bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failure of Single-Agent Rituximab for Treatment of Subcutaneous Intravascular Lymphomatosis (IVL): A Case Report.
Authors: Pirog Steven C. , Aboulafia David M. 
Published: April 2020

Abstract
IVL is an uncommon large-cell lymphoma, usually of B-cell origin. Typically, the CD20+ lymphoma cells possess defects in homing receptors. This leads to limited cell migration from the vessel endothelium, resulting in cell crowding and blockage of intravascular lumens. Patients frequently present with skin lesions, fever, and neurological dysfunction, reflecting the ability of malignant cells to infiltrate various organs. The wide spectrum of clinical manifestations of IVL, along with its propensity to afflict elderly patients with multiple comorbidities, presents a diagnostic and therapeutic challenge; most cases are discovered post-mortem. Anthracycline-based chemotherapy is the standard treatment for this malignancy, but outcomes are disappointing, with most patients destined to die from progressive lymphoma and, less commonly, chemotherapy-induced complications. An 86-year-old female underwent a lesion biopsy after bilateral thigh plaques (the largest of which measured 8 × 13 cm) became increasingly erythematous and painful, despite treatment with antibiotics and corticosteroids. She was diagnosed with subcutaneous CD20+ IVL. Laboratory studies were notable for hematocrit 29% with iron indices consistent with inflammatory block, lactate dehydrogenase 950 IU/L (normal &lt; 240 IU/L) and β2-microglobulin 1.8 mg/mL (normal &lt; 2.0mg/mL). Whole-body computed tomography and positron emission tomography fusion studies did not suggest lymphoma elsewhere. She received rituximab (375 mg/m2/week × 8 weeks) and achieved a complete remission (CR), with the disappearance of thigh discomfort and resolution of her medial thigh plaques. Three months after completion of rituximab treatment, a new left posterior chest wall mass was biopsied and proved to be recurrent IVL. She declined further treatment and was referred to hospice care. Through a Medline search we were able to identify 12 additional patients who were treated with multi-agent chemotherapy and rituximab (n=10) or rituximab monotherapy (n=2). The patients’ ages ranged from 42 to 86 years. The most common clinical presentations in these cases included fever (n=5), nervous system involvement (n=3), and skin rash (n=2). Excluding one multi-agent therapy patient who died during treatment, all patients in our search achieved CRs, with a median follow-up duration of 14 months (range, 6–36 months). Among various lymphoma subgroups (including elderly patients with high-risk features and those with IVL), rituximab has been used as a single agent and to augment the anti-lymphoma properties of multi-agent chemotherapy. Our case report is the first to describe IVL recurrence following rituximab monotherapy, and highlights the need for further investigation on the use of rituximab in the treatment of this rare lymphoma.
Initial Treatment of CD20+ Lymphocyte Predominant Hodgkin Lymphoma with Chemotherapy and the Monoclonal Antibody Rituximab-Mabthera Is Effective and Well Tolerated - Case Report.
Authors: Genadieva-Stavrik Sonja G. , Ivkovski Lubomir , Pivkova Aleksandra , Cevreska Lidija 
Published: April 2020

Abstract
Patients with lymphocyte-predominant Hodgkin disease (LPHD) often present at an early stage with slow disease progression. Although 96% of LPHD patients experience a complete remission (CR) upon first line treatment, many relapses occur. CD20+ is strongly expressed by malignant cells in LPHD, but so far there is limited information regarding the efficacy of rituximab in this patient population. We report 46-year-old woman who presented in 2004 with left cervical lymphadenopathy and weight loss.
Case report: Biopsy confirmed a diagnosis of LPHD(stage IIB disease), immunohistochemistry revealed that &gt;30% of malignant cells were CD20+, and a bulky mediastinal mass was observed by computer tomography (CT). Blood counts, erythrocyte sedimentation rate, albumin and lactate dehydrogenate were normal. The patient was treated with rituximab and ABVD (doxorubicin 25mg/m2, bleomycin 10mg/m2, vinbalstine 6mg/m2, dacarbazine 375mg/m2, six cycles). Rituximab was administered (375mg/m2) one day before chemotherapy (50mg/h for one hour and gradually escalated to a maximum of 400mg/h). Treatment was well tolerated and there were no complications. The patient was assessed immediately following treatment and every three months for the following year, by physical examination, CT, bone marrow biopsy and routine analyses. A detectable tumor mass was no observed by CT for the follow up of 2 years, the patient remains in complete remission.
Conclusion: Our case report suggests that Rituximab is both safe and effective in patients with CD20+ LPHD. Further studies with Rituximab are warranted in this patient population.
First Line Treatment with Rituximab and Chlorambucil in the Treatment of Ocular Adnexal Lymphomas.
Authors: Rigacci Luigi , Puccioni Marco , Nassi Luca , Mappa Silvia , Mazzini Cinzia , Alterini Renato , Carrai Valentina , Polito Ennio , Bosi Alberto 
Published: April 2020

