Other Tumours in Primary Cutaneous Lymphomas.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4417-4417
Author(s):  
Serena Rupoli ◽  
G. Goteri ◽  
P. Picardi ◽  
S. Pulini ◽  
A. Tassetti ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Skin Carcinoma ◽  
B Cell Lymphomas ◽  
T Cell Lymphomas ◽  
Cutaneous Lymphomas ◽  
Other Neoplasms

Abstract Patients with primary cutaneous lymphomas (PCLs) are treated with multiple therapeutic regimens, which may increase the risk of subsequent solid and haematological neoplasms. The aim of our study was to assess the incidence of other malignancies in our series of PCLs. From March 1994 to January 2007, 272 patients with PCLs (179 M, 93 F, median age 65 yr, range 14–88) were referred to our center for staging, treatment and follow-up. The clinical charts were reviewed to detect the incidence of malignancies occurred before or after the diagnosis of PCL or concomitantly. The series was composed by 228 patients (150 M, 78 F, median age 66 yrs) with T-cell lymphomas (202 Mycosis Fungoides/MF, 10 Sézary Syndrome/SS, 9 CD30+ PCL, 7 non MF/non CD30+ T cell PCL); 43 patients (28 M, 15 F, median age 60 yrs) with B-cell lymphomas (25 Follicular/FL, 14 marginal/MZL, 3 Leg-type, 1 Lymphoblastic) and one patient with CD4+/CD56+ hematodermic neoplasm. Chemotherapy was administered to 48 patients. During follow-up 12 patients died for the disease and 24 for other causes. A second tumor was observed in 41 patients (15%): 6 of them experienced more than one neoplasms: overall we observed 48 malignancies, 38 solid and 10 haematological. The other neoplasms appeared similarly before (20) and after (21) the diagnosis of PCL; in 7 cases they were diagnosed simultaneously. Solid tumours (17 preceding, 4 concurrent, 17 subsequent) were diagnosed in: skin (11), colon (5), lung (4), breast (3), CNS (3), bladder (2), liver (2), kidney (2), uterus (2), testis (1), prostate (1), stomach (1), thyroid (1). The haematological malignancies (3 preceding, 3 concurrent, 4 subsequent) were: B-cell lymphomas (4), acute myeloid leukemias (3), plasmocytoma (1), T-cell lymphoma (1), Hodgkin’s lymphoma (1). Among the six patients with more than one adjunctive neoplasms one patient had lung and kidney carcinoma preceding PCL; two patients a preceding carcinoma (skin and bladder, respectively) and subsequently a lung carcinoma; other two patients showed both a preceding and a concurrent neoplasm (skin and colon carcinoma, B-cell lymphoma and skin carcinoma, respectively). Finally a patient had a preceding skin carcinoma, a concurrent nodal Hodgkin’s lymphoma and a subsequent nodal B-cell lymphoma. So we have reported 48 other neoplasms in 41 patients within 272 PCLs (15%). The occurrence of the other malignancy was not related to the B/T phenotype of PCLs, as it was observed in 35/228 (15.4%) T-cell lymphomas (32 MF, 2 SS, 1 non MF/non CD30+ T cell lymphoma) and in 6/43 (14%) B-cell lymphomas (3 FL, 3 MZL; χ2 test: P=0.88). The interval of occurrence was longer for tumors preceding (median 60 mo.s, range 8–180) than for tumors following PCL (median 45, range 6–122). The administration of chemotherapy for PCL was not associated with an increased incidence of second neoplasm(χ2 test, P=0.77). Multicentric studies might help in elucidating the role of genetic and immunitary factors in the pathogenesis of multiple neoplasms in patients with PCLs.

