bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Efficacy and Safety of Decitabine Combined with Fludarabine and Cyclophosphamide As Conditioning Regimen in Second CD19 CAR-T Infusion
Authors: Ye Shiguang , Zhou Lili , Lu Yan , Luo Xiu , Li Shaoguang , Li Ping , Liang Aibin 
Published: December 2023

Background
Chimeric antigen receptor (CAR) T therapy is widely accept for the first line treatment of refractory/relapsed diffuse large B cell lymphoma(DLBCL). However, insufficient remission and short duration of response are the barrier of current CART therapy. More and more patients meet the failure of CD19 CART therapy. Pre-CART condition treatment is an important factor in durable responses. Decitabine, the hypomethylating agent, has been found that it can reduce T cell exhaustion, enhance T cell cytotoxicity and overcome tumor immune escape in the tumor microenvironment. We initiated this study to evaluate the efficacy and safety of decitabine combined with fludarabine and cyclophosphamide as conditioning regimen in 2nd CD19 CART therapy.
Methods
Patients are enrolled in the clinical trail (NCT02537977), inclusion and exclusion criteria are described. Pre-CART conditioning regimen is decitabine 10mg/m2 D-7~-3, fludarabine 25mg/m2 D-5~-3 and cyclophosphamide 300mg/m2 D-5~-3. The dose of second CD19 CART infusion is 5*10^6/kg. Primary outcome is the safety and secondary outcome is the efficacy.
Results
6 patients are enrolled in this trail and all patients are failure of CD19 CART. The media age is 57 year old and median line of treatment is 4. 4 patients(67%) are female. 5 patients(83%) have TP53 mutation/deletion and double expression, 4 patients(67%) have IPI ≥3.4 patients(67%) got complete remission(CR) after the first CD19 CART therapy and 2 patients(33%) got partial remission(PR). The median time of relapse/progression after first CD19 CART is 9 months.
The objective response rate is 50%, 2 patients(33%) got CR and 1 patient(17%) got PR. With median 13 months followup, the 3 patients(50%) maintain remission more than 1 year and are still under follow up. 2 patients(33%) got stable disease for 3 months and undergo salvage therapy. 1 patient(17%) had no response in 1 month and died due to disease progression. Of all 6 patients, only 1 patient(17%) received 2nd CART infusion in 3 months after 1st infusion and had detecable CART cell in peripheral blood.
2 patients(33%) got grade 1-2 cytokines release syndrome(CRS). No sever CRS and Immune effector cell-associated neurotoxicity syndrome(ICANS) were observed. Grade 3-4 adverse events are hematologic toxicity.
Conclusion
Decitabine combined with fludarabine and cyclophosphamide maybe an alternative conditioning regimen in CD19 CART therapy in high risk DLBCL patients. More patients are needed for further study and the trail is undergoing.
Selinexor, Ixazomib, Pomalidomide and Dexamethasone in Functionally High-Risk Multiple Myeloma: Results from the Myeloma Developing Regimens Using Genomics (MyDRUG) Sub-Protocol Y3
Authors: Richter Joshua , Zonder Jeffrey A. , Nathwani Nitya , Bianchi Giada , Hofmeister Craig C. , Vij Ravi , Pianko Matthew , Kaur Gurbakhash , Hultcrantz Malin , Wozniak Katie , Martillo Mercedes , Cho Hearn Jay , Kumar Shaji Kunnathu 
Published: December 2023

Background: Multiple myeloma (MM) is characterized by somatic mutations involving cancer-associated genes. The MyDRUG trial was initiated to explore the efficacy of specific molecularly-targeted therapies in combination with a standard triplet combination in MM.
Methods: MyDRUG (NCT03732703) is a genomically-guided umbrella trial for patients with functional high-risk MM, defined as early relapse following primary therapy (3 years for transplant with maintenance, 18 months without), with specific genetic abnormalities. Patients with no actionable mutation or mutations with allelic burden below 30% were randomly assigned to one of the “non-actionable” arms. Here we present the data for the Y3 arm which combines selinexor (60mg po days 1,8,15), ixazomib (4mg po days 1,8,15), pomalidomide (3mg po days 1-21) and dexamethasone (40mg po weekly) (Seli-IPD), given on a 28-day cycle. The primary objective of the Y3 sub-protocol was to evaluate the overall response rate (ORR) according to the International Myeloma Working Group consensus criteria. Secondary objectives included assessment of adverse events (AEs).
