Rare B-cell non-Hodgkin Lymphoma Research Articles

Prognostic Factors in Hospitalized Patients with HIV-Associated Burkitt's Lymphoma - Real World Data Analysis

Introduction Burkitt Lymphoma (BL) is a highly aggressive and rare B-cell non-Hodgkin Lymphoma, characterized by translocation and dysregulation of the MYC gene. BL comes in three distinct forms: endemic, sporadic, and immunodeficiency related, which is most commonly secondary to HIV. Despite improvements in antiretroviral therapy (ART), the reported incidence of BL has remained stable over time. BL is a highly curable disease in patients able to tolerate aggressive therapies. However, little is known about real-world outcomes in United States patients with HIV- related BL. Our study highlights multiple factors associated with inpatient mortality and morbidity. Methods The National Inpatient Sample database was queried from October 2015 to December 2020. Adults aged >= 18 with a primary diagnosis of BL were identified and stratified into those with and without HIV. Complications included were queried using ICD codes most found in the secondary diagnosis variables. Baseline characteristics, inpatient complications, and outcomes were compared using chi-squared and Wilcoxon rank-sum tests. Logistic regression analysis was performed to assess the risk of death before and after adjusting for multiple risk factors. Results We found 3,650 admissions with a primary diagnosis of BL, 400 (11%) of whom had HIV. Patients with HIV were younger, 49% were younger than 40 years old as compared to 29% in patients with no HIV. There was a higher percentage of black patients 115 (29%), and most had Medicaid 170 (44%), there was no difference between income, hospital bed size or geographical region. Interestingly, in multivariable analysis, there were no significant differences in length of stay, race, or mortality between patients with and without HIV. The factors associated with mortality in HIV patients included acute renal failure OR 11.4 (1.22 to 107) and Sepsis OR 38.6 (1.62 to 921) Conclusion BL is an increasingly important disease in HIV-infected patients given that the incidence remains high despite advances in ART. This nationwide data analysis demonstrates the demographic characteristics of patients with HIV-associated BL in the US and the encouraging findings that outcomes are not significantly different between patients with and without HIV. Yet our study demonstrates the disproportionate distribution of HIV-BL in females and black patients. Further studies are needed to examine gender and racial disparities.

A novel CAR-T cell product targeting CD74 is an effective therapeutic approach in preclinical mantle cell lymphoma models

BackgroundMantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma subtype which remains incurable despite multimodal approach including chemoimmunotherapy followed by stem cell transplant, targeted approaches such as the BTK inhibitor ibrutinib, and CD19 chimeric antigen receptor (CAR) T cells. CD74 is a nonpolymorphic type II integral membrane glycoprotein identified as an MHC class II chaperone and a receptor for macrophage migration inhibitory factor. Our group previously reported on CD74's abundant expression in MCL and its ability to increase via pharmacological inhibition of autophagosomal degradation. Milatuzumab, a fully humanized anti-CD74 monoclonal antibody, demonstrated significant activity in preclinical lymphoma models but failed to provide meaningful benefits in clinical trials mainly due to its short half-life. We hypothesized that targeting CD74 using a CAR-T cell would provide potent and durable anti-MCL activity.MethodsWe engineered a second generation anti-CD74 CAR with 4-1BB and CD3ζ signaling domains (74bbz). Through in silico and rational mutagenesis on the scFV domain, the 74bbz CAR was functionally optimized for superior antigen binding affinity, proliferative signaling, and cytotoxic activity against MCL cells in vitro and in vivo.ResultsFunctionally optimized 74bbz CAR-T cells (clone 42105) induced significant killing of MCL cell lines, and primary MCL patient samples including one relapse after commercial CD19 CAR-T cell therapy with direct correlation between antigen density and cytotoxicity. It significantly prolonged the survival of an animal model established in NOD-SCIDγc−/− (NSG) mice engrafted with a human MCL cell line Mino subcutaneously compared to controls. Finally, while CD74 is also expressed on normal immune cell subsets, treatment with 74bbz CAR-T cells resulted in minimal cytotoxicity against these cells both in vitro and in vivo.ConclusionsTargeting CD74 with 74bbz CAR-T cells represents a new cell therapy to provide a potent and durable and anti-MCL activity.

