bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hodgkin Lymphoma (HL), A Retrospective Analysis in Young Adults.
Authors: Koumarianou Anna A. , Xiros Nikolaos , Papageorgiou Efstathios , Pectasidis Dimitris , Economopoulos Theofanis 
Published: October 2019

Abstract
INTRODUCTION: Over the last four decades survival of patients with HL has improved. Various risk factors (stage III/IV, abnormal ESR, bulky mediastinal disease, >3 involved nodes, extranodal involvement) classify patients into prognostic groups for treatment accordingly.
PURPOSE: This study was conducted to review the risk factors, treatments and outcomes in young adults with HL over the past 25 years in our Unit.
METHODS: Retrospective chart review of 55 young adults 16–23 years old (25 women, 35 men), treated from 1978–2003, was performed. Patients were divided according to risk factors into three prognostic groups: low (stage I/II without risk factors; 5 patients [9.1%]), intermediate (stageI/II with risk factors; 19 patients [34.5%]) and advanced HL (stage IIB with bulky mediastinal disease and extranodal involvement or stage III/IV; 31 patients [56.4%]). Patients were treated with established chemotherapy regimens available at each time period including MOPP (Group A, 1978–1987; 17 patients), MOPP/ABVD (Group B, 1988–1993; 21 patients), and ABVD or BEACOPP (Group C, 1994–2003; 17 patients). Patients with bulky disease at diagnosis (>5cm) or residual disease following chemotherapy received additional radiotherapy.
RESULTS: Histological diagnosis included 42 nodular sclerosis, 10 mixed cellularity and 3 lymphocyte predominant. Thirty five patients had mediastinal involvement (16 patients with bulky disease). Following chemotherapy completion 27 patients were referred for radiotherapy. A total of 21 patients experienced relapse (5 intermediate and 16 advanced stage), of whom 14 (66 %) within the first 2 years of diagnosis. Although the follow up periods were not equal between the three treatment groups, surveillance of evaluable patients showed significant improvement of the 5-year survival and 5-year relapse rate (Group A:64.7% and 47%, Group B:80.9% and 33.3%, Group C:94.1 % and 11.7% respectively) over the years. Eight out of 10 mixed cellularity patients died. One second primary malignacy (acute non lymphocytic leukaemia) was observed. In our study albumin less than 4 g/dl, and lymphocyte count less than 8% were identified as the most important risk factors in relation to relapse and survival regardless treatment.
CONCLUSION: Survival of young patients with HL is significantly improving over the last 25 years most probably due to improved treatment resources and understanding of risk factors. Tailoring treatment according to prognostic groups and inclusion of molecular markers is expected to refine further treatment strategies and improve survival.
Results of a Multi-Center, Phase II Study of Elsamitrucin (SPI-28090) in Patients with Relapsed or Refractory Non-Hodgkin’s Lymphoma (NHL).
Authors: Foon Kenneth , Allen Steven , Sen Kaushik , Mohrbacher Ann , Sanani Shamel , Lenaz Luigi , Rosales Rosamerlinda 
Published: October 2019

