bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Autologous Stem Cell Transplantation in Adult Burkitt/ Burkitt-like Lymphoma: A Systematic Review
Authors: Joshi Utsav , Bhatt Vijaya R. , D'Angelo Christopher 
Published: November 2021

Abstract
Introduction: Burkitt and Burkitt-like lymphoma (BL/BLL) are highly proliferative germinal or post-germinal B cell tumors. Few studies have evaluated the impact of autologous stem cell transplantation (ASCT) on disease outcomes. We performed a systematic review to analyze the efficacy of ASCT in upfront consolidation and for treatment of relapsed/ refractory cases in adult BL/BLL.
Methods: A systematic search of the electronic database (PubMed, Cochrane, Google Scholar, and EMBASE) was conducted for relevant studies. Any clinical trial, prospective study, or retrospective study with clear outcome measures on the efficacy of ASCT in adult patients with BL/BLL were eligible for inclusion. The overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and progression or relapse were used to assess the efficacy.
Results: For patients who underwent ASCT in first CR, 5-year PFS and OS ranged between 70-78% and 70-83%, respectively. For relapsed/refractory disease, 5-year PFS and OS were reduced at 27% and 31%, respectively. Patients undergoing ASCT for chemoresistant disease fared poorly with an OS of 7% at 3 years versus 37% for chemosensitive disease (p ≤ 0.00001). The overall response rate (CR or PR) to ASCT for patients transplanted in first CR ranged between 71% and 92%. This was reduced to 37% for patients who were transplanted in disease status other than first CR. Disease progression/relapse was observed in 16% to 29% of the patients transplanted in first CR, and 55% to 60% in relapsed disease.
Conclusion: Our systematic review found insufficient evidence to support ASCT over chemotherapy alone in the first remission for adult BL/BLL. Evidence supports guidelines recommending ASCT for chemosensitive disease but suggests there is no benefit to ASCT for chemoresistant disease. Prospective studies of ASCT are required to definitively understand the value of ASCT for BL/BLL.
Figure 1 Figure 1.

Disclosures
Bhatt: Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; Incyte: Consultancy, Research Funding; Jazz: Research Funding; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy.
A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-Free Graft-Versus-Host Disease Prophylaxis Regimen with Post-Transplantation Cyclophosphamide and Abatacept to Standard of Care
Authors: Koura Divya , Tzachanis Dimitrios , Ball Edward D. , Costello Caitlin , Goodman Aaron M , Mangan James K. , Mulroney Carolyn , Maroge Joseph , Padilla Michelle , Breslin Peggy , Garrett Jodi , McConnell Kimberly 
Published: November 2021

Abstract
Background: Graft versus host disease (GVHD) is one the major causes of mortality and morbidity after an allogeneic stem cell transplantation. We hypothesized that we can induce post-transplant tolerance by using the combination of post-transplant cyclophosphamide (PTCy) and abatacept (CTLA4Ig) for GVHD prophylaxis. PTCy when given on Days +3 and +4 can eliminate host-reactive donor T cells. CTLA4Ig blocks the costimulatory signals given through CD28 to naïve donor T cells thus favoring an anergic phenotype that promotes tolerance towards recipient derived antigens. CTLA4Ig gives an activating signal to NK cells and therefore has the ability to preserve the graft-versus-tumor effect.
Methods: We have initiated a 50 patient randomized clinical trial. Patients with hematologic malignancies in need of a transplant and with an 8/8 matched donor are randomized 1:1 to tacrolimus and methotrexate for GVHD prophylaxis (standard of care arm) or PTCy on days +3 and +4 followed by CTLA4Ig on days +5, +14,+28, +56, +84, +112, +140 and +168. Patients are stratified by conditioning regimen (myeloablative vs reduced intensity) and by donor type (matched sibling vs matched unrelated donor). The primary endpoint is chronic GVHD at 1 year as a marker of tolerance induction. Secondary endpoints include acute GVHD rate, relapse rate, overall survival, GVHD-relapse-free-survival, transplant related mortality and infection rate. Post-transplantation immune reconstitution studies include measuring T cell and NK cell phenotype, PD-1 expression, and alloreactivity to recipient and third party at predetermined time points.
Results: 25 patients have been treated on this study, 10 of which are on the experimental arm. Patients on the experimental arm have been followed for up to 516 days post-transplant. So far no cases of chronic GVHD or grade 3-4 acute GVHD have been observed in the experimental arm. All the patients have engrafted and there have been no treatment related deaths.
Conclusions: The combination of PTCy and CTLA4Ig for GVHD prophylaxis is feasible. This ongoing study will examine its ability to induce post-transplant tolerance.