UNMET NEED IN RELAPSED/REFRACTORY (R/R) MANTLE CELL LYMPHOMA (MCL) POST‐BRUTON TYROSINE KINASE INHIBITOR (BTKI): A SYSTEMATIC LITERATURE REVIEW AND META‐ANALYSIS

Background: Most patients with MCL, a rare B-cell non-Hodgkin lymphoma, will relapse or become refractory to treatment. While the introduction of BTKis has been transformative, options for patients who fail to respond or whose disease progresses on BTKis remain limited and largely palliative in nature. We sought to characterize and quantify the unmet clinical need of patients with R/R MCL in the post-BTKi setting. Methods: MEDLINE, Embase, and CENTRAL were systematically searched to October 2022—supplemented with hand searches of select conferences—to identify studies reporting overall survival (OS), progression-free survival (PFS), and/or response outcomes of patients receiving non-CAR-T treatments or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Random effects bivariate meta-analyses of OS/PFS were conducted based on studies with published Kaplan-Meier (KM) curves from which individual patient data could be estimated. Response outcomes, based on the best response achieved, were meta-analyzed using a generalized linear mixed model. Outcomes were evaluated separately for patients treated with non-CAR-T and brexu-cel. Results: Twenty-six studies (23 observational; 3 trials), reporting the outcomes of 1845 patients treated from 2005 to 2022, were included, where patients were initially enrolled for treatment with a BTKi (12 studies) or for treatment post-BTKi (14 studies). The non-CAR-T interventions varied, with most studies reporting outcomes from cohorts of patients receiving a variety of interventions. Across the included studies, most patients were male (65-94%) and older, with the median age varying from 63 to 77 years. OS and PFS KM curves were published in 10 and 3 studies, respectively, for non-CAR-T outcomes. The pooled median OS/PFS for these patients was 9.1 and 7.6 months, respectively (Table 1). The pooled objective response rate (ORR) and percentage of patients achieving a complete response (CR) were 45% and 23%, respectively. The median OS/PFS of patients who received brexu-cel was 32.1 and 14.9 months, based on 5 and 6 studies with KM curves, respectively, with ORR/CR rates of 89% and 74%. Analyses were not sensitive to different survival distributions or fixed/random effects models. Conclusions: Treatment options in the post-BTKi setting are heterogeneous and a significant unmet clinical need persists. Though longer follow-up is needed for survival outcomes, treatment with brexu-cel is emerging as a promising option in this difficult-to-treat setting. The research was funded by: This study was funded by Kite, a Gilead company. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract M. Dreyling Consultant or advisory role Astra Zeneca, Beigene, BMS/Celgene, Gilead/Kite, Janssen, Lilly/Loxo, Novartis, Roche Research funding: Abbvie, Bayer, BMS/Celgene, Gilead/Kite, Janssen, Roche Educational grants: Janssen, Roche Other remuneration: Astra Zeneca, Gilead/Kite, Janssen, Lilly, Novartis, Roche B. Shah Consultant or advisory role Pepromene Bio; Takeda Honoraria: Kite/Gilead; BMS; Novartis; Amgen; Pfizer; Beigene; Adaptive; Century Therapeutics; Autolus Research funding: Kite; Servier; Jazz Pharma Educational grants: Kite/Gilead; Takeda Other remuneration: Chair, NCCN Adult ALL subcommittee J. Wu Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead; Amgen; Abbott; AbbVie; Avid; Curis; Viracta T. Itani Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead Sciences M. J. Zoratti Research funding: RainCity Analytics has received funds from for-profit healthcare companies for research S. Kanters Research funding: RainCity Analytics has received funds from for-profit healthcare companies for research S. W. Wade Consultant or advisory role Kite Pharma; Amgen; Allergan/Abbvie; Johnson & Johnson W. Peng Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead J. Castaigne Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead I. Kloos Employment or leadership position: Kite, a Gilead company Stock ownership: Gilead Sciences M. Wang Consultant or advisory role AbbVie; Acerta Pharma; ADC Therapeutics America; Amphista Therapeutics Limited; AstraZeneca; Be Biopharma; BeiGene; BioInvent; Deciphera; DTRM Biopharma (Cayman) Limited; Genentech; InnoCare; Janssen; Kite Pharma; Leukemia & Lymphoma Society; Lilly; Merck; Miltenyi Biomedicine; Milken Institute; Oncternal; Parexel; Pepromene Bio; Pharmacyclics; VelosBio Honoraria: AbbVie; Acerta Pharma; AstraZeneca; Bantam Pharmaceutical; BeiGene; BioInvent; Bristol Myers Squibb; CAHON; Dava Oncology; Eastern Virginia Medical School; Genmab; i3Health; IDEOlogy Health; Janssen; Kite Pharma; Leukemia & Lymphoma Society; Medscape; Meeting Minds Experts; MD Education ; MJH Life Sciences; Merck; Moffit Cancer Center; Nurix; Oncology Specialty Group; OncLive; Pharmacyclics; Physicians Education Resources (PER); Practice Point Communications (PPC); Studio ER Congressi Research funding: Acerta Pharma; AstraZeneca; BeiGene; BioInvent; Celgene; Genmab; Genentech; Innocare; Janssen; Juno Therapeutics; Kite Pharma; Lilly; Loxo Oncology; Molecular Templates; Oncternal; Pharmacyclics; VelosBio; Vincerx

