bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excellent Outcome with Rituximab-CHOP (R-CHOP) Combined with Radiotherapy (RT) in Primary Mediastinal Large B-Cell Lymhoma (PMLBCL).
Authors: Vassilakopoulos Theodoros P. , Angelopoulou Maria K. , Galani Zacharoula , Sachanas Sotirios , Katsigiannis Andreas , Dimopoulou Maria N. , Kokoris Styliani I. , Michalis Evridiki , Dimitriadou Evangelia M. , Siakantaris Marina P. , Kontopidou Flora N. , Kalpadakis Christina , Sarantopoulos Angelos , Korkolopoulou Pinelopi , Roussou Paraskevi , Pangalis Gerassimos A. 
Published: April 2020

Abstract
Introduction: Combination chemoptherapy regimens such as CHOP and MACOP-B with or without RT are considered the standard first-line treatment for PMLBCL patients. Consolidation with high dose therapy and autologous stem cell support (HDT-ASCT) at first remission is an alternative approach for this young population. However results are not optimal. Given the superiority of R-CHOP over CHOP in elderly patients with diffuse large B-cell lymphoma, the role of Rituximab added to first-line chemotherapy in younger patients is not clear.
Aims: In this study we evaluate the effectiveness of R-CHOP±RT in PMLBCL and we compare the results of this strategy to CHOP±RT in historical controls.
Patients and Methods: A total of 46 patients with PMLBCL were treated in two participating centers between 1994 and 2004. At a given timepoint R-CHOP replaced CHOP in both centers. Thus, 31 consecutive historical controls were treated with CHOP prior to that point and were compared to 15 patients who received R-CHOP thereafter.
Results: The median age of the patients was 31 years (17–58) and 32/46 (70%) were females. Baseline characteristics between the R-CHOP and CHOP groups were well balanced, including age-adjusted IPI [ ≥2 in 40% of R-CHOP and 42% of CHOP-treated patients (p=0.90)]. Complete response (CR) was achieved in 100% in the R-CHOP±RT vs 61% in the CHOP±RT group (p=0.009). No patient has relapsed after R-CHOP, while all relapses after CHOP occurred within 22 months from diagnosis. The 3-year failure free survival (FFS) was 100% and 47±9% for patients treated with R-CHOP±RT and CHOP±RT respectively(p=0.005). Within the subgroup of patients with L/LI risk IPI the corresponding 3-year FFS rates were 100% vs 61±11% (p=0.059), while they were 100% vs 26±13% (p=0.02) among patients with HI/H risk IPI for R-CHOP±RT and CHOP±RT respectively. The 3-year event free survival (EFS) was 93±7% vs 47±9% (p=0.02). The 3-year overall survival was 93±7% vs 47±9% (p=0.27), while the 3-year lymphoma specific survival was 100% vs 67±9% (p=0.049) for the R-CHOP and CHOP groups respectively.
Conclusions: R-CHOP±RT exhibited impressive efficacy with no failures among 15 patients. CR and FFS rates were significantly better in favor of R-CHOP compared to CHOP-treated historical controls. EFS and lymphoma specific survival were also improved. Based on these data, our standard approach for PMLBCL patients is the application of R-CHOP±RT. Furthermore the addition of Rituximab to front-line treatment might overcome the need for more aggressive strategies such as consolidation with HDT-ASCT in this patient population.
Clinical Features and Prognostic Factors in 135 NHL of the Head and Neck Treated by the GOELAMS 02 Trial.
