bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the Addition of Rituximab to Initial CHOP Chemotherapy Compared with CHOP Alone in Patients with Relapsed Diffuse Large B-Cell Lymphoma Who Underwent Autologous Stem Cell Transplantation.
Authors: Chen Yi-Bin , Hochberg Ephraim P. , Feng Yang , Motyckova Gabriela , Neuberg Donna , Spitzer Thomas R. , Fisher David C. , LaCasce Ann S. 
Published: October 2019

Abstract
Standard therapy for chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL) is high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) based on the results of the Parma study (NEJM1995;333:1540–5). However, the addition of rituximab to initial chemotherapy has improved progression-free and overall survival compared with CHOP alone. Patients who relapse after R-CHOP may have disease which is less sensitive to second line therapy or, alternatively, the benefit of ASCT may be independent of the impact of rituxuimab, and, therefore, the true benefit of ASCT in current patients with relapsed DLBCL is unclear. We performed a retrospective cohort analysis of patients who received ASCT for DLBCL during the period of 1997–2006. Our goal was to evaluate the benefit of ASCT for patients with relapsed DLBCL who received R-CHOP as initial chemotherapy compared to those who were treated with CHOP alone. A total of 145 patients at first relapse with chemotherapy sensitive disease who underwent ASCT were identified. 111 received a CHOP-like regimen, and 34 received R-CHOP as their initial chemotherapy regimen. All patients received salvage chemotherapy prior to ASCT. 86.5% of CHOP patients and 88.2% of R-CHOP patients achieved a CR/CRu with their initial chemotherapy (p=0.99). At initial diagnosis, Ann Arbor stage and ECOG performance status (PS) between the two groups were also similar. The two groups of patients had significant differences in the following characteristics: median age at ASCT (51 for CHOP vs 57 for R-CHOP, p=0.002), Ann Arbor stage of disease at relapse (22.5% localized disease for CHOP vs 55.9% localized disease for R-CHOP, p=0.001), and percentage of patients who underwent nuclear imaging to evaluate response to salvage chemotherapy (37.8% in CHOP vs 79.4% in R-CHOP, p<0.0001). The majority of patients in both groups received either CBV or Bu/Cy conditioning chemotherapy at ASCT. 2-year relapse-free survival (RFS) was 57% in the CHOP group versus 35% in the R-CHOP/ASCT group (p=0.10). 2-year OS was 75% (CHOP) and 67% (R-CHOP/ASCT), respectively (p=0.09). Longer follow-up is essential and further analysis examining the potential impact of rituximab containing salvage therapy in rituximab naïve patients is needed. In conclusion, although this is a retrospective comparison, the trend toward inferior RFS and OS in the patients who initially received R-CHOP suggests that the benefit of ASCT in patients who subsequently relapse after R-CHOP may be inferior compared to patients who received CHOP alone.
Figure Figure
Low Predictive Value of Functional Imaging with 18FDG-PET or Gallium Scanning in Relapsed or Refractory Hodgkin Lymphoma Prior to Autologous Stem Cell Transplantation.
Authors: Peinert Stefan , Hoyt Rosemary , Szer Jeff , Roberts Andrew , Grigg Andrew , Prince H. Miles , Rigacci Luigi , Seymour John F. , Ritchie David S. 
Published: October 2019