First-Line Treatment of Waldenström’s Macroglobulinaemia: Considerations Based on the Dutch National Guideline

Waldenström macroglobulinemia (WM) is a rare B-cell Non-Hodgkin Lymphoma. There are only few prospective randomized clinical trials to guide treatment recommendations and there is no international consensus on a preferred first line treatment approach. In the recently revised Dutch guideline for WM, we describe recommendations for practice based as much as possible on the known data. Here, we summarize the considerations for first-line treatment based on these Dutch guidelines. Available evidence is summarized, including efficacy and toxicity data. Combinations of Rituximab with chemotherapy, proteasome inhibition or BTK-inhibition are all valid first line treatment options. The Dutch WM working group considers Dexamethasone/Rituximab/Cylofosfamide (DRC) a suitable first-line treatment for many WM patients, given the efficacy, the relatively mild toxicity profile and the extensive experience with this regimen. However, the long-term toxicities of DRC are unclear and need further clarification. Other regimens such as R-bendamustine, R-Bortezomib-dexamethason are also effective options, however with specific toxicities. BTK-inhibitors are not a preferred option in first line for most patients in the Dutch WM guidelines because of the need for longterm treatment and toxicities. Based on patient preferences research, future clinical trials should focus on effective fixed-duration regimens with non-cytotoxic therapies that have a favorable toxicity profile. Further development of (combinations with) BCL-2 inhibititors, novel proteasome inhibitors and BTK-inhibition could be interesting. In addition T-cell-directed treatments including bispecific antibodies as a monotherapy or combined with other novel agents deserve further study in WM.

New Directions for Mantle Cell Lymphoma in 2022.

Mantle cell lymphoma is a rare B-cell non-Hodgkin lymphoma that is clinically and biologically heterogeneous. Risk stratification at the time of diagnosis is critical. One of the most powerful prognostic indices is the Mantle Cell Lymphoma International Prognostic Index-Combined, which integrates an estimate of proliferation (Ki67 index) with the standard Mantle Cell Lymphoma International Prognostic Index clinical factors. In addition, the presence of TP53 mutation is associated with suboptimal response to intensive chemoimmunotherapy and particularly dismal survival outcomes. Given their excellent activity in the relapsed/refractory setting, increasingly, biologically targeted therapeutics-such as covalent Bruton tyrosine kinase inhibitors, lenalidomide, and venetoclax-are being incorporated into "chemotherapy-free" regimens and in combination with established chemoimmunotherapy backbones for treatment-naïve mantle cell lymphoma. In addition, risk-adapted treatment programs are increasingly being studied. These programs tailor treatment according to baseline prognostic factors (e.g., presence of TP53 mutation) and may incorporate biomarkers of response such as minimal residual disease assessment. Although still investigational, these studies present an opportunity to move beyond the biology-agnostic, historical fitness-based treatment selection paradigm and toward a more personalized, tailored treatment approach in mantle cell lymphoma. After Bruton tyrosine kinase inhibitor failure, many promising standard or investigational therapies exist, including CAR T-cell therapy (including brexucabtagene autoleucel and lisocabtagene maraleucel), bispecific antibody therapy targeting CD20-CD3, zilovertamab vedotin (an antibody-drug conjugate that targets ROR1), and the noncovalent Bruton tyrosine kinase inhibitor pirtobrutinib. These new therapies show promising efficacy, even among high-risk patients, and will likely translate to improvements in survival outcomes for patients with progressive mantle cell lymphoma following treatment with a Bruton tyrosine kinase inhibitor.

