bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anemia in Patients Undergoing Therapeutic Phlebotomy for Polycythemia Secondary to COPD and OSA
Authors: Draviam Anna , Soundar Esther 
Published: December 2024

Background:
Therapeutic phlebotomy is performed to relieve symptoms of secondary polycythemia in chronic hypoxic lung diseases such as chronic obstructive pulmonary disorder (COPD) and obstructive sleep apnea (OSA). Excessive phlebotomy may cause iron deficiency anemia, leading to hypoxemia and resulting in vicious cycle of further erythropoiesis and hyper viscosity. Also, anemia of chronic disease is prevalent both in COPD and OSA patients due to the underlying systemic inflammation. Our aim is to find if adult patients develop anemia while undergoing prolonged therapeutic phlebotomy treatments.
Methods:
We retrospectively reviewed all outpatients that have undergone therapeutic phlebotomy from September 2018 to July 2024 in our ambulatory outpatient clinic for demographic and relevant clinical and laboratory data including hematologic indices. Cumulative incidence that represents the cumulative probabilities of anemia was computed from the life table using the Kaplan Meier method. Continuous variables with non-normal distribution are presented as median (interquartile range [IQR]).
Results:
The cohort had 19 patients among which 74% are males. Fifty eight percent were diagnosed with OSA and the remaining with COPD. The majority (68%) of patients belong to White race. The age of patients at their first therapeutic phlebotomy at our institution is 62 (IQR, 55-74) years and the median body mass index (BMI) is 31.9 (28.6 -36.6) kg/m2. The baseline hemoglobin is 18 (17-19) g/dL. The total number of therapeutic phlebotomy procedures done is 8 (4-12). The duration between the first therapeutic phlebotomy at our institution and the last one reviewed is 210 days (121-385). The cumulative incidence of anemia after 10 procedures is 37%.
Conclusions:
The incidence of anemia is high in patients undergoing therapeutic phlebotomy for mitigating symptoms of secondary polycythemia. Careful and regular monitoring is necessary to prevent anemia in this at-risk population.
The Safety and Efficacy of Inotuzumab Treatment for Elderly Unfit r/r B ALL
Authors: Lin Yuehui , Liu Dan , Xia Yu , Wu Tong , Tong Chunrong 
Published: December 2024

Introduction：B cell acute lymphoblastic leukemia(B ALL) is highly prevalent in children and has a good prognosis with a 5-year survival rate of 80-90%. However, the prognosis of elderly ALL is extremely poor, mainly due to its poor prognosis and poor tolerance to treatment. Therefore, for elderly unfit ALL patients, a safe and effective treatment is urgently needed. In recent years, immune therapies have developed rapidly, and these treatment have high efficacy and safety for relapsed and refractory(r/r) B ALL or MRD+ALL. Our aims to observe safety and efficacy of CD22 antibody inotuzumab ozogamicin conjugated with calicheamicin toxin (Ino.) treatment for elderly unfit r/r B ALL
Methods：A total of 9 elderly unfit r/r B ALL pts who received Ino. treatment from August, 2023 to July , 2024 were included. All patients expressed CD22 antige before treatment. 1 pts received three dose Ino.,other pts received Ino.1mg/W 1～2 times.
Results：9pts:5 females and 4 males with a median age of 59 years (56～72 years old),1 pts CML AP，6 pts Ph+ALL，2pts Ph-ALL.All patients were treated with chemotherapy and all Ph+ALL patients were treated with TKI. Among them, 2 patients had relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT): 1 patient had relapse after HSCT and CD19 CAR-T treatment,1 patient had relapse after HSCT and CD19 antibody blinatumomab(BITE) with COVID-19 infection;7 pts did not undergo HSCT：1 pt experienced recurrent/ineffective treatment after BITE, CD19 CAR-T, CD22 CAR-T,1 pt experienced recurrence after CD19 CAR-T twice and CD22 CAR-T twice、1 pt who was CML-AP experienced recurrence after BITE、CD19 CAR-T with renal dysfunction，1 pt relapsed after BITE accompanied by pulmonary mucormycosis infection，3 pts did not receive any immunotherapybefore：1 pt has been cured of lung cancer.Before INO.,1 pts MRD+,8 pts have hematological recurrence.All patients have safely completed the INO. treatment and after treatment:5 pts(100%) with hematological recurrence achieved CR (3 pts FG-，1 pts FCM-MRD-、FG-MRD+，1pts morphological CR with FCM/FG+），1pts MRD+;In addition, there are 3 pts who cannot evaluate the efficacy of INO: 2 pts achieved the opportunity to collect lymphocytes for CAR-T therapy, and 1 pt died due to subsequent sepsis.