Authors: Laccourreye Laurent , Desablens Bernard , Le Maignan Christine , Le Mevel Anne , Berthou Christian , Lamy Thierry , Ghandour Christiane , Guilhot François , Hunault-Berger Mathilde , Jardel Henry , Ifrah Norbert , Colombat Philippe ,   The GOELAMS Group
Published: April 2020

Abstract
From November 1984 till April 1996 135 patients (67% M, 33% F) presenting a NHL of the head and neck were treated by the GOELAMS 02 trial (3 VCAP + 40 Gy locoregional irradiation). The median age was 48.5 years (17–69) with 36 patients being 60 or over. The main localization was Waldeyer’s ring (57) including tonsil (35), nasopharynx (14), whole Waldeyer (8), neck (49), nasal cavities (14), thyroid (8) salivary gland (5), mandibular bone (2). According to the WFC, histological subtype were as F (21%), G (57%) and H (20%) and unclassified (2%). Ann Harbor classification included 80 stage 1 and 55 stage II. The IPI score was 0 (49.7%), 1 (22.3%), 2 (10.4%), 3 (2.3%) undetermined (16,3%). PS&gt;2 and bulk (= 5 cm) were observed in 7.5% and 43% of patients respectively. 94% achieved CR. 2 patients died during treatment. Relapses occurred in 23/127 (18.1%) at a median time of 31 months (5.5 – 80). 16 of these relapses occurred before 3 years of CR, 5 between 3 and 6 years and 2 after 6 years of CR. With a median follow up of 65 month (7 – 146) OS and EFS were 81.5% and 77% respectively. In univariate analysis age = 60, extension, PS &gt;2, Bulk = 5 cm, erythrocyte sedimentation rate &gt; 40 and high serum LDH significantly decrease EFS (P= 0.01, 0.047, 0.028, 0.0001, 0.004 and 0.03 respectively). In multivariate analysis only the bulk = 5 cm and the localization to salivary gland significantly decrease EFS( P=0.003 and 0.039 respectively). Even if larger studies are needed to confirm these findings, NHL of the head and neck localized to the salivary gland or having a bulk = 5 cm should already be included in new therapeutic trials in order to improve their outcome.
Phase II Study of Sphingosomal Vincristine in CHOP+/ − Rituximab for Patients with Aggressive Non-Hodgkin’s Lymphoma (NHL): Promising 3 Year Follow-Up Results in Elderly Patients.
Authors: Rodriguez Maria Alma , Dang Nam H. , Fayad Luis , Goy Andre , Hagemeister Fredrick , McLaughlin Peter , Pro Barbara , Romaguera Jorge , Younes Anas , Cabanillas Fernando 
Published: April 2020

Abstract
Background: Individuals older than 60 years have a worse prognosis than younger patients with aggressive NHL. Vincristine is an active drug in the treatment of malignant lymphomas. Sphingosomal vincristine (SV) was well tolerated with 45% ORR in patients with multiple relapses of aggressive NHL (ASH abst. 412, 1999). Based on these data, a phase II study of CHOP with rituximab (no rituximab for T-cell histology), and substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL.
Methods: Aggressive NHL histologies eligible for study were diffuse large B-cell lymphoma (DLCL), peripheral T-cell lymphoma (PTCL), follicular lymphoma grade 3 (FL gr3), anaplastic large cell lymphoma (ALCL), and indolent lymphomas with aggressive transformation (TL). Patients were treated with standard dose CHOP that included SV 2.0 mg/m2 without dose capping, ± rituximab 375 mg/m2, given every 21 days for 6 to 8 courses (ASH abst. 338, 2002).
Results: Of 73 patients enrolled on study, 68 were evaluable for response. Median age was 61 (range 22–80), 36 patients (53%) were &gt;60 years old. Overall, 24 patients (23 elderly) had an IPI score ≥3. Patients received a median of 6 study treatments (range 1–8). Diagnoses were: DLCL = 56; FL gr 3 = 4; PTCL = 4; ALCL = 2 and TL = 2. ORR was 92.6% (63/68 pts) with 55 pts achieving CR (80.1%), 7 CRu (10.3%), and 1 PR (1.5%); 3 patients had PD (4.4%) and 2 were not assessed for response (2.9%). ORR was similar in both elderly (&gt;60) and younger pts (≤60): 91.9% and 93.5% respectively. Neuropathy was generally mild (Gr.1–2). Hematological toxicities were as follows: 56% Gr.3–4 neutropenia, 6% Gr.3 anemia, and 13% Gr.3–4 thrombocytopenia. Toxicites were comparable in elderly and younger patients. The median follow up for the study is 39.6 months (mos), and overall survival 94%. There have been 9 relapses (5 DLCL, 3 T-cell, 1 FL gr3, 1 transformed) for elderly patients and 5 relapses (4 DLCL, 1 T-cell) for patients ≤60. The table below shows progression free survival (PFS) at 3 years, for all histologies, and DLCL by age. There is no difference between the age groups.