Abstract
Ocular adnexal lymphomas (OAL) are malignant neoplasms which develop in the orbit, the conjunctiva and eyelid. The majority of lymphomas occurring in the ocular adnexa are represented by extranodal marginal zone B-cell lymphomas. In patients with stage IE OAL, localized radiotherapy is the therapy of choice. Complications, however, are frequent, including dryness of the eye, corneal ulcerations, cataract and retina damage. Surgical treatment is usually recommended for conjunctival and eyelids lymphomas but fails to control the growth of lymphoma. Contralateral eye or sistemic relapses are reported in about 10–25% of cases. Therefore, a systemic approach is needed. Rituximab is an anti-CD20 monoclonal antibody, and its efficacy has been demonstrated in indolent and aggressive lymphomas in combination with chemotherapy. Since December 2003 to January 2006 we treated 9 patients with OAL with a combination of Rituximab and Chlorambucil according to this schedule: four weekly infusions of Rituximab 375 mg/m2 plus Chlorambucil 0,1 mg/Kg/die for 45 days, followed by Rituximab 375 mg/m2 once a month for four months and Chlorambucil 0,1 mg/Kg/die for two weeks every month. Eight pts had a diagnosis of extranodal marginal zone B-cell lymphoma and one patient a follicular grade I lymphoma. Median age at diagnosis was 78 years (range 56–86). All pts had a stage I disease and no pts presented systemic symptoms. Disease was localized in the conjunctiva in 6 pts (4 right and 2 left), in two pts the disease was observed in the orbit and in one patient it was localized in the eyelid. IPI was evaluable in 7 pts, and all had a low risk. All pts completed the program without delays. Toxicity, both hematological and extrahematological, was mild, in spite of the high median age of the pts. At the end of treatment 8 pts obtained a complete remission (CR), and a patient obtained a partial response. After a median follow-up of 17 months all pts are alive, and 8 out of 9 (89%) are still in CR. No late toxicity of the ocular adnexa was observed. In conclusion, we hypothesize that Rituximab in combination with Chlorambucil should be take into consideration as first line treatment of primary ocular adnexa lymphomas due to its feasibility and the lacking of severe toxicity and local sequelae.
Long Term Follow up of Hairy Cell Leukemia (HCL) Patients (PTS) Treated with Interferon-Alpha (IFN-α). The Importance of Maintenance.
Authors: Sachanas Sotirios , Angelopoulou Maria K. , Anargyrou Konstantinos , Kokoris Styliani I. , Vassilakopoulos Theodoros P. , Galani Zacharoula I. , Dimitriadou Evangelia M. , Siakantaris Marina P. , Dimopoulou Maria N. , Kontopidou Flora N. , Kyrtsonis Marie-Christine , Plata Eleni , Tsaftaridis Panayiotis , Panayiotidis Panayiotis , Pangalis Gerassimos A. 
Published: April 2020

