bluuebunny/crossref_metadata_2025_split huggingface dataset:
Provisional Prognostic Score for Plasmablastic Lymphoma
Authors: Haddad Philip A , Lerner Jaren 
Published: December 2023

Background
Plasmablastic Lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. It tends to be associated with immunosuppressive clinical contexts, such as HIV infection and immunosuppressive therapies for autoimmune disorders and organ transplants. However, due to the rarity of the disease, which needs to be better understood, varied treatment approaches have been implemented, and no optimal data or guidelines for managing PBL are available. Therefore, we conducted this study to develop a provisional PBL prognostic score (PBLPS) for this rare disease.
Methods
We used our constructed PBL database, which contains retrospective data on 300 cases. Such data included demographics such as sex, age, and race. It also included disease presentation symptoms, duration of symptoms before diagnosis, site(s) of the disease, blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 300 cases, 291 had complete survival and outcomes data, the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios.
Results
The median OS of the cohort was 25 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: LDH&gt;500 (p=0.04), CD4&lt;100 (p=0.006), bone marrow (BM) involvement (p&lt;0.0001), EBER-negative (p=0.01), HHV8+ (p=0.02), and involvement of liver (p=0.003), lungs/pleura (p&lt;0.0001), and upper GI tract (p=0.001). A prognostic model was devised using these variables to identify different levels of risk. Involvement of BM and involvement of any of the worse prognosis organs (liver, lung/pleura, and/or upper GI tract) were each assigned a score of 2 when present. CD4&lt;100, EBER-negative, and LDH&gt;500 were assigned 1 point each as they had the lowest hazard ratios of all the other variables. In this exploratory cohort, we assigned low risk a score of 0, intermediate risk a score of 1-2, and high risk a score of 3-7. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of NR, 15, and 4 months, respectively (p&lt;0.0001).
Conclusion
This PBLPS is a promising new tool for risk-stratifying patients with PBL. However, it still requires prospective validation.
Inhibition of CDC20 Suppressed the Development and Progression of Mantle Cell Lymphoma
Authors: Chen Yingtong , Yang Ping , Wang Jing , Gao Shuang , Ke Xiaoyan , Jing Hongmei 
Published: December 2023

Background: Cell division cycle 20 homologue (CDC20) is an important factor regulating the cell mitosis phase. CDC20 is highly expressed in several types of cancers, which is related to the clinicopathological characteristics and prognosis of cancer patients. This study aimed to explore whether CDC20 could affect the development and progression of mantle cell lymphoma (MCL) and the underlying mechanism.
Methods: The expression level of CDC20 was detected in peripheral blood mononuclear cells (PBMCs), bone marrow mononuclear cells (BMNCs) and pathological tissues of MCL patients and MCL cell lines (Z138, Mino, Rec1). The CDC20 inhibitor apcin was used to evaluate the effect of CDC20 on the cell phenotypes of MCL cells. The changes in cell proliferation, apoptosis, cell cycle, cell migration and invasion were determined using CCK-8, flow cytometry, and Transwell assays, respectively. The anti-tumor effect of apcin were investigated in vivo in the Z138-driven xenograft tumor model. RNA-seq was performed to explore the pathways that changed in MCL cells after apcin treatment, and then these possible changes were verified in vitro and in vivo by western blot.
Results: CDC20 was overexpressed in PBMCs, BMNCs, and pathological tissues of MCL patients and MCL cells compared with their respective control group. In Z138, Mino, and Rec1 cells, apcin could inhibit cell proliferation, migration, and invasion, promote cell apoptosis, and induce cell cycle arrest. Moreover, apcin confirmed its safety and anti-tumor activity in vivo. In apcin-treated MCL cells and mice, the PI3K/AKT pathway was significantly inhibited (Figure 1).
Conclusions: This study confirms the essential role of CDC20 in MCL tumorigenesis. Anti-tumor therapy targeting CDC20 is expected to be a powerful treatment strategy for MCL patients.