Results: 17 patients were enrolled into the Y3 arm. The average age was 62 (51-79), 65% were male with a median of 29 months since initial diagnosis and a median of 2 prior lines of therapy. The ORR (&gt; PR) was 52.9% with a clinical benefit rate (&gt; MR) of 58.8%. The median progression free survival was 10.2 months ( 95% CI: 3.9; 12.9) with a median overall survival which has not yet been reached; with all 17 patients still alive at the current data cutoff. No dose-limiting toxicities were seen. Eight patients (47.1%) experienced a serious AE with 2 patients (11.8%) experiencing an AE leading to treatment discontinuation. Two patients (11.8%) required dose reductions. The most common non-hematologic AEs were fatigue, nausea and constipation; all of which were grade 1 and 2.
Conclusions: In this platform study of patients with relapsed, functionally high-risk MM, patients who received Seli-IPd exhibited significant efficacy and a manageable AE profile. Furthermore, this provides an all-oral option for patients wishing to minimize their office visits and parenteral therapy administrations.
Transgender Women on Estrogen Have a Lower Burden of Thrombotic Events Compared to Cisgender Men: A Nationwide Hospital-Based Survey
Authors: Manchkanti Srija , Dayal Sanjana , Ramakrishna Akhila , Streeter Jennifer 
Published: December 2023

Due to public recognition and acceptance, more transgender women are being prescribed gender-affirming estrogen therapy. Traditionally, sexual dimorphism has been shown to play a significant role in the pathophysiology of thrombotic phenomena. While genetic factors remain the key players in the divergent male and female phenotypes, limited information is available regarding the thrombo-vascular effects of estrogen therapy in transgender women. Furthermore, available data has been conflicting with respect to vascular outcomes in this specific population. Therefore, more evidence is required to understand the long-term effects of gender-affirming estrogen therapy. In the current study, we investigated the thrombotic outcomes of estrogen therapy in transgender women (male sex assigned at birth), in comparison to cisgender men and cisgender women.
We performed retrospective analyses using the TriNetX database that includes de-identified data for over 250 million patients across 76 certified healthcare organizations. We included all adults over the age of 18 years and excluded those with the presence of documented prothrombotic risk factors such as obesity, diabetes, hyperlipidemia, smoking, and cancer. Within the cohort of cisgender women, we excluded pregnancy and post-menopausal status. The thrombotic outcomes within the transgender cohort were recorded after the start of hormone replacement therapy. To account for thrombotic events, we used search terms such as acute myocardial infarction (MI), cerebral infarcts, pulmonary embolism (PE), and deep vein thrombosis (DVT).
We found 12,369 transgender women, 29,746,302 cisgender men, and 32,591,972 cisgender women that were eligible for our study. The transgender women had lower incidences of MI (0.14% vs. 0.38%, P&lt;0.0001), cerebral infarcts (0.21% vs. 0.49%, P&lt;0.0001), and DVT (0.33% vs. 0.47%, P&lt;0.022) compared to cisgender men. The incidence of PE was comparable in both these groups (P=0.85). Furthermore, we observed that transgender women also experienced significantly lower incidences of cerebral infarcts (0.21% vs. 0.42%, P=0.0003) and a moderately decreased incidence of MI (0.14% vs 0.22%, P=0.062) compared to cisgender women. The incidence of venous thrombosis was similar in these two groups.
Overall, we observed a paradoxical decrease in rates of thrombotic events, suggesting that estrogen may play a protective role against the development of acute MI, cerebral infarction, and DVT in transgender women. Further investigation is required to understand the downstream targets that offer these cardioprotective effects. Importantly, our data may provide clinicians with reassurance that traditional vascular risks associated with estrogen may be less pronounced in males.
