Large B-cell non-Hodgkin Lymphoma Research Articles

Diffuse Large B-Cell Lymphoma Presenting with Bilateral Renal Masses and Hematuria: A Case Report

Renal involvement is most often seen in conjunction with multisystemic, disseminated lymphoma either by direct extension from a retroperitoneal mass or via hematogenous spread. Primary lymphoma of the kidney is not a common entity and it is a controversial issue on account of the absence of lymphatic tissues in the normal kidney. In this case report, we describe a 19-year-old male with hematuria, acute kidney injury, and bilateral renal masses due to massive lymphomatous infiltration of the kidneys, which was diagnosed as diffuse large B-cell non-Hodgkin lymphoma by Tru-Cut biopsy.

Early change in left atrial function in patients treated with anthracyclines assessed by real-time three-dimensional echocardiography.

Real-time three-dimensional echocardiography(RT-3DE) has allowed a better assessment of LA volumes and function. We sought to assess the early change in left atrial size and function in patients treated with anthracyclines using RT-3DE. 61 patients aged 44.9 ± 11.9 years with large B-cell non-Hodgkin lymphoma treated with doxorubicin were studied. Blood collection and echocardiography were performed at baseline and 1 day after completion of the chemotherapy. Global longitudinal strain (GLS), maximum, minimum and pre-atrial contraction LA volumes were measured and reservoir, conduit and booster pump function were assessed. Despite normal LVEF, passive emptying percent of total emptying (0.51 ± 0.14 vs. 0.40 ± 0.12, P < 0.001) and passive emptying index (0.29 ± 0.10 vs. 0.23 ± 0.06, P < 0.001) were remarkably reduced compared to baseline values, while active emptying percent of total emptying (0.49 ± 0.14 vs. 0.60 ± 0.12, P < 0.001) and active emptying index (0.41 ± 0.16 vs. 0.47 ± 0.16, P = 0.048) were increased. GLS (−21.64 ± 2.83 vs. −17.30 ± 2.50) was markedly reduced, cTnT levels was elevated from 0.005 ± 0.004 to 0.020 ± 0.026 ng/mL at the completion of chemotherapy (P all < 0.001). Early LA functional change occur after doxorubicin exposure in patients with preserved LVEF, which could be detected by RT-3DE.

Hypertriglyceridemia: An Open Door for Cancer Treatment?

Does lipid management have a significant role in cancer treatment? Could hypertriglyceridemia be an accelerating factor in certain tumors? These questions have grown from the long-standing recognition of the relationship of lipids to certain cancers. Cancers express high levels of lipid synthase, the enzyme responsible for the production of fatty acids. Lymphoma and other cancers have been found to have the ability to generate the lipids via de novo lipogenesis at a rate faster than other lipogenetic tissues [1]. Continuous de novo lipogenesis provides cancer cells with membrane building blocks, signaling lipid molecules, posttranslational modifications of proteins as well as energy supply to support rapid cell proliferation [2]. Protection of cancer cells by apoptosis by overexpression of fatty acid synthase (FASN) also helps the progression of the cancer [2]. Recent studies have documented the changes in lipid levels in the etiology and most importantly prognosis of cancer [3, 4]. There are many studies that have shown that the degree of lipid abnormality was directly related to the underlying tumor burden in addition to the abnormality in triglyceride clearance [5]. In one study, 25 patients with acute leukemia and nonHodgkin’s lymphoma (NHL) were studied; all patients demonstrated an abnormality in at least one plasma lipid fraction that consisted of extremely low levels of high density lipoprotein (HDL), elevated triglycerides (TG) and elevated very low density lipoprotein (VLDL). The levels were found to be normalized after recovery [5]. Another study was performed to investigate serum lipid alterations in patients with acute lymphoblastic leukemia (ALL) at diagnosis and during remission of the disease. Plasma lipids and lipoproteins were measured at diagnosis, prior to the administration of induction treatment, and every 2 months for the first 12 months of the maintenance phase of chemotherapy in 64 patients with ALL. Nearly all patients demonstrated serum lipid alterations which included elevated TG, LDL and cholesterol and values were returned back to normal during remission [6]. This points out the direct link between cancer progression and lipid levels. Metastasis is another interesting area in which the lipid level can correlate with disease burden. In one study, 205 Iranian patients from Semnan Oncology Clinic were studied and there was a significant association between higher levels of serum LDL and metastasis [7]. Aggressiveness of the tumor including metastasis can be highlighted by the levels of lipids. This brings up to the point of our case. We present a patient with stage IV diffuse large B-cell NHL with diffuse involvement of the bone and liver whose course was complicated with an incidental finding of hypertriglyceridemia. A 67-year-old Caucasian male with a past medical history of chronic obstructive pulmonary disease, diabetes mellitus, hypertension, coronary artery disease, and pulmonary embolism was admitted to the hospital for severe lower back pain and significant weight loss for 1 month. He denied any familial or personal history of hypertriglyceridemia. Physical examination was remarkable for pale conjunctivae, positive straight leg test on the left lower extremity, and a limited range of motion in his right upper extremity. There was no point tenderness noted in his back but there was mild tenderness to palpation of the right chest wall. CT abdomen imaging revealed several masses in the liver which involved the lateral segment of the left lobe, the medial segment, and an illdefined mass in the right lobe posteriorly. Biopsy of the liver demonstrated evidence for diffuse large B-cell NHL and bone marrow involvement was also seen in bone marrow biopsy. Lipid profile drawn 2 years ago were found to be TG 195 mg/ dL, cholesterol 146 mg/dL, LDL 74 mg/dL, VLDL 39 mg/dL and HDL 33 mg/dL. The lipid panel had changed dramatically during this admission demonstrating TG 1,154 mg/dL, cholesterol 204 mg/dL, and HDL 4 mg/dL, and LDL and VLDL were unable to be calculated. This unusual level of TG highlighted the aggressiveness of the tumor and more importantly the prognosis of the cancer. The patient was treated with gemfibrozil and insulin. TG levels were markedly improved from 1,154 to 690 mg/dL. The patient deteriorated before initiation of chemotherapy and expired. The issue of interest in this case is not the specific attributes of the cancer discussed but of the rise and fall of TG associated with it. The possible implications of this event may correlate with the aggressiveness of the tumor or the type of cancer and presents an intriguing possibility of manipulating this process as a means of treatment. The current standards for Manuscript accepted for publication March 24, 2016

