with a complete response (CR) rate of 76.9% (10/13). Both treatment-naïve patients achieved CR after four and six cycles of the selinexor-containing first-line regimen, respectively. They are currently experiencing sustained remission, with the longest duration reaching 13 months. For relapsed/refractory CNSL, the ORR and CR rate were 81.8% (9/11) and 72.7% (8/11), respectively. Two patients had stable disease (SD). Among the 9 patients who achieved remission, 4 patients are still in remission, with the longest duration reaching 20 months, 2 patients received CART bridging therapy, one received radiation therapy, and 2 patients experienced disease progression after 5 months, but all are currently still alive. These patients are currently under continuous observation. Due to the heterogeneity of the selinexor-based regimens, the categories and severity of adverse events (AEs) varied greatly among the different regimens. The median treatment cycle number was six (range, 2-22). One patient died due to pneumonia infection, one patient was lost to follow-up, three patients successfully bridged to CART/RT, and eight patients completed the treatment as planned. The common AEs included thrombocytopenia, infection, nausea, vomiting, and gastrointestinal bleeding(Table 1). Conclusion: This report provides encouraging evidence of the efficacy and tolerable safety of the selinexor-based regimen in the treatment of CNSL. However, further prospective studies with a larger sample size are needed to provide more comprehensive evidence regarding the efficacy of selinexor in central nervous system lymphoma and to determine the appropriate dosage and optimal combination strategies.v

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in tumors, but its clinical utility in risk stratification and early prediction of relapse for peripheral T cell lymphoma (PTCL) has not been well explored. Methods: Using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before and after first-line therapy in 41 PTCL patients. Results: For the 41 patients, we obtained a total of 36 primary tumor specimens, 41 pretreatment blood samples and 21 serial blood samples before and after first-line therapy. By the last visit in March 2023, the median follow-up duration was 10.0 (range, 2.5–18.8) months. The clinical characteristics of the 41 patients were shown in Figure 1A. All patients received CHOP-like regimen. The top 30 somatic mutations of tissues were shown in Figure 1B. Pretreatment ctDNA (Pre-ctDNA) achieved an overall sensitivity of 81.3% (159/196) in detecting variants verified in tumor, indicating that ctDNA is a reliable source for PTCL genotyping. In addition, ctDNA allowed for the identification of additional 98 somatic mutations that were undetectable in tumor gDNA, which demonstrated that ctDNA could overcome tumor spatial heterogeneity (Figure 1C). Pre-ctDNA burden was significantly associated with clinical characteristics, including extranodal involvement (P < 0.001), lactate dehydrogenase (LDH) levels (P < 0.001), age (P = 0.047), B symptoms (P = 0.038), stage (P = 0.008) and international prognosis index (IPI) score (P < 0.001) (Figure 1D). The cell-free (cfDNA) fragments profoundly reflects both genomic and chromatin characteristics. Our results suggested that all samples had a more prominent mono-nucleosomal fragments abundance (167 bp), whereas the samples of angioimmunoblastic T-cell lymphom (AITL) and the samples with high IPI scores or non-complete response (CR) in the mid-stage of treatment had a more prominent shift towards shorter cfDNA size (Figure 1E). Similarly, when we analyzed the response to treatment, significant decline in ctDNA levels was observed at end of treatment (EOT) in patients with CR compared with those who did not achieved CR. The 4 patients with CR and EOT ctDNA negative achieved continuous CR until now (Figure 1F). Furthermore, high pre-ctDNA levels presented unfavourable PFS (P = 0.002) and OS (P = 0.020) (Figure 1G). Multivariate cox regression analysis showed that high pre-ctDNA burden (P = 0.029) and TP53 mutation (P = 0.005) (Figure 1H). Subgroup analysis showed that patients without these 2 risk factors (Type 1) had longer PFS than the other patients with more than 0 risk factor (Type 2) (P < 0.001) (Figure 1I). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers No conflicts of interests pertinent to the abstract.

Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis

Follicular lymphoma (FL) is a type of B-cell lymphoma that originates at the germinal center and has a low malignancy rate. FL has become the most common inert lymphoma in Europe and America but has a relatively low incidence in Asia. To explore the clinical features, curative effects, and prognostic factors of FL. Completed medical records of 49 patients with FL who were admitted to the Ningbo First Hospital from June 2010 to June 2021 were examined. These patients were definitively diagnosed by pathological biopsy or immunohistochemical staining. The diagnostic criteria were based on the 2008 World Health Organization classification of lymphomas. Ann Arbor staging was performed according to the imaging and bone marrow examination results. Risk stratification of all patients was performed based on the International Prognostic Index (IPI), age-adjusted IPI, Follicular Lymphoma International Prognosis Index (FLIPI), and FLIPI2 to compare the efficacy of different treatment regimens and analyze the related prognostic factors. The age of onset in patients ranged from 24 to 76 years, with a median age of 51 years. Most patients developed the disease at 40-59 years of age, and the male:female ratio was 1.6:1. No significant difference was noted in the curative effect between the non-chemotherapy, combined chemotherapy, and other chemotherapy regimens (P > 0.05). Hemoglobin (Hb) level < 120 g/L, Ki-67 value > 50%, bone marrow involvement, and clinical stages III-IV were associated with a poor prognosis of FL (P < 0.05). However, the influence of other indicators was not statistically significant. Risk grouping was performed using the FLIPI, and the results showed that 24.5%, 40.8%, and 34.7% of patients were in the low-, moderate-, and high-risk groups, respectively. According to the survival analysis results, the survival rate of patients was lower in the high-risk group than in the other low-risk and moderate-risk groups (P < 0.05). FL mainly occurs in middle-aged and elderly men, primarily affecting lymph nodes and bone marrow. Hb level, Ki-67 value, bone marrow involvement, and clinical staging were used to evaluate prognosis.

Dual epigenetic agents plus rituximab-gemcitabine-oxaliplatin as salvage treatment in relapsed/refractory diffuse large B-cell lymphoma patients failure of salvage chemotherapy.

Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) patients' failure of salvage chemotherapy had extremely worse prognoses. Herein, 14R/R DLBCL patients failed to salvage chemotherapy were exposed to dual epigenetic agents (Chidamide 30mg biw*2w and Decitabine 10mg/m2 qd*d1-d5) and sequential R-GemOx (rituximab 375mg/m2 qd d6; gemcitabine 1g/m2 d7, d14; and oxaliplatin 100mg/m2 d7) for further salvage chemotherapy. Finally, 11/14(78.6%) patients achieved overall response with 6/14(42.9%) achieving complete remission and 2-year overall survival (OS)/progression free survival (PFS) rate was 42.7%, extremely higher than reported previously. Further subgroup analysis demonstrated that 2-year OS/PFS rate was significantly higher in patients achieved complete/partial remission or with low international prognosis index (IPI 0-2) than that in patients with steady disease or high IPI (3-5). Common grade 3-4 adverse events were hematological toxicities. All toxicities were transient and reversible. Our report implicates that combination of dual epigenetic agents and R-GemOx is a safe and promising alternative for R/R DLBCL patients.

P65-5 The impact of the Geriatric 8 on prognosis in patients aged 65 years and older with DLBCL

Because of the heterogeneity among elderly patients with diffuse large B-cell lymphoma (DLBCL), the establishment of an easy-to-use geriatric assessment scale to predict prognosis other than the International Prognosis Index (IPI) is unmet needs. The aim was to evaluate the impact of the Geriatric 8 (G8) score on the survival of elderly patients with DLBCL.

