bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Study of Polatuzumab Vedotin-Based Regimen for Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Chinese Cohort: Updated Results of 2-Year Follow-up
Authors: Wu Jianqiu , Li Fei , Wuxiao Zhi-Jun , Tang Weiyan , Teng Yue , Liu Yanyan , Chu Han , Wu Zhiya , Shen Yiwen , Kong Fancong , Yao Zhihua , Zhou Weilun , Feng Jifeng 
Published: December 2023

Introduction
Patients with relapsed or refractory (r/r) DLBCL had poor prognosis when ineligible to autologous hematopoietic stem cell transplantation (auto-HSCT). Polatuzumab vedotin (Pola) has demonstrated significant efficacy and acceptable safety in such patients in Clinical trials and real-world data. Here we reported long-term follow-up result of Pola-based regimen in real-world Chinese cohort.
Aims
To evaluate the efficacy and safety of Pola-based regimens for the treatment of r/r DLBCL using real-world data.
Methods
This retrospective study analyzed data from the Chinese Pola compassionate use program, conducted at four tertiary hospitals from December 2019 to June 2021. Patients with r/r DLBCL were enrolled. The treatment regimens included Pola in combination with rituximab (Pola+R) or with additional bendamustine (Pola+BR) administered for six cycles, with each cycle lasting 21 days. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were analyzed.
Results
Thirty-nine patients were included in the analysis, with a median follow-up of 23.5 months (range: 0.6-35.2). The ORR at the end of treatment was 38.5% (15/39), while the best ORR achieved was 69.2% (27/39). The median PFS and OS were 6.6 months (95%CI: 3.7-9.6) and 15.6 months (95%CI: 3.4-27.9), respectively. Compared to those who did not complete six cycles of treatment, a significantly longer PFS (12.1 vs. 3.5 months, P=0.006) and OS (18.8 vs. 6.3 months, P=0.001) was observed in patients who completed all six cycles of treatment. Among 16 patients receiving Pola+R and 23 receiving Pola+BR, the proportion of patients who completed all six-treatment cycles was 56.3% and 34.8%, respectively. Grade 3-4 AEs were reported in 48.7% of patients with most commonly occurred being neutropenia (28.2%), leucopenia (17.9%) and thrombocytopenia (15.4%).
Conclusions
The 2-year follow-up analysis demonstrated sustained progression-free and overall survival, with no new safety signals. The full cycles of Pola-based regimen may contribute to better efficacy for real-world populations. These findings supported Pola-based regimens as an effective real-world treatment option for Chinese patients with r/r DLBCL.
Key words
Diffuse large B-cell lymphoma; refractory/relapsing; polatuzumab vedotin; real-world study; China.
A Study on Heterogeneity and Early Response to Chemotherapy in Pediatric ETV6-RUNX1 Positive Acute Lymphoblastic Leukemia By RNA-Seq Expression Profile
Authors: Zheng Xueling , Zhou Chunyu , Zhang Ruidong , Gao Chao , Han Jingdong , Wang Tianyou , Zheng Huyong 
Published: December 2023

Objective
ETV6-RUNX1 positive ALL is the most common type in childhood acute lymphoblastic leukemia(ALL), and it is also a type with good prognosis. However, there are still recurrent or refractory cases in this type, and there is still heterogeneity among individuals.In this research, we investigate the heterogeneity of ETV6-RUNX1 positive ALL in children by RNA-seq expression profile, and to explore the early response to chemotherapy and microenvironment characteristics of different clusters, so as to provide evidences for the exploration of genetic high-risk factors and clinical personalized diagnosis and treatment of such children.
Method
From September 2019 to June 2021, 72 children with newly diagnosed ETV6-RUNX1 positive ALL in standard risk group were enrolled and treated with CCLG-ALL-2018 chemotherapy protocol, which were all detected by RNA-seq technology. The sequencing results were analyzed by cluster analysis and bioinformatics analysis. We explored the early response to chemotherapy and microenvironment characteristics of the different clusters.
Result
ETV6-RUNX1 positive ALL were divided into three groups according to the RNA-seq expression profile including 16 cases (22.2%) in ER1 group, 35 cases (48.6%) in ER2 group and 21 cases (29.2%) in ER3 group. The number of patients with co-negative minimal residual disease (MRD) by flow cytometry (MRD-FCM) and next-generation sequencing (MRD-Gene) on the 15th day of chemotherapy in ER1 and ER3 groups was significantly different (3/16 vs. 13/21, P=0.0178), while there were 17 cases (17/35) with co-negative MRD in ER2 group after fifteen-day chemotherapy. It showed that the proportion of NK cells ( P=0.056) and CD8 + T cells ( P=0.047) in peripheral blood in ER1 group were both higher than those in ER3 group. Compared with ER3 group, ER1 group showed low expression of RPL41 and high expression of MRPS28 and SERPIND1, which were mainly involved in stress, proliferation and drug resistance of cells and the differentiation of hematopoietic stem cell. In addition, ER1 group showed lower expression of ribosome-related genes and higher activation of mTOR pathway than ER3 group.
Conclusion
The heterogeneity in gene expression profile were presented in children with ETV6-RUNX1 positive ALL. Compared with ER3 group, patients in ER1 group may have a poorer early response to chemotherapy with a relatively higher risk due to the stronger proliferation and drug resistance of leukemic cells probably. For patients in ER1 group, even if MRD is negative on the 15th day of themotherapy, it may be necessary to strengthen the observation of early response and consider the treatment for escalated risk in time.
Hyperammonemic Encephalopathy in Multiple Myeloma: Systematic Review and Case Series
Authors: el Ghoubaira Joseph , Alsouqi Aseel , Farah Rafic J 
Published: December 2023