Daratumumab Maintenance after Autologous Hematopoietic Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma
Authors: Ma Yi , Xiao Xiubin , Yuan Shunzong , Chen Xilin , Zhao Shihua , Cheng Nana , Lu Yun , Chen Junli , Wang Yueqi , Huang Wenrong 
Published: December 2023

Background: Maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT) is a standard of care in newly diagnosed multiple myeloma (NDMM). Lenalidomide maintenance after transplantation is the most frequently recommended regimen. Daratumumab has been increasingly used as a maintenance drug in NDMM. However, there is no enough clinical information about daratumumab as maintenance strategy after ASCT. This study is aim to evaluate the efficacy and safety of daratumumab as maintenance after ASCT for NDMM.
Patients and Methods: Clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between 1 May 2022 and 30 June 2023 were retrospectively analyzed. Daratumumab-naive patients received weekly dosing (16mg/kg) for the first 8 weeks.
Results: Fifteen patients (11 males and 4 females) with median age of 58 years (41～72 years) , were included. Thirteen patients were daratumumab native, 6 patients had renal impairment, and 2 patients with high-risk cytogenetics. The median infusion times of daratumumab were 12 (6～17) times. Efficacy was evaluable in all 15 patients，and daratumumab maintenance therapy increase the rate of stringent complete response (from 6 [40%] to 9 [60%] ) by 20%，improved the renal response rate and median eGFR in patients with renal injury. During maintenance therapy with daratumumab, the most common hematological grade 3 adverse events(AE) were lymphopenia (4 [26.67%] of 15 patients), non-hematologic adverse events were infusion-related reactions (7 [46.67%] of 15 patients) and grade 3 pneumonia (5 [33.33%] of 15 patients). These 5 pneumonia patients were daratumumab naive ( 5 [38.46%] of 13 patients) , with median 8 (6～10)infusions. Among them, 3 patients chest CT showed interstitial infiltrates, and combination of methylprednisolone was effective. With a median follow-up of 12 months, one patient had died (not related to daratumumab treatment), 1-year OS rate was 93.33%.
Conclusions: Daratumumab was safe and effective as a maintenance agent for post-ASCT patients with NDMM, and adverse events were controllable. The most common AE is grade 3 pneumonia, maybe a less dose-intense maintenance regimen for the first 8 weeks can reduce the incidence of pneumonia.
The Significance of a “MGUS” Tumor Board
Authors: Mazzoni Sandra , Khouri Jack , Williams Louis S. , Faiman Beth M. , Mathur Saveta , Scott Cynthia 
Published: December 2023

Our large academic medical center consists of both a main campus and several regional sites that all offer hematology/oncology services where monoclonal gammopathy cases are referred for consultation. We receive well over 100 requests annually to see cases with abnormal monoclonal proteins. The challenge was how to triage these requests, with the goal of improving patient access to main campus myeloma experts while improving patient care and timely management. We decided to schedule cases initially referred for monoclonal gammopathy of undetermined significance (MGUS) with our advanced practice providers (APPs) both in the region and at main campus.
Due to the concern for varying experience managing MGUS, differences in diagnostic practice and limited guidance we developed a novel concept to have a tumor board to review MGUS cases that were initially seen by our APPs. The “MGUS” tumor board is ran by three of our main campus myeloma focused hematologists and our myeloma dedicated APRN-PhD. We meet twice a month to review cases.
Over the past 2 years we reviewed 147 cases providing recommendations for further work up. Of these, 41 cases (28%) were found to have a clinically significant monoclonal protein necessitating referral to a physician at main campus. The breakdown of these cases are detailed below in T able 1. Sixteen patients (11%) were started on treatment, the other 25 (17%) remained on observation.