Development of B Cell Lymphoma in Eμ-Cyclin D1 X Mutant p53 Transgenic Mice.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1907-1907
Author(s):  
Mitchell R. Smith ◽  
Indira J. Joshi ◽  
Fang Jin ◽  
Tahseen Al-Saleem
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
B Cell ◽  
Cyclin D1 ◽  
Cell Line ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mutant P53 ◽  
B Cell Lymphomas ◽  
T Cell Lymphomas

Abstract Background: Mantle cell lymphoma (MCL) is characterized by t(11;14) which dysregulates cyclin D1 expression. Eμ-cyclinD1 transgenic mice, however, are healthy. Additional genetic events must be necessary for lymphomagenesis, and knowledge of these would enhance understanding and therapy of MCL. In addition, a mouse model of MCL would be helpful in drug development. Alterations in p53 have been described in MCL, often associated with the blastic variant. Objectives and Methods: To determine whether p53 and cyclin D1 can cooperate in lymphomagenesis, we cross bred Eμ-cyclinD1 transgenic mice (Bodrug et al EMBO J, 1996, courtesy of Alan Harris) with mice transgenic for mutant p53 (Jackson Labs, Jacks et al Curr Biol, 1994). Progeny mice were monitored for presence of the transgenes by PCR of tail vein DNA and observed for development of disease. Results: Of mice carrying both aberrant genes, 24 of 38 developed B cell lymphoma. Mice did not become visibly ill until at least 12 months of age, with median age at sacrifice 15.5 (range 12–23) months. The lymphoma was generally disseminated, involving spleen, liver, diffuse adenopathy and marrow with occasional extranodal sites. Histology varied between small and large cell, with some having a vaguely follicular growth pattern. T cell lymphomas occurred in 2 other mice, while 5 developed osteosarcoma (1 of these in a mouse that also had B cell lymphoma). The B cell lymphomas were clonal by Cμ-VH PCR. Cyclin D1 expression was documented by Western analysis. A cell line has also been developed from one of the B cell lymphomas and this line rapidly grows into disseminated lymphoma in syngeneic mice. These B cell lymphomas differ from the thymic T cell lymphomas seen in heterozygous p53 mutant mice that do not co-express cyclin D1. The latency period differs from cyclin D1 x myc double transgenic mice. Conclusions: This model demonstrates cooperation between p53 and cyclin D1 pathways in B cell lymphomagenesis and should prove useful in delineating how these signals interact. The cell line may prove useful in pre-clinical testing of new agents for MCL.

Primary cutaneous lymphomas in Peru

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17566-17566
Author(s):  
B. Beltran ◽  
A. Carrasco ◽  
L. Vera ◽  
E. Salinas ◽  
M. Ticona ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Malignant Lymphomas ◽  
Large B Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Cutaneous Lymphomas ◽  
Large B Cell

17566 Background: The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the new WHO/EORTC classification in Peruvian cases of cutaneous lymphoma. Methods: We conducted a clinicopathologic retrospective study of a collection of 68 primary cutaneous lymphomas, diagnosed from 1997 to 2004 in a National General Hospital. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 67 patients with malignant lymphomas of the skin were reviewed. HTLV-1 serology was made using ELISA and Western Blot methods. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Mean age at presentation was 62 years and the female/male ratio 1.5:1. T cell lymphomas were 88.6% and 11.4% were B-cell lymphomas. The most frequent cutaneous lymphoma was mycosis fungoides (MF) 30/67 (44.7%), Adult T-cell leukemia/lymphoma (ATLL) 13/67 (19.4%), unspecified peripheral T-cell lymphoma 4/67 (6%), lymphomatoid papulosis 2/67 (3%), leg-type diffuse large B-cell lymphoma 2/67 (3%), diffuse large B-cell lymphoma 2/67 (3%), subcutaneous panniculitis-like T-cell lymphoma 2/67 (3%), anaplastic large cell lymphoma 1/67 (1.4%), Sézary síndrome 1/67 (1.4%), nasal type extranodal NK/T-cell lymphoma 1/67 (1.4%), marginal zone B-cell lymphoma 1/67 (1.4%), follicle center lymphoma 1/67 (1.4%), intravascular lymphoma 1/67 (1.4%) and unclassifiable 5/67 ( 7.4%). Clinical stages of MF were: 60% stage I; 30% stage II; 3% stage III and 7% stage IV. 5-year survival was 77%. In ATLL group, 3 had smouldering type and 10 had cutaneous type. 5-year survival was 18%. Conclusions: In this retrospective analysis, cutaneous T cell lymphomas were prevalent; both MF and ATLL had the most frequency among primary cutaneous lymphomas in our hospital. ATLL had a poor 5-year survival. No significant financial relationships to disclose.