Hypoalbuminemia predicts inferior outcome in patients with AIDS-related lymphoma

BackgroundThe prognostic value of serum albumin in acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) remains covered.MethodsWe retrospectively analyzed de novo ARL patients from 2013 to 2019 across three centers. Factors correlated with progression-free survival (PFS) and overall survival (OS) were evaluated in Kaplan–Meier, univariate and multivariate Cox proportional hazard models.ResultsA total of 86 ARL patients were enrolled with a median follow-up of 34 months. In the cohort, the OS and 2-year PFS rates were 37.5% and 35.4%, respectively. In multivariate models, older age (PFS, hazard ratios [HR] = 1.035, p = 0.037; OS, HR = 1.034, p = 0.041) and hypoalbuminemia (OS, HR = 0.910, p = 0.038) predicted inferior survival. ARL patients with hypoalbuminemia showed worse OS and 2-year PFS (p = 0.028 and p = 0.01, respectively), which was associated with poor Eastern Cooperative Oncology Group performance status (ECOG PS) and higher International Prognosis Index (IPI) score.ConclusionIn conclusion, serum albumin at diagnosis is an independent prognostic factor for overall survival in AIDS-related lymphoma.

Serum Free Light Chain Assay as a Prognostic Marker in Patients with Aggressive B-Cell Non-Hodgkin's Lymphoma: Impact on Survival Outcome.

T.M. AnoopBackground The role of serum free light chain (FLC) as a prognostic biomarker in lymphoproliferative diseases is being increasingly studied. In this study we present the 5-year survival outcome for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL) and their relation to FLC and other known prognostic markers. Materials and Methods This is a prospective study conducted in patients diagnosed with aggressive B-cell NHL. Serum FLC level and ratio were estimated prior to initiation of treatment. Results A total of 100 patients were included in the study from December 2013 to December 2015 with a median age of 53 years. Thirty-eight patients (38%) had elevated FLC level of which 26% were polyclonal and 12% were monoclonal elevations. Abnormal FLC ratio was noted in 12% patients. Median follow-up duration of the study was 75 months. Five-year relapse-free survival (RFS) for the study population was 54.4%. Five-year RFS was 64.1% for early stage and 48.2% for advanced stage diseases ( p = 0.05). The RFS was significantly better in age less than 60 years (59.5% vs 43.8%, p < 0.001). Five-year overall survival (OS) was 61.3%. OS was significantly better in younger patients (73.6% vs 33.4%, p < 0.001), with International Prognosis Index score of 0 to 2 (87.4% vs 26.7%, p < 0.001). Patients with elevated FLC had inferior RFS (50% vs 71.4%, p = 0.04). Abnormal FLC ratio also strongly corresponded to inferior RFS (54.5% vs 66.2%, p = 0.001). OS was also significantly inferior in patients with abnormal FLC ratio (72.6% vs 63.6%, p = 0.001). Conclusion In patients with newly diagnosed aggressive B-cell NHL, elevated FLC levels and abnormal FLC ratio were significantly associated with inferior survival.

An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

AbstractExtranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered.

Central Nervous System International Prognostic Index Impacts Overall Survival in Diffuse Large B-cell Lymphoma Treated with R-Chop in a third Level Cancer Center from Mexico: A Survey of 642 Patients.

Central nervous system international prognosis index (CNS-IPI) is validated in European and the USA cancer databases. However, no validation has been done in Mexican population. The objective of the study was to assess the impact of the CNS-IPI on central nervous system (CNS) relapse and survival in Mexican patients with diffuse large B-cell lymphoma (DLBCL). In this retrospective analysis, clinical, biochemical, and histological variables and the CNS-IPI were analyzed. Six hundred and forty-two patients with DBLCL were included in the study. The mean ± SD age was 56.8 ± 14.9 years. Most had an ECOG of 0-1: 75% (n = 484) had absence of B-symptoms and advanced disease (clinical stage: III-IV, n = 433, 67.4%). According to the CNS-IPI, almost one-half were in the low-risk category. According to the CNS-IPI, CNS relapse rate was 1.36% (95% CI: 83.2-92.8), 3.1% (95% CI: 132.4-162.8), and 7.4% (95% CI 61-91) for patients in the low-, intermediate-, and high-risk categories, respectively. The median overall survival in the high-risk group (CNS-IPI) was 22 months, and it has not been achieved after 80 months of follow-up for the other groups. CNS-IPI was associated with survival; therefore, we propose its use as a prognostic tool for prospective validation.

