Concurrent Diffuse Large B-cell Lymphoma Research Articles

In-situ follicular neoplasia: a clinicopathological spectrum.

In-situ follicular neoplasia (ISFN) occurs in approximately 2-3% of reactive lymph nodes, and is currently set apart from 'partial involvement by follicular lymphoma' (PFL). ISFN can progress to overt lymphoma, but precise parameters with which to assess this risk and its association with related diseases remain incompletely understood. The aim of this study was to explore these parameters. We reviewed 11 cases of ISFN and one of PFL between 2003 and 2018. Ten patients had ISFN in the lymph nodes, and one had ISFN in the spleen. Haematoxylin and eosin and immunohistochemical stains were reviewed. Involvement of follicles by ISFN was scored with a three-tier scheme. Of five patients with low ISFN scores, one had chronic myelomonocytic leukaemia, one had mycosis fungoides, and three were free of haematopoietic disease. Among them, four are alive and one was lost to follow-up. Of the six ISFN patients with high scores, two had concurrent marginal zone lymphomas, one had concurrent diffuse large B-cell lymphoma (DLBCL), one had Castleman-like disease, one had progressive transformation of germinal centres with IgG4-related disease, and one had no haematopoietic disease; all are alive except for one who died of concurrent DLBCL. The patient with PFL developed DLBCL 7 years after diagnosis. On the basis of this limited series, we conclude that only cases with high scores are associated with an overt lymphoma or an abnormal lymphoid process, and that scoring may be a useful parameter with which to assess the risk of associated lymphoma, and deserves further study. We also performed a comprehensive review of the literature.

Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study

Diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1–10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24–80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2–94.7%), 84.5% (CI95: 72.9–98%), and 97.0% (CI95: 91.3–100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.

Single-Center Analysis of Characteristics and Outcomes of De Novo, Concurrent, and Transformed Diffuse Large B-Cell Lymphoma.

Outcomes of diffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from indolent lymphoma, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone are described in retrospective studies. The efficacy of other regimens in transformed or concurrent DLBCL is largely unknown. In this single-center retrospective study, we present characteristics of concurrent and transformed DLBCL and outcomes after dose-adjusted etoposide, vincristine, cyclophosphamide, prednisone, and doxorubicin with rituximab (DA-EPOCH-R) comparative with de novo DLBCL. Of 170 patients with DLBCL, 136 were de novo, 17 were concurrent, and 17 were transformed. Transformed DLBCL had significantly lower complete response rates and progression-free survival (PFS) but similar overall survival (OS) compared with de novo counterpart. There was no significant difference between de novo and concurrent DLBCL regarding response rates, PFS, and OS. DA-EPOCH-R was associated with inferior OS. Thus, intensified treatment with DA-EPOCH-R might not improve outcomes of transformed DLBCL.

Rituximab maintenance improves outcomes of transformed diffuse large B-cell lymphoma: a retrospective study of 519 cases with de novo diffuse large B-cell lymphoma and 62 cases with concurrent diffuse large B-cell lymphoma and follicular lymphoma

Although outcomes of transformed diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL) were improved using rituximab-combined immunochemotherapy, the efficacy of subsequent rituximab maintenance (RM) remains unclear. We retrospectively analyzed the prognoses of 519 patients with de novo DLBCL and 62 patients with concurrent DLBCL and FL (concurrent-DLBCL/FL). Progression-free survival (PFS) was shorter in patients with concurrent-DLBCL/FL than in de novo DLBCL (p=.030). Twenty-four patients with concurrent-DLBCL/FL received RM after induction therapy, and they achieved better OS and PFS (p=.010 and p<.001, respectively) with lower risk of relapse (p<.001) than the non-RM group. Moreover, concurrent-DLBCL/FL showed better subsequent OS and PFS after recurrence than de novo DLBCL (p=.0083 and p=.0044, respectively). Our study indicates that in the face of a high relapse rate, concurrent-DLBCL/FL is manageable and benefits from RM.