Abstract
HCL is a chronic B-cell lymphoproliferative disorder with a specific morphology and immunophenotype of the malignant lymphocytes. Although purine analoges are the recommended first-line treatment, they are associated with significant immune suppression and secondary neoplasia. IFN-α is an alternative treatment with fewer long term side effects and considerable efficacy.
AIM: The analysis of HCL patients treated with IFN-α as first-line therapy in a single Hematology Unit.
PATIENTS AND METHODS: 75 consecutive pts diagnosed and followed in our Department between 1980 and 2005, treated with IFN-α were analyzed.
RESULTS: 77.3% were males and their median age was 51 years (30–81). 57% had splenomegaly and 12% hepatomegaly at diagnosis. Their median hemoglobin was 11.3g/dL (4.5–14.3), their median leukocyte and absolute neutrophil counts were 3.1×109/L (0.9–26) and 0.77×109/L (0.03–3.9), respectively. Their median platelet count was 79×109/L (20–295). 33% had hypergammaglobulinemia and their median percentage of bone marrow infiltration at diagnosis was 75%. 10% of the pts were splenectomized before IFN-α treatment. The median time from diagnosis to IFN-α initiation was 0.7 months. The majority of pts (68%) received IFN-α induction at a dose of 3MU/day, while 15% 3MU every other day. Median duration of IFN-α induction was 23.5 months. 8% of pts achieved a complete response with a negative bone marrow, while 73% had a partial remission with a &gt;50% reduction of bone marrow infiltration and a complete restoration of all blood counts. The median time to complete hematologic restoration was 10.7 months. 79% of pts received IFN-α maintenance, the majority of whom (58%) at a dose of 3MU/week. 69% of pts never needed a 2d line treatment, while among those who did, 65% were retreated with IFN-α. The 10-year overall survival was 80%. There were 2 cases of secondary neoplasia. At last follow-up 9% of pts were dead due to unrelated causes, 3% due to 2ary neoplasia, while none died due to disease. Two factors were of prognostic significance for freedom from 2d treatment (FF2T). FF2T was significantly longer for pts older than 51 years old (p&lt;0.0004) and for those receiving IFN-α maintenance compared to those who did not (p&lt;0.03).
CONCLUSIONS: IFN-α has significant efficacy in HCL with a slow but sustained response. Continuous maintenance seems to be important in maintaining response. Younger patients might benefit less from IFN-α.
Analysis of microRNA Patterns in Hodgkin’s Lymphoma (HL).
Authors: Navarro Alfons , Gaya Anna , Pons Aina , Abrisqueta Pau , Gel Bernat , Martinez Antonio , Lopez-Guillermo Armando , Martinez Carmen , Granell Miquel , Artells Rosa , Jansa Sonia , Urbano-Ispizua Alvaro , Montserrat Emili , Monzo Mariano 
Published: April 2020

Abstract
Mature microRNAs (miRNA) are recently discovered small RNA molecules of 21–25 nucleotides in length. They act as negative regulators of expression of important genes like those participating in cellular proliferation or apoptosis. There is evidence that miRNA play an important role in carcinogenesis. The objective of this study was to compare the miRNA expression patterns in normal lymph nodes and in lymph nodes from patients with HL. Moreover, we investigated the miRNA pattern of HL depending on Epstein-Barr Virus (EBV) expression. We assessed 156 mature miRNAs by Stem-loop RT-PCR and Real time PCR in ABI PRISM 7500 in 9 normal lymph nodes and 39 patients diagnosed with HL nodular sclerosis subtype (15 EBV+ and 24 EBV-)at a single institution. Patients median age was 27 years (range, 15–52), and clinical stage was I (n=1); II (n=22); III (n=8) and IV (n=8); 41% of the patients reported B symptoms. RNA was obtained in all cases from formalin fixed paraffin embedded tissues. miRNA expression data was normalized to let-7a miRNA and to global median. Relative quantification of miRNA expression was calculated with the 2−ΔΔCt method. The data were presented as log10 of relative quantity of target miRNA. Normal human lymph node tissue was used as calibrator for all samples. Data were analyzed by means of Significant Analysis of Microarrays (SAM), Student’s t-test (with random variance model) and Class prediction methods using BRB Array Tools version 3.4.0 and TIGR Multiexperiment Viewer version 3.1. Of the 156 miRNAs analyzed, 35 were differentially expressed between normal lymph nodes and HL (12 miRNAs were upregulated and 23 downregulated). The most differentially overexpressed miRNAs was miR-216, which inhibits apoptosis pathway. Other differentially expressed miRNAs were miR-140, 204, 19a, 20, 191 and 142-3p, which have been associated to the genesis of hematological and non-hematological malignances. With respect to EBV+ vs. EBV− cases, we found that miR-96 and miR-335 were underexpressed in the EBV+ cases as compared to EBV− (p=0.001). These miRNAs have RNF34 and BIRC2 genes as targets, which have an antiapoptotic function. We also found that miR-138 was more frequently overexpressed in clinical stages I–II versus clinical stages III–IV (p=0.004), and that miR-328 was more frequently overexpressed in stages III–IV (p=0.004). In conclusion, miRNAs might have a role in the pathogenesis of HL. The miRNA pattern is different between the EBV+ and EBV− cases, and the differentially expressed miRNAs seems to be related to the apoptotic pathway.
Alemtuzumab in Combination with CHOP and ESHAP as First-Line Treatment in Peripheral T-Cell Lymphoma.
Authors: Intragumtornchai Tanin , Bunworasate Udomsak , Nakorn Thanyaphong Na , Rojnuckarin Ponlapat 
Published: April 2020