Abstract
Background: Elsamitrucin (SPI-28090) is a novel topoisomerase I and II inhibitor. An earlier small study with Elsamitrucin, conducted prior to the introduction of rituximab, showed anti-tumor activity in patients with relapsed or refractory NHL with an acceptable toxicity profile. The objectives of this current trial are to validate these earlier findings and to generate data in patients with relapsed or refractory NHL who had previously received rituximab-based chemotherapy.
Methods: Three groups of relapsed or refractory NHL were enrolled: G1: chronic or small B-lymphocytic lymphoma/leukemia; G2: indolent lymphoma (follicular/diffuse small cell or mixed); and G3: large cell or mantle cell lymphoma. Patients were treated with weekly Elsamitrucin 25 mg/m2 IV administered over 5–10 minutes. All patients were treated until disease progression or toxicity.
Results: 55 patients (34 males/21 females) have been enrolled; median age was 70 years (range 40–84). All patients had stage III or IV disease. Most patients were heavily pretreated with a median of 4 (1–8) prior chemotherapy regimens; 54 out of 55 patients had rituximab-based chemotherapy. Other study characteristics and results are shown on Table 1. One PR occurred in a mantle cell lymphoma patient who had received five prior chemotherapy regimens and lasting for 27 weeks. Minor responses have been documented in several patients still on therapy. Most side effects were mild to moderate in severity and consisted of nausea (51%), fatigue (42%), anorexia (22%), vomiting (16%) and cellulitis (11%). Myelosuppression was uncommon: grade 3 or 4 neutropenia was reported in 2 patients, grade 3 anemia and thrombocytopenia reported in 1 patient each. There was one patient who had moderate transient increase in transaminase level. No drug related serious adverse events have been reported.
Conclusions: Elsamitrucin appears to be safe and well tolerated over periods of up to 47 weeks in these patients lymphoma. There is evidence of anti-tumor activity in this very heavily pretreated patient population. With 2 PR, several minor responses and durable stable disease observed. In view of the minimal toxicities in particular myelosuppression, we plan to combine elsamitrucin with one or more active agents in less heavily pretreated patients.
Table 1 CLL/SLL (G1) Indolent (G2) Aggressive (G3) TTP means time to progression N 14 24 17 Median LDH (U/L) 244 253 242 Median # of doses (range) 8 (2–24) 15 (4–46) 4 (1–27) Best Response PR (%) − 1 (4%) 1 (6%) MR (%) 2 (14%) 6 (25%) 1 (6%) SD (%) 9 (64%) 12 (50%) 4 (24%) TTP (days) 98.5 138 34 Range 21–216 21–330 2–245
Rituximab - Inmunotherapy Combined with Chemotherapy, CHOP for the Treatment of Patients with Difusse Large B - Cell Lymphoma (DLBCL).
Authors: Milone Jorge H. , Bezares Fernando , Ardaiz Maria del Carmen , Riveros Dardo , Palmer Luis , Cerutti Ider , Basso Alfredo , Gelemur Marta , Cánepa Carlos , Kusminsky Gustavo , Zerga Marta 
Published: October 2019

Abstract
Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL.
We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS).
Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84).
They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %.
Elevated LDH was present en 14 patients, bulky disease > 7 cm in 50% of cases.
During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient.
Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%).
With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained.
The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.
Treatments for Marginal Zone Lymphoma.
Authors: Boxer Michael , Nasr Rashad Aboul 
Published: October 2019

Abstract
Marginal Zone Lymphoma (MZL) is a low grade malignant B cell lymphoproliferative disorder that comprises 2% of all lymphomas. Often an enlarged spleen and villous lymphocytes are present. Many patients however may appear to have chronic lymphocytic leukemia or other lymphoproliferative disorders. Immunophenotyping can differentiate these low grade lymphoproliferative disorders. MZL frequently is CD 20 + but CD5, CD 10, and CD23−. Treatment regimens include observation, chemotherapy, splenectomy, and immunotherapy with or without chemotherapy. 20 patients over the past six have been identified with MZL based on pathologic and immunophenotypic characteristics. 6 patients have had no treatment and have had stable disease from 9 months to over 4 years. 2 patients underwent splenectomy from 3 months to 2 years from diagnosis and have stable disease. 1 patient was diagnosed at splenectomy and relapsed 5 1/2 years later and remitted with rituxin. 1 patient received weekly rituxin for 4 weeks and has been in remission for 40 months.1 patient received weekly rituxin for 4 weeks, relapsed 9 months later, and remitted with rituxin and then maintenance rituxin. 1 patient responded to weekly rituxin for 4 weeks and is receiving maintenance rituxin. 1 patient responded to weekly rituxin for 4 weeks and then had residual disease irradiated. 1 patient remains in remission after 50 months after a cervical node was irradiated. 1 patient with blastic MZL remitted with CHOP-rituxin. 2 patients progressed after rituxin and required chemotherapy. A 92 yo patient has had a partial response to rituxin. An 82 yo patient died from complications from MZL. 15/20 patients have so far avoided chemotherapy. Rituxin may be an appropriate treatment for MZL, but clinical trials will be necessary to confirm this approach.
Patient-Specific Three Dimensional (3D) Dosimetry for 90Y Ibritumomab Tiutexan (Zevalin®) in Patients with Follicular Lymphoma.
Authors: Assié Karine , Dieudonné Arnaud , Gardin Isabelle , Buvat Irène , Tilly Hervé , Vera Pierre 
Published: October 2019