Genetic abnormality and protein expression of C-MYC and PD-L1 in ALK-negative anaplastic large cell lymphoma

Objective: To investigate the genetic abnormality and protein expression of C-MYC and PD-L1 in the patients with ALK-negative anaplastic large cell lymphoma (ALK－ALCL), and to explore their roles in the pathogenesis of ALK－ALCL and their relationship with clinicopathological characteristics. Methods: Thirty-seven cases of ALK－ALCL diagnosed at Fujian Provincial Hospital from January 2003 to January 2017 were selected. Fluorescence in situ hybridization (FISH) was used to detect the genetic abnormality of C-MYC and PD-L1. The expression of C-MYC and PD-L1 proteins was detected by immunohistochemistry. The relationship between C-MYC and PD-L1 genes' abnormalities and protein expression was analyzed, as well as their associations with various clinicopathological parameters. Results: Among the 37 ALK－ALCL patients, 17 (45.9%) were positive for C-MYC protein, and 14 (37.8%) were positive for PD-L1 protein. There was a significant correlation between C-MYC protein and PD-L1 protein (r=0.990,P=0.014). The protein expression of C-MYC and PD-L1 (versus negative) was associated with the clinical stage of ALK－ALCL, respectively. The international prognosis index (IPI) in high-risk group was higher than that in the low-risk group (P<0.05). FISH test showed that 9 (24.3%) of the 37 cases had amplification of C-MYC gene, and no translocation of C-MYC gene was found in any of the cases. Amplification of PD-L1 gene was found in only 2 cases (5.4%). The 3-year overall survival rate of the C-MYC or PD-L1 immunohistochemistry-positive cases was significantly lower than those of the C-MYC or PD-L1 negative cases (P<0.01 and P<0.05), respectively. Conclusion: The expression of C-MYC and PD-L1 proteins are related to the clinical stage, IPI and overall survival rate of ALK－ALCL. Thus, it can be used to assess the disease's aggressiveness and to predict the prognosis of ALK－ALCL. The expression of PD-L1 in ALK－ALCL may be regulated by C-MYC, thus suggesting a possible design of combined C-MYC targeted therapy and immune checkpoint blocking for some ALK－ALCL patients.

ABCL-099: CNS Prognostic Index Impacts on Overall Survival in a Cohort of Patients with DLBCL Treated with RCHOP in a Single Mexican Institution

Context: The Central Nervous System International Prognosis Index (IPI CNS) scale has an impact to assess central nervous system relapse risk and prognosis in patients with diffuse large B-cell lymphoma (DBLCL). Objective: Determine the impact of clinical, biochemical parameters, and the IPI SNC scale in relapse and survival in Mexican population. Design: Retrospective analysis. IRB approved the review of files. Setting: Our study was developed in a cancer reference center. Patients or other participants: Inclusion criteria: patients ≥ 18 years of age, with DLBCL, treated with CHOP-rituximab at the Instituto Nacional de Cancerologia Mexico, from 2011 through 2018. Clinical characteristics included age, gender, comorbidities (diabetes mellitus, blood arterial hypertension, cardiopathy), the presence of B symptoms, bulky disease, clinical stage, IPI SNC scale, performance status (ECOG). Biochemical parameters: Lactic Dehydrogenase (LDH), and beta2 microglobulin levels, as well as histological subtype of DLBCL. Main outcome measures: Descriptive analysis. Kaplan-Meier method and differences between subgroups were compared with Log-Rank test. Cox regression analysis was used to identify the variables predicting on progression-free survival and overall survival. Results: Six hundred and forty-two cases were included. Mean age was 56.8 years, most of patients were in adequate performance status (ECOG 0-1: N=484, 75%), with absence of B-symptoms, but with advanced disease (clinical stage: III-IV, N= 433, 67.4%). According to IPI CNS, almost the half of them were in the low-risk category. Clinical response was considered as complete in most of patients (n=455, 71%). The CNS relapse rate was: 4/293 (1.36%), 10/322 (3.1%), and 2/27 (7.4%) for patients in low-, intermediate-, and high-risk categories, respectively. Mean overall survival (OS) was 46.36 months, and after Cox regression analysis, only the prognosis scores IPI & IPI-CNS scale were statistically significant on OS; median OS has not been achieved at 80 months of follow-up in low-risk group, in comparison with 22 months in high-risk group (p=0.001). Conclusions: In this population the IPI CNS scales impacted not only on CNS relapse but also in OS; therefore, the usefulness of this prognostic index becomes relevant in our population.