Impact of concurrent indolent lymphoma on the clinical outcome of newly diagnosed diffuse large B-cell lymphoma

AbstractSome patients with diffuse large B-cell lymphoma (DLBCL) present with a concurrent indolent lymphoma at diagnosis. Their outcomes in the rituximab era are not fully defined. Using a prospectively followed cohort of 1324 newly diagnosed DLBCL patients treated with immunochemotherapy, we defined the prevalence, characteristics, and outcome of DLBCL with concurrent indolent lymphoma. Compared with patients with DLBCL alone (n = 1153; 87.1%), patients with concurrent DLBCL and follicular lymphoma (FL) (n = 109; 8.2%) had fewer elevations in lactate dehydrogenase, lower International Prognostic Index (IPI), and predominantly germinal center B-cell–like (GCB) subtype, whereas patients with concurrent DLBCL and other indolent lymphomas (n = 62; 4.7%) had more stage III-IV disease and a trend toward higher IPI and non-GCB subtype. After adjusting for IPI, patients with concurrent DLBCL and FL had similar event-free survival (EFS) (hazard ratio [HR] = 0.95) and a trend of better overall survival (OS) (HR = 0.75) compared with patients with DLBCL alone, but nearly identical EFS (HR = 1.00) and OS (HR = 0.84) compared with patients with GCB DLBCL alone. Patients with concurrent DLBCL and other indolent lymphomas had similar EFS (HR = 1.19) and OS (HR = 1.09) compared with patients with DLBCL alone. In conclusion, DLBCL patients with concurrent FL predominantly had the GCB subtype with outcomes similar to that of GCB DLBCL patients. DLBCL patients with concurrent other indolent lymphoma had similar outcomes compared with patients with DLBCL alone. These patients should not be summarily excluded from DLBCL clinical trials.

Concurrent Diffuse Large B-Cell Lymphoma and Epstein-Barr Virus-Associated Smooth Muscle Tumour in the Small Bowel of an HIV-Positive Adult—a Case Report and Review of the Literature

Concurrent Diffuse Large B-Cell Lymphoma and Epstein-Barr Virus-Associated Smooth Muscle Tumour in the Small Bowel of an HIV-Positive Adult—a Case Report and Review of the Literature

Incidence and survival patterns of primary central nervous system (CNS), systemic and concurrent diffuse large B-cell lymphoma (DLBCL).

e13512Background: Concurrent CNS and systemic involvement with DLBCL is a rare presentation. To our knowledge there is no study looking at the incidence and survival patterns of concurrent CNS and ...

R-Bendamustine Vs R-CHOP As Initial Treatment for Advanced Stage Low Grade Follicular Lymphoma: A Matched-Pair Analysis

Introduction: In the randomized phase 3 clinical trial performed by the Study group indolent Lymphoma (STiL) in patients with indolent and mantle cell lymphoma, the complete response (CR) rates and progression-free survival (PFS) were superior with first-line bendamustine plus rituximab (BR) therapy compared with CHOP plus rituximab (R-CHOP) therapy. However, in a second randomized phase 3 clinical trial (the BRIGHT study) also performed in patients with indolent and mantle cell lymphoma, the CR rates were similar between BR and R-CHOP groups and PFS data has not been reported. In both trials, the toxicity profile was better for BR compared with R-CHOP. Here, we report the results of a matched-pair analysis of advanced stage low-grade follicular lymphoma patients treated with first-line BR or R-CHOP at MD Anderson Cancer Center, Houston, Texas.Methods: We reviewed the medical records of all patients (n=74) with stage III or IV grade 1 or 2 follicular lymphoma treated at MD Anderson Cancer Center with first-line BR between January 2009 and December 2013. Each BR patient was paired with a grade 1 or 2 follicular lymphoma patient treated with first-line R-CHOP matched by age, gender, and stage. Patients with histological diagnosis of concurrent diffuse large B-cell lymphoma were excluded.Results: There were no significant differences in most baseline patient characteristics including age, gender, stage, FLIPI 1 and FLIPI 2 risk groups, Ki-67 score, absolute monocyte count, and absolute lymphocyte count (p>0.05). However, more patients in R-CHOP group met GELF criteria compared with BR group (69% vs 47%, p=0.012). Also, more patients in R-CHOP group had SUVmax >10 on baseline FDG PET scan compared with BR group (74% vs 49%, p=0.011). Median number of chemotherapy cycles was 6 for both groups (range, 2-6 for BR and 4-8 for R-CHOP). The CR rates were comparable between the two groups (93% for BR and 91% for R-CHOP, p=0.142). The median follow-up was 24.4 months (range, 2.8-63.2 months) for BR patients and 68.1 months (range, 4.4-149.4 months) for R-CHOP patients. At 24 months, the PFS and overall survival (OS) were comparable between the two groups (PFS and OS of 85% and 94% for BR and 82% and 99% for R-CHOP; log rank p=0.654 for PFS and 0.158 for OS).Conclusions: In this 1:1 matched pair analysis of advanced stage low-grade follicular lymphoma patients treated with first-line BR or R-CHOP, the CR rates, PFS and OS were comparable between the two therapies. However, longer follow-up is required for better comparison of PFS, OS, and long-term toxicities between the two regimens. DisclosuresFanale:Seattle Genetics, Inc.: Consultancy, Honoraria, Other, Research Funding. Wang:Pharmacyclics, Janssen: Honoraria, Research Funding. Westin:Novartis: Research Funding.