Chidamide Combined with a Modified Bu-Cy Conditioning Regimen Improves Survival in Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoma Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Cao Xuanqi , Li Zheng , Zhang Yanming , Cui Qingya , Ma Yunju , Li Mengyun , Chen Sifan , Yin Jia , Cui Wei , Chen Jia , Sun Aining , Qiu Huiying , Chen Suning , Jin Zhengming , Zhu Xiaming , Wu De-Pei , Tang Xiaowen 
Published: December 2023

Backgrounds: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL). Relapse post-HSCT remains the major cause of mortality, highlighting the urgent need for more effective conditioning regimens in reducing relapse rates and improving outcomes for T-cell malignancy. Chidamide, as the first oral subtype-selective histone deacetylase inhibitor (HDACi) approved in China, can lead to a more relaxed chromatin structure through chromatin remodeling, particularly hyperacetylation of lysine residues in the histone tails, which facilitates the expression of tumor suppressor genes as well as the action of alkylating agents busulfan. To date, the role of chidamide in T-ALL/LBL conditioning regimens in allo-HSCT has not been explored.
Methods: We retrospectively compared the clinical efficacy and safety between chidamide combined with a modified Busulfan-Cyclophosphamide (mBuCy) and mBuCy conditioning regimen for T-ALL/LBL patients undergoing allo-HSCT. The chidamide combined with mBuCy regimen was presented in Figure1.
Results: Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only. The median follow-up time was 683 (range 296-1168) days. Patients in the Chi group showed better 2-year overall survival (OS) and leukemia-free survival (LFS) (85.4 vs. 52.9%, respectively, P = 0.021; 69.1 vs. 42.9%, respectively, P = 0.031). Multivariate analysis showed that chidamide combined with mBuCy was a major positive risk factor for OS (HR 0.18, 95%CI, 0.05-0.63; P = 0.007) and LFS (HR 0.32; 95%CI, 0.13-0.80; P = 0.015). The cumulative incidence rates of grade II-IV and grade III-IV aGVHD were similar (36.4 vs. 38.6%, respectively, P = 0.858; 13.6 vs. 20.5%, respectively, P = 0.735). Patients in the Chi group showed higher incidence of elevated γ-glutamyltransferase and hemorrhagic cystitis than that in the mBuCy group (90.9 vs. 65.9%, respectively, P = 0.029; 36.4 vs. 13.6%, respectively, P = 0.007). No transplantation-related mortality was documented within the first 100 days after transplantation.
Conclusions: Our data demonstrate that the conditioning regimen containing chidamide improves the survival of T-ALL/LBL patients without increasing the incidence of transplant-related mortality. A prospective clinical trial is expected to confirm these findings.
Characteristics and Prognosis of Epstein Barr Virus-Positive Diffuse Large B-Cell Lymphoma: A Retrospective, Single-Center Study
Authors: Lin Qiaochu , Liao Lianming , Liu Tingbo , Shen Jianzhen , Luo Xiaofeng , Fu Haiying , Li Xiaofan 
Published: December 2023

Objective:
The aim of this study was to analyze the clinical characteristics and prognosis of Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) in a Chinese cohort.
Methods:
A total of 57 patients diagnosed with EBV+DLBCL from January 1, 2013 to December 31, 2020 were included, and 228 concurrent patients with EBV-DLCBL served as control. The differences between the two groups were compared and the prognosis factors were identified by univariate and multivariate analysis.
Results:
There were 38 man in the EBV+DLBCL group, with a median age of 56 years (rang, 18 to 88). Tumor cells originated from GCB in 15 patients (26.3%), and from non-GCB in 40 patients (70.2%). There were 34 patients (59.6%) with Epstein Barr virus infection. Compared with EBV-DLCBL patients, patients with EBV+DLBCL had B symptoms, hypoalbuminemia, anemia and extranodal involvement&gt;1 more frequently, as well as higher LDH and β2-Microglobulin levels (P &lt; 0.05 foe all). The most common extranodal sites involved were digestive tract, especially, the stomach, nasopharynx, bone marrow and bone. Immunohistochemical staining showed 24 patients (42.1%) in the EBV+DLBCL group were CD30 positive, compared with xxx in patients with EBV﹣DLCBL (P &lt; 0.001). After treatment with rituximab combined with chemotherapy, the EBV+DLBCL patients had a complete response rate and a overall response rate of 55.5% (30/54) and 83.3% (45/54), respectively. With a median follow-up time of 28 months, 22.2% (10/45) patients relapsed. The overall response rate and recurrent rate were similar between the two groups. In multivariate analysis, increased β2-Microglobulin level and bone marrow invasion were independent risk factors for PFS, while increased β2-Microglobulin level and decreased HB were independent risk factors for OS in patients with EBV+DLBCL.