Conclusions：
For elderly unfit r/r B ALL pts even including those after treatment with both CD19 and CD22 CAR-T cells or HSCT, ino. treatment is safe and effective and so ino. can be the first treatment recommendation.
The Combination of Isatuximab with Pomalidomide and Dexamethasone in Second Line Relapse and Refractory Multiple Myeloma
Authors: Bobin Arthur , Soufyane Ennebet , Guidez Stephanie , Chacon Aurelia , Gardeney Helene , Basle Caroline , Dindinaud Elodie , Douma Soukaina , Roul Christophe , Corby Anne , Motard Carine , Olivier Gaelle , Denis Guillaume , Vinson Camille , Tomowiak Cecile , Gruchet Cecile , Moya Niels , Mocquot Pauline , Dessane Berangere , Boscagli Annick , Perrot Aurore , Leleu Xavier 
Published: December 2024

Introduction: The most impressive data obtained from CD38 targeting immunotherapies-based regimens were observed when used as early as possible in the MM disease course, in second line if not offered in line 1. CD38 targeting immunotherapies, Isatuximab and Daratumumab, are approved in the relapse-refractory Multiple Myeloma (RRMM) setting in triplet-based combinations with pomalidomide (P) and dexamethasone (IsaPd and DPd), however with very limited data in line 2 with IsaPd.
Methods: We conducted a multicenter review study of the patients with second line RRMM treated with CD38 targeting immunotherapies-based regimens with pomalidomide and dexamethasone backbone, IsaPd. Eligible patients were to be adult RRMM in second line, refractory to lenalidomide upfront, naïve to pomalidomide, not refractory to CD38 immunotherapy upfront. The primary endpoint of the study was median PFS. All patients received isatuximab + pomalidomide + dexamethasone until progression as per the approved regimen according to the EU approval.
Results: We recruited 35 patients,median age 72 years old (IQ 67;76), 10 (28%) ISS3, 18 (62%) RISS2-3, 8 (22%) had plasmacytomas', 5 (14%) had PCL features, 4 (11%) HR according to IMS new definition (del17 at the threshold of 50%), 6 (16%) had ASCT upfront. The patients received a median of 12 (IQ 5;20) cycles of IsaPd. At 35.4 (CI95% 35;39.5) months median follow-up, 19 (51%) relapsed and 13 (35%) died. The median PFS was 22.4 (CI95% 13.8-nr). The median OS was nr, projected 40 months was 64% from start of IsaPd. All pre-specified HR definitions had a shorted PFS median time.The median relative dose intensity in IsaPd was &gt;90%, similar to either drug. The safety profile is consistent with the approved IsaPd in ICARIA study.
Conclusions: IsaPd reported prolonged PFS median in second line in lenalidomide refractory RRMM.This study confirms IsaPd as a standard of care for second line RRMM patients.
Male Sex Had an Adverse Impact on Outcomes of Pediatric B-Lineage Acute Lymphoblastic Leukemia
Authors: LI Zhiheng , Wang Lingzhen , Cai Jiaoyang , Guo Ailian , Gao Ju , Jie Yu , Zhu Xiaofan , Li Chi Kong , Jiang Hua , Ju Xiuli , Zhai Xiaowen , Wang Ningling , Jiang Hui , Yang Liangchun , Hu Qun , Jin Runming , Pan Kaili , Fang Yongjun , Wu Xuedong , Liang Changda , Cheng Cheng , Shen Shuhong , Sun Lirong , Hu Shaoyan 
Published: December 2024

Purpose
Despite the improved overall survival of childhood B-lineage acute lymphoblastic leukemia (B-ALL) under contemporary risk-directed therapy, ~15% patients still experience relapse which calls for additional prognosis predicting factors. We aim to investigate the impact of sex on clinical outcomes in childhood B-ALL.
Patients and Methods
Between January 2, 2015, and December 31, 2019, 6916 pediatric patients with newly diagnosed B-ALL were enrolled in the Chinese Children's Cancer Group ALL-2015 clinical trial (CCCG-ALL-2015, ChiCTR-IPR-14005706).