Low back pain radiating to the leg: an atypical cause.

This study reports the case of a 47-year old female with low back pain radiating to groin and anterior regions of the left thigh and leg. At symptoms onset, electromyography showed left L3-L4 radiculopathy, and nuclear magnetic resonance revealed disc protrusion at the same level with impingement of the spinal nerve root. The clinical symptoms were ascribed to lumbar disco-radicular conflict. The patient underwent steroidal anti-inflammatory treatment with epidural steroid injections, chiropractic spinal manipulations and rehabilitation program, with no relief. Thirteen months after the onset of pain, a computed tomography of sacroiliac joints showed osteolytic lesion in the iliac bone of left joint, and a bone scintigraphy highlighted foci of intense uptake at left iliac bone and left proximal extremity of the femur. The bone biopsy and pathological examinations showed findings consistent with large B-cell non-Hodgkin lymphoma. This case report highlights the fact that in making differential diagnosis of low back pain radiating to the leg we have to consider the rare possibility that pain can be due to non-Hodgkin lymphoma that involves simultaneously the iliac bone and proximal extremity of the femur.

Benda-BEAM High-Dose Therapy Prior to Auto-SCT Is Effective in Resistant/Relapsed DLBCL

Background: The most important drawback of clinical trials of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) in lymphomas is the high heterogeneity of histological entities. Therefore, the statistical power is reduced, and data are not conclusive. We previously demonstrated the safety of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (BeEAM) prior to ASCT in resistant/relapsed lymphoma patients. This combination of drugs was able to induce a high CR rate in a population that did not have an opportunity of being cured with other therapies. However, that study enrolled both Hodgkin and non-Hodgkin lymphoma patients.Aims: We designed a phase II study to evaluate the efficacy of the BeEAM conditioning in resistant/relapsed diffuse large B-cell non-Hodgkin lymphoma (DLBCL) patients.Patients and methods: The study was registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2011-001246-14. Until now, 61 patients (median age 54 years, range 19-69) with resistant/relapsed DLBCL were enrolled. The primary end-point of the study is to evaluate the 1-year complete remission rate.Results: Briefly, 46/61 patients had advanced stage disease (III-IV); 20 were primary refractory and 41 had relapsed after a median number of 2 lines of therapy (range: 1-3). Twenty-one patients had 1 or more relevant comorbidities (range: 1- 5). 30 patients were in II or subsequent CR after salvage therapy, whereas 27 were in PR and 4 had stable or progressive disease. A median number of 5.72x106 CD34+/kg cells (range 2.21-10.60) collected from peripheral blood was reinfused to patients. All patients engrafted, with a median time to ANC>0.5x109/l of 10 days. Median times to achieve a platelet count >20x109/l and >50x109/l were 12 and 17 days respectively. Twenty-two out of 61 patients presented a fever of unknown origin (36%), whereas 24 patients (39%) presented a clinically documented infection. All patients received G-CSF after transplant for a median time of 8 days (range: 8-13). One patient died due to an incomplete hematological recovery after transplant, producing an overall transplant related mortality of 2.7%. Fifty-seven patients are evaluable for response: 48/57 (84%) obtained a CR, 3/57 (5%) a PR, whereas 6/57 (11%) did not respond to therapy. After a median follow-up of 10.5 months after transplant (range 3-37), 6/57 (11%) patients were refractory, 12/57 (21%) relapsed and 39/57 (68%) are still alive, in continuous CR.Conclusion: Our clinical trial was designed to closely resemble real-world treatment for these patients. During the study, we transplanted a similar proportion of the patients that would have received ASCT in a real-world scenario. While we cannot make sound comparisons without head-to-head trials, results from previous studies using HDT regimens in DLCBL have not been as encouraging as ours. Accordingly, our data preliminary provide the evidence that the Benda-BEAM regimen is safe and has promising high efficacy in resistant-relapsed aggressive DLBCL patients.Acknowledgments: The study was supported in part by AIL Pesaro Onlus. Mundipharma Italy is grateful acknowledged for providing Bendamustine free of charge. DisclosuresPatriarca:Janssen-Cilag, Celgene, Merck Sharp & Dohme: Honoraria. Zinzani:Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Clinicopathologic Profile and Outcome of Extranodal Diffuse Large B-Cell NHL: Egyptian National Cancer Institute Experience

Abstract Background: Primary extranodal diffuse large B-Cell lymphoma (PE-DLBCL) accounts for about one-third of all cases of DLBCL. We reviewed the clinical and pathological characteristics of cases with PE-DLBCL presented to NCI, Egypt. Patients and methods: We retrospectively studied patients with pathologically documented PE-DLBCL presented to the National Cancer Institute between January 2008 and December 2010. Revision of histopathology and sub-classification of patients to germinal centre (GC) DLBCL and non-GC-DLBCL through immunostaining of CD10, BCL-6 and MUM-1 were done. Cases that were CD10+/BCL-6±/ MUM-1- were categorised as GC-DLBCL, while cases that were CD10-/BCL-6±/MUM-1+ were categorised as non-GC-DLBCL. Clinical data regarding baseline characteristics, chemotherapy given and the response to chemotherapy was collected. Results: A total of 57 patients of PE-DLBCL were included in the study. Mean age was 48.9 years (range 21-78), and 32 patients (56.1%) were females. Most frequent locations were gastrointestinal and liver (29.9% and 22.9 %; respectively). Forty-two patients (73.7%) were sub-classified as non-GC-DLBCL. The patients who were stage III/IV were more common (52.6%). Fifty-two patients received CHOP, 5 received CVP, and 6 patients received radiotherapy after finishing chemotherapy. Complete response rate (CR) was 64.9%, there was no difference in the CR (66.7%, 64.3%) and Overall Survival (53.3%, 52.4%) in GC-DLBCL group in comparison to non-GC-DLBCL group (p = 0.24 and 0.6; respectively). The CR and OS for patients with low international prognostic index (IPI) were significantly better than patients with intermediate or high IPI (p = 0.008 and 0.08, respectively). Conclusion: Non-GC-DLBCL is more common than GC-DLBCL in PE-DLBCL in Egyptian population. The most affected sites are gastrointestinal and liver reflecting the association between high frequency of hepatitis B and C and hepatic non-Hodgkin’s lymphoma (NHL). Stage of the disease and IPI remains the most important prognostic factor for PE-DLBCL.