Conclusion: The majority of EBV+DLBCL patients were non-GCB.β2-Microglobulin level and bone marrow invasion were independent risk factors for PFS in patients with EBV+DLBCL, while β2-Microglobulin and HB were independent risk factors for OS in patients with EBV+DLBCL. The therapeutical potentials of targeted medicines, such as CD30 inhibitors and PD-1 inhibitors, deserve to be explored in the future.
Keywords：Epstein Barr virus, diffuse large B-cell lymphoma, prognostic factors
Incidence-Based Mortality (IBM) and Survival for Chronic Myeloid Leukemia (CML) By Age Group: Is There Any Relationship between Age of Diagnosis, IBM and Survival?
Authors: Kenmoe Jerry , Ghimire Calvin , Batool Narjis , Kunadi Arvind 
Published: December 2023

Incidence-Based Mortality (IBM) and Survival for Chronic Myeloid Leukemia (CML) by Age group: Is there any relationship between age of diagnosis, IBM and Survival?
Background:
CML is known to affect different age groups differently, with a predominance in adults. CML accounts for about 15% of all new cases of leukemia, with over 50% of the cases being diagnosed in individuals 65 or older.
Our study looked at the variation in 5 and 10 years survival, and probability of death from CML based on different age groups in the US adult populations from 2000-2019 via SEER.gov database.
Methods:
We used Incidence -Based Mortality SEER Research Data, 17 Registries, Nov 2021 Sub (2000-2019), which provides the broadest geographic coverage for incidence-based mortality rates and is roughly 26.5% of the US population (based on the 2020 Census) for the calculation of Incidence-Based Mortality and Survival rates of CML. SEER*Stat 8.4.1 was used to obtain cause-specific survival, with Death due to cancer. We used Join-point software, version 5.0.2. by the National Cancer Institute, annually to create log-linear time trends.
Results:
Fig 1: CML 10-Year Survival rates per 100,000 and age-adjusted to the 2000 US standard population by age groups (50-79)
Our results revealed a significant change in the probability of dying from CML for age groups 60-64 and 70-74.
The Average Annual percent Change (AAPC) for incidence Based Mortality by age groups were 3.71%*(95% CI 1.55 to 6.42 ), 2.87%*(95% CI 0.74 to 5.56), 6.09%*(95% CI 2.97 to 9.03 ), 2.33%*(95% CI 0.38 to 5.84), 4.86%*(95% CI 2.74 to 7.18), 3.38%* (95% CI 2.08 to 4.97) for age groups 50-54, 55-59,60-64,65-69,70-74, and 75-79 respectively.
The trend for 10 year survival shows increasing survival across all age groups.
The AAPC for 10 year survival were 1.74%*(95% CI 0.08 to 4.04), 4.08%*(95% CI 2.25 to 7.33), 2.52% (95% CI -0.22 to 6.21), 5.29%* (95% CI 3.34 to 7.70), 5.42%* (95% CI 2.13 to 9.71), 2.29% (95% CI 1.88 to 6.92).
Conclusion:
Our Study shows a significant difference in the survival rates at 10 years based on age groups, with a pattern of lower survival rates and higher probability of death from CML with increased age at diagnosis.
Does Implementing Calendars Outlining Inpatient Chemotherapy Schedules in Patient Rooms Improve Patient's Experience?
Authors: Wani Kashmira , Dabak Vrushali S. 
Published: December 2023

Background: Patients who receive inpatient chemotherapy for malignancy are dealing with both a physically and mentally challenging admission. Their chemotherapy regimen is predetermined and usually only discussed during rounds. Often times, patients feel overwhelmed and may miss the outline of their schedule. Furthermore, patients families may not be able to attend morning rounds and may miss the proposed schedule. This can lead to a feeling of loss of control in both the patient and their family, and thus, frustration. First year medicine residents are also overwhelmed with a large patient load and having to keep track of multiple chemotherapy regimens. We are hoping that by providing a calendar that outlines patient's anticipated chemotherapy schedule, we may be able to give patients a small sense of control back and help residents provide the best care to their patients. Ultimately, we hope that this leads to a better inpatient experience.