Autologous Stem Cell Transplantation Improves Survival for Patients with Follicular Lymphoma in First or Second Relapse: Results of a Comparative Effectiveness Instrumental Variable Analysis

IntroductionThe role of high dose therapy with autologous stem cell transplantation (ASCT) in relapsed follicular lymphoma (FL) remains controversial, with lack of comparative studies in the Rituximab (R) era. We conducted a comparative effectiveness analysis to evaluate the use of ASCT at first or second (1st/2nd) relapse on survival outcome in two cancer centers in Alberta. Both centers treat a similar catchment population within the same government-funded health care system, providing simultaneous access to new cancer treatments. Treatment center A however, routinely offers ASCT at 1st/2nd FL relapse whereas treatment center B tends to offer ASCT later or never. Both centers occasionally offer allogeneic transplantation later in the disease course.MethodsThe Alberta Cancer Registry was interrogated to identify FL patients diagnosed between 2001 and 2010. Patients who were aged 18-60 years at initial diagnosis and experienced a relapse post initial chemotherapy treatment regardless of first-line management (watch and wait, chemotherapy, chemoimmunotherapy or radiation) were included in this analysis. Patients who had grade 3B or areas of concurrent diffuse large B-cell lymphoma at initial diagnosis were excluded.ResultsA total of 568 patients aged 18-60 years were diagnosed with FL during the 10 year study period in Alberta, and 180 patients meeting inclusion criteria experienced relapse from chemotherapy and received treatment at center A (n=96) or center B (n=84). There were no statistically significant differences in patient and disease characteristics at diagnosis or at relapse between the two centers. The median follow-up was 104.4 months (28.1-156.1) from diagnosis and 65.3 months (0.3-151.8) from first relapse post chemotherapy.The proportion of patients ever receiving ASCT was higher at center A compared to B (61.46% vs.16.67%, p<0.001) especially those receiving at 1st/2nd relapse (58.3% vs. 7.1%, p<0.001). Center A also utilized allogeneic transplantation more frequently (16.7% vs. 3.6%, p=0.004). The use of R-chemotherapy (89.6% vs. 82.1%, p=0.46), R-maintenance therapy (34.4% vs. 39.3%, p=0.50), Doxorubicin-based chemotherapy (60.4% vs. 61.9%, p=0.84), Fludarabine (19.8% vs. 29.8%, p=0.12) were similar for center A vs. B, respectively, although center A less commonly enrolled patients on clinical trials (12.5% vs. 39.3%, p<0.01).The projected 5-year overall survival (OS) from first relapse was significantly higher in center A vs. B (88.9% vs. 59.5%, HR 3.24, p<0.001) (Figure 1). For these 180 patients, the projected 10-year OS from initial diagnosis was 85.4% in center A vs. 60.5% in center B (HR 3.02, p=0.003).The factors associated with improved OS from relapse at univariate analysis were female gender (p=0.01), no co-morbidities (p=0.01), FLIPI score 0-2 at diagnosis (p<0.001) and TTP >1 year (p=0.002). Receiving ASCT was highly associated with improved OS (p=0.006) as well as timing of the ASCT (p<0.001). Patients receiving ASCT at 1st/2nd relapse had projected 5-year OS of 92.4% vs. 66.5% for no ASCT vs. 62.5% for ASCT beyond second relapse (p<0.001) (Figure 2). In contrast, allogeneic transplantation did not affect OS (p=0.62).In multivariate analysis, factors that were independently associated with improved OS were treatment center A (HR 3.16, p=0.001), FLIPI score 0-2 at diagnosis, no transformation, ever use of Rituximab with chemotherapy, and ever use of R-maintenance. Another multivariate model examining the OS of all patients without considering treatment center found that ASCT at 1st/2nd relapse was associated with improved OS (HR 4.55, p=0.002) independent of FLIPI score 0-2 at diagnosis, no transformation, ever use of Rituximab with chemotherapy, and ever use of R-maintenance. Because treatment center and use of ASCT at 1st/2nd relapse were highly correlated, they could not be combined within the same multivariate model.ConclusionsThis is the first study assessing the comparative effectiveness of different treatment approaches in FL patients in their first relapse post chemotherapy, in particular the use of ASCT. Our results illustrate significantly improved survival in patients treated with high dose therapy with ASCT as well as highlighting the importance of timing of ASCT. We therefore support the use of ASCT at 1st/2nd relapse in relapsed FL patients. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