Non-Hodgkin Lymphomas: Impact of Rituximab on Overall Survival of Patients with Diffuse Large B-Cell and Follicular Lymphoma

Information comparing treatment outcome for diffuse large Bcell (DLBCL) and follicular (FL) non-Hodgkin lymphoma (NHL) patients treated with schemes with and without rituximab from low- and middle-income countries is scarce. Clinical characteristics, response to therapy and long-term outcome of DLBCL and FL patients were studied. Patients with DLBCL and FL diagnosed over 8years at a reference center in northeast Mexico were included. Kaplan-Meier method was used to determine overall survival (OS) and progression-free survival (PFS). Cox regression model was used to evaluate the association between risk factors, rituximab therapy and clinical outcome. One hundred-sixteen patients with DLBCL and 65 with FL in advanced stages were included. Median age was 57.8 and 56years, respectively. Clinical characteristics between groups receiving or not receiving rituximab were comparable. Stages III and IV were found in 63.8% of DLBCL and 84.6% in FL patients, respectively. OS and PFS at 60months were 63.8 and 51.2% in DLBCL and 70.6 and 33.8% in FL. No difference in OS was found in DLBCL and FL when rituximab-based regimens vs. non rituximab-based regimens were compared, but a statistically significant difference was documented in PFS in FL patients. Addition of rituximab to CHOP-like regimens did not improve OS in DLBCL and FL NHL subtypes. In comparison to developed countries, diagnosis of NHL was made a decade earlier and in advanced clinical stages. Cost-efficiency of adding rituximab to therapy for these patients should be assessed.

Persistent Disparities Among Patients With T-Cell Non-Hodgkin Lymphomas and B-Cell Diffuse Large Cell Lymphomas Over 40 Years: A SEER Database Review.

As of 2013, more than 550,000 people are living with non-Hodgkin lymphoma (NHL). We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of aggressive T-cell and B-cell NHL patients, with a focus on various ethnicities. The final analysis included 7662 patients with T-cell and 84,910 with B-cell NHL. Survival analysis revealed that male sex and increasing age were independent predictors of worse overall survival (OS; P < .001). For aggressive T-cell NHL, there was no significant improvement in median OS between 1973 and 2011 (P = .081), and ethnic minorities (Asians, Hispanics, and African Americans) had significantly worse OS than whites (P < .001). There were similar trends for age, sex, and race for diffuse large B-cell NHL, but a significant improvement in median OS was seen over time (P < .001). These results are the first to elicit outcomes in a broad classification of ethnic minorities and underscore the urgency for development of novel therapeutics, especially in T-cell NHL. In addition, in-depth studies of disease biology and health care utilization are required for better triage of health care resources, especially for ethnic minorities.

The Effect of FcγRIIIA Gene Polymorphism on the Treatment of Diffuse Large B-cell Non-Hodgkin Lymphoma: A Multicenter Prospective Observational Study.

Objective:The curative treatment approach for diffuse large B-cell lymphoma (DLBCL) is controversial even in the rituximab (R) era. The aim of this study was to examine the FcγRIIIA gene polymorphism distribution of DLBCL patients who had been treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Furthermore, we investigated the impact of FcγRIIIA gene polymorphism on the overall response rate (ORR) and overall survival (OS).Materials and Methods:Patients from 3 centers in the Aegean region of Turkey who had newly diagnosed CD20-positive DLBCL were enrolled in the study. The single nucleotide polymorphisms of the FcγRIIIA gene were analyzed by real time-PCR. The response to treatment was determined in the middle and at the end of the protocol. During 2 years of follow-up, the patients were clinically and radiologically evaluated for disease status every 3 months.Results:Thirty-six patients were included in the study and the distributions of F/F, V/F, and V/V types of alleles of FcγRIIIA were 25%, 50%, and 25%, respectively. Twenty-seven patients were considered as evaluable according to ORR and OS. The patients’ ORR was 87.5%, 100%, and 50% in the F/F, V/F, and V/V allele groups, respectively. We did not establish any statistically significant differences among the 3 alleles groups in respect to ORR (p=0.93). The OS within 2 years in the F/F, V/F, and V/V allele groups was 62.5%, 100%, and 100%, respectively. The OS in the F/F allele group was found to be lower than in the other 2 allele groups (p=0.01).Conclusion:The distribution of gene polymorphisms in our study group was similar to those of previous studies. While ORR was similar between the groups, our results highlight a lower OS in F/F patients compared to other allele groups of FcγRIIIA.

Case Report of Patient with Relapse of B-cell Lymphoma in the Breast Parenchyma.

