bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Preliminary Assessment of 99m tc-HYNIC-Fab´s (Rituximab) for Non-Hodgkin Lymphoma Diagnosis
Authors: Camacho Ximena , Machado Camila , Banchero Agustina , García Maria Fernanda , Calzada Victoria , Fernández Marcelo , Moreno María , Gambini Juan Pablo , Alonso Omar , Chammas Roger , Cabral Pablo , Riva Eloísa 
Published: October 2019

Abstract
Introduction: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy; more than 90% are B cell lymphomas and express CD-20 antigen. Rituximab® (RTX) is an IgG1κ chimeric anti-CD20 mAb that binds specifically to the CD20-antigen on B lymphocytes. Our group previously reported that 99mTc-RTX represents a promising molecular imaging agent for NHL [1]. When used for tumor imaging, intact IgG exhibits high liver uptake. Antibody fragments (Fab´s) are quickly eliminated from blood and normal tissues (except kidneys), achieving high tumor/blood and tumor/normal tissue ratios with renal clearance. The development of radiolabeled Fab´s directed against specific targets may become a new strategy for NHL staging and surveillance.
Objective: To radiolabel Fab´s (RTX) with 99mTc and to perform its chemical and biological evaluation.
Methodology: We performed antibody fragmentation with papain and, once purified, fragments were identified by MaldiTOF/TOF and derivatized with Suc-HYNIC as a bifunctional coupling agent. A mixture of Tricine/SnCl2.2H2O was added to Fab´s (RTX)-HYNIC and radiolabeled with 99mTcO4-. Radiochemical purity was determined by HPLC. The in-vitro radiochemical stability of the radiolabeled Fab´s were analyzed in saline and serum up to 4 h. In-vitrobinding and competition assays were performed using Ramos and Raji cell lines up to 90 min. Biodistribution studies were evaluated in normal Balb/c mice and in Raji tumor-bearing Nude mice at 0.5 and 1 h.
Results: Radiochemical purity of radiolabeled Fab´s were ≥90%. The in-vitro radiochemical stability studies showed that the radioconjugate was stable and no significant transchelation was detected. In-vitro binding and competition assays confirm that after its derivatization and radiolabeling, Fab´s (RTX) retained its specificity of binding to CD-20 antigen. This results confirm that Fab´s (RTX) affinity for CD20+ NHL cells remained unaffected after its derivatization. In-vivobiodistribution studies show that radiolabeled Fab´s has renal uptake with neglectable uptake in other organs, indicating that the primary route of clearance is renal. Lymph-node/muscle ratios of 4.00 and 2.55 at 0.5 and 1 h post injection, respectively.
Conclusions: Fab´s (RTX) were easily and rapidly labeled demonstrating good stability and radiochemical purity. Based on lymph-node uptake and lymph-node/muscle ratios, 99mTc-HYNIC-Fab´s (RTX) may be useful for tumor molecular imaging agent for NHL.

Disclosures
No relevant conflicts of interest to declare.
Preventive Effects of Cardotoxicities By Liposomal Anthracyclines non Pegilated in 95 Perspective Patients Affected By Lymphoma and Monitored By Biomarkers and Ecocardiography
Authors: Gini Guido , Olivieri Jacopo , Bocci Caterina , Sampaolo Michela , Trappolini Silvia , Olivieri Attilio , Offidani Massimo , Rupoli Serena , Poloni Antonella , Scortechini Anna Rita , Capelli Debora , Montanari Mauro , Scortechini Ilaria , Perna Gian Piero , Leoni Pietro 
Published: October 2019