Abstract
Patients diagnosed with peripheral T-cell lymphomas (PTCL) generally had a poorer prognosis compared to B-cell non-Hodgkin’s lymphomas. With conventional treatment, the 5-year overall and failure-free survivals (OS and FFS) were 36% and 23%, respectively (Vose et al, Blood2005;106:abstract 811). Between February 2005 and January 2006, 13 consecutive patients newly diagnosed with PTCL (5, extranodal nasal NK/T-cell lymphoma, 4 subcutaneous panniculitis-like, 3 PTCL, unspecified and 1 enteropathy type) were enrolled. The median age was 44 years (range, 21–56) and male:female was 1.6:1. Fifty-four percent had stage III/IV, 31%, PS 2–3, 69%, B-symptoms, 15%, bulky disease, 46%, &gt; 1 extranodal site, 38%, elevated serum LDH and 39%, aaIPI 2–3. Twenty-three percent had thrombocytopenia. Patients were treated with alemtuzumab 30 mg. sc. D1-3 of cycle 1–5 plus CHOP (day 1 of cycle 1, 3, 5) and ESHAP (day 1 of cycle 2, 4, 6) at 28-day intervals. Valacyclovir 500 mg tid and trimethoprim/sulfamethoxazole were given for prophylaxis of CMV and Pneumocystis carinii infection, respectively. Of the evaluable 10 patients, complete remission was obtained in 8 patients, 1 had partial remission and 1 had CNS progression while on treatment. Infection was a major adverse complication: 54% had CMV reactivation (1 had CMV disease), 54%, febrile neutropenia and 15%, tuberculosis. With a median follow-up time of 8 months, the 2-year OS and FFS were 75% (95%CI, 41–92) and 48% (95%CI, 14–76), respectively. From the standpoint of this result, alemtuzumab in combination with CHOP and ESHAP is an effective front-line therapy for patients newly diagnosed with PTCL.
Fc Engineered Anti-CD19 Monoclonal Antibodies with Enhanced In Vitro Efficacy Against Multiple Lymphoma Cell Lines.
Authors: Zhukovsky Eugene A. , Chu Seung , Bernett Matthew , Hammond Philip , Karki Sher , Dang Wei , Edler Collin , Polder Nephi , Chan Cheryl , Jacinto Jonathan , Desjarlais John 
Published: April 2020

Abstract
CD19 is a pan-B cell surface receptor that is expressed from early stages of pre-B cell development through terminal differentiation into plasma cells. It is an attractive immunotherapy target for cancers of lymphoid origin since it is also expressed on the vast majority of Non-Hodgkin Lymphoma (NHL) cells. Although the anti-CD20 monoclonal antibody rituximab is efficacious for the treatment of lymphoid tumors, a growing population of rituximab-refractory patients has resulted in an unmet need for alternative B cell-specific immunotherapeutics. Engineered Fc variants that increase the affinity of IgG antibodies for Fc gamma receptors (FcγR) can dramatically enhance antibody-dependent cell-mediated cytotoxicity (ADCC). This technology has been applied to a humanized anti-CD19 antibody (XmAb™ CD19) and demonstrates ADCC against multiple cell lines representative of follicular lymphoma (FL/DOHH-2), chronic lymphocytic leukemia (CLL/MEC-1), B-cell acute lymphoblastic leukemia (B-ALL/VAL), mantle cell lymphoma (MCL/JeKo-1), hairy cell leukemia (HCL/BONNA-12), and Burkitt’s lymphoma (Raji). The ADCC activity observed is in striking contrast with a wild type IgG1 version of the antibody, which mediates little or no ADCC. Moreover, the XmAb™ CD19 activity is comparable to that of rituximab for the majority of cell lines tested and occasionally superior. Fc variants of this antibody are being evaluated in vitro for their ability to conduct ADCC by various effector cell populations, and in relevant in vivo efficacy models. In summary, these data suggest that anti-CD19 Fc variant antibodies with increased effector function could be promising as NHL immunotherapeutics, particularly for rituximab-refractory NHL.
TRAIL Receptor 1 and TRAIL Receptor 2 Monoclonal Antibodies Induce Apoptosis and Increase Susceptibility to Cytostatic Agents in Mantle Cell Lymphoma.
Authors: Rieken Malte , Pastore Alessandro , Weigert Oliver , Weinkauf Marc , Hutter Grit , Zimmermann Yvonne , Hiddemann Wolfgang , Dreyling Martin 
Published: April 2020

