bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultimate Outcomes of Patients with Recurrent Diffuse Large B Cell Lymphoma Who Do Not Respond to Second-Line Chemotherapy
Authors: Elstrom Rebecca , Martin Peter , Ostrow Katya , Barrientos Jacqueline , Furman Richard R. , Ruan Jia , Schuster Michael , Shore Tsiporah , Chadburn Amy , Coleman Morton , Leonard John P. 
Published: April 2020

Abstract
Background: Patients with diffuse large B cell lymphoma (DLBCL) who relapse after or are refractory to initial therapy can in some cases experience long term disease free survival after second-line chemotherapy alone or followed by autologous stem cell transplantation. The major predictor of outcome for patients undergoing autologous transplant is response to prior (second-line) chemotherapy. Patients not responding to second-line regimens may receive third-line or subsequent chemotherapy regimens in hopes of achieving response and proceeding to transplant, but available outcome data from this group have been limited.
Methods: We used pathology and treatment records to identify patients with relapsed or refractory DLBCL (excluding transformed lymphoma) at the Weill Cornell Medical Center for whom data on response to second-line chemotherapy could be determined. An online social security database verified survival. Median overall survival (OS) was calculated by the Kaplan-Meier method.
Results: One hundred eight patients with relapsed or refractory DLBCL who underwent second line chemotherapy were identified, and adequate treatment records were available for 74 of these patients. Chemotherapy consisted of ifosfamide-containing regimens in 60 patients (81%), platinum-containing regimens in 61 (82%) and included rituximab in 29 (39%). Forty-seven patients (64%) achieved at least a partial response (R), while 27 patients (36%) did not respond (NR). Median OS from second therapy was 4 months (range 1–61) in the NR group, and was projected at 66 months (range 2–106) in the R group. Only one patient in the NR group (4%) survived for greater than one year. Twenty-four NR patients underwent third-line therapy, of whom 5 of 19 with available response data achieved a clinical response (5 died prior to response assessment) and 3 underwent autologous transplantation. Two patients progressed within 3 months of transplantation, with OS from transplantation of 4 months, while the third patient is alive in remission at 59 months after transplant. Neither longer duration of first remission (HR 1.00, p=0.85) nor choice of subsequent aggressive chemotherapy over less intensive approaches (HR 0.81, p=0.65) conferred a survival benefit in patients who had not responded to second-line therapy.
Conclusion: Patients with recurrent DLBCL who do not respond to second-line chemotherapy have poor outcomes, with only rare patients achieving extended survival following subsequent chemotherapy. Clinical trials of novel therapeutic regimens should be prioritized as management strategies for these patients.
Analysis of Long-Term Outcome and the Risk of Second Malignancies in Hodgkin Lymphoma Survivors
Authors: Cedrych Ida , Blamek Slawomir , Deptala Andrzej , Skladowski Krzysztof 
Published: April 2020

Abstract
Background: Therapy of Hodgkin lymphoma (HL) can contribute to delayed impairments of health, which some of them (e.g. secondary cancer) can be fatal.
Aim: The purpose of this retrospective study was to evaluate long-term outcome of HL survivors and the risk of second malignancies.
Methods: The medical report data analysis of 170 patients (pts) with HL treated in one oncological center in Poland between 1979–2005 has been performed. There were 88 females and 82 males, median age 30.5 years (range 16–72). Among the patients there were 22 pts (12.5%) in CSI, 95 pts (55.8%) in CSII, 26 pts (15.4%) in CSIII and 27 pts (15.8%) in CSIV. Half of the 170 pts presented B-symptoms. Chemotherapy (ABVD, MOPP/ABV or MOPP regimen) was given to 155 (93.5%) pts, and radiotherapy alone (mantle-field or involved-field) was given to 11 pts (6.5%). Chemoradiotherapy received 105 pts (61.8%).
Results: CR achieved 136 pts (80%), PR 11 pts (6.4%), and progression of HL was observed in 23 pts (13.5%). With a median follow-up of 242 months (range 0–439), there were 37 relapses (21.7%), and 25 deaths (14.7%), usually due to HL progression (20 pts), and also because of secondary cancer (4 pts = 2.4%) and coronary heart disease (1 patient). Five year DFS and OS were 80% and 90% respectively. There was no statistical difference between ABVD and MOPP/ABV regimen efficacy (p=0.94). Late impairments of health were revealed in 78 pts (45.9%), and there were: secondary malignancies, amenorrhea/infertility, skeletal lesions, depressive syndromes, pulmonary fibrosis, polyneuropathy, hypothyroidism, cardiovascular disease, and gastro-duodenal peptic ulcer. Nine pts (5,3%) developed secondary malignancies, i.e.: 2 melanomas, 2 skin basal-cell carcinomas, 1 osteosarcoma, 1 thyroid carcinoma, 1 non-small cell lung cancer, 1 colon carcinoma, 1 cervical carcinoma, and 1 prostate carcinoma. A median time from the end of the treatment to the development of secondary cancer was 114 months (range 28–434). The risk of secondary malignancies development among pts treated with either initial chemotherapy alone or combined modality therapy was similar, and did not reach statistical significance (p=0.20).
Conclusions: Chemotherapy or chemoradiotherapy of HL provides freedom from the disease in more than 3/4 of our patients. In the group of fairly young patients such treatment caused a substantial amount of variety of health impairments including secondary malignancies. Despite the high rate of HL curability our study indicates the need of a careful, long term medical surveillance of HL survivors.
Study on Treatment of Lymphoma-Associated Hemophagocytic Syndrome with Fludarabine Combined with Methylprednisolone and Globulin
Authors: Wang Yini , Wang Zhao , Feng Cuicui , Chen Xi 
Published: April 2020