Baseline FDG-PET/CT detects bone marrow involvement in follicular lymphoma and provides relevant prognostic information

AbstractIn follicular lymphoma (FL), detection of bone marrow (BM) involvement (BMI) by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) improves the accuracy of staging vs BM biopsy (BMB) alone. Our objective was to determine the diagnostic utility of PET for BMI FL and the prognostic value of BMI by PET (positive PET result [PET+]). Records of patients (2002-2016) with PET and BMB at the time of initial treatment were reviewed. BMI was identified by positive BMB result (BMB+) and/or unifocal or multifocal BM FDG uptake on blindly reviewed PET scans with no corresponding CT abnormality (PET+). Among 261 patients, BMI was diagnosed in 78 patients (29.9%) by PET+, in 81 patients (31.0%) by BMB+, and in 113 patients (43.3%) by either PET+ or BMB+. PET+ upstaged 24 patients to stage IV, including 10 from stages I or II to stage IV. Median duration of follow-up was 6.0 years (range, 0-16.6 years). In univariate analysis, a high Follicular Lymphoma International Prognosis Index (FLIPI) score, PET+, and BMB+ correlated with shorter progression-free survival (PFS; all P ≤ .03), and high FLIPI, PET+, and combined PET+ and BMB+ with shorter overall survival (OS; all P ≤ .01). In multivariate analysis, PET+ was the only independent predictor of PFS, whereas high FLIPI score and PET+ predicted OS (P ≤ .03). Combined PET and BMB identify BMI more accurately than either BMB or PET alone, but BMB rarely adds critical information. For patients initiating treatment of FL, identification of BMI by PET is predictive of PFS and OS.

Characteristics and treatment outcomes of patients with primary ocular adnexal lymphoma in Northern Thailand

Purpose: To assess the characteristics and treatment outcomes of patients with primary ocular adnexal lymphoma (OAL) in Northern Thailand.&#x0D; Design: Retrospective cohort study.&#x0D; Methods: Data was collected from electronic medical records and operative notes from Chiang Mai University Hospital between January 2009 and December 2014. All available tissue biopsies of 54 patients were reviewed by agreement of two pathologists. The clinical characteristics and treatment outcomes were collected and analyzed.&#x0D; Results: A total number of 54 patients were identified of which 57.4% were female. The median age was 61.0 years (range, 4-86). The most common subtype of lymphoma was extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT) (n = 46, 85.2%). Seventy-five percent of the patients presented with a mass at the ocular adnexa, while 14.8% of the patients presented with proptosis. The sites of origin were as follows: lacrimal (46.3%), orbit (31.5%), conjunctiva (13%) and eyelid (7.4%). Two-thirds of the patients had Ann-Arbor Stage I, while 22% of patients had Stage IV. The majority of the patients (68.1%) had a low-risk international prognosis index (IPI). Treatment modalities involved field radiation (IFRT, 50%), chemotherapy (31.6%), combined chemoradiotherapy (7.9%) and surgical resection (10.5%). The overall response rate was 100% with a complete response rate of 77.8%. In patients with low-grade lymphoma, including MALT lymphoma, the 3-year progression-free survival (PFS) and overall survival were 69.9% and 92.5%, respectively.&#x0D; Conclusion: ENMZL of MALT was the major subtype of primary OAL. Radiotherapy was an effective treatment for the lower stages of disease providing a high response rate and encouraging survival outcomes.