Abstract
Anthracyclines (AC) still constitute the mainstay of the 1st line treatment in lymphoma: their use, however, is limited by the occurrence of Cardiac Toxicity (CT). The exact prevalence of AC CT occurring after widely used regimens such as R-CHOP or ABVD is unknown and there is uncertainty about the best monitoring method and possible prophylactic or therapeutic interventions.
METHODS: We started a prospective observational trial in lymphoma patients undergoing treatment with conventional or liposomal AC. We used a comprehensive approach to monitor for AC CT, using a telemedicine(TM) system integrating echocardiography, ECG and biomarkers (Troponin I - TnI).
RESULTS: In this final analysis, 95 patients completed the planned treatment (52 males and 43 females). Median age was 56.03 years (range 19.1 to 78.5 years), and 36 patients were > 65 years. 23 were HL and 72 NHL (DLBCL was the most represented subtype with 47 cases). Liposomal AC was used in 31 patients and classical AC in 64, with mean cumulative doses of 283.33 and 272.76 mg/sqm, respectively.
10/95 patients (11%) developed a TnI rise above 0.08 ng/ml and 39/95 (41%) above 0.03 ng/ml. With both cut-offs, the rises occurred more frequently at cumulative doses >200 mg/sqm. The major arising occurred in the group underwent classical AC, while in the group underwent liposomal AC although the value before first infusion was in 10% more than 0.03 at the cumulative dose of 300 mg /sqm there's a plateau of troponin value.
Thanks to this monitoring system we noticed 2 Acute cardiac toxicity events with resolution in 100% of cases. Furthermore in those cases where has registered a subclinical CT has begun a prompt Cardiological therapy by ACE inhibitors and Beta Blocker to reduce the relative risk of Cardiological events.
CONCLUSIONS: Even with low cumulative doses, with a median follow up of 13 months, subclinical signs of AC CT were found in at least 11% of patients. The use of liposomal AC allow the safe treatment of patients with a previous heart disease diagnosis rather it seem protective in the higher cumulative doses.
A longer follow up will be able to clarify the impact of arising of TnI more than 0.03 and 0.08 on the developing of AC CT in all our series.
On the basis of our experience a multicentric trial has begun on behalf Italian Lymphoma Foundation (FIL)
In a low-risk setting for AC CT, a monitoring strategy combining clinical, imaging, instrumental and biomarker data seems to enhance the sensitivity of separate methods. This strategy is feasible and resource-saving thanks to the integration in a TM system.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Langerhans Cell Histiocytosis: A Single Institution Retrospective Analysis of Eleven Patients
Authors: Stefoni Vittorio , Broccoli Alessandro , Casadei Beatrice , Derenzini Enrico , Gandolfi Letizia , Pellegrini Cinzia , Quirini Federica , Argnani Lisa , Zinzani Pier Luigi 
Published: October 2019

Abstract
Langerhans cell histiocytosis (LCH), is a rare disorder which has a substantially unknown etiology, pathophysiology, and may manifest through a variety of clinical presentations ranging from solitary eosinophilic granuloma to severe multisystem disease. LCH is more common in children, although it can affect any age; the most common sites of involvement are bone, skin, and lung.
From a histological point of view LCH derives from accumulation of proliferating cells with surface markers and ultrastructural features similar to cutaneous Langerhans cells, intermixed with inflammatory cells, particularly eosinophils.
Below, a retrospective analysis of LCH patients treated at our institution.
Between 1997 and 2013 we have treated 11 LCH patients, including 6 females and 5 males with a median age at time of diagnosis of 42.9 years (range 22.2-62.3). All diagnoses were reviewed by our pathologist.
With regard to the site at onset, 9 patients had bone involvment, among these, four patients had only bone involvment, the other five patients also lung, oral cavity and lymph nodes.
At time of onset 4 patients showed no symptoms, while the remaining 7 showed a variety of symptoms ranging from B symptoms to tinnitus, dizziness, and other neurological symptoms such as diplopia. Among the study group 6 patients had multisystemic involvement.
All patients except one had CT scan performed before, during, and at follow-up, the remaining patient was studied and followed through follow-up with PET scan.
As first-line therapy 8 patients underwent chemotherapy, 2 patients radiation therapy, 1 patient required only steroid therapy. The most frequently used chemotherapy regimen for these 8 patients was MACOP-B, a third generation, CHOP-like regimen.
Responses to first-line therapy were as follows: 7 complete remissions (CR), resulting with chemotherapy (5), radiation therapy and steroid therapy, two partial remissions (both obtained with chemotherapy) and two stable diseases (1 with chemotherapy and 1 with radiation therapy).
Two patients relapsed, of whom one has ran several lines of chemotherapy, including autologous stem cell transplantation. Both are alive at the time of the last follow-up.
To date all patients are alive but one, who died of pulmonary embolism while he was in stable disease. Six patients are in CR (60%), two in SD (20%) and two in PD (20%).
In conclusion, our monocentric experience of 11 LCH patients confirms what reported in the literature in terms of heterogeneity of presentation, age, sites of involvement, symptomatology and treatment demanded. Coming to the the results our retrospective analisys shows that ten of the eleven study population patients (90.9%) are to date still alive after a significant median time of follow-up; six out of these ten patients (60%) are in CR.