We present a patient with relapse of B-cell non-Hodgkin's lymphoma in the breast that was clinically presented as a primary breast cancer. A 72-year old female was treated with chemotherapy and monoclonal antibodies (anti-CD20) due to diffuse large B-cell non-Hodgkin's lymphoma. Complete remission was achieved. Three years later, she was presented with a palpable left breast lump in the perimammillar area of the left breast, dimensions up to 3 cm. Laboratory results were within normal range. Mammography re-vealed a solitary, bilobulated, non-calcified mass of the left breast. On ultrasound, the lesion was hypo-echoic with blurred edges, with posterior acoustic enhancement, measuring 2 × 3 × 7 × 2 cm. Histological findings of ultrasound-guided fine needle aspiration and core needle biopsy were corre-spondent to diffuse large B-cell lymphoma. Pathohistological report showed cells with CD20+/Bcl- 2+/Bcl-6-/MUM-1+/CD3- imunophenotype. The breast parenchyma was infiltrated with B-cell lym-phoma. After diagnosis was confirmed, radiotherapy was initiated. Repeat ultrasound studies showed complete regression of the left breast lesion as did positron emission tomography- computed tomography (PET/CT) scan three months after therapy. In conclusion, the relapse of lymphoma in the breast is very rare. In patients previously treated for lymphoma, differential diagnosis should always include relapse, although it clinically presents itself as a primary breast cancer.

Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth

Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of α catalytic and β regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2α immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-κB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL.

Sclerotic changes on plain X-ray led to early diagnosis and successful treatment of primary lymphoma of iliac bone.

Sir, A previously healthy 54-year-old woman presented to our hospital with a 3-month history of pelvic pain. There was no history of constitutional symptoms such as unintentional weight loss, fever, and loss of appetite. Clinical examination revealed pain on deep palpation of the right iliac region. There was no evidence of soft tissue swelling or redness in the site of patient's pain. The rest of physical exam was unremarkable. Laboratory investigations were within normal limits (erythrocytes sedimentation rate of 20 mm in the 1st h, negative C-reactive protein and white blood count of 4800 per μl). A plain radiograph of the pelvis showed slightly lytic-sclerotic changes of right iliac bone with indistinct margins, which at a shallow observation confused with bowel gases [Figure 1]. A computed tomography (CT) was performed and showed a slightly expansile lytic-sclerotic lesion with small soft tissue component in the right iliac bone [Figure 2]. The bone scan also revealed isolated uptake of technetium-99m in the right ilium [Figure 3]. According to the patient age, the differential diagnosis included metastasis, lymphoma, plasmacytoma, and chronic osteomyelitis. Figure 1 Radiograph of pelvis demonstrates lytic-sclerotic changes of right iliac bone Figure 2 Pelvic computed tomography image shows a slightly expansile lytic-sclerotic lesion in the right iliac bone with no extension to the sacroiliac joint Figure 3 Bone scan revealed isolated uptake of technetium-99 m in the right ilium The core needle biopsy result was consistent with the diagnosis of diffuse large B-cell nonHodgkin's lymphoma. There was not any other site of involvement on CT scan of the chest, abdomen, and pelvis. Positron emission tomography (PET) also showed no secondary absorption of fluorodeoxyglucose [Figure 4]. The diagnosis of primary nonHodgkin lymphoma of bone was made, and the patient was successfully treated with a combination of chemotherapy and radiotherapy. Figure 4 Positron emission tomography scan showed no secondary absorption of fluorodeoxyglucose NonHodgkin's lymphoma of bone is a rare entity which is limited to the long bones and axial skeleton, with the femur being the most common site of involvement. Primary involvement of iliac bone is extremely rare. There are no clinical or radiological characteristics which be diagnostic for primary bone lymphoma. The image findings in radiograph or CT scan are variable and nonspecific, range from near normal to diffuse permeative pattern.[1,2,3,4,5,6] A review article performed by Mulligan et al., revealed that the most common features on imaging studies are lytic (70%), including permeative or moth-eaten pattern, and mixed lytic and sclerotic density (28%). Periosteal reaction and soft tissue mass were reported in 58%, and 80-100% of cases, respectively, in this study.[2] Sequestrum formation considered as a radiological feature which may help to differentiate between plasmablastic lymphoma (PBL) and other conditions such as metastasis and myeloma. Sequestrum formation has been reported in 11-16% of PBL cases.[7] Cross-sectional imaging studies are useful adjuncts to conventional radiography. Extensive involvement of bone marrow cavity with a surrounding soft tissue component and without extensive cortical destruction is a pattern, which is reported only in PBL, Ewing sarcoma, and myeloma.[8] The key educational message of our case is that any change on plain X-ray is valuable and should not be overlooked. This case also reminds us the importance of considering primary nonHodgkin lymphoma as a valuable differential diagnosis in lytic and sclerotic lesions of iliac bone. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Primary Bilateral Non-Hodgkin's Lymphoma of the Adrenal Gland Presenting as Incidental Adrenal Masses.