High calcium risk in patients with diffuse large B-cell lymphoma during the chemotherapy: report of one case and review of literature

Objective To improve the understanding of high calcium risk in patients with diffuse large B-cell lymphoma (DLBCL) during the chemotherapy. Methods The diagnosis and treatment of high calcium risk in one patient with DLBCL during the chemotherapy in the Second Affiliated Hospital of Anhui Medical University was retrospectively analyzed, and the relevant literatures were reviewed. Results A 52-year-old man who was diagnosed with DLBCL (non-specific, non-germinal center source; stage Ⅳ group A; International prognosis index score 4 points, high-risk group) in June 2017. Two times R-CHOP chemotherapy was performed before diagnosis. This patient was admitted to the hospital for the third chemotherapy, and the disease assessment showed that the enlarged lymph nodes were not significantly smaller than before, and the tumor burden was still high. Therefore, the chemotherapy regimen was adjusted to R-GDP regimen. However, on the 8th day after the end of rituximab treatment, the patient had head pain, which might be related to the patient's poor sleep and primary invasion of the primary disease (blood calcium: 2.94 mmol/L). And then the ibuprofen and diuresis treatments were given, but the symptoms were still gradually worsening, and vomiting appeared on the 9th day, systemic fatigue with drowsiness and irritability appeared on the 12th day. Review blood calcium: 5.02 mmol/L. Adequate fluid hydration, diuretic, renal replacement treatments were given, and the level of blood calcium gradually returned to normal. Finally, the patient's symptoms were improved significantly, and he successfully completed R-GDP chemotherapy. Conclusion If a DLBCL patient has symptoms such as headache, lethargy, irritability or even coma during the chemotherapy, it is necessary to alert the possibility of hypercalcemia and to timely improve the relevant examination and make symptomatic treatment. Key words: Lymphoma, large B-cell, diffuse; Hypercalcemia; Antineoplastic combined chemotherapy protocols

Clinical profile of women diagnosed with Fabry disease non receiving enzyme replacement therapy

Introduction and objectiveFabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency of the α-galactosidase A enzyme. Although women were historically considered only carriers, many studies have contradicted this fact. The main aim of this work was to set the first Spanish study out of the on-going registries on health status and management of women diagnosed with FD who were not receiving enzyme replacement therapy (ERT). Material and methodsAn epidemiological, cross-sectional, descriptive and multicentre study was assessed in women diagnosed for FD who were not receiving ERT. Assessments on symptomatology and severity were collected using several clinical questionnaires. Additionally, clinical information and lab tests were obtained from clinical records. ResultsThirty-three women with a mean age of 45.6±16.2 years were studied. Symptom onset was at a median age of 35.5 years old (range: 30.0–51.5), being diagnosed a median of 2 years later (range: 1.0–1.5). Missense mutations were the most prevalent mutation (n=22, 68.8%). Although 69% considered themselves as asymptomatic, 22 (66.7%) showed at least one FD-related clinical symptom. Using Mainz Severity Score index and Fabry International Prognosis Index neurological symptomatology obtained higher scores both for severity and prognostic. The EQ-5D questionnaire showed 42.2% patients referring to some anxiety or depression, and 30.3% thought that their life was somehow altered by the pain. 62.5% were not receiving any treatment and ERT was offered only to one patient (3.6%) who refused it. ConclusionsAlthough most of the heterozygous women for FD had not received ERT or either symptomatic treatment, they present symptoms of disease. Careful follow-up of female patients or some adjuvant treatment may be considered to delay progressive organ damage and improve patient quality of life.

PF309 IMPACT OF LATE RELAPSES ON OUTCOMES IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL)