Disclosures
No relevant conflicts of interest to declare.
The Assessment of Risk Factors for Thrombosis in Children Treated for Non- Hodgkin Lymphoma
Authors: Smalisz-Skrzypczyk Katarzyna , Klukowska Anna , Malinowska Iwona , Sobocinska-Mirska Agata , Romiszewski Michal , Matysiak Michal 
Published: October 2019

Abstract
Thrombosis occurs quite frequently in patients with NHL, it is
a complication resulting from the presence of neoplastic disease and vascular catheter
and a side effect of the treatment (corticosteroids, L-asparaginase).
The aim of the study was to assess the factors predisposing to thrombosis in children
treated for non-Hodgkin's lymphomas.
6 cases of thrombosis in 31 children (19%) treated in the Department in 2007-2013 due to the NHL were analyzed. All patients with thrombosis were assesed: age of onset, location, cause of the thrombosis and the anticoagulant treatment. A analyzed patients underwent testing
for congenital thrombophilia.
Age at onset of thrombosis ranged from 2 to 17.5 years, median 9.5 years.
Arterial thrombosis occurred in 1 (17%), venous thrombosis in 5 (83%) patients. Thrombosis
occurred in 4 children with lymphoblastic lymphoma (LBL), 1 child with large cell anaplastic lymphoma (LCAL) and 1 child with primary mediastinal B-cell lymphoma (PMBCL). Most of the cases were concerned to central catheter (n = 5, 83%). Massive thrombosis
occurred in 2 children (33%). There was no recurrence of thrombosis. The most common
causes of thrombosis were: the presence of the central catheter (n = 5, 83%) and treatment with L-asparaginase (n = 4, 66%). The presence of mutation on the factor
V Leiden was discovered in 1 patient. 2 patients were treated with a recombinant tissue plasminogen activator in systemic infusion (16%), low molecular weight heparin was used
in 5 patients (83%), then changedd to warfarin in 3 (50%) children.
The bleeding complications of the treatment were not observed. All the children showed total
resolution of thrombi.
Conclusions:
1 The predominant location and cause of thrombosis in children with NHL is a central catheter
.2 Thrombosis occurs the most often in children with LBL.
3 The risk factor of thrombosis in children is the treatment with L-asparaginase
4 It was not found that congenital thrombophilia iss an additional risk factor for thrombosis
in children with NHL.
5 Thrombosis in children with NHL responds well to treatment with anticoagulants.

Disclosures
Klukowska: Octapharma AG: Investigator Other.
Outcome of Lymphocyte Predominant Hodgkin Lymphoma
Authors: Khalid Arifa , Zafar Huma , Wali Rabia , Riaz Shazia , Badar Farhana 
Published: October 2019

Abstract
BACKGROUND: Lymphocyte predominant Hodgkin Lymphoma (LPHL) , also known as Hodgkin paragranuloma or lymphocytic and histiocytic predominant Hodgkin disease. It accounts for 5% of the lymphoma in the western world Since LPHL is a rare type of lymphoma different treatment modalities used to treat it including radiotherapy alone, combined chemotherapy and radiotherapy, chemotherapy alone and recently the use of Rituximab anti CD20 monoclonal antibody as LPHL expresses CD20 marker . The results are variable. Patients of LPHL also have frequent relapses beyond 5 years of treatment as compared to cHL and high rates of transformation to DLBCL .
OBJECTIVE:
To review outcome of LPHL patients treated with various chemotherapy regimens ( ChlVpp/ABVD) and (ABVD/COPDac) alone or in combination with radiotherapy.
METHODS AND MATERIALS: Data of total 301 patients reviewed . Out of which 15 were of LP Hodgkin (4.98%). Retrospective review of 15 patients of LP Hodgkin Lymphoma patients enrolled between January 2006 to December 2013 was done. Data regarding age, sex, stage of disease , treatment and outcome was analyzed.
RESULTS: Total 15 LP HD patients with age range from 2 to 18 years were included from 2006 to 2013. Mean age of patients was 10 years. Median was 9. Out of these 13 (86.7% ) were males and 2 (13.3%) females, most of them are of stage III (40%). Majority , 9 patients (60 %). were treated with ChlVpp/ABVD protocol. XRT was given to 5 patients (33.3%). Total 12 (80%) are still on follow up and 3 (20%) relapsed.
CONCLUSION: Patients of Lymphocyte predominant Hodgkin Lymphoma treated with chemotherapy had a better outcome .