Conclusions: This regimen, with sphingosomal vincristine in CHOP +/− Rituximab, has a high overall response rate. It is a well-tolerated therapy with mild neurotoxicity for all patients. At 3 years, the PFS in elderly patients with DLCL treated with RCHOP is comparable to that of younger patients, despite a larger fraction of high risk IPI in the older patients. This regimen merits randomized comparison to RCHOP in DLCL.
Age (Yrs) All Histologies (n=68) DLCL (n=56) ≤60 84%, CI [66–93] 85%, CI [66–94] &gt;60 83%, CI [66–92] 86%, CI [66–94]
Ongoing Variability in Transfusion Practices in Cardiac Surgery Despite Established Guidelines.
Authors: Snyder-Ramos Stephanie A. , Moehnle Patrick , Weng Yi-Shin , Boettiger Bernd W. , Kulier Alexander , Levin Jack , Mangano Dennis T. 
Published: April 2020

Abstract
Although blood utilization has been under considerable scrutiny for the past two decades, particularly for surgery, the international evolution of standards remains unknown. Therefore, the objective of this study was to compare the perioperative transfusion of blood components in patients undergoing coronary artery bypass graft (CABG) surgery in different countries. Transfusion practice was investigated prospectively among 16 countries (70 centers). Five-thousand sixty-five (5,065) randomly selected cardiac surgery patients in the Multicenter Study of Perioperative Ischemia Epidemiology II (EPI II) Study were evaluated. Utilization of red blood cells, fresh frozen plasma, and platelets was assessed by day, prior to, during and after surgery until hospital discharge. Intraoperative red blood cell (RBC) transfusion varied from 9 percent to 100 percent among the 16 countries, and 25 percent to 87 percent postoperatively (percent of transfused patients). Similarly, transfusion of fresh frozen plasma (FFP) varied from 0 percent to 98 percent intraoperatively and 3 percent to 95 percent postoperatively, and platelet (PL) transfusion from 0 percent to 51 percent and 0 percent to 39 percent, respectively. An analysis of the EuroSCORE (an internationally validated risk evaluation system for cardiac surgery) risk indices of the countries with the highest and lowest frequencies of use or amounts of each of type blood product failed to demonstrate a correlation between EuroSCOREs and maximum vs minimum frequency of use or amount of blood product administered. Establishment of international guidelines for utilization of blood products in CABG surgery appears necessary.
Survival in Individuals with Profound Anemia Treated without the Use of Blood Transfusions.