Methods: Patients admitted to the hematology/oncology floor at Henry Ford Health Hospital in Detroit, Michigan over three months were screened, and those receiving inpatient chemotherapy were selected. Within this group, any patient that was getting inpatient chemotherapy for longer than three days was asked if they would like to participate in the study. If the patient agreed, they were provided a calendar that outlined their chemotherapy schedule. Calendars were updated if any adjustments were made to the schedule. At the end of their inpatient stay, patients filled out a questionnaire asking if the calendar helped them understand their schedule better. The primary resident caring for the patient was also asked if the calendar helped them keep track of their patient's schedule.
Results: Overall, patients responded positively to the calendars. We have preliminary data on ten patients and four providers from three months. On average, on a scale of 1-10 (with 1 indicating not helpful at all, and 10 indicating extremely helpful) patients rated the calendars helping them at a level of 7.5. Patients found that the calendars particularly helped their families who were not able to come visit in the hospital. Providers found the calendars extremely helpful, rating the calendars at a level of 10. We will continue to collect data and update our results.
Conclusions: Implementing patient calendars in inpatient rooms helps patients keep track of their chemotherapy schedules and leads to a positive inpatient experience. We are hoping to implement this as a standard of care in all inpatient rooms on the hematology/oncology floor.
Ruxolitinib Versus Best Available Therapy for Polycythemia Vera: A Systematic Review and Meta-Analysis
Authors: Roca Mora Maria Meritxell , Ribeiro Guimaraes Catharina , Afzal Farhan , Godoi Amanda , Valenzuela Andres 
Published: December 2023

Background: Polycythemia vera (PV) is characterized by dysregulated Janus kinase (JAK) activation, leading to excessive production of blood cells, increased risk of thrombotic and hemorrhagic events, and an impairment on the quality of life of patients. Ruxolitinib, a JAK1/JAK2 inhibitor, has shown promising results in recent trials, but its comparative efficacy to best available therapy (BAT) remains unclear. We aimed to perform a systematic review and meta-analysis comparing the efficacy and safety of Ruxolitinib versus BAT for patients with PV.
Methods: We systematically searched PubMed, Embase, and Cochrane Central for clinical studies published up to July 1st comparing Ruxolitinib to BAT. BAT was defined as hydroxyurea, interferon or pegylated interferon, pipobroman and anagrelide. Efficacy outcomes assessed were complete response to therapy and reduction in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) score; safety outcomes were thromboembolism, anemia, and herpes. We pooled outcomes as risk ratios (RR) with 95% confidence intervals (CI). Statistical analysis was performed with Review Manager version 5.4.1. Heterogeneity was assessed with I² statistics. The protocol was registered in PROSPERO (ID: CRD42023427977).
Results: A total of five studies met our inclusion criteria, of which four were randomized trials. Our analysis encompassed a population of 684 patients, including 336(49%) allocated to the Ruxolitinib group, and 348(51%) allocated to the BAT group. Ruxolitinib had a significantly greater response to treatment compared to BAT (RR 1.97; 95% CI 1.03 -3.77; p=0.04; I²=60%; Fig 1A) and significantly reduced MPN-SAF score by at least 50% (RR 2.50; 95% CI 1.29-4.86; p=0.007; I²=76%; Fig 1B). Additionally, use of Ruxolitinib showed a significantly higher incidence of herpes infection (RR 3.57; 95% CI 1.27 -10.04; p=0.02; I²=0%; Fig 1C) and anemia (RR 1.97; 95% CI 1.15-3.37; p=0.01; I²=50%; Fig 1D). There were no significant differences between the two treatment groups regarding thromboembolic events (p=0.07; Fig 1E).
Conclusion: Our meta-analysis reveals that Ruxolitinib exhibits superior efficacy in achieving a complete response for PV patients compared to BAT and in reducing MPN-SAF score by ≥50%. While no significant difference was observed in thromboembolic events, Ruxolitinib demonstrated significant risk of anemia and herpes infection.