Abstract
Hemophagocytic syndrome (HPS) is a life-threatening condition of severe hyperinflammation caused by the uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. Lymphoma-associated hemophagocytic syndrome (LAHS) clinically featured by histiocytic proliferation, fever, hepatosplenomegaly, cytopenia, deranged liver function and frequent coagulopathy. The immediate aim of therapy in LAHS is suppression of the severe hyperinflammation, which can be achieved with immunosuppressive/immunomodulatary agents and cytostatic drugs. In this study, we diagnosed 11 cases of LAHS according to HLH-2004 diagnostic criteria in Beijing Friendship Hospital during the period from June 2005 to Jan 2008, and collected informations about the patients with LAHS: primary diseases, manifestions, laboratory findings and survival. 2 cases large B cell lymphoma, 1 case mantle lymphoma, 4 cases extranodal NK/T cell lymphoma, 3 cases peripheral T cell lymphoma and 1 case angioimmunoblastic T-cell lymphoma were included in this research. The median age was 49 years, and the range was 33–74 years. 7 out of 11 were female and 4 were male. All the 11 patients received regimens containing fludarabine (25mg/m2/d, d1–5), methylprednisolone (2mg/kg/d, d1–14, 1mg/kg/d, d15–28) and immunoglobulin (0.5g/kg/d, d1–14) after finally diagnosed. 7 of the 11 patients were markedly improved after treatment and then received lymphoma chemotherapy. The median survival time had reached to 1.4 year. The other 4 aggravated. This outcome was much better than what A-Reum Han had reported (Ann Hematol2007; 86: 493–498). It suggests that fludarabine will be a promising agent in the therapy of LAHS.
Thalidomide: An Active Agent in AILT Lymphoma
Authors: Henderson Ross , Simpson David , Hanna Merit , Chunilal Sanjeev 
Published: April 2020

Abstract
Angioimmunobalstic T cell lymphoma (AILT) is a relatively rare subtype of lymphoma, accounting for approximately 1 – 2% of all cases of NHL. The pathogenesis is thought due to clonal expansion of follicular T-helper cells which subvert normal germinal centre function. It is characterised by systemic disease and significant immune dysregulation with frequent atypical infections and autoimmune disease. It has a poor prognosis with a median survival of less than 3 years using CHOP or CHOP-like regimens. Dose intensification, or anthracycline use, appears to be ineffective. Thalidomide is an immunomodulatory agent with isolated case reports of activity in this disease. We report 3 cases of AILT where thalidomide was effective at inducing or providing a sustained remission.
Case 1 was an 86 year old woman who presented with systemic symptoms, widespread lymphadenopathy and a polyclonal increase in immunoglobulins. AILT was diagnosed from both lymph node biopsy and bone marrow biopsy. Symptoms improved only temporarily with prednisone. She commenced thalidomide at 200mg daily with improvement in symptoms and resolution of lymphadenopathy and after 2 months the dose was reduced to 100mg daily. She continued the thalidomide at the same dose and remained in remission until her death from unrelated causes 4 years later
Case 2 was a 72 year old man who initially presented with autoimmune haemolytic anaemia and red cell aplasia which was unresponsive to steroids, intravenous immunoglobulins (IVIG), cyclosporine and splenectomy. He then developed cervical and axillary lymphadenopathy, biopsy of which showed AILT. Bone marrow examination showed no evidence of AILT. He commenced thalidomide at 150mg daily with resolution of the haemolysis and red cell aplasia within 12 days and reduction in all lymphadenopathy. He remains in remission 3 months after commencing thalidomide and is currently on 100mg daily.
Case 3 was a 57 year old woman presented with ITP with platelets &lt; 10, systemic symptoms, widespread lymphadenopathy and hepatosplenomegally. AILT was diagnosed from lymph node biopsy and bone marrow biopsy. She commenced on prednisone and IVIG for the ITP, then proceeded to CHOP chemotherapy. Her first cycle was complicated by Pneumocystis jirovecii infection. Following the chemotherapy, her systemic symptoms subsided and the lymphadenopathy and organomegaly resolved. She commenced thalidomide at 100mg daily and has remained in remission 2 months later.
There are now several case reports in the literature indicating that thalidomide is effective in AILT which is reflected by the cases reported here. Given the poor prognosis of AILT using conventional chemotherapeutic regimens, such as CHOP, prospective clinical trials using thalidomide, or the newer derivatives such as lenalidomide, are warranted.
Skeletal Disorders as Late Complications in Hodgkin Lymphoma Survivors
Authors: Cedrych Ida , Blamek Slawomir , Deptala Andrzej , Skladowski Krzysztof 
Published: April 2020