Background:The advent of rituximab has improved the prognosis of patients with DLBCL. Nevertheless, up to 30–40% of these patients will be refractory or will relapse after treatment. Late relapses (LR), arbitrarily defined as those occurring 24 months after diagnosis, are rare and have been linked to better prognosis in some studies. In addition, it is unclear whether these LR are eventually related to the original lymphoma or they represent a de novo lymphoma.Aims:To review clinical and biological characteristics of patients who received immunochemotherapy and then relapsed 24 months after diagnosis.Methods:All patients diagnosed with DLBCL in two Spanish hospitals from 2003 to 2016 were included. Amongst which, those who relapsed after having achieved complete remission with front‐line immunochemotherapy were identified and analyzed retrospectively for clinical characteristics. Furthermore, clonal relationship between the initial and relapsed lymphoma was analyzed by matching IGH gene rearrangements.Results:Ninety‐seven of 853 patients (11%) relapsed, out of which 42 (43%) were LR. The median age at diagnosis of LR patients was 66 years (range, 23–86). At diagnosis, patients with LR more frequently had a low or intermediate international prognosis index (n = 23; 58%) (p = 0.008), normal serum LDH (n = 14; 40%) (p = 0.01), and lack of bone marrow infiltration (n = 37; 88%) (p = 0.017) compared to early relapses.During the initial diagnostic work‐up, 44% (12/27) of LR patients had a germinal centre (GC) cell of origin phenotype determined by the Hans algorithm. When patients were reassessed at relapse, GC phenotype was found in 69% (n = 16) of LR patients and 30% (n = 7) of early relapse patients. In 8 out of 9 LR patients the clonal relationship was established between diagnosis and relapse.In the LR subgroup, median time from diagnosis to relapse was 4.4 years (range 2–11) and 17 patients (17%) relapsed 5 years from the diagnosis. Intensive salvage therapy was given to 20 (47%) LR patients, and 15 (35%) subsequently underwent ASCT. Of note, LR patients achieved a higher rate of complete remissions (n = 24; 62%) after salvage therapy than early relapse patients (n = 22; 41%) (p = 0.047).Median follow‐up was of 27 months (range, 6 months‐12 years) for the whole series. Event‐free survival at 2 years for LR patients and early relapse patients was 38% [95% CI, 23–54%] and 31% [95% CI, 19–44%] (p = 0.3) respectively, while 2‐year overall survival (OS) from relapse was 57% [95% CI, 39–71%] and 42% [95% CI, 29–55%] respectively (p = 0.36). However, better 2‐year OS from relapse was observed between the LR and early relapse subgroups in the cohort of patients younger than 70 at the time of relapse (p = 0.043) (figure 1).Summary/Conclusion:Patients with LR show favourable prognostic markers at diagnosis and respond better to salvage therapy. In our series, no differences in 2‐year OS from relapse, between patients with LR or early relapse were observed. Conversely, it appears that in the subgroup of young patients the overall survival is better in late relapsers.image

Clinical profile of women diagnosed with Fabry disease non receiving enzyme replacement therapy

Introduction and objectiveFabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency of the α-galactosidase A enzyme. Although women were historically considered only carriers, many studies have contradicted this fact. The main aim of this work was to set the first Spanish study out of the on-going registries on health status and management of women diagnosed with FD who were not receiving enzyme replacement therapy (ERT). Material and methodsAn epidemiological, cross-sectional, descriptive and multicentre study was assessed in women diagnosed for FD who were not receiving ERT. Assessments on symptomatology and severity were collected using several clinical questionnaires. Additionally, clinical information and lab tests were obtained from clinical records. ResultsThirty-three women with a mean age of 45.6±16.2 years were studied. Symptom onset was at a median age of 35.5 years old (range: 30.0–51.5), being diagnosed a median of 2 years later (range: 1.0–1.5). Missense mutations were the most prevalent mutation (n=22, 68.8%). Although 69% considered themselves as asymptomatic, 22 (66.7%) showed at least one FD-related clinical symptom. Using Mainz Severity Score index and Fabry International Prognosis Index neurological symptomatology obtained higher scores both for severity and prognostic. The EQ-5D questionnaire showed 42.2% patients referring to some anxiety or depression, and 30.3% thought that their life was somehow altered by the pain. 62.5% were not receiving any treatment and ERT was offered only to one patient (3.6%) who refused it. ConclusionsAlthough most of the heterozygous women for FD had not received ERT or either symptomatic treatment, they present symptoms of disease. Careful follow-up of female patients or some adjuvant treatment may be considered to delay progressive organ damage and improve patient quality of life.

