Treatment of Diffuse Large B-Cell Lymphoma of the Liver with Yttrium-90 Microsphere Embolization.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4510-4510
Author(s):  
Heather L. Benjamin ◽  
Timothy S. Fenske ◽  
Steven H. Kroft ◽  
Eric J. Hohenwalter ◽  
William S. Rilling
Keyword(s):  
Ct Scan ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Clinical Activity ◽  
Large B Cell Lymphoma ◽  
Hepatic Lesions ◽  
Residual Lymphoma ◽  
Large B Cell ◽  
Yttrium 90

Abstract We present a case of successful treatment of chemoresistant hepatic lymphoma using yttrium-90 micropheres. A 41 year-old male with a history of hepatitis C presented with fatigue, night sweats, right upper quadrant pain, a 20 pound weight loss, and hypercalcemia. CT scan of the abdomen revealed a 13.4 x 10.0 cm mass involving the right hepatic lobe, along with portohepatic, celiac, and retroperitoneal lymphadenopathy. Ultrasound-guided core biopsy of the portohepatic mass showed diffuse large B-cell lymphoma (DLBCL). The patient had a partial response to R-CHOP, and was subsequently treated with 3 additional chemotherapeutic regimens. Despite this extensive therapy, as well as surgical resection of hepatic lesions, he had residual lymphoma within the liver. Due to inadequate chemosensitivity, he was not a candidate for stem cell transplantation. Repeat biopsy showed loss of CD20 expression, eliminating radioimmunotherapy as an option. Because the residual lymphoma was confined to the liver, the patient was treated with yttrium-90 microspheres (TheraSphere®). The patient had a significant improvement in his abdominal pain. Furthermore, six weeks after treatment, a complete response in the hepatic lesions was documented by PET/CT scan. Although the patient later developed recurrent disease outside of the liver, the case clearly demonstrates the potential clinical utility of this approach in properly selected lymphoma patients. To our knowledge, this is the first reported case documenting clinical activity of yttrium-90 microspheres for lymphoma.

Antitumor Effect Of Sepantronium Bromide (YM155), a Survivin Suppressant, In Combination With Bendamustine and Rituximab In Diffuse Large B-Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3073-3073
Author(s):  
Naoki Kaneko ◽  
Keisuke Mitsuoka ◽  
Nobuaki Amino ◽  
Kentaro Yamanaka ◽  
Aya Kita ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cell ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Clinical Activity ◽  
Triple Combination ◽  
Large B Cell Lymphoma ◽  
M Phase ◽  
Large B Cell