Structural Variations Involving Programmed Death Ligands in B-Cell and T-Cell Lymphomas

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4105-4105
Author(s):  
Keisuke Kataoka ◽  
Hiroaki Miyoshi ◽  
Yasunori Kogure ◽  
Yasuharu Sato ◽  
Kenji Nishida ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Sequencing Data ◽  
B Cell Lymphomas ◽  
Structural Variations ◽  
Chugai Pharmaceutical ◽  
T Cell Lymphomas

Abstract Immune checkpoint blockade using anti-PD-1 or anti-PD-L1 antibodies is a highly promising therapy that can induce a durable anti-tumor response and a long-term remission in many patients with multiple cancer types. In particular, the excellent efficacy of anti-PD-1 antibody has been reported in advanced cases with classical Hodgkin lymphoma (cHL), of which high frequency of genetic lesions involving PD-L1 and/or PD-L2 somatic alterations is a defining feature, suggesting a close link between the relevant genetic lesions and the efficacy of anti-PD-1/PD-L1 therapy. In addition to cHL, several subtypes of B-cell lymphomas are shown to have structural variations (SVs) involving PD-1 ligands, such as gene amplification and chromosomal translocation causing promoter replacement. Moreover, recently we reported unique SVs disrupting the 3′-untranslated region (UTR) of PD-L1 in a diversity of cancers, including adult T-cell leukemia/lymphoma (ATL) and diffuse large B-cell lymphoma (DLBCL). However, the comprehensive landscape of PD-L1 and PD-L2 alterations in non-Hodgkin lymphomas has not been fully elucidated. Therefore, in this study, we interrogated PD-L1 and PD-L2 genetic aberrations and characterized their features in a variety of non-Hodgkin lymphomas. To do this, lymphoma-derived DNA was captured for the entire region of PD-L1 and PD-L2 genes including their exons, introns, and 3′- and 5′-untranslated regions (UTRs) and subjected to high-throughput DNA sequencing. More than 300 samples from different lymphoma subtypes were analyzed, including DLBCL, follicular lymphoma, mantle cell lymphoma, MALT lymphoma, primary mediastinal B-cell lymphoma, peripheral T-cell lymphoma-not otherwise specified, and cutaneous T-cell lymphoma. We also analyzed publicly available sequencing data as well as our own data for lymphomas, which included Burkitt and angioimmunoblastic T-cell lymphomas as well. PD-L1/PD-L2-involving SVs were most frequently observed in PMBCL, accounting for 26.3% of the cases, but widely observed in various B- and T-cell lymphomas at varying but generally low frequencies. However, in contrast to PD-L1-involving SVs, which were found in both B- and T-cell lymphomas, PD-L2-involving SVs were exclusively seen in B-cell lymphomas. Depending on samples, different SV types were observed, including deletion, inversion, tandem duplication, and translocation, but most of SVs resulted in a truncation of the 3'-UTR of the PD-L1 or PD-L2 genes. Unlike previous reports, we rarely found those SVs that translocate PD-L1/PD-L2 to an ectopic regulatory element. Of particular interest were those cases in which multiple, independent SVs that converged to PD-L1 and PD-L2, were observed in a single tumor sample, underscoring the importance of PD-L1 and PD-L2 SVs in clonal selection and expansion of these tumors Given that PD-L1-involving SVs are detected not only in aggressive lymphomas but also in a variety of solid cancers, we hypothesized that PD-L2 genetic alterations are also present in other human cancers. However, no PD-L2-involving SVs were identified among > 10,000 cancer samples from 32 tumor panels, for which RNA sequencing data were available from the Cancer Genome Atlas (TCGA). These results suggest that PD-L1 is affected in a broad spectrum of human malignancies, whereas PD-L2 SVs are a characteristic alteration of B-cell lymphomas, which is consistent with their expression patterns. Based on these findings, we assessed whether disruption of PD-L2 3'-UTR also induces PD-L2 overexpression as seen for that of PD-L1 3'-UTR. When introduced in T2 human B and T lymphoblast hybrid cell line using the CRISPR/Cas9 system, SVs involving an almost entire PD-L2 3'-UTR sequence actually induced a significant elevation of PD-L2 expression, confirming the relevance of 3'-UTR in the regulation of PD-L2 expression. Taken together, our findings clarified the entire picture of PD-L1/PD-L2-involving SVs ligands in B- and T-cell lymphomas. Detection of these SVs might help the identification of patients with non-Hodgkin lymphomas who potentially benefit from PD-1/PD-L1 blockade therapy. Disclosures Kataoka: Kyowa Hakko Kirin: Honoraria; Boehringer Ingelheim: Honoraria; Yakult: Honoraria. Izutsu:Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Mundipharma KK: Research Funding. Ohshima:Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau; CHUGAI PHARMACEUTICAL CO.,LTD.: Research Funding, Speakers Bureau. Ogawa:Kan research institute: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy, Research Funding; Sumitomo Dainippon Pharma: Research Funding.

Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1513-1519 ◽  
Author(s):  
Xin Mao ◽  
Guy Orchard ◽  
Debra M. Lillington ◽  
Robin Russell-Jones ◽  
Bryan D. Young ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphomas ◽  
Cutaneous Lymphomas ◽  
Time Amplification ◽  
High Level

Primary cutaneous lymphomas (PCLs) represent a heterogeneous group of extranodal T- and B-cell malignancies. The underlying molecular pathogenesis of this malignancy remains unclear. This study aimed to characterize oncogene abnormalities in PCLs. Using genomic microarray, we detected oncogene copy number gains of RAF1(3p25), CTSB (8p22), PAK1 (11q13), and JUNB (19p13) in 5 of 7 cases of mycosis fungoides (MF)/Sezary syndrome (SS) (71%), gains of FGFR1 (8p11), PTPN (20q13), andBCR (22q11) in 4 cases (57%), and gains ofMYCL1 (1p34), PIK3CA (3q26), HRAS(11p15), MYBL2 (20q13), and ZNF217 (20q13) in 3 cases (43%). Amplification of JUNB was studied in 104 DNA samples from 78 PCL cases using real-time polymerase chain reaction. Twenty-four percent of cases, including 7 of 10 cases of primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL), 4 of 14 MF, 4 of 22 SS, and 2 of 23 primary cutaneous B-cell lymphoma (PCBCL) showed amplification ofJUNB, and high-level amplification of this oncogene was present in 3 C-ALCL and 2 MF cases. JUNB protein expression was analyzed in tissue sections from 69 PCL cases, and 44% of cases, consisting of 21 of 23 SS, 6 of 8 C-ALCL, 5 of 10 MF, and 9 of 21 PCBCL, demonstrated nuclear expression of JUNB by tumor cells. Overexpression of JUNB also was detected in 5 C-ALCL and 2 SS cases. These results have revealed, for the first time, amplification and expression patterns of JUNB in PCL, suggesting thatJUNB may be critical in the pathogenesis of primary cutaneous T-cell lymphomas.

scholarly journals Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2020 ◽  
Vol 38 (32) ◽  
pp. 3805-3815
Author(s):  
Kathryn M. Cappell ◽  
Richard M. Sherry ◽  
James C. Yang ◽  
Stephanie L. Goff ◽  
Danielle A. Vanasse ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