Disclosures
Tzachanis: Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Partner: Consultancy; Fate Therapeutics: Research Funding; Genentech: Research Funding; Bristol Myers Squibb: Research Funding; Incyte: Research Funding; EUSA: Consultancy; Takeda: Consultancy, Speakers Bureau; Magenta: Consultancy; Kyowa Kirin: Consultancy. Goodman: Seattle Genetics: Consultancy, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria. Mangan: Elevate Bio: Other: ad board.

OffLabel Disclosure:
abatacept: using as part of graft versus host disease prophylaxis
Plasma Lipidome Acts As Diagnostic Marker and Predictor for Cyclosporin Response in Patients with Aplastic Anemia
Authors: Ruan Jing , Han Bing , Wang Zhao , Yang Chen , Du Yali , Chen Miao 
Published: November 2021

Abstract
Background：The lipid metabolomic profile has been well defined in the pathogenesis and differential diagnosis in patients with different myeloid diseases. However, the role of plasma lipidome was rarely explored, especially in aplastic anemia (AA), a disease which has close connection with lipid metabolism.
Methods: Peripheral fasting serum levels of patients newly diagnosed with AA from March 2019 to December 2019 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the serum lipid profiles. Meanwhile, the lipidomes for patients with hypocellular myelodysplastic syndrome (h-MDS) and age and sex matched healthy volunteers were taken as controls. The lipid profiles were tested again 6 months after standard cyclosporin A（CsA）treatment in patients with AA. For all the patients, those with a history of hyperlipidemia, diabetes, obesity (body mass index &gt; 28 kg/m 2) or complications with other malignant diseases at diagnosis were excluded.
Results: The study enrolled 15 patients with AA, 11 patients with h-MDS and 20 healthy controls. All the enrolled AA patients were non-severe and transfusion dependent, and were treated with CsA 3-5mg/kg/d for at least 6 months. For h-MDS patients, five were MDS with single lineage dysplasia, three were MDS with multilineage dysplasia, and three were MDS-Excess Blasts 1 (MDS-RAEB1). Metabolites in arachidonic acid pathway and retinol metabolism were significantly decreased in the AA patients compared with the healthy controls (P&lt;0.05). AA patients had decreased arachidonic acid pathway metabolites and retinol metabolism-related metabolites as compared with h-MDS（P&lt;0.05), whereas h-MDS patients had increased metabolism of proline and threonine and abnormal sphingolipid metabolism compared with AA patients and the normal controls. After 6-month of CsA treatment, leukotriene B4, 15(S)-HETE, all-trans-retinal and protectin D1 decreased significantly. Patients who had response to CsA had higher levels of baseline protectin D1 (p=0.011), leukotriene B4 (p=0.011), 15(S)-HETE (p=0.004) and all-trans-retinal (p=0.000) than those who had no response.
Conclusion: The lipid profiles showed significant difference not only between patients with AA and healthy controls, but also between AA and h-MDS. Meanwhile, some of baseline value and the change in lipid molecules may predict the CsA response at 6 months.

Disclosures
No relevant conflicts of interest to declare.
CD44 Expression in Different Plasma Cell Diseases
Authors: Ning Xueqin , Wei Xiaolei , Chen Bingyuan , Li Zhen , Zheng Zhongxin , Yi Zhengshan , Feng Ru , Wei Yongqiang , Liu Qifa 
Published: November 2021