Another aspect of the tumor board is to provide education regarding clinically significant scenarios that involve monoclonal proteins. This tumor board offers CME credit for both APPs and physicians. By developing a team of knowledgeable APPs we have shifted 72% of monoclonal gammopathy referrals to remain under the care of APPs which improved access to main campus myeloma physician experts. This allowed the myeloma team at main campus to see more second opinions, open more clinical trials and expand our cell-therapy options for patients. Our referral base has grown and we have hired more APPs in the region and two additional myeloma physicians at main campus since starting the “MGUS” tumor board.
Overall, we were successful in transitioning “MGUS” referrals to our APPs, but there were higher than expected percent of patients with clinically significant monoclonal proteins. Our data shows that it is essential for there to be some standardization for reviewing and working up “MGUS” referrals. This is especially important at large centers with multiple regional locations. We recommend a tumor board style review as it allows for discussion and education of “MGUS” referrals which prove to be far more complex in many cases.
Compared to Venetoclax Plus Hypomethylating Agents, High Dose Cytarabine Based Intensive Chemotherapy Induction for Newly Diagnosed Acute Myeloid Leukemia (AML) Leads to a Faster Remission Resulting in Better Survival
Authors: Solh Melhem M. , Solomon Scott R. , Morris Lawrence , Holland H Kent , Bachier-Rodriguez Lizamarie , Zhang Xu , Jackson Katelin C , Bashey Asad 
Published: December 2023

Hypomethylating agents plus venetoclax is a commonly used induction regimen for newly diagnosed AML patients who are not eligible for standard intensive chemotherapy (IC). Due to the high remission rates and the easier administration of Venetoclax plus hypomethylating agents in the outpatient settings and community practices, some patients receive such induction even if IC eligible. We retrospectively analyzed 206 newly diagnosed AML patients, age 56-80 years who received either Venetoclax plus hypomethylating agents (n=65) or high dose cytarabine based IC ( n=141) to assess the difference in remission rates, time to achieve remission and the impact of time to achieving remission on survival endpoints.
Patients who received IC ( FLAG or CLAG +/- Idarubicin) were younger ( median age 66 (56,79) vs 73(56,79) years, p&lt;0.001) but had similar race distribution, NCCN cytogenetics risk and distribution of primary versus secondary leukemia compared to patients with hypomethylating agents plus venetoclax. Patients who received IC has similar chance of achieving CR (89% vs 71%, p=0.89) and transplant rate compared to venetoclax/hypomethylating agents. Patients who received IC had better DFS (p=0.026), a trend towards better OS (p=0.06) and similar relapse risk (p=0.69) compared to venetoclax/hypomethylating agents (figure 1). In a logistic regression analysis, patients who received IC and patients with favorable/intermediate risk AML had higher likelihood of achieving CR in the first 60 days post induction ( HR 2.34, 95% CI 1.19-4.61; P=0.01 for IC versus Venetoclax/hypometh; and HR 0.24 , 95% CI 0.12-0.49, P&lt;0.001 for NCCN adverse versus favorable/intermediate risk AML). A cox model for survival endpoints where age was factored into three equal size groups (56-63, 64-70 and 71-79) and NCCN risk fitted as strata, was performed on survival endpoints. Achieving CR1 within 60 days of induction treatment had significant impact on overall survival (HR 0.24, 95% CI 0.13-0.46, p&lt;0.001).
Our data shows that among patients aged 55-80 years with newly diagnosed AML, receiving high dose cytarabine based IC have similar rates but more likely to achieve CR within 60 days than venetoclax plus hypomethylating agents. Achieving CR within 60 days of induction is a predictor of better overall survival. Based on our analysis, high dose cytarabine based IC should remain the preferred choice for patients eligible for such treatment.