Although lymphoma may occasionally involve the adrenal glands as part of a generalized disease process, primary adrenal lymphoma (PAL) is a rare disease. We present a case of a 62-year-old woman with a history of mild/moderate hereditary spherocytosis with a well-compensated baseline haemoglobin, who presented with rapidly progressive symptomatic anaemia. During the diagnostic workup, imaging revealed bilateral large adrenal masses and she was later diagnosed with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), with the adrenal glands being the dominant site of the disease. The patient was started on systemic chemotherapy, but her disease progressed with neurological involvement which responded to second-line therapy. Her adrenal disease however was refractory to further therapy.

Non-anthracycline chemotherapy associated with a poor outcome in elderly Egyptian patients with diffuse large B-cell non-Hodgkin lymphoma

Journal of Cancer Metastasis and Treatment is an open access journal, focusing on basic and clinical studies related to cancer cell, cell biology, oncology, radiation therapy and radiology, obstetrics and gynecology, pediatrics, surgery, hematology, neuro-oncology, etc.

Treatment of Recurrent Posttransplant Lymphoproliferative Disorder with Autologous Blood Stem Cell Transplant.

Background. Posttransplant lymphoproliferative disorders (PTLDs) occur after solid organ transplantation. Treatment guidelines include reduction in immunosuppression (RIS), radiation, rituximab, chemotherapy, and immunological agents. We present a rare case of recurrent diffuse large B-cell lymphoma presenting as a PTLD in a heart transplant patient treated with autologous blood stem cell transplant (ASCT) after failure of conventional therapy. Case Presentation. A 66-year-old male presented with a neck mass. He has a history of Hodgkin's disease status after staging laparotomy with splenectomy and heart transplantation due to dilated nonischemic cardiomyopathy 8 years prior to the development of PTLD. His examination was remarkable for right submandibular swelling. An excisional biopsy confirmed the diagnosis of diffuse large B-cell NHL. Patient received RIS, rituximab, chemotherapy, and radiation therapy with a complete remission. His lymphoma relapsed and he subsequently was treated with RICE salvage chemotherapy and consolidative high-dose chemotherapy with BEAC regimen followed by ASCT resulting in a complete remission. Conclusion. Patients with PTLD present a difficult therapeutic challenge. In this case, the patient's prior history of Hodgkin's disease, splenectomy, and a heart transplant appear to be unique features, the significance of which is unclear. ASCT might be a promising therapy for patients with relapsed or refractory PTLD.

Outcome Disparities in T-Cell Non-Hodgkin Lymphoma and the Lack of Significant Improvement over the Years: A SEER Database Review