SUVmax on Pre-Treatment FDG PET Scan Is Not Predictive of Outcome in Follicular Lymphoma after R-CHOP Threapy

Introduction: High standardized uptake value (SUV) on FDG PET scan in follicular lymphoma (FL) suggests aggressive disease and possible transformation to diffuse large B-cell lymphoma. Schoder et al, J Clin Oncol, 2005, reported that SUV >10 predicted aggressive lymphoma with >80% certainty and SUV >13 with >90% certainty. However, it is unknown whether the maximum SUV (SUVmax) on FDG PET scan at baseline, suggesting the possibility of focal aggressive or transformed disease, has prognostic value in FL. Here, we determined the prognostic value of SUVmax on baseline FDG PET scan in patients with advanced stage FL treated uniformly with R-CHOP chemoimmunotherapy at initial diagnosis.Methods: We reviewed medical records of all patients with stage III or IV FL who had FDG PET scan at initial diagnosis and were treated with R-CHOP chemoimmunotherapy at MD Anderson Cancer Center between January 2001 and December 2012. Patients with histological diagnosis of concurrent diffuse large B-cell lymphoma were excluded. Results: For the 225 patients studied, the median age was 57 years (range, 20-82). 83 (37%) patients were >= age 60, 137 (61%) had grade 1 or 2 FL, and 88 (39%) had grade 3A (n=57, 25%) or 3B (n=31, 14%). The Ki-67 score was <=40% for 85 (60%) patients and >40% for 56 (40%) patients. FLIPI risk groups were 54 patients (24%) low, 74 (33%) intermediate, and 97 (43%) high. GELF criteria were met in 133 (59%) patients. Tumor bulk of >= 6 cm was seen in 97 (43%) patients. The absolute lymphocyte count (ALC) was normal or high in 155 (69%) patients and low in 70 (31%). Sixty-nine (31%) patients received rituximab maintenance. There was no correlation between baseline SUVmax on FDG PET scan and Ki-67 score (Pearson correlation co-efficient of 0.168). The overall and complete response rates were 96% and 87%, respectively. The median follow-up time was 66 months. At 5 years, progression-free survival (PFS) was 85% and overall survival (OS) was 90%. Male gender, stage IV, high risk FLIPI, presence of GELF criteria, high beta-2 microglobulin, and low ALC were associated with significantly inferior PFS and OS (p<0.05). Histological grade was not associated with PFS or OS. Age >= 60 was associated with inferior OS but not PFS. Rituximab maintenance was associated with improved PFS but not OS. On baseline FDG PET scan, median SUVmax was 13.7 and the SUVmax range was 1.5-42.1. 105 (47%) patients had SUVmax <=13 and 120 (53%) had SUVmax >13. Patient characteristics including age, gender, histological grade, Ki-67 score, and FLIPI risk groups were not significantly different between the two SUVmax populations (p>0.05). The overall response rates were 94% and 96% for the SUVmax <=13 and SUVmax >13 groups, respectively. The complete response rate was 87% in both groups. At 5 years, the PFS and OS were not significantly different between the low and high SUVmax groups (61% vs 63% for PFS, p=0.98 and 90% vs 89% for OS, p=0.63). PFS and OS were not significantly different even when the patients were grouped into SUVmax <=10 vs >10 (p=0.9 and 0.61, respectively) or when other cut-offs were used. SUVmax was also not predictive of PFS and OS when only the patients meeting GELF criteria were analyzed.Conclusions: In this large cohort of advanced stage FL patients treated uniformly with R-CHOP chemoimmunotherapy, SUVmax on baseline FDG PET scan was not predictive of clinical outcome or correlated with other features. It is possible that the doxorubicin-based chemotherapy regimen may have benefited patients with high SUVmax who may have underlying aggressive or undiagnosed transformed disease. It remains to be determined whether SUVmax is predictive of clinical outcome in FL patients treated with other commonly used therapies such as rituximab monotherapy, rituximab and bendamustine, or R-CVP. [Display omitted] DisclosuresWang:Pharmacyclics, Janssen: Honoraria, Research Funding. Westin:Novartis: Research Funding.