Results
Among the 6916 cases pediatric B-ALL, the ratio of males to females was 1:0.74 (males 3982, 57.6%; females 2934, 42.4%). An inferior 5-year EFS was observed in males compared with females (79.7%; 95%CI, 78.5-81.0 vs 83.5%; 95%CI, 82.1-84.9; P&lt; .001). Male sex was identified as an independent poor EFS predictor by a multivariant cox model (HR, 1.19; 95%CI, 1.05-1.35; P= .006). Incidence of relapse was the major difference between the two groups. Males had increased relapse risk compared with females, with a 16.4% (95%CI: 15.2-17.6) 5-year cumulative incidence of relapse (females: 12.2%; 95%CI, 11.0-13.4; P&lt; .001) and a 2.9% (95%CI: 2.4-3.5) 5-year cumulative incidence of central nervous system leukemia relapse (females: 1.6%; 95%CI, 1.2-2.2; P&lt; .001). Although the sex impacted the EFS and CIR, males and females achieved a comparable 5-year OS (93.2%; 95%CI, 92.3-94.2 vs 93.2%; 95%CI, 92.4-94.0; P= .800), indicative of the successful salvage therapy for males. Compared with females, males more often had BCR::ABL1 fusion (5.83%, 232/3982 vs 3.31%, 97/2934; P&lt; .001), but no sex-associated difference in the incidence of ETV6::RUNX1, KMT2A-rearranged or TCF3::PBX1 subtypes were noted. Males with BCR::ABL1 fusion or ETV6::RUNX1 fusion exhibited higher relapse rates than females in the same subtype (BCR::ABL1: 38.4%, 89/232 vs 26.8%, 26/97; P= .045; ETV6::RUNX1: 11.9%, 100/838 vs 4.9%, 30/615; P&lt; .001). Such difference was not seen in KMT2A-rearranged or TCF3::PBX1 subtypes. BCR::ABL1 was identified as a male-specific relapse predictor using the multivariate competing risks model.
Conclusions
Sex impacts the prognosis of childhood B-ALL. Males has an inferior EFS and is identified as a relapse predictor in B-ALL which warrants the development of male-adapted regimen to prevent disease reoccurrence. The mechanism underlying the sex impact needs further investigation.
Bortezomib-Based Triplet Therapy As First Line Treatment in Newly Diagnosed Multiple Myeloma Patients in Perú
Authors: Vasquez Jule F , López Córdova Naty , Castillo Claudia , Saavedra Alexandra , Calle Cindy , Lopez Chavez Lourdes Isabel , Alcarraz Cindy Elizabeth , Lovato Rios Pedro Eduardo , La Torre Matuk Alejandra , Laboriano Jorge , Vilcarano Abner , Tokumura Carmen , Quintana Shirley , Samanez-Figari Cesar , Vidaurre Tatiana 
Published: December 2024

Introduction
Standard treatment in multiple myeloma is based on triplet and more recently in quadruplet therapy, with lenalidomide being the preferred immunomodulatory drug, however in low-and middle-income countries novel therapies are not readily available. Bortezomib-based triplet is the standard treatment in Peru. We aimed to determine the outcomes with the different combinations of bortezomib.
Methods
We retrospectively reviewed medical records of patients with newly diagnosed multiple myeloma (MM) treated at 5 institutions from Perú including the National Cancer Institute (public institution) and Oncosalud-AUNA (private institution). Patients with MM who received bortezomib-based triplet therapy from 2017 to 2023 were included for the analysis. Smoldering MM and plasma cell leukemia were excluded. Baseline characteristics were evaluated, and overall survival was analyzed using STATA program.
Results
During the period of study 164 patients were included. The median age was 59 (range 30-83). Most were male (60%). Ig G subtype was seen in 61% of cases, followed by Ig A (24%) and light chain myeloma (14%). Non-secretor myeloma accounts for 1% of cases. According to ISS classification ISS I, ISS II, ISS III and unknown were 34%, 21%, 40% and 5%, respectively. 75% were eligible for transplant. However, only 46% of the entire cohort underwent autologous transplantation, all patients with VRd received transplant. 91% (149) received VTd, 8% (14%) VRd and only 1% VCd. 150 patients had evaluation of the treatment response, the overall response rate (ORR) was 83%, complete response + strict complete response was obtained in 43%, followed by very good partial response in 30% of and partial response in 13%. Cytogenetics risk stratification was not available due to the lack of FISH. The median follow-up was 23 months (range 1 -122m). The median overall survival for the entire cohort was not reached (IQR 80-NR). The 5-y OS was 79.5% (95 IC, 71.2-85.6). The 5y OS for the VTd group was 77% and 100% for the VRd group.