Abstract
Background: Long-term complications of musculoskeletal system are rare in adult Hodgkin lymphoma (HL) survivors, thus is uncertain whether these complications are treatment-related.
Aim: The goal of this study was to analyze risk, frequency and type of skeletal damage in HL survivors.
Methods: The study comprises of a retrospective analysis of 170 patients (pts) suffered from HL, and treated in an oncological center in Poland between 1979–2005. There were 88 females and 82 males, median age 30.5 years (range 16–72). According to the Ann Arbor clinical staging system there were 22 cases (12.5%) in CSI, 95 cases (55.8%) in CSII, 26 cases (15.4%) in CSIII and 27 cases (15.8%) in CSIV. Fifty six percent of the patients presented B-symptoms, and 60% had bulky disease. Vast majority of cases were diagnosed as classical HL, with histologic subtypes of nodular sclerosis grade 1 in 45%, nodular sclerosis grade 2 in 14%, mixed cellularity in 21%, lymphocyte depletion in 5.2%, and lymphocyte-rich in 7%. However 5.8% of the cases were unclassified by a histopathologist. Chemotherapy with a median of 6 cycles/patient was given to 93.5% of cases (ABVD – 29.4%, MOPP/ABV – 37.6%, MOPP – 24.1%, other – 2.25%). Chemoradiotherapy was given to 61.8% of pts. Radiotherapy alone (mantle-field or involved-field), with a median dose of 40 Gy (range 21–46.8) received 6.5% of pts. For statistical analysis we used Kaplan-Meier method and log-rank test
Results: With a median follow-up of 242 months (range 0–439) a skeletal disorder (SD) was detected in 27 (15.8%) of the patients. Median time to identify SD was 29.5 months. Skeletal disorders were diagnosed as follows: osteoarthritis (11 pts), avascular (aseptic) necrosis of bone (3 pts), osteoporosis (3 pts), osteopenia (3 pts), rheumatoid arthritis (2 pts), vertebral osteochondritis (2 pts), idiopathic (nontraumatic) subluxation of wrist (1 patient), fibrosis of vertebral body (1 patient), and inflammation of nucleus pulposus (1 patient). In the statistical analysis there was no relationship between the risk of SD and: sex, bulky disease, B symptom, involvement of extralymphatic organ, histologic subtype, radiotherapy, chemotherapy, and chemotherapeutic regimen. However, we found an association of SD risk with clinical stage. The difference between CSI and CSIII was statistically significant (p = 0.0235). There were no differences between CSII and CSIII (p = 0.0564), as well as CSIII and CSIV (p = 0.0787).
Conclusions: In our group of adult HL survivors skeletal disorders caused substantial amount of long-term complications. We found no relationship between treatment modality and the risk of a skeletal disorder, despite high median dose of radiotherapy and extensive use of alkylating agents. The association between skeletal disorder and more advanced clinical stage is difficult to explain, however it might suggest a possible role of initial tumor burden and excessive crosstalk between cancer and reactive immune/inflammatory cells.
Successful Treatment of Primary Refractory Bulky Diffuse Large B-Cell Lymphomas with Concomitant Radio-Chemotherapy Followed by Autologous Stem Cell Transplantation : A Single Center Experience
Authors: Couturier Marie-Anne , Champeaux-Orange Elise , Senecal Delphine , Lissandre S.éverine , Benboubker Lotfi , Barillot Isabelle , Calais Gilles , Colombat Philippe , Gyan Emmanuel 
Published: April 2020