scholarly journals Systematic Literature Review of the Clinical Evidence in Relapsed/Refractory (R/R) Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5821-5821
Author(s):  
David G. Maloney ◽  
Fei Fei Liu ◽  
Lisette Nientker ◽  
Cathelijne Alleman ◽  
Brian Hutton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Frontline treatment is curative in ~60% of patients (pts); however, ~30% of pts relapse and ~10% are refractory to frontline treatment. Treatment options for pts with relapsed/refractory (R/R) disease, especially in the third-line or greater (3L+) setting, have been primarily salvage chemotherapies (CTs). Recently, 2 CAR T cell products, axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), and the antibody-drug conjugate, polatuzumab vedotin (Polivy®), were approved in the 3L setting. A systematic literature review (SLR) of R/R LBCL was conducted to identify relevant evidence on clinical outcomes in LBCL pts, including these new therapies, within the second-line and greater (2L+) or 3L+ setting, and to define the unmet medical need. Methods: This SLR was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and European Union Health Technology Assessment requirements. The review identified randomized and nonrandomized/observational studies within R/R LBCL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma grade 3B (FL3B), primary mediastinal large B-cell lymphoma (PMBCL), DLBCL transformed from indolent lymphomas, and R/R DLBCL with secondary central nervous system (SCNS) involvement. Sources were EMBASE, MEDLINE, The Cochrane Library, and clinical conferences (ASCO, ESMO, EHA, ASH, ICML, AACR, and EORTC) from Jan 2000 to Apr 2019. Results : Following screening of 8683 database records and additional sources, 103 publications covering 78 unique studies were identified. Studies identified were characterized by line of treatment and R/R LBCL subtype (Figure). OS, PFS, DOR, OR, and safety observed from the identified studies were described. Disease subtypes, pt eligibility criteria, and length of follow-up varied notably across studies. In the 3L+ population, 11 salvage CT and 2 CAR T cell therapy studies reported survival outcomes. With salvage CT, the reported ORR across studies ranged from 0% to 54%, while CR ranged from 5.6%-31%. Median OS (mOS) ranged between 3-9 months, with one outlying study reporting mOS at 20 months. Median PFS (mPFS) reported within the salvage CT studies ranged from 2-6 months. Among CAR T cell therapies, pts treated with axicabtagene ciloleucel (n=101) reported a CR rate of 58% and median DOR (mDOR) was 11.1 months after a median follow-up of 27.1 months. mPFS was 5.9 months and mOS was not reached. At a median follow-up of 19.3 months, pts treated with tisagenlecleucel (n=115) had a CR of 40% but the mDOR was not reached. mOS was 11.1 months for all infused patients. In the 2L+ transplant-eligible population (36 studies), pts who received high-dose CT + HSCT achieved mOS between 9 months to 5 years. In the transplant noneligible population, 16 studies reported mOS between 3-20 months. Studies involving mixed transplant-eligible and noneligible populations (30 studies) reported mOS of 1-17 months. A few studies with limited sample sizes were found to report outcomes in LBCL subtypes (eg, PMBCL, SCNS lymphoma, DLBCL transformed from non-FL indolent lymphoma, FL3B). In the 3L+ setting, 1 study reported that mOS was not reached after a median of 6.6 months. In the 2L+ setting, 4 studies reported mPFS and mOS outcomes ranging between 2-9 months and 10-16 months, respectively. Among studies assessing safety of salvage CTs in R/R LBCL, neutropenia, leukocytopenia, thrombocytopenia, and infections were the most commonly reported adverse events (AEs), with neutropenia being the most reported. Among the 3 studies reporting safety outcomes of CAR T cell therapy, data suggest that hematologic AEs (possibly related to lymphodepleting CT), cytokine release syndrome, and neurotoxicity are the most reported. Conclusions : Despite the availability of new therapies for 2L+ and 3L + LBCL, examination of the current evidence has shown that there exists a high unmet need for additional therapeutic options that provide favorable benefit/risk and durable response for these patients. Furthermore, limited data are available for the rarer subtypes of LBCL. Both findings represent important treatment gaps for R/R LBCL that must be addressed in future research geared toward improvement of the current treatment landscape. Disclosures Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Liu:Celgene Corporation: Employment. Nientker:Celgene Corporation: Consultancy; Pharmerit Cöoperatief U.A.: Employment. Alleman:Pharmerit Cöoperatief U.A.: Employment; Celgene Corporation: Consultancy. Garcia:Celgene: Employment, Equity Ownership.