Abstract
Introduction: 18FDG-PET early during first-line chemotherapy of Hodgkin Lymphoma (HL) has a high positive and negative predictive value. The predictive value of functional imaging (FI) in refractory or relapsed HL after salvage treatment and prior to high-dose (HD) chemotherapy and autologous stem cell transplantation (AUSCT) is less well established.
Methods: A retrospective analysis was undertaken of the clinical characteristics, FI results, event free survival (EFS) and over all survival (OS) data for 66 consecutive patients (pts) with refractory or relapsed HL treated with salvage chemotherapy and AUSCT between 1997 and 2007.
Results: The median follow-up was 52 months (range 0 to 125 months). Following salvage chemotherapy, and prior to AUSCT, 63 of the 66 evaluable pts (96%) had response assessment with a conventional CT scan, 53 pts also had FI with a gallium scan (n=18), 18FDG-PET scan (n=31) or both (n=4). Of the 53 pts with FI prior to AUSCT, 21 (40%) were in metabolic complete remission (FI-negative) and 32 pts (60%) had residual disease (FI-positive). The median EFS and OS for the whole cohort were 29 and 52 months, respectively. Median EFS was 31 and 13 months (p=0.096), and median OS was 60 and 39 months (p=0.35) for those with negative and positive FI, respectively. Significantly more pts with negative FI achieved CR with conventional imaging compared to those with positive FI (9/19 = 47% vs. 2/32 = 6%, p=0.001). Male pts were disproportionately represented in the cohort with positive FI (20/32) compared to the pts with negative FI (7/21, p=0.038). There was no association between FI-positivity and the clinical features of age, short duration (<12 months) of initial response, presence of B-symptoms or extranodal disease at the time of relapse, or the type of AUSCT conditioning used.
Conclusion: We did not demonstrate a strong predictive value of FI outcome prior to AUSCT for relapsed or refractory HL despite a trend for improved EFS for pts with negative FI. We did demonstrate that males had a higher rate of FI positivity suggesting this is also an adverse risk factor for failure of salvage therapy in relapsed/refractory HL.
Novel Efficient Primary Human Peripheral Blood Progenitor Cell-Targeted Recombinant Adeno-Associated Viral Vectors.
Authors: Veldwijk Marlon R. , Sellner Leopold , Stiefelhagen Marius , Kleinschmidt Jürgen A. , Laufs Stephanie , Topaly Julian , Wenz Frederik , Zeller W. Jens , Fruehauf Stefan 
Published: October 2019

Abstract
Introduction: G-CSF mobilized peripheral blood progenitor cells (PBPC) are an excellent target for the cure of acquired and inherited disorders of the hematopoietic system. AAV-based vectors have an advantageous safety profile, due to their low immunogenicity, the lack of any associated human disease and its episomal localization. Unfortunately, currently standard rAAV2-based vectors lack the required efficiency for gene transfer into human blood progenitor cells. To increase the gene transfer efficiency on primary hematopoietic cells we applied an AAV random peptide library on primary human CD34+ PBPC.
Materials and Methods: The AAV random peptide library was applied on primary human CD34+ PBPC samples (3 selection rounds). Several mutant blood progenitor-targeted rAAV2 capsid clones were obtained and sequenced. Five new rAAV vectors with the most efficient clones were produced. Titers were verified using real time PCR-based titration. To determine efficiency and specificity, a panel of leukemia (CML and AML) and non-leukemia cell lines, as well as primary human CD34+ PBPC were transduced. GFP expression was determined against uninfected control cells.
Results: On a panel of leukemia cell lines at least one capsid mutant was significantly more efficient (%GFP+; p<0.01) than standard rAAV2 vectors. On solid tumor cell lines rAAV2 was more efficient, suggesting the increased specificity of our capsid mutants for hematopoietic cells. Significantly higher gene transfer efficiency (up to 16% GFP+ cells) could be obtained with the newly generated vectors compared to standard rAAV2 (up to 9-fold higher; p<0.01). Using a different approach, up to 25% gene transfer into CD34+ PBPC was observed.
Conclusion: These novel vectors may finally enable efficient (>20%) gene transfer using rAAV-based vectors into primary human PBPC and may offer a safe alternative to other vector systems which is applicable in vivo.
Evaluation of a Powered Intraosseous Device for Bone Marrow Sampling.
Authors: Cohen Stephen C. , Soroka Jill M. 
Published: October 2019