Conclusion
Bortezomib-based triplet therapy is highly effective in patients with newly diagnosed multiple myeloma more than the published in international reports. Most patients used VTd as first line treatment. Three-quarters of patients were eligible for transplant. However less than half actually received transplant. Overall survival is good being 100% at 5 years for the VRd group compared to 77% for the VTd group, although seems that the benefit is due to the transplant for the VRd group. The lack of the availability FISH test is very important to stratify our patient to give a better treatment.
Antibody Drug Conjugates with a Novel Translation Inhibitor Payload Demonstrate Cytotoxicity and Tumor Growth Reduction in Multiple Myeloma Models
Authors: Chapman-Arvedson Tara L. 
Published: December 2024

Background
Antibody drug conjugates (ADCs) are a validated modality for the targeted delivery of cytotoxic payloads to myeloma cells while sparing healthy tissue. To achieve the full potential of ADCs in multiple myeloma patients, it will be important to have ADCs that incorporate payloads with non-overlapping mechanisms of action (MOA) as compared to existing therapies. By mining a proprietary collection of small molecule natural products (NPs), Hexagon Bio has identified a novel protein translation inhibitor, HB-06510, which exhibits favorable physicochemical properties and significant sensitivity in myeloma cell lines. HB-06510 has been conjugated to antibodies that bind myeloma antigens and has been shown to induce myeloma cell cytotoxicity in vitro and in vivo.
Methods and Results
Hexagon Bio has established a platform to identify new NPs and determine their MOA. This platform uses a proprietary algorithm integrated with machine learning, genetic screening, and synthetic biology to identify, produce, and define the MOAs of new NPs, primarily isolated from our fungal library comprising &gt; 100,000 strains. Using this platform, we identified a NP that was potently cytotoxic across a panel of cancer cell lines, including multiple myeloma (≤ 3.2 nM average EC50 and 100% killing across 10 cell lines in a 72 hour assay). To determine the mechanism of action, we used genetic screening and found that this NP inhibited protein translation. Physicochemical evaluation of the NP revealed it had good properties for a potential ADC payload (good solubility, low lipophilicity, good stability in human plasma and lysosomal preparations, no reactivity with glutathione), it has a site for linker attachment and is amenable to semi-synthesis and medicinal chemistry. Further cytotoxicity profiling demonstrated that HB-06510 is cytotoxic to multi-drug resistant cells, including those expressing high levels of efflux pumps such as Pgp and ABCG2, indicating that HB-06510 is not a substrate for these pumps. We also demonstrated that HB-06510 is cytotoxic to both fast- and slow-cycling cells and induces immunogenic cell death.
To evaluate the potential for HB-06510 to be an ADC payload, we conjugated HB-06510 to antibodies that bind myeloma antigens BCMA, CS1 and CD38 and have demonstrated anti-myeloma cell cytotoxicity in vitro and in vivo. These results will be presented.
Conclusions
We have identified a novel protein translation inhibitor payload that is highly potent, has good drug-like properties and shows effective anti-myeloma cell activity in vitro and in vivo when conjugated to anti-myeloma antibodies. ADCs with this MOA are distinct from both currently-available targeted therapeutics and chemotherapy and have the potential to provide benefit to patients.
Cutting Costs and Enhancing Care: The Financial Burden of Factor VIII Testing in Thrombosis and Stroke Workup
Authors: Singh Anaiya , Gaddam Shiva Jashwanth , Ramadas Poornima 
Published: December 2024

Introduction:
Elevated factor VIII is often linked to increased thrombosis risk and has been used as a tool to measure outcomes and prognostication in thrombotic events, but its direct contribution remains uncertain. Current guidelines suggest limited benefit in testing of factor VIII levels in thrombophilia(s) and stroke(s). Despite this, factor VIII testing is frequently performed during routine workup of venous thromboembolic events (VTEs) and cerebrovascular accidents (CVAs). Our study examines the financial impact of unnecessary and clinically irrelevant factor VIII testing in these scenarios.