T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients.

1995 ◽  
Vol 13 (7) ◽  
pp. 1742-1750 ◽  
Author(s):  
J P Greer ◽  
W R Macon ◽  
R E Lamar ◽  
S N Wolff ◽  
R S Stein ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Combination Chemotherapy ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
B Cell Lymphomas ◽  
Intermediate Grade ◽  
Large B Cell

PURPOSE Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas.

scholarly journals Comparison of peripheral T-cell lymphomas and diffuse large B-cell lymphoma

Cancer ◽  
2007 ◽  
Vol 109 (6) ◽  
pp. 1146-1151 ◽  
Author(s):  
Naoto Tomita ◽  
Shigeki Motomura ◽  
Rie Hyo ◽  
Hirotaka Takasaki ◽  
Sachiya Takemura ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Large B Cell ◽  
Peripheral T Cell Lymphomas

bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related.

1998 ◽  
Vol 16 (6) ◽  
pp. 2080-2085 ◽  
Author(s):  
F A Geelen ◽  
M H Vermeer ◽  
C J Meijer ◽  
S C Van der Putte ◽  
E Kerkhof ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
European Organization ◽  
Clinical Behavior ◽  
Large B Cell Lymphoma ◽  
Cutaneous Lymphomas ◽  
Distinct Disease ◽  
Large B Cell

PURPOSE Primary cutaneous large B-cell lymphoma (PCLBCL) that presents on the leg has recently been recognized as a distinct disease entity. These lymphomas have a reduced disease-free survival and a worse prognosis as compared with the more common, morphologically similar PCLBCL that present on the head or trunk. Studies in noncutaneous diffuse large B-cell lymphomas suggest a relationship between the expression of bcl-2 protein and clinical behavior. In the present study, we investigated whether these two groups of PCLBCL differ in the expression of bcl-2 protein and the presence of t(4;18), known as one of the causes of bcl-2 overexpression. PATIENTS AND METHODS Paraffin sections from pretreatment biopsies of 14 PCLBCLs of the head or trunk and nine PCLBCLs of the legs were investigated for expression of bcl-2 protein using immunohistochemistry, and for the presence of the 14;18 translocation using polymerase chain reaction (PCR) amplification with primers against both the major breakpoint region (mbr) and the minor cluster region (mcr) of bcl-2. For reasons of comparison, nine secondary cutaneous large B-cell lymphomas (SCLBCLs) were also studied. RESULTS Expression of bcl-2 protein was found in all nine PCLBCLs of the leg and in all nine SCLBCLs, but not in any of the 14 PCLBCLs on the head and trunk. The t(14;18) was only detected in two of seven SCLBCLs, but not in the five PCLBCLs of the leg or the eight PCLBCLs on the head or trunk studied. CONCLUSION The striking differences in bcl-2 expression between PCLBCL of the head or trunk and PCLBCL on the leg suggest that bcl-2 expression is site-related and may contribute to the different clinical behavior between these two groups of lymphomas. In addition, they underscore that PCLBCL on the head and trunk and PCLBCL on the leg are distinct disease entities, as recently recognized in the European Organization for Research and Treatment of Cancer (EORTC) classification for primary cutaneous lymphomas.

Pegylated Liposomal Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (CBVD) in the Treatment of Advanced Primary Cutaneous Lymphomas.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3717-3717
Author(s):  
Elisabetta Abruzzese ◽  
Massimiliano Postorino ◽  
Tullio Faraggiana ◽  
Daniela Renzi ◽  
Manuela Rizzo ◽  
...  
Keyword(s):  
B Cell ◽  
Liposomal Doxorubicin ◽  
Cell Lymphoma ◽  
Pegylated Liposomal Doxorubicin ◽  
B Cell Lymphoma ◽  
Nodal Involvement ◽  
Cutaneous Lesions ◽  
Cutaneous Lymphomas ◽  
Number Of Patients