Integrating AI and ML in Myelodysplastic Syndrome Diagnosis: State of the Art and Future Prospects
Authors: Elshoeibi Amgad , Badr Ahmed , Elsayed Basel , Metwalli Omar , Elhadary Mohamed , Alhuraiji Ahmad , Cherif Honar , Khadadah Fatima , Yassin Mohamed A 
Published: December 2023

Introduction:
Myelodysplastic syndrome (MDS) is a diverse group of hematological malignancies characterized by dysfunctional pluripotent stem cells, leading to abnormal hematopoiesis and cytopenia. Early diagnosis is crucial for improving patient outcomes. Artificial Intelligence (AI) and Machine Learning (ML) have emerged as powerful tools in healthcare for disease diagnosis and monitoring. This review aims to summarize the current state of AI application in the diagnosis of MDS, discussing various ML models, their advantages, disadvantages, and performance metrics.
Methods:
A comprehensive search strategy was developed using Medical Subject Headings (MeSH) terms and relevant keywords related to MDS and AI/ML. Pubmed, Embase, and scopus were searched, and duplicates were removed. Only original research articles studying ML algorithms in the diagnosis of MDS in human subjects were included. Studies on animals, reviews, non-original articles, and non-English papers were excluded. For each article, data on the area under the receiver operating curve, sensitivity, specificity, and accuracy for the best preforming model were collected.
Results:
The search yielded 313 articles, and after screening, 16 articles met the inclusion criteria. These articles were grouped based on the data utilized in the training of their models. Five articles utilized bone marrow smears for the training of their data. Their models aimed to detect dysplastic cells and blasts in bone marrow smears. The majority of these studies utilized convolutional neural network (CNN), a ML algorithm, for image recognition. One study utilized decision tree models. The AUC of these models ranged between 0.8 and 0.996. All the models were internally validated but were not externally validates. Three studies utilized peripheral blood smears for the training of their ML models. Two of these studies also utilized CNN for the detection of dysplasia and subsequent diagnosis of MDS. One study utilized CART to create a decision tree algorithm. The AUC for these models ranged between 0.982-0.99. Four studies utilized flowcytometry data from bone marrow samples for the training of their AI models. These models achieved AUC ranging between 0.935-0.97. Two of these models were both internally and externally validated, one of which was on a prospective cohort.
Conclusion:
The integration of AI and ML in MDS diagnosis holds promise for early detection and improved patient care. The reviewed studies showed encouraging results, indicating that AI-based approaches can complement traditional diagnostic methods and aid in making more informed clinical decisions especially when it comes to analysing blood/bone smears. However, many of these models need to be externally validated in large prospective cohorts to establish AI's role in routine clinical practice.
The Correlation between Alterations in the Intestinal Microbiome and Early Outcomes of Autologous Hematopoietic Cell Transplantation in Diffuse Large B-Cell Lymphoma
Authors: Sheng Lixia , WANG Jiaping , Lin Zhouning , Lai Yanli , Ouyang Guifang 
Published: December 2023

Introduction: Prior research has documented a decline in the diversity of fecal microbiota among individuals with diffuse large B-cell lymphoma (DLBCL) who undergo autologous hematopoietic cell transplantation (auto-HCT). Nevertheless, the potential influence of gut microbiota on hematopoietic reconstitution, immune reconstitution, and early complications in this specific patient cohort remains uncertain.
Methods: A total of 42 fecal samples were obtained from 21 adult individuals who underwent autologous hematopoietic cell transplantation (auto-HCT) for diffuse large B-cell lymphoma (DLBCL), both prior to and two weeks following allogeneic stem cell transplantation (ASCT). The diversity of fecal microbiota was assessed using 16S ribosomal gene sequencing. Additionally, correlations between alterations in the fecal microbiome and clinical characteristics, as well as host immune indices, were examined.