Abstract
CD44 expression in different plasma cell diseases
Introduction
Myeloma is a genetically complex disease which develops via a multistep process whereby plasma cells are driven towards malignancy through the accumulation of genetic "hits" over time. This multistep process permits myeloma to have four recognisable clinical stages including monoclonal gammopathy of undetermined significance (MGUS) , smouldering multiple myeloma (SMM) , multiple myeloma (MM) and plasma cell leukemia (PCL). CD44 as a complex adhesion molecule, is highly expressed in a variety of solid tumors and involved in metastasis and chemotherapy resistance . Previous studies had found that CD44 was also highly expressed in MM, and associated with advanced clinical stage, extramedullary myeloma (EM) and poor survival. However the relation of CD44 expression in different plasma cell disease remain unknown.
Patients and Methods
Newly diagnosed MGUS (n=12), SMM (n=11), MM (n=133) and PCL (n = 8) patients who were hospitalized in our hospital from December 2017 to December 2020 were enrolled. The diagnosis was based on the criteria of the International Myeloma Working Group. CD44 was detected by flow cytometry as follows: 2 ml of heparin anticoagulated bone marrow was collected from the patients at the time of diagnosis, 1×10 6 cells were detected, and a gate was set for identifying abnormal plasma cells characterized by CD138 and CD38. CD44 positive was defined as more than 20% of the plasma cells expressed CD44.
Results
From December 2017 to December 2020, a total of 164 patients diagnosed in our hospital were included in the study, including 12 MGUS patients, 11 SMM patients, 133 MM patients and 8 PCL patients. The expression proportion (7.9%±11.9%, 11.2%±15.5%, 40.2%±37.7%, 81.9%±25.6%, P &lt; 0.001) and expression intensity (the mean fluorescence intensity was 1 742.8±1 023.1, 2 915.7±923.0, 6 692.6±11 275.5, 25 359.6±22 604.5, P=0.001) of CD44 on the monoclonal plasma cells of MGUS, SMM, MM and PCL patients gradually increased. In 133 MM patients, 73 cases were for CD44 positive. CD44 positive patients were more likely to show ＞3 focal bone lesion (75.3% VS 50.0%, P=0.002), and international staging system（ISS）III stage (68.5% VS 51.7%, P=0.048) compared those with CD44 negative. CD44 expression rate was significantly higher in MM patients with extramedullary disease (n=26) than those without (n=107) (56.7%VS 36.2%, P=0.031)
Conclusion: Our study showed that from MGUS, SMM, MM to PCL, the CD44 expression on abnormal plasma cells was gradually increased. CD44 overexpression was associated with osteolytic lesions, advanced ISS staging and extramedullary myeloma. The results indicated that CD44 was related to the invasion degree of plasma cell disease, and could be used as a marker for differential diagnosis between different plasma cell disease.

Disclosures
No relevant conflicts of interest to declare.
Complete Remissions to PD-1 Blockade in Combination with Reduced-Dose ICE Chemotherapy in Two Cases of Relapsed or Refractory Classical Hodgkin Lymphoma with Bulky Lung Involvement after Failed PD-1 Blockade
Authors: Xiu Bing , Li Bing , Zhu Xinyu , Xiao Gangfeng , Luo Xiu , Yang Zhi-Zhang , Liang Aibin 
Published: November 2021

Abstract
Objective: To report 2 cases of relapsed or refractory classical Hodgkin lymphoma with bulky lung involvement who failed PD-1 blockade, obtained long-term complete remission after treatment with PD-1 blockade in combination with ICE chemotherapy, and provide an alternative regimen for this kind of patient.
Methods: The clinical data of 2 patients suffering refractory or relapsed Hodgkin's lymphoma with bulky lung involvement who were resistant to PD-1 monoclonal antibody were collected, the treatment processes, efficacy and toxic side effects of the patients were summarized.
Results: Both HL patients relapsed after multi-line chemotherapies and radiotherapy. One patient relapsed after autologous hematopoietic stem cell transplantation. The main manifestations were cough and dyspnea caused by large lung masses. Both patients received 3 kinds of PD-1 blockade. One progressed after stopping Nivolumab and enrolled the clinical trial of decitabine and Camrelizumab for 6 courses and got stable disease（SD）, then changed to Camrelizumab combined with ICE for 4 cycles and obtain complete metabolic remission（CMR）. The other patient progressed with Nivolumab or Camrelizumab combined with A (B) VD regimen, and 2 courses of BV. She was then treated with Sintilimab combined with ICE for 4 cycles and obtain CMR. Both patients' cough and dyspnea were significantly improved, and lung lesions were significantly reduced after receiving 1 cycle of PD-1 blockade with ICE regimen and the quality of life was greatly improved. After 4 courses of treatment, the PET/CT assessment achieved CMR. The main side effect was a second-degree bone marrow suppression and can be tolerable for the patient.
Conclusion: PD-1 blockade combined with ICE regimen chemotherapy has significant curative effect and mild adverse reactions, can be used to treat cases of relapsed or refractory classic HL with bulky lung involvement resistant to PD-1 blockade.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Hemoglobin Variants Influence Plasmodium Falciparum Sexual Differentiation
Authors: Flage Bethany , Dent Matthew , Tejero Jesús , Ofori-Acquah Solomon Fiifi 
Published: November 2021