Disclosures
No relevant conflicts of interest to declare.
a Pediatric Primary Renal Lymphoma Case Presenting with Acute Renal Failure Findings
Authors: Akici Fahrinnisa Ferhan , Tugcu Deniz , Aydogan Gonul , Salcioglu Zafer , Sayilan Sen Hulya , Akcay Arzu , Kiyak Aysel , Dogan Oner , Kilinc Yurdanur - 
Published: October 2019

Abstract

Lymphomatous involvement of the kidneys is a common manifestation of systemic non-Hodgkin’s lymphoma (NHL). In contrast, lymphoma originating within the kidneys is a rare event in children. In this study we report a case of primary renal lymphoma presenting with acute renal failure in a 14-years-old boy. According to histopathological and immunohistochemical examinations, the diagnosis of B-cell renal lymphoma was established.
A fourteen years old boy presented to our Pediatric Hematology - Oncology Unit, with 4-month history of weakness and anorexia. He had mild abdominal pain. Physical examination revealed no significant abdominal or systemic. The laboratory data were white blood cell count 4100/mm3; hemoglobin level 10.8 g/dL, mean corpuscular volume 107 fL; mean corpuscular hemoglobin concentration 33.6 g/dL); platelet count 179,000/mm3;erytrocyte sedimentation rate 50mm/h; blood urea nitrogen level 142 mg/dL; creatinine level 4.85 mg/dL; lactate dehydrogenase level 465 IU/L. There were no pyuria or hematuria, and urinary culture and stain results were negative. An abdominal ultrasonography revealed an increase in bilateral kidney sizes. Abdomen computed tomography scan showed an increase in thickness of renal parenchyma with hypodense appearance and with bilateral mild ectasia in pelvicalyceal system.
An ultrasonography guided renal biopsy demonstrated precursor B-cell lymphoblastic lymphoma. Hematoxylin and eosin section of these renal masses revealed neoplastic lymphoma cells with increased nuclear-cytoplasmic ratio, prominent nucleoli and mitotic figures.The lymphoma cells stained positivie for terminal deoxynucleotydyl transferase and B-lymphocyte marker CD10 and CD20 immuno-histochemical stain. Extrarenal abdominal involvement was excluded by imaging techniques. Bone marrow examination was normal. He was diagnosed as non-Hodgkin’s lymphoma, pre B-cell type and was treated with multidrug chemotherapy (induction regimen of prednisolone, vincristine, daunorubicin and L-asparaginase) and prophlactic intratecal methotrexate according to British-French-Munster (BFM) protocol. After the initial therapy, renal function test were improved rapidly and during consolidation and maintenance chemotherapy, they continud as normal. The patient is still in complete remission and was followed normal renal function with no sign of disease recurrence 5 years later diagnosis..In conclusion, diagnose of PRL is difficult. Percutaneous kidney biopsy is the most expeditious method towards the establishment of an early diagnosis for appropriate chemotheraph. Early diagnosis and urgent therapy, with supporting therapy are necessary for good prognosis.

Disclosures
No relevant conflicts of interest to declare.
Intravenous Administration of Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphomas (PCBCLs): A Retrospective Study
Authors: Paterno Giovangiacinto , Zizzari Annagiulia , Nasso Daniela , Tonialini Lorenzo , Angeloni Cecilia , Vaccarini Sara , Postorino Massimiliano , Pupo Livio , Franceschini Luca , Provenzano Ida , Rizzo Manuela , Giannì Laura , Anemona Lucia , Mauriello Alessandro , Lombardo Giuseppe Alfonso , Scala Enrico , Cantonetti Maria 
Published: October 2019