Authors: Ford Patricia , Keck Gina , Mastoris Jason 
Published: April 2020

Abstract
Although there is an emerging trend to reduce blood transfusions, there is still very little randomized data outside of the critical care setting that identifies the risks and benefits of transfusion support. Many clinicians base the decision to transfuse primarily on the hemoglobin (Hb) level independent of symptoms. Little is known about the clinical consequences of profound anemia although there is concern that withholding transfusion support will result in adverse outcomes in those with advanced age or underlying cardiovascular conditions. Prior studies have reported a significant mortality rate with Hb levels under 5 g/dL. This in part has led to the use of extreme measures such as hyperbaric chambers, ventilation or paralysis for profound anemia and the establishment of specialized Centers for Bloodless Medicine and Surgery to care for individuals refusing blood products. A retrospective chart review of 128 patients declining blood transfusions with Hb values under 7 g/dL from January 2002 until August 2005 was performed. This population included a broad range of medical, surgical and obstetrical cases with a mean age, Hb and length of stay of 52 years, 5.4 g/dL and 11 days respectively. Table 1 summarizes the survival rates based on the severity of anemia. Our nonblood approach included simultaneous interventions to stimulate erythropoiesis, control bleeding, enhance hemostasis, minimize iatrogenic blood loss and maintain hemodynamic stability. All patients received erythropoietin and iron with antifibrinolytic agents added for any active bleeding. To keep laboratory sampling at a minimum, physicians were required to rely on their basic clinical assessment skills to manage patients. The need for critical care monitoring, volume resuscitation and oxygen support was determined based on changes in blood pressure, heart rate, urine output, and cognitive function. Patients experienced slower recovery times with more frequent cardiac monitoring and increased length of hospital stays. This series demonstrates that the majority of individuals can survive with Hb levels as low as 2.5 g/dL utilizing simple nonblood strategies. The low mortality rate supports the elimination of any predetermined transfusion trigger. Survival Rates in Patients with Profound Anemia
Table 1 Survival Rates in Patients with Profound Anemia Hb Level (g/dL) Proportion Who Survived 2.5–3.0 6/7 (85.7%) 3.1–4.0 9/11 (81.8%) 4.1–5.0 29/32 (90.6%) 5.1–6.0 30/30 (100%) 6.1–7.0 48/48 (100%) Overall 122/128 (95.3%)
Neonatal Alloimmune Thrombocytopenia (NATP) Associated with Maternal-Fetal Incompatibility for Blood Group B.
Authors: Curtis Brian R. , McFarland Janice G. , Fick Andrea , Lochowicz Andrew J. , Ball Robert H. , Richard Aster H. 
Published: April 2020

Abstract
In most individuals, A and B blood group antigens are weakly expressed on platelets, allowing ABO incompatible platelets to be tolerated when transfused. However, in a minority of normal subjects (high expressers, H-Exp), platelets carry 10–20 times the usual number of A or B epitopes (up to 20,000/platelet, Blood2000;96:1574). Post-transfusion survival of incompatible H-Exp platelets has not been systematically studied. We recently encountered a family in which NATP in two infants appears to have been caused by maternal anti-B reacting with H-Exp fetal platelets inherited from a father with the group B H-Exp trait. The first two children (C1 and C2) born to a G4P2 group O mother and A2B father were positive for blood group B, and had neonatal thrombocytopenia (TP) (C1 = 33K/μL, C2 = 61K/μL), anemia, positive direct antiglobulin test, elevated reticuloytes and hyperbilirubinemia requiring phototherapy. C1 required 3 platelet transfusions and RBC transfusion, and C2 required RBC transfusion. Both recovered in the immediate neonatal period. A third child (C3) inherited blood group A2 from the father and was born with a normal platelet count. The parents were incompatible for HPA-2b and -3b, but no platelet-specific antibodies were detected in maternal serum. High titer IgG antibodies were detected in maternal serum against father’s platelets in both flow cytometry and modified antigen capture ELISA. This activity was completely removed by absorption with normal, washed group B RBCs. When tested by flow cytometry with monoclonal anti-B and anti-A, the father’s platelets were shown to carry 17 times the normal level of B antigen, and only trace amounts of A antigen. We previously showed that the potent glycosyltransferase activity associated with the H-Exp trait causes essentially all H antigen on platelets and RBCs to be converted to A and/or B antigen. Consistent with this, father’s platelets and RBCs were found to express no detectable H. Quantitation of B and H antigens on platelets and RBCs from C1 and C2 is pending receipt of samples. Findings made in this family indicate that maternal anti-B (and presumably anti-A) IgG antibodies can cause NATP in infants with the ABO “high expresser” trait. Maternal-fetal ABO incompatibility should be considered as a cause of NATP when maternal antibodies against platelet-specific antigens cannot be demonstrated. The possibility that ABO incompatibility can aggravate thrombocytopenia caused by antibodies against recognized platelet-specific antigens also deserves consideration.