Objectives: To better understand the presentation and clinical outcomes of hyperammonemic encephalopathy in multiple myeloma, we report 3 cases from our institution and present 55 published cases from the literature.
Background/Intro: Hyperammonemia is a rare but life-threatening complication of multiple myeloma with poor survival despite treatment. Little is known about the clinical presentation and outcomes of patients suffering from this entity. We hereby report a systematic review and a meta-analysis of cases with hyperammonemic encephalopathy.
Methods: Case reports and case series were identified using the Medline database, as well as PubMed search engine. Clinical and pathological data were collected and stratified by demographics and treatment. The data was further analyzed using SPSS.
Results: A total of 58 patients were included in the study. The mean age of the affected patients was 64.4 years, male to female ratio was 1.15:1. The median ammonia level measured was 123 μmol/L. Stage III disease was most prevalent in reported cases (89%). Most common MM subtype was IgG (38%) followed by IgA (36%). Thirty-seven patients (64%) had relapsed disease, while 17 (29%) were new diagnoses. Overall, 35 out of 58 (60%) patients died while being treated as inpatients. Chemotherapy was the only variable associated with an improved survival with p-0.02.
Conclusion: Hyperammonemia in the setting of multiple myeloma is an uncommon complication. It is associated with poor prognosis. Treatment should begin as soon as the diagnosis is confirmed with myeloma directed therapy in order to improve survival.
Multicenter Open Label Phase 2 Study of Quadruplet-Based Regimen Iskpd (isatuximab plus pomalidomide and dexamethasone with carfilzomib) in Early Relapsed or Refractory Multiple Myeloma - IFM2018-03
Authors: Bobin Arthur , Lambert Jerome , Ragot Stéfanie , Perrot Aurore , Manier Salomon , Karlin Lionel , Caillot Denis , Benboubker Lotfi , Chalopin Thomas , Araujo Carla , Fontan Jean , Braun Thorsten , Mariette Clara , Scherman Elodie , Decaux Olivier , Blade jean Sebastien , Keddar Faiza , Roul Christophe , Dib Mamoun , Corre Jill , Orsini Piocelle Frederique , Vincent Laure , Touzeau Cyrille , Moreau Philippe , Avet Loiseau Herve , Leleu Xavier 
Published: December 2023