Abstract
Introduction. Rituximab has been demonstrated to be effective either as intralesional or as systemic therapy in PCBCL, We report our experience in the treatment of PCBCL with intravenous Rituximab.
P atients and Methods From February 1999 to February 2014 we treated 75 patients: 47 Follicle Center Lymphoma, 23 Marginal Zone Lymphoma, 5 Diffuse Large Lymphoma Leg type. The stage was T1 in 38 pts, T2 in 22 pts and T3 in 15 pts. In 24 patient prior treatment included: CHT (11), Radiotherapy (4), Surgery (4) or alpha2Interferon (IFN) (5). Rituximab at dosage of 375 mg/m2 for a minimum of 4 cycles, was administered alone (51 patients) or in association with CHT (13). RT (2) or IFN (3).
Results. No patient presented adverse effects during the Rituximab infusion. A reduction of circulating B lymphocytes was observed for 11 months, on the average, without an increased risk of infections. No added toxicity was observed in patients treated with Rituximab plus CHT. Overall response rate was 97,3% (CR 82,6 %, PR 14,6 %). Five–years Overall Survival (OS) was 86,9% with Disease Free Survival of 57%. According to stage OS was in T1 94,3%, in T2 90,5%, in T3 73,6%. (T1+T2 vs T3: p<0,05).
Conclusions. Rituximab is effective and safe in the treatment of PCBCL even in heavily-treated or elderly patients. In our patients only the stage of disease was significant for the prognosis. A higher number of patients are necessary to indicate Rituximab in biological and clinical subsets of patients as a front-line therapy.

Disclosures
No relevant conflicts of interest to declare.
Turning a Tumor into a Vaccine Factory: In Situ Vaccination for Low-Grade Lymphoma
Authors: Marron Thomas , Bhardwaj Nina , Crowley Elizabeth , Keler Tibor , Davis Thomas A. , Brody Joshua 
Published: October 2019

Abstract
BACKGROUND: Lymphomas are the 5th most common cancer in the U.S. and most are incurable with standard therapy. Previously, we completed three trials of ‘in situ vaccination’ - combining low-dose radiotherapy (XRT) with intratumoral administration of TLR9 agonist (CpG). We demonstrated induction of anti-tumor CD8 T cell responses and clinical remissions of patients’ non-irradiated sites of disease, lasting up to 4+ years. One limitation may have been the paucity of intratumoral dendritic cells (DC). DC are uniquely able to endocytose dying (e.g. irradiated) tumor cells for cross-presentation to anti-tumor CD8 T cells.
METHODS: Flt3L– the predominant DC differentiation factor– induces tumor leukocyte infiltration and regression of lymphoma tumors pre-clinically and a new formulation of this cytokine -CDX-301- was shown to mobilize BDCA-1 and BDCA-3 DC subsets in an early phase trial. These DC subsets respond to several TLR agonists and cross-present antigens more effectively than plasmacytoid DC (the CpG-responsive DC subset). We initiated a phase I/II study of a new iteration of the in situ vaccine, adding Flt3L-priming and replacing the prior TLR9 agonist with the TLR3 agonist poly-ICLC (Fig 1A). The vaccine consists of:
-intratumoral Flt3L administration to increase DC within the tumor
-low-dose XRT to induce immunogenic tumor cell death and release tumor-associated antigens, and
-intratumoral poly-ICLC administration to activate tumor antigen-loaded DC.
RESULTS: Six patients have been enrolled, two patients have completed therapy. Treated patients had 2-200-fold increases in BDCA1 and BDCA3 intratumoral DC after Flt3L administration and marked DC activation after XRT and poly-ICLC. Both treated patients have had partial remissions of untreated sites per Cheson criteria, persisting or improving for >6 months after vaccination. These include regressions of bulky lymph nodes (Fig 1B), as well as peripheral blood (Fig1C) and bone marrow disease. A patient with significant peripheral blood tumor burden experienced >10-fold decrease in malignant B cells with concurrent increase in non-tumor B cells, suggesting a degree of cell specificity in the tumor-killing mechanism. Adverse effects have been mild.
CONCLUSIONS: Preliminary results suggest that the Flt3L-primed in situ vaccine is feasible, safe and immunologically and clinically effective, warranting further study.
Figure 1 Figure 1.

Disclosures
Off Label Use: CDX-301 - the purpose of which is to mobilize dendritic cells to an injected tumor site.. Crowley:Celldex Therapeutics Inc: Employment. Keler:Celldex Therapeutics, Inc.: Employment. Davis:Celldex Therapeutics Inc: Employment.