Abstract Background Diffuse large B-cell lymphoma (DLBCL) responds well to treatment with rituximab (RTX, an anti-CD20 antibody) based regimen, but a subset of patients still fail to achieve complete or durable responses and are not eligible for high-dose chemotherapy followed by autologous stem cell transplant. Therefore novel effective therapies with less toxicity for relapsed or refractory DLBCL patients are needed. Bendamustine (BEN) is a bifunctional alkylating agent for the treatment of multiple hematological tumors, including indolent and RTX-resistant NHL, and the combination of BEN with RTX showed clinical activity in patients with relapsed or refractory DLBCL in the Phase II study 1. Sepantronium bromide (YM155), a survivin suppressant, shows potent antitumor activities against a wide range of cancer cells, and NHL including DLBCL is one of the most sensitive tumor types to YM155. YM155 showed clinical activity when combined with RTX in patients with relapsed DLBCL 2. In the present study, we evaluated therapeutic potential of YM155, in combination with BEN or BEN and RTX using DLBCL models. Results The combination of YM155 with BEN decreased cell viability to a greater extent than either single agent alone in DB, SU-DHL-8, and WSU-DLCL2 human DLBCL cell lines. Bliss additivism analysis revealed that the combined effects were synergistic. In addition The combination of YM155 with BEN induced a greater sub-G1 population, indicative of apoptosis, than either agent alone. The percentages of sub-G1 population induced by YM155, bendamustine, and combination of both were 5.9%, 6.5%, and 27% in DB cells; 19%, 32%, and 58% in SU-DHL-8 cells; and 46%, 30%, and 71% in WSU-DLCL2 cells, respectively. BEN induced γ-histone 2AX (γ-H2AX), a marker of DNA damage and phosphorylation of ATM substrates including p53, and check point kinase-2 (Chk2) which leads to phosphorylation of cdc2. Further BEN induced G2/M arrest associated with the increase of survivin. The combination of YM155 with BEN inhibited phosphorylation of p53, chk2, and cdc2 and accumulation of survivin at G2/M phase, and induced greater DNA damage and cleaved PARP than either single agent alone. In human DLBCL DB xenografts, 7-day continuous s.c. infusion of YM155 at 1 mg/kg/day enhanced antitumor activity of BEN at 50 mg/kg (i.v.) and induced complete regressions in 6 out of 8 mice without affecting body weight. Further, in an activated B-cell-like (ABC)-DLBCL disseminated xenograft model, the combination of YM155 with BEN and RTX significantly prolonged survival associated with the decrease in the FLT-PET signals in lymph node compare with either the combination of BEN with RTX and YM155 with RTX. Conclusions Our data indicates that YM155 enhances the antitumor activity of BEN against DLBCL models through inhibition of DNA damage responses as well as survivin accumulation at the G2/M phase. Further, triple combination of YM155 with BEN and RTX showed survival benefit in comparison with either BEN-RTX combination or YM155-RTX combination, supporting the further clinical investigation of this triple combination for the treatment of relapsed or refractory DLBCL. Reference: 1. Ohmachi et al. J Clin Oncol. 2013 Jun 10;31(17):2103-9 2. Papadopoulos et al. American Society of Hematology Annual meeting Abstract No. 2731. 2012. Disclosures: No relevant conflicts of interest to declare.