Abstract
Objectives: Dosimetry calculations for radioimmunotherapy are usually performed using a two dimensional (2D) protocol based on planar whole body (WB) scintigraphy and fixed organ masses derived from the MIRD anthropomorphic model (Wiseman GA et al., J Nucl Med2003:44;465–74). We compared the absorbed dose obtained with this method with an approach involving patient-specific 3D dosimetry based on quantitative SPECT and patient organs mass estimation.
Methods: Five patients with follicular lymphoma in partial or complete remission underwent a CT scan, and five successive WB and SPECT scans at day 0 (D0) 1 hour, D0 4 hours, D1, D4 and D6 after injection of 111In ibritumomab tiutexan (185 MBq). WB scans were used to estimate the activity in the liver, spleen and kidneys. SPECT images were reconstructed using a quantitative processing including corrections for scatter, attenuation, and partial volume effect. The organs mass and activity values were estimated in 3D volumes of interest manually drawn on the CT scan and registered to the SPECT scan. Absorbed doses after administration of 15 MBq/kg of 90Y ibritumomab tiutexan were derived from both 111In WB and SPECT data accounting for the fractions of injected activity measured in each organ at the five time points.
Results: The mean differences between the organs mass estimated from the patient CT and the MIRD anthropomorphic model were 8%, 105% and 12% for liver, spleen and kidneys respectively. Measurements on an abdominal phantom filled with 111In showed that errors in organ activity estimates ((estimated activity - true activity)/true activity) for WB and SPECT protocols, were 37% and −6% respectively in the liver, 20% and −10% in the spleen, −26% and −23% in the left kidney, and 47% and −9% in the right kidney. Patient liver, spleen and kidney activity values determined from the SPECT scans were on average 35%, 60% and 39% less than those found from the WB scans. The absorbed doses calculated with the 3D patient-specific protocol were less than those calculated with the 2D protocol, by 46±14%, 77±14% and 70±22% in the liver, spleen and kidneys respectively, except in one patient kidney where SPECT dose exceeded WB dose by 2%.
Conclusions: Accounting for patient-specific organ mass and using SPECT activity quantification have a great impact on estimated absorbed doses of 90Y ibritumomab tiutexan if compared with the 2D protocol. This method could improve the correlation between dosimetry and clinical consequences of this treatment, especially in view of dose escalation with stem cell rescue.
High pH Lysis Allows Immunoprecipitation of p210BCR-ABL in Primary Chronic Myeloid Leukaemia.
Authors: Patel Hetal , Marley Stephen B. , Gordon Myrtle Y. 
Published: October 2019