Results: The beta diversity index of intestinal microecology exhibited a significant decrease following transplantation, whereas the alpha diversity index remained unaltered. Prior to transplantation, the abundance of g_Prevotella_7, g_Sutterella, and g_Enterococcus demonstrated a positive correlation with intestinal infection caused by Carbapenem-resistant Enterobacteriaceae. Conversely, the abundance of g_Blautia prior to transplantation and g_Lachnospira following transplantation exhibited a negative correlation with the duration of post-transplant fever. The abundance of g_Enterocococcus, g_Veillonella, g_Sutterella, g_Prevotella_7, and g_Streptococcus following transplantation exhibited a positive correlation with the occurrence of diarrhea. Conversely, the abundance of g_Weissella displayed a negative correlation with the duration of neutrophil and megakaryocyte engraftment, while g_Prevotella_7 exhibited a positive correlation with the duration of neutrophil engraftment. Additionally, the abundance of g_Sutterella and g_Prevotella_7 prior to transplantation, as well as the abundance of g_Lachnoclostridium, g_Blautia, g_Lachnospira, g_Veillonella, and g_Sutterella following transplantation, were positively correlated with host immunity.
Conclusions: The intestinal microbiome experienced significant fluctuations throughout the autologous stem cell transplantation (ASCT) procedure in patients with diffuse large B-cell lymphoma (DLBCL), and these changes exhibited a strong correlation with both early prognosis and post-transplant immune reconstitution. Consequently, additional investigation is necessary to establish strategies for modulating the gut microbiota and enhancing the efficacy of ASCT in DLBCL patients.
Downregulation of Mitochondrial Complex II (MC II) in Myelodysplastic Syndromes
Authors: Sezaki Maiko , Hashimoto Michihiro , Yokota Asumi , Salomonis Nathan , Grimes H. Leighton , Huang Gang 
Published: December 2023

Myelodysplastic syndromes (MDS) are a group of diseases of hematopoietic stem cells (HSCs) that occur in the aging population and following therapy for unrelated cancers. The standard of care for MDS involves hypomethylating agents (HMAs) that invariably result in resistance and disease progression. We previously determined the role of mitochondrial metabolism in MDS pathophysiology, whereby suppression of mitochondrial activity leads to the accumulation of oncometabolites that competitively inhibit α-ketoglutarate-dependent dioxygenases (2OGDDs). Consequently, hypermethylation of epigenomes and hypoxia-inducible factor 1A (HIF1A) activation ensues a pseudohypoxia state that drives MDS pathogenesis.
Our recent informatics analyses of primary MDS samples identified a patient subset with high TGF-β signaling in which mitochondrial complex II (MC II) genes were downregulated. MC II, or succinate dehydrogenase (SDH) is the smallest complex of the oxidative phosphorylation system that oxidizes succinate to fumarate and thereby donates electrons to reduce FAD to FADH 2 and the ubiquinone pool. Its downregulation results in the accumulation of Krebs cycle intermediate metabolites that can act as antagonists for 2OGDDs. To understand whether SDH dysregulation alone can contribute to MDS pathobiology, we generated a doxycycline-inducible and reversible mouse model (SDH-KD) that expresses shRNAs against the SDH subunits (SDHA, B, and D) in HSCs. These mice showed a gradual buildup of intracellular succinate in c-Kit + bone marrow (BM) cells and the peripheral blood, and a corresponding decrease of fumarate levels after induction for 2 weeks, 4 weeks, and 2 months. We found that knocking down Sdh was sufficient to induce pancytopenia and trilineage dysplasia in SDH-KD mice, while intracellular iron granules that surround the nucleus of erythroblasts, similar to ring sideroblasts commonly observed in MDS patients were also detected in BM and spleen smears. Of note, removing doxycycline and restoring Sdh expression rescued macrocytic anemia among other MDS phenotypes. Furthermore, treating SDH-KD mice with HMAs restored mitochondrial respiration and reversed HIF1A activation through the upregulation of SDH subunits. Using another MDS model, MllPTD/WT/ Vav1-Cre/Runx1 Flox/Flox, we found that HMA-treated HSCs differentiate towards CD11b +Gr1 + mature myeloid cells and that this requires Sdh expression.
In conclusion, our results indicate that pseudohypoxia- and TGF-β signaling-associated changes in metabolic regulation caused by SDH downregulation underlie MDS pathogenesis. Elucidating the role of MC II in MDS pathobiology may provide alternative targets that can be combined with HMA or luspatercept therapy for MDS.