Clinical Relevance Of Cachexia Assessed By An Anthropometric Tool In Elderly Patients With Diffuse Large B-Cell Lymphoma Treated By Immunochemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2926-2926
Author(s):  
Helene Lanic ◽  
Jerome Kraut ◽  
Romain Modzelewski ◽  
Florian Clatot ◽  
Jean-Michel Picquenot ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Elderly Patients ◽  
Ct Scan ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background Cancer Cachexia is a metabolic syndrome that can be present even in absence of weight loss and associated with significantly impaired survival. Muscle wasting represents a key-symptom of this syndrome and we recently demonstrated the strong prognosis impact of sarcopenia assessed by computed tomography (CT)-scan in diffuse large B-cell lymphoma (DLBCL) (Lanic et al. Leukemia & Lymphoma 2013). Conversely, the clinical relevance of loss of fat mass (adipopenia) remains unclear. The aim of this study was (i) to investigate the prognostic impact of a multidimensional tool combining a nutritional parameter (albuminemia) and body composition measurements (skeletal muscle and body fat composition) in elderly patients with DLBCL treated by chemotherapy and rituximab (R) (ii) to document the evolution of sarcopenia after immunochemotherapy. Methods This retrospective analysis included 80 DLBCL patients older than 70 years (y) and treated by R-CHOP or R-miniCHOP. Skeletal muscle (SM), visceral (V) and subcutaneal (S) adipose (A) tissues were measured by analysis of stored CT images at the Lumbar vertebrae 3 (L3) level. The surface of the muscular and adipose tissues was selected according to CT Hounsfield unit. Values were normalized for stature to calculate the L3 SM index (LSMI, in cm2/m2), the LVAI and the LSAI and used to define sarcopenia and visceral/subcutaneal adipopenia. Results The characteristics of the patients were as follows: median age = 78 y [70-95]; 36 males; IPI 0-2 = 22, 3-5 = 58; treatment by R-CHOP (n = 45) or R-miniCHOP (n = 35); median body mass index (BMI; in kg/m2) = 23.9. According to the sex-specific defined cut-offs for LSMI (< 55.8 cm²/m² for men and 38.9 cm²/m² for women), 44 DLBCL patients (55 %, 23 males) were considered as sarcopenic. With a median follow-up of 39 months, the 2y overall survival (OS) in the sarcopenic population was 46% as compared to 84% in the non-sarcopenic group (HR = 3.12; CI95%, 1.66-5.88; p=0.0004). The median LSAI was 76.3 cm2/m2 [10-167] in females and 47.4 cm2/m2[22-100] in males. The median LVSAI was 43.5 cm2/m2[3-141] in females and 50.4 cm2/m2[14-159] in males. Adipopenia, defined by a low LVAI and/or a low LSAI was also highly predictive of the outcome. The 2y OS of the low LVAI population was 48% as compared to 82% for the non-adipopenic group (HR = 2.20; CI95%, 1.19-4.05; p=0.01). The 2y OS in the low LSAI population was 48% as compared to 80% in the non-adipopenic group (HR = 2.28; CI95%, 1.23-4.21; p=0.008). A Three-point cachexia score (CS) including adipopenia, sarcopenia and hypo-albuminemia (defined by an albuminemia < 35 g/L) was build and delineates three distinct risk-groups (Figure 1). More importantly the CS remains predictive of the prognosis in a multivariate analysis including BMI (< or >= 25 kg/m2), age (< or >= 80y), IPI and gender (HR=2.5; CI95%= 1.14-5.39; p =0.02). LMSI was subsequently reassessed in thirty seven patients during the routine CT scan follow-up [mean = 10 months after pre-treatment CT scan (range 2.8-19.2)]. 15 (40%) patients displayed a 5% decrease of their LSMI, whereas 13 (35%) and 9 (25%) displayed no significant change or increase (>5%) of the LMSI respectively. Conclusion Our study demonstrates that sarcopenia and adipopenia estimated by CT-scan define cachexia more accurately than BMI or weight loss in elderly DLBCL patients. These factors can be integrated in a cachexia scoring tool which predicts the outcome independently of the BMI and of the IPI. CT scan follow-up indicates that cachexia is a reversible process that should be integrated as part of the therapeutic target in combination with lymphoma treatment. A prospective multicentric trial (registered as NCT01715961/Clinical.gov) is ongoing to validate these anthropometric and nutritional parameters and compare to geriatric assessment scales. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High-grade B-cell lymphoma masquerading as peritoneal lymphomatosis

2019 ◽  
Vol 12 (8) ◽  
pp. e231238 ◽  
Author(s):  
Samuel Kareff ◽  
Chao Yin ◽  
John Feigert
Keyword(s):  
Ct Scan ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Shortness Of Breath ◽  
Rare Presentation ◽  
Large B Cell Lymphoma ◽  
Efficacious Treatment ◽  
Large B Cell

Peritoneal lymphomatosis represents a rare presentation of any type of non-Hodgkin’s lymphoma, with relatively few cases reported in the literature. We present here the case of a 61-year-old man who originally presented with increased abdominal distention associated with shortness of breath and diaphoresis who was found to have evidence of peritoneal carcinomatosis on CT scan. Biopsy confirmed diffuse large B-cell lymphoma, and the working diagnosis was subsequently modified to peritoneal lymphomatosis. The patient was treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) therapy with initially good response. His course was complicated by tumour lysis syndrome. We review the limited literature discussing peritoneal lymphomatosis and discuss the importance of facilitating rapid and efficacious treatment.