Methods:
At our institution, we performed a retrospective study approved by the Institutional Review Board (IRB), analyzing data from 462 patients who underwent factor VIII level testing from December 2019 to December 2022. We excluded patients whose tests were performed for reasons other than evaluating thrombophilia or cerebrovascular accidents (CVAs) and analyzed data for 157 patients. Our data collection encompassed patient demographics, indications for testing, and insurance coverage. This information was used to assess the financial impact on our institution related to the unnecessary testing of factor VIII levels in patients with an increased risk of thrombosis and stroke.
Results:
The median age of testing for factor VIII levels was 34+/-7 years, with females (96) constituting 61.1% and males contributing (50) 38.9%. Factor VIII levels were tested for 61 patients with Transient Ischemic Attacks (TIAs) and CVAs and in 96 patients with VTEs. Out of all the 157 patients tested, 27 were covered by Medicare, 71 by Medicaid and 59 benefitted from private-based insurance. In-house testing for this gene costed approximately $180 per test in 2019, with the cost inflation up to $260 after 2020.
Conclusions:
Over a three-year period, our analysis revealed an expenditure of approximately $30,000 USD on factor VIII level testing as part of the diagnostic workup for thrombophilia and stroke, despite insufficient clinical evidence supporting its necessity. This study aims to disseminate these findings within our institution to minimize clinically unwarranted testing, enhance patient outcomes, and optimize the cost-benefit ratio by educating clinicians. By addressing this, we hope to reduce the financial burden on healthcare systems while adhering to clinical guidelines.
B12 Deficiency: It's Not Always about Nerves!
Authors: Gibson Spencer , Thomas Melissa , Wang Angelina , Moss Arianna S , Quy Ray , Zhao Eva , Debeusscher Ben P , Pakbaz Zahra 
Published: December 2024

Background:
Vitamin B12 deficiency can have numerous health consequences including neurological dysfunction, immune dysfunction, and decreased cognitive function [1,2]. It is lesser recognized that B12 deficiency can result in anemia as well as other cytopenias often seen on CBCs collected during visits with first-contact physicians. This leads to delayed or missed diagnosis of B12 deficiency. The primary objective of the current study is to assess physician knowledge gaps in diagnosing B12 deficiency and adequate workup for cytopenias before referring to a hematologist.
Methods:
This study is a retrospective chart review of 862 adults (Mean age 52.9 ± 18.4, 497 female) seen in a single-provider non cancer hematology clinic at an academic center between February 2020 and July 2023. Data collection included patient demographics, referral reason or diagnosis, referring provider specialty type, and the diagnosis made by the consulting adult classical hematologist in this clinic. Patients lost to follow-up after initial referral have been excluded from this data analysis. B12 deficiency was defined as B12 &lt;400 pg/ml.
Results:
Out of 862 analyzed referrals to this clinic, only 3 included vitamin B12 deficiency within the reason for referral. Of the 360 patients who were referred for various cytopenias (Anemia 43%, Thrombocytopenia 23%, Neutropenia 21%, Bicytopenia 6.5%, Pancytopenia 6.5%), 24% were diagnosed with B12 deficiency by this classical hematologist. Of note, 14% of these B12 deficient patients were referred from Hematology/Oncology providers. Further workup by this classical hematologist showed that 17% of cytopenia cases only had B12 deficiency, while the cause of cytopenia in the remaining was found to be multifactorial and they were found to have other vitamin/mineral deficiency, autoimmune conditions, or viral infection in addition to B12 deficiency. None of the B12 deficient patients presented to this clinic with neurological signs or symptoms.
Conclusion:
Data presented here demonstrates that diagnosing B12 deficiency and adequate work up for cytopenias are a challenge both in primary care and specialty clinics, including Hematology/Oncology specialists. Educational interventions are necessary to improve healthcare providers' skills for timely diagnosis of B12 deficiency and etiology of cytopenias before referring to a hematologist. Last but not least, adding a classical hematologist to the care team for patients with non-cancer blood disorders improves patient outcomes.
Citations:
1. Kumar N. Neurologic aspects of cobalamin (B12) deficiency. Handb Clin Neurol. 2014;120:915-26. doi: 10.1016/B978-0-7020-4087-0.00060-7. PMID: 24365360.
2. Green R, Miller JW. Vitamin B12 deficiency. Vitam Horm. 2022;119:405-439. doi: 10.1016/bs.vh.2022.02.003. Epub 2022 Mar 11. PMID: 35337628.