Different Histopathological Subtypes of Hodgkin Lymphoma Have Significantly Different Levels of FDG Uptake.
Authors: Hutchings Martin , Jakobsen Annika L. , Hansen Mads T. , Ralfkiaer Elisabeth , Specht Lena 
Published: April 2020

Abstract
Background: Functional imaging with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) is an important tool in the staging of Hodgkin lymphoma (HL). FDG-PET enables quantitative information about the tumour metabolism, most commonly measured as the semiquantitative standardised uptake value (SUV). The aim of this study was to investigate if the level of FDG uptake varies between the different subtypes of HL.
Methods: Sixty consecutive patients with newly diagnosed HL were prospectively included in the protocol. At least one lymph node biopsy was obtained from each patient and all patients underwent an FDG-PET/CT scan along with other staging procedures. The highest SUV in each patient (SUVmax/total) and in each affected region or organ (SUVmax) was recorded. Differences in SUVmax between histopathological subgroups were analysed with independent-samples student’s t-test and one-way analysis of variance (ANOVA).
Results: 38 patients had nodular sclerosis (NS), 11 patients had mixed cellularity (MC), seven patients had nodular lymphocyte predominance (NLP) and four patients had classical HL, not otherwise specified (CHL-NOS). Mean SUVmax/total was 9.3 g/ml in NLP patients, 16.3 g/ml in NS patients, 20.8 g/ml in MC patients, and 19.5 g/ml in CHL-NOS patients (Figure 1). The difference between the histopathological subgroups was highly significant (ANOVA, p = 0.011). Out of 780 potential sites of disease (600 lymph node regions plus 180 organs), 208 sites were affected with HL. Mean SUVmax was 8.3 g/ml in the 12 sites affected with NLP, 11.2 g/ml in the 147 sites affected with NS, 14.6 g/ml in the 36 sites affected with MC, and 13.1 g/ml in the 13 sites affected with CHL-NOS (ANOVA, p = 0.011, Figure 2). Mean SUVmax in sites with NS was significantly higher than in sites with NLP (t-test, p = 0.042) and significantly lower than in sites with MC (t-test, p = 0.011).
Conclusion: There is a significant difference in FDG/glucose uptake between the different histopathological subtypes of HL. The SUVs in NLP, NS and MC lymphomas are significantly different, while the uptake in CHL-NOS lymphomas resembles the uptake in MC lymphomas. SUV analysis is frequently used in situations where the qualitative evalutation of a site on FDG-PET is uncertain. In those situations, it is helpful to know that the level of uptake varies from subtype to subtype. Since the subtypes have different FDG metabolism, they should ideally be regarded separately in future studies of FDG-PET and FDG-PET/CT in HL.
1. Highest SUV anywhere in the body of each patient 1. Highest SUV anywhere in the body of each patient
Prognostic Significance of Immunohistochemical Markers in Classical Hodgkin Lymphoma Response to Treatment A Study of 59 Cases.