Background. RRMM (relapsed or refractory multiple myeloma) is associated to shortened OS (survival) with subsequent relapses and needs optimized treatment approaches. The current treatment paradigm is based on triplet-based association of antiCD38 immunotherapy (antiCD38 IT) with either Imids (Pomalidomide) and dexamethasone or proteasome inhibitors (PI) such as Carfilzomib and dexamethasone. However, quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) have transformed the treatment landscape in the upfront setting, improving MRD (minimal residual disease) and survival.
We hypothesized that a quadruplet-based regimens (antiCD38 immunotherapy +Imids +PI +dexamethasone) would further improved MRD and survival in early RRMM. We describe a phase II multicentric, open-label study, of isatuximab, pomalidomide and dexamethasone plus carfilzomib (IsKPd/ IFM2018-03, NCT04287855) for patients with early RRMM.
Study design and Methods. Approximately 90 patients will receive the association of isatuximab, pomalidomide and dexamethasone with carfilzomib (IsKPd), and the study has fully enrolled 82 patients as of January 2023. Eligible patients are adults aged ≥18 years old with RRMM previously treated with 1 or 2 lines of therapy, including lenalidomide, prior to the study entry. Patients were excluded if they were refractory to any anti-CD38 monoclonal antibody or to carfilzomib, or if they were previously exposed to pomalidomide. Isatuximab will be given by IV route at 10 mg/kg on days 1, 8, 15, and 22 of cycle 1, on days 1 and 15 from cycle 2 to 12 and on day 1 only from cycle 13, 28-day cycles. Carfilzomib will be given by IV route at 20/27 mg/m² on days 1-2, 8-9, 15-16 during cycle 1, at 56mg/m² on days 1, 8, 15 from cycle 2 to 13 and at 56mg/m² on days 1 and 15 after cycle 13. Pomalidomide will be administered by oral route at 3 mg daily on days 1 to 21 in cycle 1 and at 4 mg daily from cycle 12. Dexamethasone will be given by oral route at 40/20 mg daily on days 1, 8, 15 and 22. The primary objective is to evaluate the MRD rate at 10-5 in patients with RRMM treated with IsKPd. Patients will pursue Isa-KPd until progression or unacceptable toxicity. Key secondary objectives include the survival analysis (OS, PFS, EFS, TTNT), response rates and duration of response and evaluation of the safety profile.
The study is expected to read out in January 2024 with sustained MRD reported.
CCL1 As a Biomarker of Engraftment Syndrome of Hematological Stem Cell Transplantation
Authors: Maki Hiroaki , Honda Akira , Masamoto Yosuke , Kurokawa Mineo 
Published: December 2023

BACKGROUND
Many complications occur in the practice of hematopoietic stem cell transplantation, especially those presenting with fever, which can be caused by infection as well as engraftment syndrome (ES), which is difficult to distinguish. The mechanism of ES is unknown, and no characteristic biomarkers have been identified.
METHODS
We attempted to identify cytokines specific to the engraftment syndrome by cytokine array analysis of sera from 7 patients who underwent HSCT at our institution from January 2019 to March 2022 and who developed fever between 1 week before and the day of engraftment.
Cases in which pathogens were detected in blood culture at the time of fever were diagnosed as infections, and cases in which blood culture was negative or clinically treated as engraftment syndrome or fever associated with engraftment were diagnosed as engraftment syndrome. Cases that did not present with fever from infusion to engraftment were used as negative controls.
RESULTS.
Three of the seven patients had fever due to infection and four had fever due to engraftment syndrome. Median age was 41 (21-62) years, 5 males and 2 females. Four patients had acute leukemia, one had chronic myelomonocytic leukemia, and two had nonhematologic tumors. The donors were blood related in 3 cases, unrelated in 3 cases, and cord blood in 2 cases. Pretreatment was myeloablative (MAC) in 2 patients and reduced intensity pretreatment (RIC) in 5 patients.
Cytokine arrays identified five cytokines that were elevated in the ES group. Of these, cytokine The cytokine CCL1 (I-309) tended to be elevated in the ES group (p=0.06). The validity of CCL1 with respect to the diagnosis of fever of engraftment was examined using sera from another 16 hematopoietic stem cell transplant cases performed at the same period, and the results showed that CCL1 was only mildly elevated in cases diagnosed with infection, regardless of the elevated values of fever and inflammatory response, but tended to be elevated in fever of engraftment (area under ROC curve: 0.74 (95% confidence interval 0.422-1)).
CONCLUSIONS.
CCL1 was identified as a cytokine specific for ES, indicating that CCL1 may be useful in differentiating ES from infection. CCL1 is mainly secreted by T lymphocytes and its oversecretion during the hematopoietic recovery process may be involved in immune activation and the engraftment syndrome.
Voltage-Dependent Anion Channel 2 (VDAC2) Drives Rituximab Resistance Via Inhibiting Ferroptosis in Diffuse Large B Cell Lymphoma
Authors: Li Qiong , Xia Jing , Li Xinlei , Zhang Xi , Rao Jun 
Published: December 2023