Abstract
Diffuse large B cell lymphomas (DLBCL) with bulky presentation display a poor prognosis because of a substantial rate of primary refractory disease. Second and third lines of standard chemotherapy associated with rituximab do not always achieve a complete response (CR) Autologous stem cell transplantation (ASCT) provides the best progression-free survival when patients are transplanted in CR. Concomitant radio-chemotherapy (CRC) has been used in the treatment of solid carcinomas, and may be useful in the treatment of locally refractory DLBCL to obtain a better tumor control with a minimal risk of systemic progression. We report 5 retrospective cases of patients (less than 60 years old) treated at our institution with CRC for bulky DLBCL with localized refractory disease assessed by CT and/or PET-Scan. All 5 patients presented at diagnosis with at least one adverse prognostic factor : 4 with elevated LDH, 4 with stage III or IV. The largest diameter of the bulky sites ranged between 70 and 160 mm. All 5 patients experienced locally refractory disease after one (2/5) or two (3/5) lines of immuno-chemotherapy, at mediastinal (2/5) or abdominal (3/5) sites. They were treated by 3 cycles of rituximab (375 mg/m2 on d1), CDDP (30 mg/m2 d1–3) and etoposide (120 mg/m2 d1–3) at 21d intervals and concomitant radiotherapy delivered to the residual disease sites, administrated in 2 Gy fractions once daily to a total dose of 30 Gy, beginning on d21. For one patient, CDDP was replaced by carboplatin because of previous renal toxicity and another received standard DHAP together with radiation therapy as a second-line treatment. The whole procedure was feasible, with no grade III or IV toxicities. One patient died of early disease progression outside the irradiation field. Four patients out of 5 achieved a complete response and were subsequently transplanted. With a follow-up ranging between 2 and 75 months, all 4 patients are alive and free of disease as well as of long-term toxicity. These preliminary results suggest that CRC deserves further investigation as an option for the management of localized refractory DLBCL.
Diffuse Large Cell Lymphoma Transformed from Rosai-Dorfman Disease
Authors: Jendiroba David , Sampaio Marcus Magnus , Gonçalves Márcia Vilela , Rodrigues Juliana Alves , Jendiroba Daniella Barqueti , Cabanillas Fernando 
Published: April 2020

Abstract
INTRODUCTION: Rosai-Dorfman disease, also known as Sinus Histiocytosis with Massive Lymphadenopathy, is an almost rare benign entity which mimics non-Hodgkin’s lymphoma, and is characterized by enlargement of lymph nodes. Knowing the difference between these two diseases is critical for the adequate therapeutic approach. The most common presentation of the disease is within the cervical basin, and most of the times, lymph node dissection and removal of their chains is enough for cure.
PATIENT AND METHODS: We describe a 23-yo white woman with past history of persistent cervical lymphadenopathy, who underwent 4 surgical procedures to remove left cervical nodes, diagnosed as Rosai-Dorfman disease within the last 3 years. When relapse after the 4th surgery happened, the patient came to our Service and sought for a 2nd opinion consultation.
RESULTS: Pathology reviews were done on the previously collected material, corroborating Rosai-Dorfman disease, except for the review of the slides of the last material, which showed inconclusiveness. Histopathology and immunohistochemistry were then repeated for the last surgical specimens at 2 different Pathology labs, and both confirmed diffuse large cell lymphoma. Patient started on chemo with CHOP 6×, and showed a partial response up to the 3rd cycle, when the tumor started progressing during the 4th cycle. Chemo was then changed to ESHAP, which was well-tolerated and promoted CR after 6 cycles. The patient is currently in CR and asymptomatic.
CONCLUSION: Rosai-Dorfman disease is a proliferative reaction to an unknown, unidentified pathogen or specific cause, which leads to lymph node enlargement and extra nodal involvement in 25% of the cases. Some studies have attempted to correlate the presence of klebsiella as a proliferative stimulus present in this disease, but there is not enough evidence to confirm this hypothesis. Interestingly, it may seem that Rosai-Dorfman is a middle step between a truly benign process and malignancy itself because, not only other cases of lymphoma transformed after Rosai-Dorfman’s disease have been reported, but also extra nodal cancer following extra nodal presentation of the disease. Although many clues point to its involvement in the process of carcinogenesis, more clinical and molecular evidence are necessary to tie the link between Rosai-Dorfman disease and cancer.
Potent Anti-Cancer Activity of Anti-NTB-a Monoclonal Antibodies in Preclinical Leukemia and Lymphoma Models
Authors: Korver Wouter , Zhao Xiaoxian , Singh Shweta , Pardoux Cecile , Barman Ishita , Aguilar Gerard , Zhao Jingsong , Hsi Eric , Abo Arie 
Published: April 2020