Authors: Canioni Danielle , Deau Benedicte , Taupin Pierre , Bosq Jacques , Ribrag Vincent , Delarue Richard , Vasiliu Viorel , Brousse Nicole , Hermine Olivier 
Published: April 2020

Abstract
Classical Hodgkin lymphoma (cHL) belongs to the most curable lymphomas in adults. Some cHL however, are primary refractory to usual treatments including anthracyclins regimen. Currently, only clinical factors are considered as relevant for prognosis. In a previous study of a small cohort of patients, we showed that some immunohistochemical markers could help for predicting the treatment response of cHL. In this study, we extended the markers and increased the number of included patients. We performed a retrospective study on pre-treatment biopsy specimen of 59 patients, 18 with primary refractory cHL and 41 responders to chemotherapy and free of disease for at least 3 years. Most refractory cHL had a nodular sclerosis (NS) histological type, except one which was a mixed cellularity type. Thirty six responders had a NS type, 3 patients had a mixed cellularity type and the 2 others an interfollicular cHL. The semi-quantitative immunohistochemical study used CD20, CD3, CD30, bcl2, p53, Ki67, TiA1 and c-kit antibodies. The results were statistically evaluated using a Fisher ’s exact test or a Wilcoxon sum rank test depending on the variable studied. CD30 and Ki67 stained strongly Hodgkin (Hg) and Reed-Sternberg (RS) cells regarless the response status. In contrast, these cells expressed significantly less frequently CD20 in refractory cHL than in responders (p= 0.032) and were never stained with CD3. P53 and bcl2 had a significantly higher expression on Hg or RS cells in refractory cHL (median = 63% & 51%) compared to responders (median = 40% & 12%) (p=0.004 & p=0.015 respectively). The cytotoxic marker TiA1 stained significant higher number of small lymphocytes in refractory cHL (median=42.5 per high power field (hpf)) compared to responders (median= 21 per hpf) (p= 0.0006). C-kit antibody was negative in Hg or RS cells but stained significant more mastocytes in refractory cHL (median=9 per hpf) comparing to responders (median=3.8 per hpf) (p= 0.001). These results indicate that immunohistochemical markers are useful in cHL and should be used in association with clinical parameters for predict the cHL treatment response. The prognostic significance of CD20 expression in cHL is controversial but in this study seems predictive of a better treatment response and is merely a marker of different gene expression program that may be associated with a more favorable outcome. A high bcl2 and p53 expression in refractory cHL supports the notion that an intact apoptosis cascade is essential for cell killing effect of chemotherapy. The increasing of TiA1 and c-kit positive cells raises the importance of the environmental non-neoplastic cells in cHL and suggests that targeted therapy against mast cells could improve prognosis of refractory cHL.
Cloning of B Cell Lymphoma-Associated Antigens Using Modified Phage Displayed Expression cDNA Library and Immune Patient Sera.
Authors: Cha Soung-chul , Biragyn Arya , Ruffini Pier Adelchi , Qin Hong , Neelau Sattva S. , Kwak Larry W. 
Published: April 2020

Abstract
Active immunization of follicular lymphoma patients with idiotypic vaccines elicits antigen-specific antibody responses, T-cell responses, and antitumor effects (Bendandi, M. et al., Nat Med5, 1171). We hypothesized that these vaccinated patients could generate tumor specific immune responses, not only against idiotype, but also against other tumor associated antigens (TAA) by a mechanism of epitope spreading. We further hypothesize that these antigens may represent tumor rejection targets for immunotherapy. To identify potential antigens, a phage surface expressed cDNA library derived from primary tumor cells was screened with sera from idiotype-vaccinated patients. Consistent with our hypothesis, we identified two immunogenic peptides (FL-aa-7 and 18), unrelated to idiotype, which were recognized by postvaccine sera but not by prevaccine or normal human sera. These peptide sequences derived from the 5′-untranslated regions of the human GTPase, IMAP family member 7 gene (FL-aa-7) and an alternative reading frame of U1-snRNP 70 (FL-aa-18), respectively, suggesting that epitope spreading had occurred. To further determine the specificity of these patients’ post vaccine sera, the corresponding FL-aa-7 and FL-aa-18 peptides were synthesized and tested for serum binding. As expected, post-vaccine but not pre-vaccine or normal, specifically bound the FL-aa-7 and FL-aa-18 peptides, respectively. Furthermore, both peptides specifically inhibited the binding of post-vaccine sera to the respective FL-aa-7 and FL-aa-18 phage clones in a dose-dependent manner. These data suggest that Id vaccinated patients generated specific antibodies to novel peptides FL-aa-7 and FL-aa-18, unrelated to Id. Overall, these data indicate that Id-vaccinated B cell lymphoma patients mounted antibody responses specifically for FL-aa-7-1 and FL-aa-18 peptides, which may represent a potential immunotherapeutic tumor antigen. The clinical and biological relevance of the response is to be elucidated.