Background: The underlying mechanism of rituximab resistance is still unclear; it is important to explore novel therapeutic targets to improve the outcomes of the patients. Here, we tried to identify the effects of Voltage-dependent anion channel 2 (VDAC2) on rituximab resistance as well as its therapeutic value in diffuse large B-cell lymphoma (DLBCL).
Methods: VDAC2 was identified by transcriptome and proteome sequencing analysis of rituximab-resistance cells. The effects of VDAC2 in rituximab resistance were investigated by gain-of-loss function experiments. The effects of VDAC2 regulating ferroptosis was evaluated with lipid ROS, MDA and GSH detection assays. Evaluate effect of VDAC2 on therapeutic efficacy was performed by Xenograft mouse model.
Results: Transcriptome and proteome sequencing analysis of rituximab-resistance and control DLBCL cells identified that VDAC2 was highly expressed in rituximab-resistance cells, and we found that VDAC2 could predict the prognosis of patients treated with RCHOP regimens, but not CHOP regimen. Knock-down of VDAC2 significantly inhibited cell proliferation and arrested cell cycle in S phase, as well as enhanced sensitivity to rituximab. Moreover, we found that knockdown expression VDAC2 significantly repressed lactate production, the extracellular acidification rate, treatment with exogenous lactate could abrogated the effects mediated by VDAC2. Meanwhile, we further found that ferroptosis was responsible for VDAC2 mediated rituximab resistance. Knockdown expression of VDAC2 increased lipid ROS and MDA levels, decreased the GSH levels, and repressed expression of SLC7A11 and Gpx4. Moreover, the lactate administration could rescue ferroptosis and sensitivity to rituximab induced by knockdown expression of VDAC2.
Conclusions: This study revealed a novel mechanism of rituximab resistance mediated by VDAC2 via inhibiting ferroptosis, which provides a potential therapeutic target for overcoming rituximab resistance in DLBCL patients.
Keywords: Diffuse large B cell lymphoma, rituximab resistance, VDAC2, Ferroptosis
Steroid-Refractory Paroxysmal Cold Hemoglobinuria in a 6-Year-Old Male
Authors: Donahue Nolan , Kanakis Constantine , Krum Kristen 
Published: December 2023

Background
Paroxysmal Cold Hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) that is often seen as a sequela of viral upper respiratory tract infections and immunizations in children. It is characterized by a positive Coombs test with a biphasic auto anti-P IgG known as the “Donath-Landsteiner antibody,” which sensitizes red cells and fixes complement at 0-4°C, and hemolyzes red cells near body temperature. The mainstay treatment of PCH includes cold avoidance, intravenous hydration, and supportive blood transfusions. Glucocorticoids may be used in the setting of significant hemolysis, with debated efficacy. We present a case of steroid-refractory PCH in a 6-year-old boy secondary to human rhinovirus/enterovirus.
Methods
Patient clinical data was abstracted from the electronic medical record. Blood bank testing was performed through the in-house blood bank. Donath-Landsteiner testing was performed at a reference laboratory.
Findings
A 6-year-old male with a history of mild upper respiratory tract infection 1 week prior presented to the emergency department with abdominal pain, dark urine, and jaundice. Initial laboratory evaluation uncovered anemia with hemoglobinuria, hyperbilirubinemia, elevated LDH, and decreased haptoglobin, raising concerns for acute hemolytic anemia (Table 1). Follow-up blood bank testing revealed a cold autoantibody. Viral PCR was positive for human rhinoenterovirus.
Despite supportive therapy through intravenous fluids and warming, the patient's anemia worsened significantly (Hgb 5.1g/dL) and packed red blood cell (pRBC) transfusion was required. Methylprednisolone 0.8 mg/kg IV twice daily was initiated as empiric therapy for autoimmune hemolysis without significant improvement. Blood was sent for Donath-Landsteiner antibody testing at a reference laboratory and revealed a bi-phasic hemolysin consistent with paroxysmal cold hemoglobinuria. The patient required an additional pRBC transfusion and was discharged after 4 days inpatient.
Conclusion
Our case supports a growing body of evidence that finds steroid therapy inefficacious in the treatment of hemolysis in the setting of PCH.
Blood Basophil Concentration at Diagnosis Corelates with Prognosis in Newly-Diagnosed Persons with Chronic Myeloid Leukaemia
Authors: Vrablova Lucia , Zhang Xiaoshuai , Kriegova Eva , Kudelka Milos , Radvansky Martin , Yang Sen , Juranova Jaroslava , Papajik Tomas , Gale Robert Peter , Jiang Qian , Faber Edgar 
Published: December 2023