Abstract
NTB-A is a CD2-related cell surface protein expressed on lymphoid cells including B-lymphocytes from Chronic Lymphocytic Leukemia (CLL) and lymphoma patients. We have generated a series of mAbs against NTB-A and assessed their therapeutic potential in preclinical models. Selected mAbs to NTB-A were further tested in functional Complement Dependent Cytotoxicity (CDC) and Antibody Dependent Cellular Cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL and lymphoma patients. Potent cytotoxic activity was demonstrated against B cells isolated from CLL patients and B lymphoma cell lines. Chimeric anti-NTB-A mAbs demonstrated anti-tumor activity equal to rituximab against CA46 human lymphoma xenografts in nude mice at a low dose. In a chimpanzee safety study, a single dose of lead anti-NTB-A mAb 994.1 resulted in near-complete depletion of peripheral lymphocytes while having a minimal effect on T cell activation. Taken together, these results demonstrate NTB-A as a promising target with an acceptable safety profile for immunotherapy of leukemia and lymphomas.
Fatty Acid Synthase and Diffuse Large B Cell Lymphoma
Authors: Uddin Shahab , Hussain Azhar , Bavi Prashant , Al-Kuraya Khawla 
Published: April 2020

Abstract
Diffuse Large B-cell Lymphoma (DLBCL) is considered to be the most common type of lymphoma in adults, accounting for 30–40 percent of cases of non-Hodgkin’s lymphoma. The incidence of DLBCL is about 40–60% in Saudi Arabian population. The reason of high rate for DLBCL in Saudi Arabian population is not known, however recent studies suggests that differences in molecular signature as compared to western population accounts for this incidence. Although patients with DLBCL are potentially curable with combination chemotherapy, the disease proves fatal in approximately 50% of patients. The cause of most DLBCLs remains unknown; however several studies suggest that dysregulated survival/apoptosis or defective repair pathways have been implicated. Many human cancers, particularly those with a poor prognosis express high levels of fatty acid synthase (FASN), a key metabolic enzyme linked to the synthesis of membrane phospholipids in cancer cells. Over-expression of FASN can be largely attributed to activation of phosphatidylinositol-3′-kinase (PI3K)/AKT pathway. However, the role of FASN in the pathogenesis of DLBCL has not been elucidated. Therefore, in this study, we investigated the role of FASN in a large series (301) of DLBCL patient samples and a panel of DLBCL cell lines. Using immunohistochemistry, FASN was detected in appreciable number of DLBCL tumors and was strongly associated with the expression of p-AKT protein. We next examined the effect of C-75, a synthetic slow binding inhibitor of FASN activity on DLBCL cell lines (SUDHL4, SUDHL5, SUDHL8 and OCI-LY19) in vitro and found that C-75 treatment inhibits growth and induces apoptosis in all 4 DLBCL cell linesused in the study. We show based on in vitro studies employing a variety of experimental tools using different FASN inhibitors, FASN siRNA and AKT siRNA that FASN exert its oncogenic action in DLBCL cells via activated AKT. Our data show that inhibition of FASN leads to de-phosphorylation of p-AKT and it’s down stream effectors, FOXO1 and GSK-3. This, in turn leads to activation of the intrinsic apoptotic pathway by, initially causing conformational changes of the Bax protein leading to changes in the mitochondrial membrane potential and release of cytochrome c into cytosole. This causes activation of caspases-9 and -3 and cleavage of PARP. zVAD-fmk, a universal inhibitor of caspases prevents caspase-9 and -3 activation and abrogates apoptosis induced by C-75 treatment. Finally, C-75 treament of DLBCL cell lines causes down-regulation of the inhibitor of apoptosis proteins, XIAP, cIAP1 and Survivin. In summary, data presented here demonstrate a significant correlation between the expression of FASN and active AKT in DLBCL and indicate that inhibition of PI3K/AKT signaling synergize the FAS inhibitors to induce apoptosis in DLBCL cell lines with constitutively active AKT. This may have significant clinical implications. Therefore, FASN has become a promising target for anti cancer drug development.