Abstract
It has long been recognized that individuals who express variations of the hemoglobin-A (HbA) protein experience less severe malaria disease. As malaria remains to be one of the most significant infectious diseases in history, this human adaptation has led to the persistence of HbA variants (HbVARs) in the population. The intricate lifecycle of the parasite which causes the most cases of clinical malaria, Plasmodium falciparum, relies on both asexual and sexual reproductive cycles, with host to vector transmission reliant on sexual stage gametocyte formation. Multiple epidemiological studies have shown that HbVARs may influence gametocyte production during P. falciparum infection, with greater gametocyte numbers reported in individuals with hemoglobin variant containing erythrocytes (Hb VAR-Ery) when compared to hemoglobin A containing erythrocytes (Hb A-Ery). Here we provide experimental support for these studies by showing significantly higher sexual differentiation rates among parasites grown in Hb S containing erythrocytes (Hb S-Ery) obtained from sickle cell patients than those differentiated in Hb A-Ery (p=0.038). Because the digestion of hemoglobin is such an integral part of the intraerythrocytic cycle, we then sought to determine whether there was a difference between the hydrolysis efficiencies of HbA and other hemoglobin variants (HbVAR). By using a prominent recombinant P. falciparum hemoglobinase we found the hydrolysis efficiency of HbA to be significantly (p=0.0058) more efficient after 24 hours compared to a HbVAR sample containing mixed amounts of HbA, HbF, and HbS. To further determine whether there is a link between hemoglobin digestion efficiency and sexual differentiation, we therapeutically inhibited the hemoglobin digestion and hemozoin formation process in a culture of P. falciparum using sub-optimal doses of chloroquine diphosphate. We found a significant difference (p&lt;0.001) among gametocyte conversion rates between treated and non-treated cultures, as well as a moderate negative correlation between hemozoin formation and gametocyte conversion rate (Pearson r=0.72, p=0.008). Gene expression analysis also revealed patterns of expression that were consistent with increased gametocytogenesis. We conclude that hemoglobin type plays a significant role in the process of sexual conversion in P. falciparum. Though further studies should be completed in order to confirm these results, these findings may suggest hemoglobin digestion efficiency as a causative factor for sexual differentiation. As individuals with hemoglobinopathies make up approximately 7% of the global population, and malaria infection rates have been shown to differ depending on these genetic dynamics, these findings may support the creation of targeted initiatives to reduce transmission specifically in areas where there is a high percentage of hemoglobinopathy carriage.

Disclosures
No relevant conflicts of interest to declare.
Sickle Cell Disease Bias: An Early Opportunity for Intervention?
Authors: Patel Viral M , Ibrahim Ibrahim F. 
Published: November 2021

