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Haematologica ◽  
2022 ◽  
Author(s):  
Karoline Koch ◽  
Julia Richter ◽  
Christoph Hanel ◽  
Andreas Huttmann ◽  
Ulrich Duhrsen ◽  
...  

The sole distinguishing feature of follicular lymphoma grade 3B and diffuse large B-cell lymphoma is the growth pattern assessed by histopathology analysis. Diffuse growth defines diffuse large B-cell lymphoma but the clinical relevance of this finding when occurring in follicular lymphoma grade 3B is uncertain. To address this question, individual and coexisting follicular lymphoma grade 3B and diffuse large B-cell lymphoma were separated and analyzed for immunophenotype and molecular genetic features by fluorescence in situ hybridization, targeted sequencing and gene expression profiling. Clinical features of follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma were studied in homogeneously treated patients from a prospective randomized trial. Follicular lymphoma grade 3B and diffuse large B-cell lymphoma frequently show intermediate growth pattern and/or occurred simultaneously in the same tissue at the time of initial diagnosis. When occurring simultaneously follicular lymphoma grade 3B and diffuse large B-cell lymphoma do not differ significantly in genetic aberrations or phenotype but distinct features in gene expression reflect divergent microenvironment. Follicular lymphoma grade 3B with and without coexisting diffuse large B-cell lymphoma do not differ in major clinical parameters such as international prognostic index, response to immunochemotherapy, progression or overall survival. Follicular lymphoma grade 3B and simultaneous diffuse large B-cell lymphoma are molecularly homogenous. Histological detection of diffuse large B-cell lymphoma is not associated with features of a more aggressive disease and does not reflect transformation or progression of follicular lymphoma Grade 3B.


Author(s):  
Emelie C Rotbain ◽  
Max J Gordon ◽  
Noomi Vainer ◽  
Henrik Frederiksen ◽  
Henrik Hjalgrim ◽  
...  

The chronic lymphocytic leukemia comorbidity index (CLL-CI) is an efficient, CLL-specific tool derived from the Cumulative Illness Rating Scale. The CLL-CI is based on the assessment of the organ systems found to be most strongly associated with event-free survival in CLL: vascular, upper gastrointestinal, and endocrine, at the time of initiation of CLL therapy. The CLL-CI categorizes patients into low, intermediate, and high risk groups. In the present study, we have employed the CLL-CI in a population-based cohort comprising 4 975 patients with CLL. We demonstrate that CLL-CI retains prognostic significance in this large cohort and is associated with overall survival and event-free survival from time of first therapy. Furthermore, CLL-CI associates with overall survival, event-free survival, and time to first treatment from diagnosis independently of the CLL International Prognostic Index. These findings support the use of the CLL-CI both in research and in clinical practice.


Blood ◽  
2022 ◽  
Author(s):  
Matthew R. Wilson ◽  
Toby Andrew Eyre ◽  
Amy A Kirkwood ◽  
Nicole Wong Doo ◽  
Carole Soussain ◽  
...  

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.


2022 ◽  
Vol 50 (1) ◽  
pp. 030006052110630
Author(s):  
Yizhen Liu ◽  
Jinjin Jiang ◽  
Lianfang Liu ◽  
Zezhou Wang ◽  
Baohua Yu ◽  
...  

Objective Primary mediastinal B-cell lymphoma (PMBCL) lacks standard treatment regimens. This study aimed to identify the disease’s clinical features and prognostic factors. Methods This retrospective study included 56 patients with PMBCL. Patient demographic details and clinicopathological characteristics were summarized, and their effects on progression-free survival (PFS) and overall survival (OS) were analyzed. Results The median patient age was 29 years (range, 14–56). Twenty-two patients received DA-EPOCH-R (dose-adjusted etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone, as well as rituximab), and 34 patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Clinical/laboratory parameters, overall response rates, and 5-year PFS and OS rates did not differ between the treatment groups. Kaplan–Meier analysis indicated that late-stage disease and a higher International Prognostic Index (IPI) were associated with shorter PFS and OS. Furthermore, patients with B symptoms and first-line treatment non-responders exhibited worse OS. 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters, such as higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were corrected with shorter PFS. Conclusions This study revealed that stage IV disease, higher IPI, and B symptoms were poor prognostic factors in patients with PMBCL. Significantly, higher MTV and TLG portended worse PFS.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 188
Author(s):  
Gian Maria Zaccaria ◽  
Simone Ferrero ◽  
Eva Hoster ◽  
Roberto Passera ◽  
Andrea Evangelista ◽  
...  

Background: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313). Methods: We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0–9.6; High→Int, HR: 2.3, 95% CI: 1.5–4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential.


2021 ◽  
Author(s):  
Gopila Gupta ◽  
Vikas Garg

Follicular lymphoma (FL) is one of the most common type of indolent non- Hodgkin’s lymphoma. It originates from germinal center B cells and has characteristic translocation t(11,14) involving immunoglobulin heavy chain gene (chromosome 14q32) and Bcl2 gene (chromosome 18q21) in 90% of patients. FL presents with lymphadenopathy and/or bone marrow involvement. Diagnosis is confirmed by histological examination of lymph nodes. FL is a slow growing tumor with frequent remission and relapses. Follicular lymphoma international prognostic index (FLIPI) and progression of disease within 24 months (POD24) are most important prognostic markers. Early-stage disease is usually treated with radiotherapy. Management of advanced stage depends on disease burden. Patients with advanced stage disease may be observed in case of low burden disease and those with high disease load require treatment with chemo-immunotherapy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xue Shi ◽  
Xiaoqian Liu ◽  
Xiaomei Li ◽  
Yahan Li ◽  
Dongyue Lu ◽  
...  