Fatal interstitial pneumonitis in a patient with relapsed diffuse large B cell lymphoma following yttrium-90 ibritumomab tiuxetan

2010 ◽  
Vol 29 (5) ◽  
pp. 1098-1101 ◽  
Author(s):  
Moon Jin Kim ◽  
Gyeong-Won Lee ◽  
Jong Woo Seo ◽  
Hyun-Jung Kim ◽  
Sung-Nam Lim ◽  
...  
Keyword(s):  
B Cell ◽  
Interstitial Pneumonitis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ibritumomab Tiuxetan ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Yttrium 90

A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab As Maintenance Therapy Following R-CHOP Chemotherapy for Patients with High Risk Diffuse Large B-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3668-3668
Author(s):  
Nishitha M. Reddy ◽  
Rhea M Simons ◽  
Meghan E Caldwell ◽  
Heidi Chen ◽  
Madan Jagasia ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Clinical Activity ◽  
Large B Cell Lymphoma ◽  
One Year ◽  
Large B Cell

Abstract Abstract 3668 Background: Diffuse large B-cell lymphoma (DLBCL) patients with an intermediate/high to high risk international prognostic index (IPI) score are at an increased risk of disease relapse in the first year after completion of standard therapy with R-CHOP. Lenalidomide (LEN), an immunomodulatory drug, enhances the natural-killer cell mediated antibody-dependant cellular cytotoxicity of rituximab in lymphoma cell lines, inhibits angiogenesis, alters cytokine production, and has been shown to have clinical activity against B-cell lymphoma including relapsed DLBCL. Methods: DLBCL patients with high risk features (IPI scores of 3 or greater) who achieved CR after R-CHOP were randomized to LEN (arm A) alone or LEN and rituximab maintenance therapy (arm B) within 12 weeks of last dose of R-CHOP. The primary endpoint of the study was to assess the one year relapse-free survival. We expected that a 25% difference of relapse compared with current standard therapy will have clinical significance. Patients in arm A received LEN at a dose of 25 mg daily for 21 days of 28 days. Patients in arm B received LEN at a dose of 20mg daily for 21 days of 28 days along with rituximab (375mg/m2) on day 8 of even cycles. Treatment on both arms was continued for one year. Treatment was discontinued for disease progression. LEN dose adjustments were incorporated in the protocol. Results: Thirty five patients, 19 arm A/16 arm B, 20 female/15 male, with a median age of 59 yrs were enrolled. The median IPI was 3 for all patients. For patients over the age of 60 the median IPI score was 4 and the median aa-IPI was 3. Two patients received XRT to areas of bulky disease at the completion of R-CHOP prior to start of maintenance. At a median follow up of 22 months, the 2 yr PFS and DFS was 86% and 96% respectively. For patients in arm A and arm B the 2 yr PFS was 92% vs.77% and the 2 yr DFS was 100% vs. 92% respectively (p=0.52). Two patients discontinued treatment due to adverse events. Grade 3–4 toxicities include neutropenia (25%), fatigue (17%), diarrhea (8%), DVT (3%), rash (3%), febrile neutropenia (3%). Related grade 1–2 toxicities include hypothyroidism (11%) and rash (47%). There were no treatment related deaths. Conclusions: Lenalidomide as maintenance therapy demonstrates encouraging clinical activity following standard chemotherapy and results in superior survival outcomes in DLBCL patients with high risk prognostic features. The 2-yr OS was 90% in our study as compared with historical controls of 70%. Our study suggests that maintenance strategy with lenalidomide based therapy may increase cure rate and needs to be prospectively evaluated in a phase III study. Disclosures: Reddy: Celgene: Research Funding. Off Label Use: Lenalidomide in Lymphoma. Park:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Research Funding.

scholarly journals Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Vadim Gorodetskiy ◽  
Wolfram Klapper ◽  
Natalya Probatova ◽  
Vladimir Vasilyev
Keyword(s):  
Ct Scan ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Liver Lesion ◽  
Low Grade ◽  
Non Hodgkin Lymphoma ◽  
Molecular Features ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Sjögren’s syndrome (SS) has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan) of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

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