Abstract
Background: Sickle cell disease (SCD) is a genetic condition leading to multi-organ dysfunction and chronic pain, with 1 out of 13 African Americans having the trait. Despite its prevalence and debilitating symptoms, SCD remains a disease with limited therapeutic interventions and decreased life expectancy. There is a clinical bias to undertreat the pain of patients with SCD with opioid medications, despite their effectiveness (Zempsky 2009). Early education about SCD may lead to improvements in provider perceptions and disease management.
Methods: An anonymous survey was sent to first-year medical students at an academic institution prior to their hematology course. Data was collected about demographics, prior exposure to SCD, perceptions about opioid use disorder (OUD) in SCD, and baseline knowledge of management. Identical questions were asked for cancer-related pain. The survey was sent again after the completion of the hematology course to assess whether the curriculum was effective at characterizing misperceptions about patients with SCD.
Results: Fifty-five medical students answered the survey prior to the course. Students were 38% male and 62% female. Seventy-five percent of students (N=41) had never encountered a patient with SCD. Forty percent (N=22) answered that OUD in patients with SCD is more likely, 60% as likely (N=33), and 0% less likely than the general population. Seventy-one percent (N=39) believed opiates should play a minor role, 5% (N=3) a major role, and 24% (N=13) said opioids should be avoided when managing SCD-related pain. After course completion, 35 students who had completed the survey prior to the course responded, 29% male and 71% female. Fifty-four percent (N=19) answered that OUD in patients with SCD is more likely, 43% (N=15) as likely, and 3% (N=1) less likely than the general population. Seventy-one percent (N=25) thought opiates should play a minor role, 9% (N=3) a major role, and 20% (N=7) said they should be avoided when managed SCD-related pain.
Conclusion: After course completion, a higher percentage of medical students thought that OUD was more frequent in patients with SCD than the general population, with a similarly high percentage determining that opioid medications should play a minor role or be avoided in SCD. Opioid medications are an important part of treatment for SCD, especially for acute vaso-occlusive pain. Patients with SCD are no more likely to have OUD than the general population and have a lower rate of OUD than other patients with chronic pain conditions (Solomon 2008). This pilot study highlights that there is an opportunity to intervene in misperceptions of patients with SCD in early medical school education.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Harnessing Extracellular Vesicles from Red Blood Cells for Targeted Delivery of Therapeutic Peptides and RNAs for Leukemia Treatment
Authors: Jayasinghe Migara Kavishka , Pirisinu Marco , Chen Huan , Yang Yuqi , Peng Boya , Shi Jiahai , Le Minh TN 
Published: November 2021

Abstract
Extracellular vesicles (EVs) are emerging as a new class of natural drug carriers with intrinsic ability to deliver bioactive cargo at high efficiency and low toxicity. However, clinical applications of EVs are limited by the production scale and the delivery specificity. We have recently established a new platform for purification and surface modification of EVs from red blood cells (RBCs) that are scalable and versatile for targeted delivery of small-molecule drugs and RNA therapeutics (Usman et al, Nat. Com. 2019 and Pham et al, J. Extracell. Vesicles 2021). Here, we describe a new development of the method for conjugation of RBC-EVs to obtain a higher targeting efficiency. We conjugate RBC-EVs, not only with peptides and nanobodies, but also with monoclonal antibodies, by coupling peptide conjugated EVs with streptavidin-bound biotinylated antibodies. Our data demonstrate that the conjugation is stable and does not affect the physicochemical characteristics of EVs. Conjugation of EVs with a cyclic peptide targeting CXCR4 or a monoclonal antibody targeting CD33 promotes specific binding and uptake of the conjugated EVs by leukemia cells expressing the corresponding receptors. We further use CXCR4-targeting RBC-EVs to specifically deliver the pro-apoptotic peptide KLA to CXCR4-expressing leukemia cells. Delivery of KLA using CXCR4-targeting EVs significantly suppresses leukemia burden and increases survival in a leukemia xenografted mouse model. Antibody-conjugated RBC-EVs are used to deliver RNA antisense oligonucleotides to knockdown FLT3 and miR-125b in cell lines and in patient-derived xenograft models of leukemia. Finally, we demonstrate that peptide/antibody conjugated RBC-EVs are biocompatible and nonimmunogenic. Our study provides a new platform for targeted delivery of therapeutic peptides and RNAs that is highly efficient, stable, versatile and biocompatible for potential clinical applications in leukemia treatment.
Migara Kavishka Jayasinghe, Marco Pirisinu, Huan Chen, and Yuqi Yang contributed equally to this work as first authors.

Disclosures
Jayasinghe: Carmine Therapeutics: Patents & Royalties. Shi: Carmine Therapeutics: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Le: Carmine Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.