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhongqi Li ◽  
Fang Yu ◽  
Wenle Ye ◽  
Liping Mao ◽  
Jiansong Huang ◽  
...  

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of large lymphoid B cell malignancy with distinct clinical and genetic features. Recently, NOTCH1 mutations were identified in DLBCL cases by Next-generation sequencing (NGS), but the clinical features and prognostic impact were not systematically studied. Here, NOTCH1 genes in 161 DLBCL samples were sequenced by NGS. The prognostic value of NOTCH1 mutations was assessed in the context of clinical and laboratory factors, such as international prognostic index (IPI), cell-of-origin classification, double expression of BCL2 and c-MYC. The combined data from three Western cohorts were used to validate these results. As a result, NOTCH1 mutations were found in 17(10.6%) patients, and three patients had a hotspot mutation of c.7541_7542delCT. The presence of NOTCH1 mutations was significantly associated with poor complete response and progression free survival(PFS), which was independent of established clinical and laboratory parameters. In addition, 30 (1.92%) of 1562 patients treated with R-CHOP regimen in those combined Western cohorts had NOTCH1 mutations. Meta-analysis of the Western cohorts confirmed that NOTCH1 mutations were also associated with poor PFS and OS. In conclusion, DLBCL patients with the NOTCH1 mutations have worse PFS and OS, and the NOTCH1 mutations can be used as an independent predictor for patients with DLBCL.


Author(s):  
Yu. N. Vinogradova ◽  
N. V. Ilyin ◽  
M. S. Tlostanova ◽  
A. A. Ivanova

Visual analysis of positron emission tomography/computed tomography (PET/CT) scans and semiquantitative parameter of glucose’s standardized uptake value are used in PET/CT with 18F-fluorodeoxyglucose (18F-FDG). Recently some volumetric parameters, which can evaluate metabolic tumor volume for patients with lymphomas and total lesion glycolysis in the tumor sites are established. In our study this problem was analyzed for different types of lymphomas considering clinical importance of these rates and their bond to known factors of international prognostic index.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1436-1436
Author(s):  
Brady E Beltran ◽  
Denisse Castro ◽  
Luis Villela ◽  
Efreen Montaño Figueroa ◽  
Ana Florencia Ramirez-Ibarguen ◽  
...  

Abstract Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. Current prognostic models such as the Oyama and the International Prognostic Index (IPI) score have limited prognostic value in this patient population. Therefore, we aim to evaluate the ability of these models to risk stratify patients and propose a novel prognostic model in the largest cohort of Latin American patients with EBV+ DLBCL, NOS. Methods: This retrospective cohort study included patients ≥18 years from six Latin American countries diagnosed and treated at tertiary centers from 2010 to 2020. Hematopathologists at each institution reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL, NOS. We collected clinicopathological data by reviewing the medical records of the patients. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last visit. The secondary endpoint, progression-free survival (PFS), was defined as the time from diagnosis until death, progression, or last visit. Our novel model (Grupo de Estudio Latinomericano de Linfoproliferativos [GELL] Score) includes the Eastern Cooperative Oncology Group (ECOG) performance status ≥2, extranodal involvement >1, serum albumin <3.5 g/dL, serum lactate dehydrogenase (LDH) above the upper limit of normal, and platelet-to-lymphocyte ratio >455. We assigned a value of 1 to each of the abovementioned elements in the score and classified the patients as low (0 points), intermediate (1-2 points), and high (3-5) risk. OS and PFS probabilities were computed with the Kaplan-Meier method and compared with the log-rank test. We used Cox regression to evaluate the proportional hazard ratios (HR) of each score for our study outcomes. The C-index was employed to measure discrimination of each model. We used cross-validation to evaluate the model performance. Results: A total of 154 patients with EBV+ DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with a slight male predominance (53%). EBER was positive in all cases (range 1-100%). Clinically, 39% presented ECOG ≥2, 57% had B symptoms, 50% had an extranodal disease as a primary tumor, and 71% had Ann Arbor stage III/IV. Fifty-one percent of the patients had an elevated LDH level, and 43% had albumin <3.5 g/dL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was administered in 79% of individuals as first-line treatment. The overall response rate was 80% (62% complete response and 18% partial response). With a median follow-up of 61 months, the 5-year OS and PFS rates were 61% and 47%, respectively. The 5-year OS rates of patients with low, intermediate, and high-risk disease according to the GELL score was 90%, 59%, and 33%, respectively (Fig 1A). The 5-year PFS rates were 82%, 39%, and 23%, respectively (Fig 2A). Table 1 shows the Cox regression and the discrimination analysis for each of the scores. The GELL score has the highest discriminatory index for OS and PFS compared to the IPI, Revised-IPI, National Comprehensive Cancer Network-IPI, and the Oyama score (Figure 1 and 2). Conclusions: This study proposes a novel score for risk stratification of patients with EBV+ DLBCL, NOS. The GELL score appears to better discriminate OS and PFS than previous scores. Our results should be validated in an independent prospective cohort. Figure 1 Figure 1. Disclosures Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.


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