Abstract
Background: TRAIL is a member of the TNF-family of cytokines, which induces apoptosis in various solid tumors by activation of the death receptors DR4 and DR5. Previous studies demonstrated that human agonistic antibodies to TRAIL receptors TRAIL R1 (ETR1) and TRAIL R2 (ETR2) activate the apoptosis pathway via caspase 8. Also, preliminary data suggest an efficacy of the antibodies in human lymphoma cell lines; however, little is known about the effects of ETR1 and 2 in mantle cell lymphoma (MCL), a distinct lymphoma subtype with an especially poor clinical outcome.
Methods: 4 MCL cell lines (HBL2, GRANTA 519, Jeko-1, NCEB-1) and two lymphatic control cell lines (Jurkat, Karpas 422) exposed to different doses of ETR1 and ETR2 were studied for inhibition of proliferation (cell count) and metabolism (WST-1 assay); cell apoptosis was quantified by flow cytometry (Annexin V staining). In addition, all cell lines were also exposed to combinations of ETR1 and various cytostatic compounds (cytarabine, fludarabine or mitoxantrone) to explore potential synergism.
Results: Inhibition of proliferation and induction of apoptosis was achieved in all cell lines in a dose and time dependent manner, but susceptibility varied strongly between the MCL cell lines. With the notable exception of NCEB-1, ETR1 inhibited cell proliferation more effectively than ETR2. IC50 values after 24 hours exposure of ETR1 was 3,26 μg/ml (HBL-2) and 1,09 μg/ml (Jeko-1), whereas no IC50 was reached in the remaining MCL cell lines. Accordingly, HGS-ETR1 at a concentration of 2μg/ml induced apoptosis in 9% (Granta 519) to 63% (Jeko-1) of cells after 24 hours, respectively. In contrast, IC50 values of ETR 2 were only reached in Jeko-1 (0,85μg/ml). Preliminary data indicate a synergistic effect of HGS-ETR1 in combination with conventional cytostatic agents, confirmatory experiments will be presented at the meeting.
Conclusions: Our data indicate that both, ETR1 and ETR2, induce apoptosis in MCL cell lines; however, ETR1 seems to be more effective. Interestingly, combination experiments suggest that induction of apoptosis by TRAIL receptor antibodies may overcome chemotherapy resistance. These results form the rationale for combined approaches in future clinical trials.
Z-Guggulsterone Downregulates Survivin and Induces Cell Death in Large B Cell Lymphoma Cells In Vitro.
Authors: Angelopoulou Maria K. , Lilakos Konstantinos , Salpeas Vassilios , Sachanas Sotirios , Korkolopoulou Penelope , Siakantaris Marina P. , Vassilakopoulos Theodoros P. , Panayiotidis Panayiotis , Pangalis Gerassimos A. 
Published: April 2020

Abstract
Introduction: Survivin is a member of the Inhibitor of Apoptosis Proteins and has recently gained attention as a possible therapeutic target in malignancies, due to its dual role both as an antiapoptotic protein and as a cell cycle regulator. It is overexpressed in malignant cells and confers resistance to chemotherapy and other stimuli triggering apoptosis. Z-Guggulsterone (Z-GGS) is a plant sterol, which has been used in inflammatory conditions and has been recognized as a potent NF-kB suppressor. Since Survivin, as well as other antiapoptotic proteins, are under NFkB regulation, we studied the effect of Z-GGS on two B-cell lymphoma cell lines.
Methods: DB and HT cell lines were treated with increasing concentrations (10μM, 20μM and 30μM) of Z-GGS, for 24, 48 and 72 hours. Survivin expression was tested with Flow Cytometry and Survivin transcripts were measured with quantitative real time PCR using the Universal Probe Library hydrolysis probes and expressed as Survivin/abl ratio. Cell viability was assessed with the MTT assay.
Results: Both cell lines were positive for Survivin at baseline by flow cytometry (66% of total cells for DB and 95% for HT). Treatment of DB cells with 10, 20 and 30μM Z-GGS resulted in a 44%, 49% and 68% reduction of Survivin expression at 24 hours, respectively, whereas the effect on HT was less prominent with a 10% reduction at 24 hours with 30μM Z-GGS. Survivin transcripts decreased as well, with the maximum effect observed at 72 hours with 30μM Z-GGS for both cell lines: Survivin/abl was 0.009 for untreated cells vs 0.0008 with 30μM Z-GGS for DB cells and 0.0135 vs 0.0005 for HT cells. Linearity was observed for increasing concentrations of Z-GGS at 72 hours. Cell viability was practically unaffected at any time point with 10 and 20μM Z-GGS for both cell lines, whereas 30 μM Z-GGS resulted in a 63% and 78% cell death at 48 and 72 hours respectively for DB cells and 67% and 83% for HT cells.
Conclusions: The steroid Z-GGS downregulates Survivin expression in B-lymphoma cells in vitro and induces cell death at 30μM concentration. Further experiments will clarify its possible role in the treatment of B-cell malignancies.