Dismantling the Status Quo: Venetoclax in Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma, and remains a clinically challenging disease entity, particularly in the relapsed setting where outcomes are poor. However, recent innovations in targeted therapeutics have expanded treatment options and demonstrate significant efficacy even in relapsed disease. MCL frequently harbours aberrations of apoptosis pathways including over-expression of the anti-apoptotic protein BCL2. Such aberrancy promotes and sustains lymphomagenesis, thus rendering MCL an attractive target for venetoclax, the highly specific, orally bioavailable inhibitor of BCL2. Pre-clinical and early clinical data of venetoclax monotherapy demonstrated high response rates in relapsed/refractory MCL, though the durability of response in high-risk patients appears modest. More recently, clinical trials deploying combination strategies that pair venetoclax with other novel agents have been undertaken, with some promising early data reported. In this article, we review the biological rationale for deploying venetoclax in MCL, as well as the emerging data from clinical trials of venetoclax monotherapy and novel combinations.

Mantle cell lymphoma treatment options for elderly/unfit patients: A systematic review.

Mantle cell lymphoma (MCL) is a rare B‐cell non‐Hodgkin lymphoma (NHL) that is aggressive and incurable with existing therapies, presenting a significant unmet clinical need. MCL occurs mainly in elderly patients with comorbidities; thus, intense treatment options including allogeneic stem cell transplantation (Allo‐SCT) are not feasible. New treatment options are emerging for this elderly/unfit treatment group, we therefore conducted a systematic review to determine whether they offered an advance on the existing recommended treatment, R‐CHOP. The search strategies to identify MCL therapies were designed to capture the most relevant studies from 2013 to 2020. Following preferred reporting items for systematic reviews and meta‐analyses and population,interventions, observations and study design analysis, R‐CHOP, ibrutinib and bendamustine plus rituximab (BR) were taken forward for critical and statistical analysis. All three therapies were effective in increasing the overall survival (OS) and progression‐free survival of elderly/unfit patients with MCL. However, none resulted in a significant increase in OS compared to R‐CHOP. In addition, R‐CHOP had a better toxicity profile when compared to both ibrutinib and BR. We therefore conclude that treatment of elderly/unfit patients with MCL is still a significant unmet clinical need; and suggest that outside of the clinical trial setting, R‐CHOP should remain the recommended front‐line treatment for this patient group.

Inflammatory Infiltrate and Angiogenesis in Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is an aggressive and rare B-cell non-Hodgkin lymphoma classified in two clinicopathological subtypes according to SOX11 expression and mutation state of immunoglobulin variable region heavy chain (IgVH) gene. The transcription factor SOX11, overexpressed in 78%-93% of MCL patients, plays a central role in modulating tumor microenvironment prosurvival signals and angiogenic genes. In this work, we have explored the lymph node microenvironment of three subgroups of MCL patients classified according to SOX11 expression as negative, light, and strong. CD34+ microvessels, CD4+ and CD8+ T-lymphocytes, CD68+ and CD163+ macrophages, and the oncogene p53 expression were evaluated by immunohistochemistry. Moreover, STAT3 mRNA expression was analyzed by RNA-scope assay.Our results confirmed increased angiogenesis in the sample of patients positive to SOX11 compared to the negative ones and demonstrated that angiogenesis and SOX11 expression positively correlate to a higher T-lymphocytes inflammatory infiltrate. On the contrary, angiogenesis and SOX11 expression negatively correlate with macrophage's inflammatory infiltrate and p53 expression. STAT3 mRNA expression level was not relevant concerning angiogenesis or SOX11 expression. Overall, our data indicate that, in MCL, SOX11 expression is associated with increased angiogenesis and a high CD4+ and CD8+ T-cell infiltration, which are not sustained by CD163+ macrophages infiltrate and p53 expression.

Massive lymphadenopathy and hypereosinophilia in cd5-negative small lymphocytic lymphoma

Small lymphocytic lymphoma (SLL) is a relatively rare B-cell non-Hodgkin lymphoma that is considered to be the tissue equivalent of the much more common entity chronic lymphocytic leukemia (CLL). Most patients with SLL present with indolent generalized lymphadenopathy, which has frequently been present for several years. We hereby describe an unusual case of SLL in a patient who presented with a huge swelling at the right shoulder region and a single right enlarged axillary lymph node. The other uncommon findings were the presence of peripheral blood hypereosinophilia and CD5 immunonegativity.