Abstract
The importance of bone marrow examination in the evaluation of leukemia, multiple myeloma, anemia, pancytopenia, and other disorders is well established. The objective for this study was to evaluate the ability of a powered bone marrow aspiration device to penetrate the intraosseous medullary space of the iliac crest, and to aspirate bone marrow samples for the ultimate purpose of diagnosing disease and monitoring the course of disease and medical therapy. The device was used to obtain bone marrow samples in accordance with accepted practice guidelines and device’s directions for use. Among other data, insertion success, time to insertion, and complications were recorded. Patient pain levels were rated from 0 to 10 (10=extreme pain). Device operators rated the use of the device from 0 to 10 (10=outstanding). There were 55 patients in the study from three centers. Successful insertion and aspiration of bone marrow samples were achieved in 54 of the 55 patients (98.1%). Mean insertion time was 4.9±3.0 seconds; significantly faster than the 7.3 minutes reported by Kuball et al* (one-sample t-test, p<0.001). There were no complications. The mean insertion pain score was 2.5±2.2 and the mean aspiration pain score was 3.7±2.5. On a scale of 0 to 10, the six operators rated the ease of use of the device at a mean score of 8.3±1.7. Findings suggest that the powered aspiration device is safe and effective for bone marrow aspirations.
Nonhematological Tumor Metastasis in the Bone Marrow: An Analysis of 10112 Unselected Plastic-Embedded Biopsy Sections.
Authors: Li Xiao , Tao Ying , Liu Yizhi , Song Luxi , Wu Lingyun , Ying Shaoxu , Chang Chunkang , Pu Quan 
Published: October 2019

Abstract
We investigated the frequency of bone marrow (BM) involvement by nonhematological tumors in unselected BM biopsy samples from 10,112 patients. Plastic embedded BM biopsy sections were retrospectively analyzed, with special focus on
Frequency of BM involvement by nonhematological malignancies, the advantage of plastic-embedded BM biopsy specimens over paraffin-embedded samples, Complementarity of marrow biopsy to aspiration smears. the causes of false-negative results when using aspiration smears, and analysis of primary sites of metastatic solid tumors.
Overall 101 of the 10112 BM samples showed nonhematological tumor metastases, accounting for 1.0% of all analyzed specimens, which was higher than data reported on the basis of paraffin embedded samples. Of 74 aspiration smears obtained concurrently with the 101 biopsy sections, 55 were also positive for metastatic carcinoma. That is, the detection rate of metastatic tumors based on the aspiration smears was 74.3% relative to the rate observed on biopsy sections. All 101 sections with metastatic tumors showed various degrees of myelofibrosis (including 67cases with severe myelofibrosis [+++]) which was thought to be partly responsible for false negative results on aspiration samples. Primary tumors were documented ante-mortem in 50 of the 101 BM biopsy-positive patients (49.5%). The most frequent primary sites were lung, gastroinyestinal tract, and breast, in good agreement with data in the literature. In conclusion, nonhematological tumor metastases in unselected bone marrow are not exceptional findings. Plastic embedded BM biopsy examination is helpful in detecting unknown metastatic nonhematological malignancies and apparently more sensitive than paraffin embedded BM biopsies.
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The Association between Hematological and Inflammatory Factors and Stress Fractures among Female Military Recruits.
Authors: Merkel Drorit , Moran Daniel S. , Yanovich Ran , Evans Rachel K. , Finestone Aharon S. , Constantini Naama , Israeli Eran 
Published: October 2019

Abstract
Background: With growing number of females accepted for combat-related military duties in Israel, the special needs of these women should be addressed. Previous studies on women in combat training have found a high prevalence of iron deficiency at recruitment, as well as an increased rate of Stress Fractures (SF) and overuse injuries during training in comparison with men. The aim of this study was to assess the association between hematological and inflammatory variables and stress fracture occurrence among military recruits during basic training.
Methods: We followed 3 companies of females and males inducted to a gender integrated light infantry unit, prospectively. Females inducted for a medics and dental assistants’ courses served as controls. Hemoglobin, iron, transferrin, ferritin, CRP and IL-6 levels were measured for all participants, at recruitment, and after 2 and 4 months of training. SF’s were diagnosed radiographically or scintigraphically according to the IDF protocol.
Results: 227 female combatants, 83 male combatants and 128 female controls were recruited. At induction, 18% of the female combatants had anemia compared with 8% of the males and 19% of the female controls. Iron deficiency was noted in 40%, 6%, and 38% respectively. There were no clinically significant changes during training. Twelve percent of female combatants developed stress fractures, while there were no occurrences of SF among the male combatants or female controls. Subjects with SF had significantly lower levels of serum iron and iron saturation.
Conclusions: A relatively high incidence of anemia as well as iron deficiency was found in this young asymptomatic cohort, with no significant change during training. The lower stores of iron in the female combatants with stress fractures warrants further investigation.
Canonical Correlation Analysis (CCA) of Imatinib Treatment (ImRx) Nonadherence (NA) with Associated Patient Variables (APVs) in Chronic Myeloid Leukemia (CML) - Results from the ADAGIO Study.
Authors: van Lierde Marie-Anne , De Rop Larissa , Serra Filipo , Strobbe Eric , MacDonald Karen , Vancayzeele Stefaan , De Geest Sabina , Letvak Laurie , Albrecht Tara , Abraham Ivo 
Published: October 2019