Diffuse Large B-cell Lymphoma Complicated with Autoimmune Thrombocytopenia

A patient was diagnosed with autoimmune thrombocytopenia and concurrent diffuse large B-cell lymphoma (DLBCL). Both autoimmune thrombocytopenia and DLBCL were successfully treated using chemotherapy, while steroid therapy, rituximab monotherapy, and high-dose parenteral glucocorticoid therapy combined with high-dose intravenous immunoglobulin failed to improve thrombocytopenia. A greater understanding of the pathogenesis and treatment options can only be definitively clarified by analyses of settings such as the present case, as autoimmune thrombocytopenia is uncommon in patients with malignant lymphoma and the etiology and optimal treatment remain unclear.

F-18 fluorodeoxyglucose positron emission tomography and/or computed tomography findings of an unusual breast lymphoma case and concurrent cervical cancer: a case report

IntroductionBreast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B-cell lymphomas or as mucosa associated lymphoid tissue lymphomas. Concurrent cases of breast lymphoma and cervical cancer are extremely rare.Case presentationWe report a case of a 46-year-old woman of unknown ethnic origin diagnosed with concurrent diffuse large B-cell lymphoma of the breast and squamous cell cancer of the cervix that was detected and followed with F-18 fluorodeoxyglucose (FDG) positron emission tomography and/or computed tomography (PET/CT). The metastatic pattern of this case of breast lymphoma is similar to that of a typical metastatic breast carcinoma. These findings have never been described in the literature. PET/CT also demonstrated an incidentally intense FDG focus in the uterine cervix ultimately leading to the pathologic diagnosis of squamous cell carcinoma of the uterine cervix. An appropriate staging of breast lymphoma and cervical cancer with FDG PET/CT is important because of therapeutic consequence. This case report and review of the literature highlights the role of FDG PET/CT in staging and restaging of both breast lymphoma and cervical cancer.ConclusionsWe report a case of a breast lymphoma with a metastatic pattern similar to that of typical metastatic breast carcinoma. The FDG PET/CT scan also diagnosed a rare case of concurrent breast lymphoma and cervical cancer. This concurrence has not been reported previously in the medical literature.

Composite EBV negative peripheral T-cell lymphoma and diffuse large B-cell lymphoma involving the ileum: A case report and a systematic review of the literature

We report a case of an intestinal peripheral T-cell lymphoma (PTCL) with a concurrent diffuse large B-cell lymphoma (DLBL) involving the ileum and a regional lymph node. The patient presented with an abdominal mass. The terminal ileum showed a diffuse and monotonous population of small CD3-positive T cells. The T-cell receptor γ (TCRγ) gene was rearranged by PCR while the immunoglobulin heavy chain (IgH) gene was not. A separate section of the ileum showed a colliding large B-cell proliferation. The regional lymph node showed a diffuse proliferation of large centroblasts positive for CD20 and CD79a admixed with small T cells and showed a rearranged IgH receptor gene without evidence of a clonally rearranged TCRγ gene. Both the PTCL and DLBL components were negative for EBV. A review and analysis of the pertinent literature describing composite T- and B-cell lymphomas is performed and reported.

Primary non-Hodgkin's lymphoma and malakoplakia of the vagina: A case report

The vagina is a rare site for both primary non-Hodgkin's lymphoma and malakoplakia. We report a case of concurrent diffuse large B-cell lymphoma and malakoplakia of the vagina in a 67-year-old woman presenting with a vaginal discharge and a vaginal mass. The patient had two biopsy specimens reported as showing malakoplakia only, followed by a third biopsy specimen 10 months later which was diagnosed as diffuse large B-cell lymphoma. Review of the first two biopsy specimens showed areas of histiocytes with Michaelis-Gutman bodies merging with areas of cells with slightly larger nuclei and more amphophilic cytoplasm. Immunohistochemistry for the B-cell marker L-26 (CD20) and polymerase chain reaction analysis of the immunoglobulin heavy chain gene were helpful in retrospectively distinguishing the population of diffuse large B-cell lymphoma from the areas of malakoplakia. The third biopsy specimen showed sheets of large atypical lymphoid cells characteristic of a large cell lymphoma. Malakoplakia has been described in association with a variety of cancers, and this is only the second report of malakoplakia associated with non-Hodgkin's lymphoma. Considering the rarity of these two entities in the vagina, it is unlikely that the association in this case is coincidental, raising the possibilities of an unusual reaction to the presence of lymphoma or a common pathogenesis such as underlying chronic inflammation. Epstein-Barr virus DNA was detected in the second biopsy specimen, suggesting a possible role in the pathogenesis of this lymphoma.