Abstract
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder, which is characterised by the presence of the Philadelphia translocation (Ph) (t (9; 22)). The translocation occurs when parts of the c-ABL gene, located on chromosome 9 fuse with the BCR gene, located on chromosome 22. BCR-ABL fusion results in the production of p210BCR-ABL, a chimeric protein with the molecular weight of 210kda. p210BCR-ABL is located in the cytoplasm and has constitutive protein tyrosine kinase activity. Numerous publications have reported that p210BCR-ABL forms complexes with multiple cytoplasmic proteins which affect several signalling pathways. However this published data exists for cell lines expressing p210BCR-ABL and not for primary CML cells. The lack of information based on primary CML cells is due to the presence of a degradative activity which is released when cells are lysed under standard conditions, destroying p210BCR-ABL rapidly and permanently. This prevents quantification or investigation of proteins co-precipitating with p210BCR-ABL in primary CML cells. The degradative activity can be assayed by co-lysing K562 cells, a Ph+ cell line that does not contain the activity, with primary CML cells. Using this assay we show that the degradative activity found in the primary CML cells destroys the p210BCR-ABL present in the K562 cells. The same assay was used to show that the activity is present in both primary CML and normal mononuclear cells (MNC). Conventional protease inhibitor cocktails have not proven effective in inhibiting this degradative activity. We show here that the degradative activity in primary cells is associated with the cell lysosomes and may be an acid dependent hydrolase. By lysing primary CML cells at pH12 we have shown that the degradative activity can be significantly inhibited thereby allowing us to detect p210BCR-ABL in primary CML cells by western blotting. Furthermore, p210BCR-ABL can be immunoprecipitated from primary CML cells when cells are lysed at high pH; however immunoprecipitation is more effective when the pH of lysate is reduced to pH8. We demonstrate that the alterations in pH during the immunoprecipitation procedure do not disrupt the co-immunoprecipitation of p210BCR-ABL-Cbl and Crkl - Cbl associations. Thus, this method is capable of confirming or refuting in primary cells the molecular associations that have been demonstrated in CML cell lines.
Assessing the Benefit/Risk Balance of Long-Term Anagrelide Hydrochloride (Xagrid®/Agrylin®) Treatment for Essential Thrombocythemia.
Authors: Petitt Robert M. 
Published: October 2019

Abstract
Essential thrombocythemia (ET) is a myeloproliferative disorder (MPD) associated with thrombohemorrhagic complications. The disease uncommonly progresses to myelofibrosis or acute leukemia; the risk of transformation may be increased by cytoreductive treatments. Anagrelide (Xagrid®/Agrylin®) is a non-cytotoxic agent that selectively reduces platelet production. A retrospective analysis of an open-label, multi-center trial including MPD patients treated by long-term anagrelide was performed.1 The total safety population comprised 3660 MPD patients (2251 with ET) with a maximum follow-up of 11.4 years. Prior myelosuppressive therapy had been administered in 81% of patients; 33% of these patients were changed to anagrelide because of previous toxicity and 31% because of poor platelet control. Efficacy and safety data hereafter are described for the ET population. There were 934 ET efficacy evaluable patients: with a response seen in 78.7% of them (complete and partial response: 67.2% and 11.5%, respectively). This was similar to that of patients who failed previous therapy (78.8%) or were intolerant (75.6%). After the first year, platelet count decreases were well maintained. Results were similar for both sexes, different age groupings and ethnic origins. AEs occurred in 40.2% of the patients and were generally mild. Anagrelide was discontinued in 38.6% of patients (adverse events accounting for 29.2% of patients stopping treatment). At baseline, 163/934 (17.5%) patients reported ET-related symptoms including GI and other bleedings, arterial or venous thrombosis, angina, pulmonary embolism, transient ischemic attacks, peripheral ischemia and paresthesia. This had reduced to 7.9% (63/796, P<0.001) after 12 weeks and was maintained during follow up (4.3%: 15/470 at 1 year, 3.2%: 6/239 at 2 years, P<0.001.2 Transformation to AML/MDS occurred in 47/2251 (2.1%), but only in subjects who had previously been exposed to cytoreductive treatment. Mortality rate in the safety population was as to be expected in ET patients: 8.8%. Most common reason for death (> or =1%) were CML, reason unknown or unspecified and sepsis. Anagrelide (Xagrid®/Agrylin®) effectively reduces platelet counts and thrombohemorrhagic complications in patients with ET. This is independent of gender, age, ethnic origin and prior therapy. The drug demonstrates a recognized safety profile. Benefits are maintained during long-term follow-up without an increase in disease transformation.
The Role of Histone Acetylation and Death Receptor 5 (DR5) Expression in the Treatment of Chronic Lymphocytic Leukemia (CLL).
Authors: Graham Bonnie A. , Kuschak Brenda , Johnston James B. , Gibson Spencer B. 
Published: October 2019