Abstract
BACKGROUND. ImRx for CML is a long-term treatment potentially compromised by NA. Identifying APVs may assist in reducing NA and optimizing treatment outcomes.
OBJECTIVE. To model the relationships between two NA measures and selected APVs using CCA, a multivariate analog of multiple regression to accommodate multiple criterion variables.
DESIGN AND PATIENTS. Data subset from prospective, 90d observational, open-label, multicenter study. 169 evaluable pts on ImRx for minimum 30d at enrollment [1].
MEASUREMENTS. NA at 90d vector: Basel Assessment of Adherence Scale for pts (pBAAS; 0/1 with 1=NA); and % of ImRx taken per pill count (%ImRx, subtracted from 100 to reflect NA). APVs at BL vector: age; months since CML diagnosis (mCML); months since ImRx initiation (mImRx); knowledge of CML disease, treatment, and ImRx (KCMLRx); and general health (SF-8).
RESULTS. The criterion (dependent) vector of NA indicators included pBAAS and %ImRX. The predictor (independent) vector of APVs included: age, mCML, mImRx, KCMLRx, and SF-8. Two canonical correlations were generated: 0.389 (Bartlett Chi-squared=23.564, P=0.009) and 0.170 (Bartlett Chi-squared= 3.590, P=0.464); the second correlation was deleted due to nonsignificance from zero. The canonical loadings (or structure coefficients) for the retained model were: age 0.951, mCML 0.205, mImRx 0.145, SF-8 0.016, and KCMLRx -0.367. Redundancy analysis showed that 22.1% of variance in the predictor set was explained by variables within that set.
CONCLUSIONS. The patient NA vector (composed of a binary assessment of NA per pBAAS 0/1 with 1=NA) and continuous quantification of % of ImRx not taken was related to the APV vector as follows: NA increased as patients were older, had been diagnosed with CML for a longer period of time, had been on imatinib treatment for a longer period time, and were in slightly better health at enrollment. These may be considered warning signs for NA for clinicians to consider in practice, given the long-term nature of ImRx. Importantly, better patient knowledge of disease and treatment, a clinically modifiable APV, was associated with a decrease in NA. The initial insights in patient NA with ImRX provided by these findings, though some are counterintuitive to the NA literature at large, must be studied further to better understand the dynamics of NA in the CML population.
LMO2 Protein Expression Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma in the Pre- and Post-Rituximab Treatment Eras.
Authors: Natkunam Yasodha , Farinha Pedro , Hsi Eric D. , Hans Christine P. , Tibshirani Robert , Sehn Laurie H. , Connors Joseph M. , Zhao Shuchun , Pohlman Brad , Spinelli John , Bast Martin , Nagler Arnon , Levy Ronald , Gascoyne Randy D. , Lossos Izidore S. 
Published: October 2019

