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1.  Pre-Diagnosis Cigarette Smoking and Overall Survival in Non-Hodgkin Lymphoma 
British journal of haematology  2013;163(3):352-356.
We examined whether smoking prior to non-Hodgkin lymphoma (NHL) diagnosis was associated with overall survival (OS) and conducted a meta-analysis to assess the evidence relating pre-diagnosis cigarette smoking with OS. Among 523 NHL patients, worse OS was suggested for greater pre-diagnostic smoking habits when compared to never smokers. In the meta-analysis (n=5 patient populations), inferior OS was observed for greater number of cigarettes smoked per day, years of cigarette smoking, and pack-years of cigarette smoking. The inferior survival was more pronounced for follicular than for diffuse large B-cell lymphoma. Pre-diagnosis cigarette smoking may adversely impact the survival of NHL patients.
doi:10.1111/bjh.12512
PMCID: PMC3797194  PMID: 23909494
cigarettes; smoking; non-Hodgkin lymphoma; pooled analysis; meta-analysis
2.  The Efficacy and Tolerability of ABVD and Stanford V in Older Hodgkin Lymphoma Patients: A Comprehensive Analysis from the North American Intergroup Trial E2496 
British journal of haematology  2013;161(1):76-86.
SUMMARY
There is a lack of contemporary prospective data examining the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ≥60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% versus 0.3% for patients aged <60 years (p<0.001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs 74%, respectively, p=0.002; 5-year overall survival: 58% and 90%, respectively, p<0.0001), while time-to-progression (TTP) was not significantly different (5-year TTP: 68% versus 78%, respectively, p=0.37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, p=0.30); however, the incidence of death without progression was significantly increased for older HL patients (22% versus 9%, respectively, p<0.0001). Thus, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.
doi:10.1111/bjh.12222
PMCID: PMC3906856  PMID: 23356491
Hodgkin lymphoma; elderly; treatment-related toxicity; bleomycin lung toxicity
3.  Paradoxical Regulation of Hypoxia Inducible Factor-1α (HIF-1α) by Histone Deacetylase Inhibitor in Diffuse Large B-Cell Lymphoma  
PLoS ONE  2013;8(11):e81333.
Hypoxia inducible factor (HIF) is important in cancer, as it regulates various oncogenic genes as well as genes involved in cell survival, proliferation, and migration. Elevated HIF-1 protein promotes a more aggressive tumor phenotype, and greater HIF-1 expression has been demonstrated to correlate with poorer prognosis, increased risk of metastasis and increased mortality. Recent reports suggest that HIF-1 activates autophagy, a lysosomal degradation pathway which may promote tumor cell survival. We show here that HIF-1α expression is constitutively active in multiple diffuse large B cell lymphoma (DLBCL) cell lines under normoxia and it is regulated by the PI3K/AKT pathway. PCI-24781, a pan histone deacetylase inhibitor (HDACI), enhanced accumulation of HIF-1α and induced autophagy initially, while extended incubation with the drug resulted in inhibition of HIF-1α. We tested the hypothesis that PCI-24781- induced autophagy is mediated by HIF-1α and that inhibition of HIF-1α in these cells results in attenuation of autophagy and decreased survival. We also provide evidence that autophagy serves as a survival pathway in DLBCL cells treated with PCI-24781 which suggests that the use of autophagy inhibitors such as chloroquine or 3-methyl adenine in combination with PCI-24781 may enhance apoptosis in lymphoma cells.
doi:10.1371/journal.pone.0081333
PMCID: PMC3842257  PMID: 24312289
4.  Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP 
Journal of Clinical Oncology  2010;28(6):1017-1024.
Purpose
Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1α in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated.
Patients and Methods
We studied the immunohistochemical protein expression of HIF-1α on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome.
Results
Median follow-up for all patients was 80 months. Among all patients, HIF-1α was expressed in 62% of germinal center and 59% of non–germinal center patients. With HIF-1α analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1α protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1α–positive patients was 71% v 43% for HIF-1α–negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1α remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1α correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1α and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2).
Conclusion
The expression of HIF-1α protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.
doi:10.1200/JCO.2009.24.1893
PMCID: PMC2834428  PMID: 20048181
5.  Multicenter Analysis of 80 Solid Organ Transplantation Recipients With Post-Transplantation Lymphoproliferative Disease: Outcomes and Prognostic Factors in the Modern Era 
Journal of Clinical Oncology  2010;28(6):1038-1046.
Purpose
Adult post-transplantation lymphoproliferative disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined.
Methods
We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008).
Results
Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, ≥ 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001).