Background: As of 2013, approximately 558,340 people are living with non-Hodgkin lymphoma (NHL). Outcome disparities have been reported in lymphoid malignancies but a comprehensive analysis, especially with expanding ethnic minorities is necessary. We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of T-cell and B-cell NHL patients (pts), with a focus on various ethnicities.Methods: The SEER 18 Registry data (1973-2011) was utilized for pts with a confirmed diagnosis of T-cell or B-cell NHL. Cases that received a diagnosis at death certificate or autopsy, no follow-up records, no documented age at diagnosis, sex, or race/ethnicity were excluded. Cox proportional hazards models, adjusted for gender, age, race, year (yr) of diagnosis, and stratified by SEER registries were used to evaluate association between pt characteristics and survival. All statistical tests were two-sided and utilized the SAS software (v9.4) with a two-sided significance level of 0.05.Results: The final analysis included 7,662 pts with T-cell NHL and 84,910 pts with B-cell NHL. The pt demographics are shown in Table 1. Pts were stratified based on yr of diagnosis to study the impact of therapeutic developments on pt outcomes (Table 1). Pts were also divided by T-cell NHL subtype: mature T-cell (9702/3) 51%, angioimmunoblastic T-cell (9705/3) 16%, anaplastic large cell (ALCL) (9714/3) 32%, and hepatosplenic gamma-delta cell (HSϒd) (9716/3) 0.8%. Median age at diagnosis was youngest for AA pts (54 yrs) and oldest for Asian pts (65 yrs) (Figure 1 A). Survival analysis revealed that females had a better median OS than males (3.3 yrs vs. 2.3 yrs, HR 0.876; 95% CI 0.824, 0.932; p<0.001). Increasing age was an independent predictor of worse overall survival, with pts age 18-44 having a median OS 9.4 yrs (HR 0.345; 95% CI 0.312, 0.382) and pts age ≥75 having a median OS of 1.0 yr (p<0.001). There was no statistically significant difference seen in median OS for pts with respect to yr of diagnosis (p=0.081). Among the different T-cell NHL subtypes, pts with ALCL had the best (3.8 yrs, HR 0.766; 95% CI 0.714, 0.822) and pts with HSϒd had the worst median OS (0.7 yrs HR 1.959; 95% CI 1.424, 2.695) (p<0.001). AA pts (1.7 yrs, HR 1.292; 95% CI 1.176, 1.419) and Hispanic pts (1.9 yrs, HR 1.215; 95% CI 1.087, 1.357) had significantly worse OS compared to White pts who had the longest median OS (3.1 yrs) (p<0.001) (Figure 1 B). To compare and contrast with aggressive B-cell NHL, similar analyses were performed using diffuse large B-cell (DLBCL) NHL (9680/3). DLBCL showed similar trends regarding sex, age and race. Ethnic minorities had significantly worse median OS including Hispanic (2.8 yrs, HR 1.154; 95% CI 1.111, 1.198) and AA pts (3.3 yrs, HR 1.261; 95% CI 1.212, 1.312) compared to White pts with a median OS of 5.8 yrs (p<0.001). B-cell NHL pts had a significant improvement in median OS over time with pts diagnosed in 2007-2011 having more than 3 times the median OS of pts diagnosed in 1973-1991 (7 yrs vs. 2.4 yrs; p<0.001).Conclusions: Studies of outcome disparities are important for evaluating disease characteristics and their relationship to specific pt populations over time. We have performed the largest population-based analysis for T-cell and B-cell NHL including various ethnicities in the novel therapeutic agent era. We observed that males, older pts and ethnic minorities had worse median OS for both T-cell and B-cell NHL. Despite novel therapeutics targeting T cells there has been no statistically significant improvement in OS over time. In contrast, significant improvement in B-cell NHL OS has been noted, presumably due to the advent of monoclonal antibodies. These results underline the urgency for the development of novel therapeutics as well as aggressive studies of disease biology and healthcare utilization for better triage of healthcare resources, especially for ethnic minorities. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Incidence of Human Leucocyte Antigen Antibodies in Lymphoma Patients Treated with and without Rituximab