Bone Marrow Involvement in Primary Mediastinal B-Cell Large-Cell Lymphoma

Abstract Introduction: Primary Mediastinal Large B-cell Lymphoma (PMBCL) is one of the primary extranodal lymphomas and originating from the thymic medulla B-cells. PMBCL is localized in the anterior and upper mediastinum, often with compression of the superior vena cava and with tumor infiltration of the pericardium, lungs, pleura. Sometimes there is impairment of the kidneys, adrenals, liver and central nervous system. Usually the bone marrow is not including. According to the WHO Classification 2008, if bone marrow is infiltrated by large B-cell lymphoma with mediastinal tumor mass, differential diagnosis between diffuse large B-cell lymphoma (DLBCL) andPMBCLshould be performed. Evaluation of the expression level of the genes JAK2, PDL1, PDL2, MAL, TRAF1 by polymerase chain reaction allows to different PMBCL and DLBCL. Diagnosis the PMBCL is established if detection of hyperexpression two or more genes. We did not find any publications with description of PMBCL with bone marrow involvement. We present here 2 clinical cases. Materials and methods: 154 patients with PMBCL treated in our center were examined. 16 (10,4%) of them had an extra-mediastinal localization. 2 patients (1,3%) were diagnosed with PMBCL with bone marrow involvement. Results: Case 1 A 42 years old female was hospitalized for vital indications with respiratory failure and syndrome of compression of the superior vena cava. In the mediastinum a tumor was 138x116.5 mm, involving the upper and middle lobes of the right lung. Tumor infiltrated the soft tissues of anterior wall of the chest, pericardium. The biopsy of the mediastinal tumor revealed the fragments of fibrous fat tissue with a dense infiltrate of medium size and large cells with oval nuclei, with one large or smalls nucleoli, a moderately pronounced light cytoplasm (Fig.1). Tumor cells expressed the CD20, PAX5, co-expressed CD23, CD30-, IgM-, Ki-67 80%. LDH level in blood was 578 E/l (208-378 E/l). International Prognosis Index (IPI) - 4. Peripheral blood was normal. Histology of the bone marrow showed diffuse interstitial infiltration by lymphoid cells of medium and large size with several small distinct nucleoli, mainly with the morphology of centroblasts, increased mitotic activity (Fig. 2). Tumor cells of bone marrow were CD20 +. Hyperexpression of JAK2, PDL1, TRAF1 genes in the bone marrow was revealed by PCR method. So the PMBCL was diagnosed. The patient received 6 courses of R-DA-EPOCH-21. At the end of treatment tumor lesions were still positive by PET/CT (Deauville score 5). The patient received the second line therapy, with HSCT. PET/CT was positive again (Deauville score 5). Hyperexpression of JAK2, PDL1, TRAF1 genes persisted in the bone marrow. The patient is alive now at 18 month from start of treatment. According to the CT there is no signs tumor progression. Case 2 B 69 years old female complained of weakness, profuse sweating, pain in the left scapular, temperature 38,0 C, weight loss by 11% of body weight, for the last 3 months. In the left hemithorax tumor mass of 135x67 mm, embracing the first rib with a pathological fracture. Tumor cells expressed CD20, PAX5, CD79α, TNFAI2, co-expressed CD23 and CD30, Ki-67 - 80%. LDH level in blood 994 E/l. IPI - 4. Peripheral blood was normal. Histological study of the bone marrow revealed a focal-interstitial lymphoid infiltration with small and medium sized cells with oval and irregularly shaped nuclei. Hyperexpression of the genes JAK2, MAL, TRAF1 was revealed in the bone marrow. The patient received 6 courses of R-DA-EPOCH-21. After the end of treatment FDG-PET/CT was positive (Deauville score 5). The patient received the second line therapy. After the treatment disease progression was established. Hyperexpression of JAK2, MAL, TRAF1 genes persisted in the bone marrow. The patient is alive now at 18 month from start of treatment, but with PMBCL. Conclusion: Both cases demonstrated resistant to R-DA-EPOCH lymphoma, though the frequency of complete remissions in patients with PMBCL is almost 90%. New approadies should be developed in such cases. Each year, with the accumulation of research data it became evident that within each well-defined nosological form there are borderline cases or those in which our understanding is insufficient to explain a particular phenomenon. The detection of bone marrow involvement in patients with PMBCL makes one think about the criteria for diagnosing the disease. Download : Download high-res image (228KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.