Conclusion
This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.
doi:10.1200/JCO.2009.25.4961
PMCID: PMC2834429  PMID: 20085936
6.  The Novel Expanded Porphyrin, Motexafin Gadolinium, Combined with Ytrrium-90 Ibritumomab Tiuxetan for Relapsed/Refractory Non-Hodgkin Lymphoma: Pre-Clinical Findings and Results of a Phase I Trial 
Purpose
Therapeutic strategies to enhance the efficacy of radioimmunotherapy have not been explored. Motexafin gadolinium (MGd) is a novel anti-cancer agent that targets redox-dependent pathways and enhances sensitivity of tumor cells to ionizing radiation.
Experimental Design
We performed pre-clinical studies examining MGd combined with rituximab and/or radiation in lymphoma cells. We subsequently completed a phase I clinical trial combining escalating doses of MGd concurrently with standard yttrium-90 (90Y)-ibritumomab tiuxetan for patients with relapsed/refractory non-Hodgkin lymphoma.
Results
In HF1 lymphoma cells, MGd and rituximab resulted in synergistic cytotoxicity (combination index 0.757) through a mitochondrial-mediated caspase-dependent pathway, while cell death in Ramos and SUDHL4 cells was additive. MGd/rituximab combined with radiation (1–3Gy) resulted in additive apoptosis. Twenty-eight of 30 patients were evaluable on the phase I clinical trial. Median age was 65 years (47–87), and histologies were: marginal-zone (n=1), mantle-cell (n=3), diffuse large-cell (n=6), and follicular lymphoma (n=18). 86% of all patients were rituximab-refractory. Therapy was well-tolerated and no dose limiting toxicity was seen. Overall response rate (ORR) was 57% (complete remission (CR) 43%) with median time-to-treatment failure (TTF) of 10 months (1–48+) and median duration-of-response of 17 months. Of note, all responses were documented at 4 weeks. Furthermore, in rituximab-refractory follicular lymphoma (n=14), ORR was 86% (CR 64%) with median TTF of 14 months (2–48+).
Conclusions
This represents the first report of a novel agent to be combined safely concurrently with radioimmunotherapy. Further, tumor responses with 90Y-ibritumomab tiuxetan/MGd were prompt with a high rate of CRs, especially in rituximab-refractory follicular lymphoma.
doi:10.1158/1078-0432.CCR-09-0905
PMCID: PMC2763343  PMID: 19825958
lymphoma; radioimmunotherapy; rituximab-refractory; oxidative stress; MGd
7.  The genetic landscape of mutations in Burkitt lymphoma 
Nature genetics  2012;44(12):1321-1325.
Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.
doi:10.1038/ng.2468
PMCID: PMC3674561  PMID: 23143597
8.  Glutathione Depletion Enhances Arsenic Trioxide-Induced Apoptosis in Lymphoma Cells Through Mitochondrial-Independent Mechanisms 
British journal of haematology  2010;150(3):365-369.
doi:10.1111/j.1365-2141.2010.08197.x
PMCID: PMC2910124  PMID: 20408844
non-Hodgkin lymphoma; arsenic trioxide; apoptosis; oxidative stress; ROS
9.  Hypoxia-Inducible Factor-Alpha Activation in Lymphoma and Relationship to the Thioredoxin Family 
British journal of haematology  2008;141(5):676-680.
Hypoxia-Inducible-Factors (HIFs) activate oncogenic pathways, while thioredoxins, including thioredoxin-1 (Trx1) and thioredoxin reductases-1 and -2 (TrxR1 and TrxR2), promote HIF-α stabilization. Elevated levels of thioredoxin or HIF have been associated with poor outcomes in solid tumors and each represent potential therapeutic targets. In lymphoma cell line immunoblotting studies, we found that Raji and SUDHL4 cells exhibited normoxic HIF-2α protein-stabilization. Furthermore, five lymphoma cell-lines showed increased TrxR1 expression, while only Namalwa, HF1, and SUDHL4 had Trx1 and TrxR2 activation. Utilizing tissue microarrays from diffuse large B-cell (DLBCL) and follicular lymphoma (FL) patient specimens (n=82), we found different frequency of HIF expression in FL versus DLBCL as well as differing HIF-1 versus HIF-2 expression within each histologic subgroup. Forty-four percent of DLBCL versus 11% of FL cases had moderate-to-high expression of both HIF-1α and HIF-2α (p=0.0017), while 56% of DLBCL and 32% of FL samples had at least low HIF-1α and HIF-2α expression (p=0.042). Survival analysis among newly-diagnosed DLBCL cases showed 44% 2-year event-free survival (EFS) and 67% overall survival (OS) with high HIF-1α and HIF-2α expression compared with 67% and 76%, respectively, (p=0.10 and p=0.64, respectively) without high expression. These data demonstrate that HIF and the thioredoxins are activated in lymphoma and that HIF expression may influence prognosis.