Introduction: Platelet support in patients who are pancytopenic after autologous stem-cell transplantation (auSCT) is difficult in the presence of human leukocyte antigen antibodies (HLA-AB) class I. Multiple transfusions and pregnancy are risk factors for development of HLA-AB. In renal transplantation rituximab (R-mab) is used to reduce HLA-AB levels in HLA-incompatible kidney transplantation. We evaluated whether the incidence of HLA-AB was lower in lymphoma patients who were treated with R-mab during salvage therapy prior to auSCT.Methods: Single-centre retrospective evaluation of patients treated with DHAP-VIM-DHAP salvage (with or without R-mab) and BEAM plus auSCT for B-cell non-Hodgkin lymphoma (B-NHL) or Hodgkin’s lymphoma (HL). After becoming available R-mab was given to patients with CD20-positive lymphoma; R-mab was not used before it’s availability and in CD20-negative lymphoma. HLA-AB were measured in case of insufficient platelet yield after transfusion.Results: Between January 1st 1999 and December 31st 2013, 164 patients with a B-NHL or HL underwent auSCT (Table). Age at auSCT was median 52.5 (17.8 – 70.2) years, 73 (45%) patients were female and 89 (54%) were treated with R-mab. Type of lymphoma was diffuse large B-NHL (DLBCL) in 82 (50%) patients, HL in 46 (28%) patients, follicular lymphoma (FL) in 30 (18%) patients and other in 6 (4%) patients. All transfused cellular blood products were leucoreduced.Of R-mab treated patients, 42 (47%) were female versus 31 (41%) non R-mab treated patients, p=0.529 (Table). R-mab treated patients were older at auSCT than non R-mab treated patients: median 57.4 (18.3 – 70.2) years versus 48.1 (17.8 – 64.6) years, p<0.001. Type of lymphoma in R-mab patients was DLBCL in 61 (69%), HL in 2 (2%), FL in 23 (26%) and other in 3 (3%) patients. In non R-mab treated patients type of lymphoma was DLBCL in 21 (28%, p=<0.001), HL in 44 (59%, p=<0.001), FL in 7 (9%, p=0.008) and other in 3 (4%, p=1.000) patients. In R-mab treated patients median 6 (1 – 53) random platelet concentrates (rPC) were transfused versus median 5 (1 – 54) in non R-mab treated patients, p=0.529. HLA-AB were found in none of 89 R-mab treated patients and in 3 of 75 non R-mab treated patients, p=0.094.All 3 patients who developed HLA-AB were female (100%) versus 44% (n=70) of patients without HLA-AB, p=0.086. All 3 women (100%) with HLA-AB have been pregnant versus 51 (73%) women without HLA-AB (p=0.704); in 8 women without HLA-AB their history of pregnancy was unknown. None (0%) of 3 patients with HLA-AB were treated with R-mab versus 89 of 161 (55%) patients without HLA-AB, p=0.094. Age at auSCT was median 44.2 (39.1 – 52.4) years in patients with HLA-AB and median 52.6 (17.8 – 70.2) years in patients without HLA-AB, p=0.246. Number of rPC transfused was median 7 (4 – 14) in patients with HLA-AB and median 6 (1 – 54) in patients without HLA-AB, p=0.666. There was no significant difference seen in type of lymphoma between patients with and without HLA-AB.Conclusion: The incidence of HLA-AB in our cohort of lymphoma patients treated with DHAP-VIM-DHAP salvage with or without rituximab followed by BEAM plus auSCT for B-NHL or HL is very low. A trend was seen towards treatment