Abstract
Finding new prognostic markers in diffuse large B-cell lymphoma (DLBCL) is of importance because the disease is heterogeneous and current therapies fail to cure many affected patients. Previously, we showed that the expression of LMO2 mRNA was the strongest single predictor of superior outcome in patients with DLBCL in a multivariate model based on the expression of six genes (Lossos et al, NEJM 2004). Subsequently, we generated an anti-LMO2 monoclonal antibody and showed that LMO2 protein is expressed in a subset of germinal center-derived B-cell lymphomas including DLBCL, and that its expression predicted a superior outcome in DLBCL patients who were treated with anthracycline-based regimens (Natkunam et al, Blood 2006 & 2007). We have now expanded this cohort to include DLBCL patients treated at five international medical centers and have also tested the prognostic impact of LMO2 in patients treated with the addition of rituximab to CHOP (R-CHOP), a regimen which was recently demonstrated to improve the outcome of DLBCL patients (Coiffier et al, NEJM 2002; Sehn et al, JCO 2005; Habermann et al, JCO 2006; Pfreundschuh et al, Lancet Oncol 2006). Immunohistochemistry for LMO2 was performed on tissue microarrays containing cores of diagnostic biopsy specimens from patients with de novo DLBCL treated with anthracycline-based chemotherapy (280 patients) or with R-CHOP (80 patients) who had been followed for clinical outcome. The results show that in the pre-rituximab group staining for LMO2 was strongly correlated with overall survival (OS) and progression-free survival (PFS) (p=0.0018 and p=0.00071, respectively). Similarly, in the post-rituximab group LMO2 protein expression was associated with a significantly longer OS (p=0.0048) and PFS (p=0.0087). In multivariate Cox regression analyses, the expression of the LMO2 protein was found to be independent of the clinical IPI and most strikingly, was more robust than the conventional IPI in predicting OS and PFS, particularly in the post-rituximab DLBCL group of patients (OS p = 0.03, PFS p = 0.01). The capacity of LMO2 protein to identify DLBCL patients with improved outcome in an IPI-independent manner indicates its potential role in risk stratification of this disease. We conclude that the prognostic value of LMO2 protein expression remains significant in the era of R-CHOP treatment and recommend its assessment in all newly diagnosed DLBCL patients to confirm these results and eventually to optimize patient management.
Long-Term Dosing of AMG 531 in Thrombocytopenic Patients with Immune Thrombocytopenic Purpura: 2-Year Update.
Authors: Bussel James B. , Kuter D.J. , de Wolf J.Th.M , Guthrie T.H. , Newland A. , Wasser J.S. , Hamburg S.I. , Bjorkquist L. , Guo M. , Nichol J. 
Published: October 2019

Abstract
AMG 531, a novel thrombopoiesis-stimulating peptibody, increases platelet production by stimulating the TPO receptor. This study is an ongoing, open-label extension assessing the safety and efficacy of long-term, weekly, SC administration of AMG 531 in patients with chronic ITP who completed a previous AMG 531 study. Patients previously treated with AMG 531 received the same starting dose as the final dose given in the previous study; placebo-treated patients began the extension at 1μg/kg. Doses could be adjusted based on platelet response. As of an April 2007 analysis, 137 patients were enrolled and 136 had received AMG 531. The longest treatment duration was 122 weeks; 22 patients were followed for 96 weeks or longer. At baseline, 91 women and 46 men had a mean age of 53±15(SD) years and a median (range) platelet count of 18(1–50)x109/L; 82 patients (60%) had undergone splenectomy. The most frequently reported adverse events (AEs) were headache (overall incidence 31%), contusion (27%), fatigue (24%), diarrhea (24%), epistaxis (23%), nasopharyngitis (21%), and arthralgia (20%). Exposure-adjusted analysis showed no trend for AEs to increase in frequency with increased drug exposure (table). Eleven patients had serious AEs judged by investigators as treatment-related including 3 withdrawn from study (vaginal hemorrhage, increased reticulin in the bone marrow reported as myelofibrosis, and initial report of multiple myeloma later reclassified as monoclonal gammopathy of undetermined significance - 1 report each) and 8 who continued on-study (bone marrow disorder/reticulin fibrosis - 3, unacceptably high platelet count - 2, thrombosis - 2, and cerebral thrombosis/papilloedema/temporary blindness - 1). One patient developed neutralizing antibodies to AMG 531 (absent on retesting 4 months after drug cessation), with no clinical sequelae and no cross-reactive antibodies to TPO. Overall, 112 patients (82%) achieved a platelet response (≥50x109/L and doubling of baseline). From week 4 onward, weekly incidence of platelet response ranged from 52–73% (figure). Median number of weeks to first response was 2 (median dose 3μg/kg). Of 30 patients with baseline use of concurrent ITP therapies, 13 were able to discontinue them and 6 additional patients had a >25% dose reduction. Individualized weekly doses of AMG 531 provide a therapeutic option for long-term treatment of chronic ITP. The safety profile has been acceptable, and most patients have been able to maintain a platelet response and discontinue or reduce concurrent ITP therapies.
Exposure-Adjusted incidence of AEs with Overall Incidence ≥ 20% Platelet Response (≥ 50x109/L and Doubling of Baseline) by Study Week Platelet Response (≥ 50x109/L and Doubling of Baseline) by Study Week