doi:10.1111/j.1365-2141.2008.07093.x
PMCID: PMC2894542  PMID: 18422776
10.  The Histone Deacetylase Inhibitor PCI-24781 Induces Caspase and ROS-Dependent Apoptosis Through NF-kB and is Synergistic with Bortezomib in Lymphoma Cells 
Purpose
We investigated the cytotoxicity and mechanisms of cell death of the broad-spectrum histone deacetylase inhibitor (HDACi), PCI-24781, alone and combined with bortezomib in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cell lines and primary lymphoproliferative (CLL/SLL) cells.
Experimental design
Apoptosis, mitochondrial membrane potential, cell cycle analysis, and reactive oxygen species (ROS) were measured by flow cytometry, while caspase-activation was determined by Western blot. NF-kB-related mRNAs were quantified by RT-PCR, NF-kB-related proteins by Western blotting, and NF-kB DNA binding-activity by electromobility shift assay. Finally, gene expression profiling (GEP) was analyzed.
Results
PCI-24781 induced concentration-dependent apoptosis that was associated with prominent G0/G1 arrest, decreased S-phase, increased p21 protein, and increased ROS in HL and NHL cell lines. Dose-dependent apoptosis with PCI-24781 was also seen among primary CLL/SLL cells. PCI-24781-induced apoptosis was shown to be ROS- and caspase-dependent. Combined PCI-24781/bortezomib treatment resulted in strong synergistic apoptosis in all NHL lines (combination indices: 0.19-0.6) and was additive in HL and primary CLL/SLL cells. Further, PCI-24781/bortezomib resulted in increased caspase cleavage, mitochondrial depolarization, and histone acetylation vs either agent alone. GEP showed that PCI-24781-alone significantly downregulated several antioxidant genes, proteasome components, and NF-kB pathway genes, effects which were enhanced further with bortezomib. RT-PCR confirmed downregulation of NF-kB1 (p105), c-Myc, and IkB-kinase subunits, while NF-kB DNA-binding activity was decreased.
Conclusion
We show that PCI-24781 results in increased ROS and NF-kB inhibition, leading to caspase-dependent apoptosis. We also demonstrate that bortezomib is synergistic with PCI-24781. This combination or PCI-24781 alone has potential therapeutic value in lymphoma.
doi:10.1158/1078-0432.CCR-08-2365
PMCID: PMC2704489  PMID: 19417023
HDAC inhibition; reactive oxygen species; NFκB; apoptosis; lymphoma
11.  Vaccination history and risk of non-Hodgkin lymphoma: a population-based, case-control study 
Cancer causes & control : CCC  2008;20(5):517-523.
Objective
As factors that alter the immune system have been implicated in non-Hodgkin lymphoma (NHL) etiology, it is of interest to explore the association between vaccination and risk of NHL. Results of few epidemiologic studies conducted thus far are inconsistent, and only one has examined the association by histologic subtype.
Subjects
A population-based, case-control study of 387 patients with NHL and 535 controls conducted in Nebraska between 1999 and 2002.
Methods
Information on vaccination for tetanus, polio, influenza, smallpox, and tuberculosis, as well as important environmental factors, was collected by telephone interview. Risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounders.
Results
We found that NHL risk was inversely associated with ever receiving a polio (OR=0.59, CI=0.40–0.87) or smallpox (OR=0.71, CI=0.51–0.98) vaccination, and positively associated with influenza vaccination (OR=1.53, CI=1.14–2.06). No significant association was found for tetanus or tuberculosis vaccination. The patterns of association were similar between men and women. Analysis by histologic subtypes showed that polio vaccination was associated with a lower risk of follicular (OR=0.54, CI=0.31–0.92) and chronic lymphocytic leukemia/small lymphocytic lymphomas (OR=0.29, CI=0.12–0.69) and smallpox vaccination was associated with a lower risk of marginal zone lymphoma (OR=0.41, CI=0.19–0.88). In contrast, ever receiving an influenza vaccination was associated with a higher risk of follicular (OR=1.98, CI=1.23–3.18) and diffuse large B cell lymphomas (OR=1.88, CI=1.13–3.12).