Classic and extracavitary primary effusion lymphoma in 51 HIV‐infected patients from a single institution

Human immunodeficiency virus (HIV)-associated primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma with poor prognosis. Lymphoma cells are always infected with human herpesvirus-8 (HHV-8) and in most cases coinfected with Epstein-Barr virus. In classic presentation, PEL is characterized by body cavity effusions with or without mass lesions. A variant with only extracavitary localization has also been described. We report on a large single-center series of patients with PEL in the era of combined antiretroviral therapy (cART). The main objective was to compare the characteristics and the outcome of patients with classic (n = 34) and extracavitary (n = 17) variant PEL. At PEL diagnosis, no major difference was observed between the two groups in terms of demographic and HIV characteristics. Extracavitary localizations were exclusively nodal in six patients and involved various organs in 11 patients. Another HHV-8-associated disease was observed in 31 patients, Kaposi sarcoma in 25, and multicentric Castleman disease in 18 patients, without difference between the two groups. Thirty-two patients were treated with CHOP associated with high-dose methotrexate, 13 were treated with CHOP-derived regimen alone, and six patients received low-dose/no chemotherapy. Complete remission was achieved in 21 (62%) and seven (41%) patients of the classic and extracavitary groups, respectively. The median overall survival (OS) was 10.2 months. Despite a higher disease-free survival in the extracavitary group, there was no difference in OS between the two variants. Based on this series, characteristics of classic and extracavitary variants were very close. Although prognosis of PEL remains very severe in cART era, the median survival compares favorably with earlier series.

Rituximab Maintenance Therapy Is an Effective Therapy in over-Sixties with Mantle Cell Lymphoma

IntroductionMantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma (NHL) accounting for 5 percent of NHLs. Most patients with MCL are 60 years of age and older. The prognosis of patients with MCL is moderately aggressive and variable; the median overall survival is 3-5years. MCL international prognostic index(MIPI)is related to prognosis of the patients with MCL, however, it is unclear whether MIPI predicts outcomes of MCL over sixties. Out therapeutic strategy in elderly patients with newly diagnostic MCL is not high-dose chemotherapy with autologous stem cell transplantation. Instead of aggressive chemotherapy, Rituximab maintenance is considered as an effective and feasible option.Thus, we investigated whether MCL international prognostic index (MIPI) relates overall survival (OS) or progression free survival (PFS), and whether maintenance therapy with Rituximab improved OS or PFS in patients with newly diagnosed MCL patients 60 and older.MethodsWe analyzed retrospectively 60 years of age and older patients with MCL who have achieved complete response (CR) or partial response (PR) after induction chemotherapy with rituximab at our hospital from December 2005 to February 2015. Two of primary refractory patients were excluded because analysis is for patients who are eligible for rituximab maintenance therapy. The patients were diagnosed by hematopathologist in our hospital. According to the MIPI, patients were stratified into low risk (0 patients, 0%), intermediate risk (9 patients, 41%), and high risk (13 patients, 59 %). Induction chemotherapy regimens were six cycles of R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone), four cycle of R-hyper CVAD/MA (rituximab-cyclophosphamide-vincristine-doxorubicin-dexamethasone alternating with rituximab-methotrexate-cytarabine), six cycles of R-CVP (rituximab- cyclophosphamide-vincristine-predonisone), R-VP16 (rituximab-etoposide), or six cycles of VR-CAP (bortezomib-rituximab-cyclophosphamide-doxorubicin- predonisone). Rituximab maintenance therapy started 6 months after the last induction chemotherapy and underwent four weekly infusion every 6 months for 2 years.ResultsA total of 22 MCL patients were analyzed. The number of patients who had achieved CR was 14 and PR was 8. 14 of 22 patients were treated rituximab maintenance. Median age was 73 years old. MIPI could predict OS of MCL. 3-year-OS was significantly superior intermediate risk to MIPI high risk (3-years-OS: 87.5 %vs.51.9 %,p=0.0232), whereas PFS didn't have correlation with MIPI(3-years PFS70.0 %vs.38.5 %,p=0.136). 3-years OS was significantly superior maintenance group to no maintenance group (3-years survival rate 91.7 % vs. 25.0 %, p=0.00188, figure 1), and 3-years PFS tend to improve in the maintenance group (3-years PFS, 65.8 % vs.25.0 %, p=0.0773, figure 2).Conclusion:In this study, MIPI correlates with OS, however doesn't show with PFS. Rituximab maintenance therapy is effective, and prolongs OS for 60 years of age and older patients with MCL. [Display omitted] [Display omitted] DisclosuresNishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Mishima:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.

Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases.

Plasmablastic lymphoma (PBL) is a rare B-cell non-Hodgkin lymphoma often associated with Epstein-Barr virus (EBV) infection. To gain insight in this aggressive lymphoma subtype, the clinicopathologic characteristics of 25 unpublished single-center PBLs (2 in acquired immunodeficiency syndrome patients, 11 in immunocompetent individuals [IC-PBL], 12 in transplant recipients [PT-PBL]) and of 277 reported PBLs were summarized. In the reported series, PBL patients were predominantly male (77%) with a median age at diagnosis of 46 years (range, 1.2 to 87 y). The majority of the biopsies (66%) was EBV positive. Extranodal presentation was most frequent (88%, of which 35% were oral, 18% gastrointestinal, 12% cutaneous). PBL was diagnosed in acquired immunodeficiency syndrome patients (50%), immunocompetent individuals (35%), and transplant recipients (14%). These subgroups differed in age at diagnosis (median: 41, 64, 47 y, respectively), primary localization (oral, oral, cutaneous, respectively), EBV positivity (75%, 50%, 67%, respectively), CD45 expression (31%, 33%, 70%, respectively), and C-MYC aberrations (78%, 44%, 38%, respectively). Ann Arbor stage I, EBV positivity, CD45 expression, and lack of C-MYC aberrations were associated with better outcome (P<0.05). Our series of IC-PBL and PT-PBL cases revealed differential expression of CD10 (0% vs. 42%, respectively), CD56 (22% vs. 42%, respectively), TP53 (67% vs. 8%, respectively), and BCL2 (88% vs. 25%, respectively). Gene expression analysis of 5 of our PT-PBLs revealed upregulation of DNMT3B, PTP4A3, and CD320 in EBV-positive PT-PBL and suggested a role for cancer/testis antigens. The results of this retrospective study suggest different pathogenic mechanisms of PBL in different immunologic settings and a potentially important impact of EBV and CD45 on prognosis.

A Case of HIV-Negative Primary Effusion Lymphoma Treated with Bortezomib, Pegylated Liposomal Doxorubicin, and Rituximab

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma that usually occurs in HIV-positive patients and has a very poor prognosis with limited treatment options. Prospective studies are lacking to define the standard of care for this disease, and various case series report median survival at 6 months with anthracycline-based chemotherapy. Reports of antiviral agents, immune modulators, and some targeted therapies are present in the literature with variable results. Herein, we report a case of an elderly HIV-negative man of Mediterranean origin who was diagnosed with primary effusion lymphoma and responded dramatically to 6 cycles of a combination of bortezomib, pegylated liposomal doxorubicin, and rituximab. He has since been maintained on rituximab and remains in complete remission 2 years after diagnosis. In this report, we discuss the rationale for using these agents in this patient and advocate the further study of bortezomib-based therapy in PEL.

A 62‐YEAR‐OLD MAN WITH CHRONIC PYOTHORAX

June 2005. Pyothorax-associated lymphoma (PAL) is a rare B-cell non-Hodgkin lymphoma (B-NHL) which develops in the pleural cavity after a 20- to 64-year history of chronic pyothorax. We present here the case of a 62-year-old man who suffered from chronic pyothorax after pneumectomy 44 years ago, and complained of progressive ataxia. A MRI of the head revealed a solitary lesion in the vermis cerebelli, and a biopsy showed a lymphoma displaying immunoblastic features. Immunohistochemistry revealed an aberrant dual B/T phenotype and an Epstein-Barr virus (EBV) type III LMP-1+/EBNA-2+ latency profile. In-situ hybridization disclosed EBV-encoded RNAs in the tumor cells. PCR for the detection of rearranged immunoglobulin heavy chain (IgH) genes followed by GeneScan analysis demonstrated a clonal B-cell population with DNA amplificates of identical size in the brain manifestation, and a large mediastinal tumor analyzed post mortem. Among the largest series of 106 PALs collected through a nationwide survey in Japan, central nervous system (CNS) involvement was detected in 5 (14%) of 36 patients where an autopsy had been performed. To best of our knowledge, this is the first case of a pyothorax-associated lymphoma initially diagnosed on brain biopsy.