Abstract
Chronic lymphocytic leukemia (CLL) is a disease in which two-thirds of patients will require therapy, usually with the alkylating agent, chlorambucil (CLB) or the nucleoside analog, fludarabine (FLU). TRAIL is a death receptor ligand that has shown selective cytotoxicity towards a variety of malignancies. CLL cells, however, are relatively resistant to this agent. We have previously demonstrated that CLB- and Flu-induced apoptosis is partially mediated through activation of the TRAIL apoptotic pathway and this is related to the up-regulation of the TRAIL death receptors, DR4 and DR5 (Oncogene, 22:8356–8369, 2003). Combining CLB or Flu with TRAIL produced a synergistic apoptotic response in CLL cells. In contrast, the upregulation of DR5 and the synergistic apoptotic response was not observed in normal lymphocytes. We have subsequently demonstrated that the up-regulation of DR5 is mediated by transcription factors, nuclear factor κB (NFκB) and p53, and histone acetylation. Using chromatin immunoprecipitation assays, we have found that the p65 subunit of NFκB and p53 are bound to the DR5 gene in CLL cells following either CLB or Flu treatment. In addition, histone 3 is acetylated following CLB and Flu treatment corresponding to histone acetylase p300 binding to the DR5 gene. Histone deacetylase 1 (HDAC1) also binds to the DR5 gene following CLB or Flu treatment, but generally at later time points. Overall histone acetylation was also found to be increased in CLL cells, as compared to normal lymphocytes. Treatment with HDAC inhibitors, which are being evaluated in clinical trials, resulted in increased binding of p53 and NFκB, but not HDAC1, to the DR5 gene and increased DR5 mRNA levels in cells. Furthermore, enhanced apoptosis was also observed in CLL cells treated with combinations of SAHA (another HDAC inhibitor) and TRAIL. These findings suggest that histone acetylation is important in regulating DR5 expression and that HDAC inhibitors increase DR5 expression mediated by p53 and NFκB. This could provide a mechanism to sensitize CLL cells to TRAIL-induced apoptosis.
Transactivation of CCL20 Gene by CD30 in Hodgkin’s Lymphoma.
Authors: Mori Naoki , Okudaira Taeko , Yamamoto Kazuo , Horie Ryouichi , Watanabe Toshiki , Matsuyama Toshifumi 
Published: October 2019

Abstract
Hodgkin’s lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Hodgkin/Reed-Sternberg (H/RS) cells, and an admixture of reactive cells including lymphocytes, plasma cells, eosinophils, and histiocytes. Chemokines produced by H/RS cells play a major role in leukocyte trafficking. These molecules with specific receptor affinities contribute to the maintenance of a favorable environment for survival of H/RS cells. The C-C chemokine CCL20 is expected to play a crucial role in the initiation of immune responses and tumor growth. However, expression of CCL20 in HL has not been studied. We found that in lymph nodes from patients with HL, CCL20 was expressed in H/RS cells by immunohistochemistry. CCL20 was expressed in HL cell lines KM-H2 and L428 established from B-cell type HL patients, but not in cell lines L540 and HDLM-2 established from T-cell type HL patients. CD30 was identified in H/RS cells of HL and has attracted much interest as a molecular marker of HL. All four H/RS cell lines expressed CD30, but not CD30 ligand. CD30 induced CCL20 mRNA expression. Analysis of the CCL20 promoter showed the importance of NF-κB binding site for CD30-induced CCL20 expression. Coexpression of IκB, IKK, NIK, and TRAF dominant-negative constructs with CD30 inhibited CD30-induced activation of CCL20 promoter, suggesting that CD30 induces CCL20 via NF-κB signaling. Electrophoretic mobility shift assay showed the NF-κB complexes that consisted of p50, p65, and c-Rel in KM-H2 and L428 cells. In contrast, the NF-κB complexes contained p50 homodimer that was transcriptionally repressive in L540 and HDLM-2 cells. The CCL20 promoter was activated by the C-terminal region of CD30, which activated NF-κB signaling. A decoy CD30 lacking the cytoplasmic region inhibited CCL20 promoter activity in KM-H2 and L428 cells. Thus, in B-cell derived H-RS cells, ligand-independent activation of CD30 signaling activates NF-κB and this leads to constitutive CCL20 expression.