Conclusion
Risk of NHL is inversely associated with polio and smallpox vaccination and positively associated with influenza vaccination. These associations appear to differ by histologic subtype.
doi:10.1007/s10552-008-9259-x
PMCID: PMC3446202  PMID: 19011978
non-Hodgkin lymphoma; vaccination; risk factors; epidemiology
13.  Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone Andrographolide, the active component of Andrographis paniculata 
Purpose
Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, anti-viral and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines.
Experimental Design
We studied the Burkitt p53 mutated Ramos cell line, the mantle-cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1 and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL.
Results
We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin-V/propidium iodide (PI) in the presence and absence of the antioxidant N-acetyl-L-cysteine (NAC), the glutathione-depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by PARP cleavage and activation of caspases 3, 8 and 9. We measured BAX conformational change, and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and in patient samples.
Conclusions
Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted.
doi:10.1158/1078-0432.CCR-10-0883
PMCID: PMC2948634  PMID: 20798229
non-Hodgkin lymphoma; andrographolide; apoptosis; oxidative stress; ROS; caspase
14.  All trans retinoic acid nanodisks enhance retinoic acid receptor mediated apoptosis and cell cycle arrest in mantle cell lymphoma 
British journal of haematology  2010;150(2):158-169.
Summary
Mantle cell lymphoma (MCL) is characterized by translocation t(11;14)(q13;q32), aggressive clinical behaviour, and poor patient outcomes following conventional chemotherapy. New treatment approaches are needed that target novel biological pathways. All trans retinoic acid (ATRA) is a key retinoid that acts through nuclear receptors that function as ligand-inducible transcription factors. The present study evaluated cell killing effects of ATRA-enriched nanoscale delivery particles, termed nanodisks (ND), on MCL cell lines. Results show that ATRA-ND induced cell death more effectively than naked ATRA (dimethyl sulphoxide) or empty ND. ATRA-ND induced reactive oxygen species (ROS) generation to a greater extent than naked ATRA. The antioxidant, N-acetylcysteine, inhibited ATRA-ND induced apoptosis. Compared to naked ATRA, ATRA-ND enhanced G1 growth arrest, up-regulated p21and p27, and down regulated cyclin D1. At ATRA concentrations that induced apoptosis, expression levels of retinoic acid receptor-α (RARα) and retinoid X receptor-γ (RXRγ) were increased. Compared to naked ATRA, ATRA-ND significantly stimulated transcriptional activity of RARA in a model carcinoma cell line. Furthermore, the RAR antagonist, Ro 41-5253, inhibited ATRA-ND induced ROS generation and prevented ATRA-ND induced cell growth arrest and apoptosis. In summary, incorporation of ATRA into ND enhanced the biological activity of this retinoid in cell culture models of MCL.
doi:10.1111/j.1365-2141.2010.08209.x
PMCID: PMC2907750  PMID: 20507312
Nanodisks; Mantle Cell Lymphoma; ATRA; Reactive Oxygen Species; Apoptosis
15.  Yttrium-90 Ibritumomab Tiuxetan Doses Calculated to Deliver up to 15 Gy to Critical Organs May Be Safely Combined With High-Dose BEAM and Autologous Transplantation in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma 
Journal of Clinical Oncology  2009;27(10):1653-1659.
Purpose
To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 (90Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation.
Patients and Methods
Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized 90Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of 90Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation.
Results
Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively.
Conclusion
Dose-escalated 90Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.
doi:10.1200/JCO.2008.19.2245
PMCID: PMC2668971  PMID: 19255322
16.  Primary mediastinal large B-cell lymphoma in HIV: report of two cases 
Journal of Hematopathology  2009;2(1):45-49.
Primary mediastinal large B cell lymphoma (PMLBCL) is a subtype of diffuse large B cell lymphoma arising in the mediastinum with distinctive clinical and morphological features. Though diffuse large B cell lymphoma is one of the most common non-Hodgkin lymphoma associated with AIDS, there are no data available regarding the association of HIV and PMLBCL. We report here two cases of PMLBCL arising in AIDS patients. In both cases, PMLBCL presented in a setting of low CD4 T-cell count as rapidly enlarging mediastinal mass. The morphologic and immunophenotypic findings are characteristic of PMLBCL. One of the two patients, a 25-year-old woman who had localized disease and evidence of Epstein–Barr virus in lymphoma cells, did not respond to chemotherapy and died of disease progression 5 months after diagnosis. The second patient, a 38-year-old male with disseminated disease, responded to therapy and is disease-free after 9 months of follow-up.
doi:10.1007/s12308-009-0022-3
PMCID: PMC2713493  PMID: 19669223
Primary Mediastinal Large B Cell Lymphoma; HIV; EBV

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