without R-mab and female gender, not towards a history of pregnancy. TableOverallRituximabNo Rituximabpn16489 (54)75 (46)Female (n)73 (45)42 (47)31 (41)0.529Age auto-Tx (years)52.5 (17.8 – 70.2)57.4 (18.3 – 70.2)48.1 (17.8 – 64.6)< 0.001HLA-antibodies (n)3 (2)03 (4)0.094Transfused rPC (n)6 (1 – 54)6 (1- 53)5 (1 – 54)0.529Type of lymphomaDLBCL (n)82 (50)61 (69)21 (28)< 0.001Hodgkin (n)46 (28)2 (2)44 (59)< 0.001FL (n)30 (18)23 (26)7 (9)0.008Other (n)6 (4)3 (3)3 (4)1.000Denoted as median (range), categorical variables as number (%). DisclosuresNo relevant conflicts of interest to declare.

GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin's B lymphomas via NF-κB-dependent induction of HIF-1α.

Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also has non-glycolytic roles in tumors. However, the contribution of these non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote nuclear factor-κB (NF-κB) activation via binding to tumor necrosis factor receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia-inducing factor-1α (HIF-1α). Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B-cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1α, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-κB-dependent induction of HIF-1α and has a key role in lymphoma vascularization and aggressiveness.

Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses presenting as cavernous sinus syndrome.

Primary paranasal sinus lymphoma is an uncommon malignancy that accounts for only 0.17% of all lymphomas and is often difficult to diagnose. Initially, tumors in this area cause very few symptoms and are at an advanced stage at the time of diagnosis. Ophthalmologic signs and symptoms occur early in the disease process because of close proximity of the orbit to the paranasal sinuses. We report on a case of primary malignant lymphoma of the sphenoid and ethmoid sinuses with involvement of the cavernous sinus, initially presenting with ophthalmologic signs and symptoms in association with cavernous sinus syndrome.

A case of chylothorax due to primary renal lymphoma

Chylothorax is a type of pleural effusion which develops by collection of lymphatic fluid in the pleural cavity after disruption or blockage of the thoracic duct. The posterior-anterior lung graphy revealed a left pleural effusion during routine controls of an asymptomatic 79 year-old male patient. Pleural fluid with a chylous appearance drained by thoracentesis had a triglyceride level of 409 mg/dL. As chylothorax was thought as diagnosis, thoracoabdominal computed tomography revealed a left renal mass and left pleural effusion. There was a mass lesion taking origin from the superior pole of the left kidney with multiple periaortic and perirenal lymphadenopathies in magnetic resonance imaging of the abdomen, which was interpreted as lymphoma. The tru-cut biopsy from renal lesion revealed as diffuse large B-cell non-Hodgkin lymphoma (NHL). Non-traumatic chylothorax is most commonly due to malignancy. Lymphoma is the most common cause of chylothorax with approximately 75%. Primary renal lymphoma, a type of NHL, has not ever found as a cause of chylothorax in our literature investigation. In this paper, we report this rarely seen case.