Background Basophilia is common in chronic myeloid leukaemia (CML) and is associated with a poor prognosis. Previously it was quantified by percentage and a binary &lt; or ≥ 20%. However, blood basophil concentration at diagnosis may be a better prognostic co-variate.
Methods The hypothesis generating cohort was a 135 newly-diagnosed subjects with BCR::ABL1-positive CML receiving a tyrosine kinase-inhibitor (TKI). Median follow-up was 6.3 years (range, 4-16 years). Data were analyzed by Kaplan-Meier curves and multi-variable patient similarity network (PSN). A cohort of 1919 subjects was used to validate the test hypothesis. Subject gave informed consent for non-interventional data collection and the study was approved by Ethics Committees.
Results Multi-variable PSNs of the hypothesis generating cohort indicated 5 subject clusters. Incidence of TKI switch was highest in clusters 1 (45%), 5 (40%) and 4 (30%) which were characterized by the increased basophil concentrations at diagnosis compared with clusters 2 (13%) and 3 (14%) with the low basophil concentrations at diagnosis. PSNs identified the combination of basophil concentration ≥ 8x10E+9/L, basophil percentage ≥ 5 % and WBC ≥ 164x10E+9/L to be associated with significantly worse FFS (p &lt; 0.001) and PFS ( p = 0.02) but not survival ( p = 0.18). Basophil concentration ≥ 8x10E+9/L and WBC concentration ≥ 164x10E+9/L were associated with worse EFS (p &lt; 0.001), (FFS (p &lt; 0.001; Figure 1) but not PFS or survival. Basophil percentage at diagnosis had no impact on outcomes using ≥ 5% or ≥ 20% cutoffs. In the validation cohort the combination of basophil concentration ≥ 8x10E+9/L, basophil percentage ≥ 5% and WBC ≥ 164x10E+9/L at diagnosis was associated with worse FFS ( p &lt; 0.001) but not PFS or survival. Basophils ≥ 5% was associated with worse survival ( p = 0.04) and ≥ 20% with worse FFS ( p = 0.04) and survival ( p = 0.009). Basophil concentration ≥ 8×10E+9/L was associated with worse PFS ( p &lt; 0.001; Figure 1) and survival ( p = 0.03). There was no effect of WBC concentration on any outcome.
Conclusion We show blood basophil concentration at diagnosis correlates with diverse outcomes in newly-diagnosed persons with CML receiving TKI-therapy.
Support IGA_LF_2023_05, MH_CZ-DRO (FNOL, 00098892)
Risk of Bleeding and Thrombosis with CAR T-Cell Therapy: A Scoping Review
Authors: Abufarhaneh Mohammed , Pandya Rudra , Lazo-Langner Alejandro , Iansavitchene Alla , Dematagoda Dewmini 
Published: December 2023

Introduction:
Chimeric antigen receptor (CAR) T-cell therapy is emerging as a novel and revolutionary therapy in the treatment of relapsed or refractory lymphoma and other hematological malignancies. Patients with hematological malignancies are at risk of bleeding and thrombosis due to multiple risks factors. As there is an ongoing exploration of the incidence and characteristics of bleeding and thrombosis after CAR T-cell therapy, there is no existing published data that incorporates both peer-reviewed and non-peer-reviewed literature.
Aim:
Assess the risk of bleeding and thrombosis in CAR T-cell recipients for hematological malignancies.
Method:
We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL electronic databases from inception to October 2022 using a combination of subject headings and text words. We included studies that assessed thrombotic and bleeding complications in patients eighteen or older who underwent CAR T-cell therapy for a hematologic malignancy. Our search strategy yielded 14 studies in the form of abstracts and full-text articles. The review process consisted of two levels of screening: (1) a title and abstract review and (2) a full-text review.
Result:
Of 3354 records, we included 14 studies based on our inclusion criteria [figure 1]. Majorities of the studies were retrospective. Most of the patients in these studies received CAR T-cell therapy for refractory diffuse large B-cell lymphoma. Patients received at least 2 lines of therapy or more before CAR T-cell treatment. Different types of CAR T-cell therapy were used. Based on the included studies, the risk of bleeding was higher than thrombosis [figure 2]. Bleeding sites were variable, but gastrointestinal (GI) bleeding was predominant. In Ma et al, GI bleeding occurred in 11 (42.3%) patients. In Qi et al and Johnsrud et al, bleeding occurred in 44 (11%) and 12 (9.4%) patients respectively. Variable sites of thrombosis were noticed. In Hashmi et al incidence of thrombosis was 10.8%. Although there are some risk factors associated with bleeding and thrombosis in this population, the exact mechanism is still unknown. We think future studies to determine the exact mechanism of this toxicity and to assess the underlying risk factors would be crucial to decrease morbidity and mortality in this population and to develop risk assessment tools.