Abstract Abstract 3717 Poster Board III-653 Introduction Primary cutaneous lymphomas (PCL) present in the majority of histologic variants an indolent behaviour and a good prognosis with a prolonged survival. In a very small number of patients (pts), PCL is aggressive at the onset while in pts who are resistant or have relapsed after repeated topic or systemic therapies an advanced disease is more frequently observed. In these patients no therapy is capable of inducing a stable remission of the disease. The efficacy and low toxicity of Pegylated Liposomal Doxorubicin (PLD) as a single agent in second-line therapy of PCL was recently demonstrated. In our study we tested the safety and efficacy of PLD (Caelyx®) (C) in association with three drugs of proven effectiveness in nodal lymphoprolipherative and other primary cutaneous neoplastic disorders: Bleomycin (B), Vinblastine (B) and Dacarbazine (D) (CBVD). Patients and Methods From February 2003 to December 2008 we observed 37 consecutive pts with advanced PCL: 19 Cutaneous T-Cell Lymphomas (CTCL) and 18 cutaneous B-Cell Lymphomas (CBCL). The CTCL pts were: 15 males and 4 females, with median age 59 (27-86) years, of which 7 pts with Anaplastic Large Cell Lymphoma (ALCL) CD30 positive, 7 pts with transformed Mycosis Fungoides (tMF), 3 pts with CD30 negative ALCL, 1pt with Panniculitis-like (Pl) Lymphoma and 1 pt with transformed Sezary Syndrome (tSS), according to the WHO-EORTC consensus classification. Nine pts presented with a nodal involvement and 10 pts were resistant or relapsed after 1 or more systemic treatments. Among the CBCL pts there were: 8 males and 10 females, with median age 61 (42-84) years, 12 pts had a Follicular Centre Lymphoma (FCL), 3 a Marginal Zone Lymphoma (MZL) and 3 a Diffuse Large B-Cell Lymphoma Leg Type (LT). Five pts presented a nodal involvement and 11 pts had received 1 or more previous systemic therapy. All 37 pts received CBVD therapy at following dosage: C: 20 mg/m2, B: 10 mg/m2, V: 6 mg/m2, D: 325 mg/m2 at days 1 and 15, administered intravenously every 4 weeks for a maximum of 6 cycles. Rituximab (R) at dosage of 375 mg/m2 was administered to CBCL pts at 1st day of each cycle. Before the treatment, pts were submitted to a complete staging of disease including TC-scan, bone marrow biopsy, and immunophenotyping of peripheral blood cells. Results In the CTCL group 4 pts received 4 CBVD cycles, 14 pts received 6 CBVD cycles and 1 pt presented a progressive disease after the 1st cycle. Overall Response Rate (ORR) was 94.7% (18/19 pts). Sixteen out of 18 pts (88.8%) had a Complete Remission (CR) with disappearance of nodal involvement and cutaneous lesions, 2/18 pts obtained a Partial Remission (PR) with disappearance of nodal involvement and 75% of cutaneous lesions. In the CBCL group 3 pts received 2 R-CBVD cycles, 3 pts 4 cycles and 11 pts 6 cycles: ORR was 100% and all pts obtained a CR. The occurrence of palmoplantar erytrodisesthesia in 5 pts and grade 2-3 granulocytopenia in 12 pts did not modify the therapy program. Two CTCL pts (1 tSS, 1Pl) and 1 CBCL (LT) pt in CR after therapy received an allogeneic Hemopoietic Stem Cells (HCS) transplant and 1 CBCL(FCL) pt a syngeneic HCS transplant. In CTCL group 11 (61%) pts maintained their response after a median follow up of 15.5 (9-71) months. Among CBCL pts 14 (77.7%) pts are still in CR after a median follow up of 15 (4-36) months. Conclusions Our experience demonstrates that the CBVD association is an effective and safe therapy for advanced PCL in inducing an important tumour burden reduction with a high CR rate. The assessment of response duration requires a longer observation. A larger number of patients in a multicentric trial are needed to confirm our promising results. Disclosures: Off Label Use: liposomial doxorubicin has a peculiar cutaneous tropism and low cardiac toxicity compared with other anthracyclines.

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