Acta Haematologica最新文献

{"title":"Factor VIII Levels and ISTH Disseminated Intravascular Coagulation Scores Do Not Distinguish Disseminated Intravascular Coagulation from the Coagulopathy of Liver Disease.","authors":"Cecily Allen, Marina Heskel, Ayesha Butt, Christopher Tormey, Alexander B Pine, Alfred I Lee, Samir Gautam","doi":"10.1159/000540239","DOIUrl":"10.1159/000540239","url":null,"abstract":"<p><strong>Introduction: </strong>Distinguishing disseminated intravascular coagulation (DIC) from the coagulopathy of liver disease represents a common clinical challenge. Here, we evaluated the utility of two diagnostic tools frequently used to differentiate between these conditions: factor VIII (FVIII) levels and the International Society on Thrombosis and Hemostasis (ISTH) DIC score.</p><p><strong>Methods: </strong>To this end, we conducted a retrospective chart review of patients with DIC, liver disease, or both. Multiple logistic regression was performed, and receiver operating characteristic curves were generated to calculate the area under curve (AUC) for distinguishing DIC in the setting of liver disease.</p><p><strong>Results: </strong>Among 123 patients with DIC, liver disease, or liver disease plus DIC, FVIII levels did not differ significantly. ISTH scores were lower in patients with DIC than in liver disease with or without DIC. Addition of several laboratory parameters to the ISTH score, including mean platelet volume, FV, FVIII, international normalized ratio, and activated partial thromboplastin time, improved AUC for distinguishing DIC in liver disease from liver disease alone (AUC = 0.76; p < 0.0001).</p><p><strong>Conclusion: </strong>We conclude that FVIII levels do not distinguish DIC from liver disease, and ISTH DIC scores are not predictive of DIC in patients with liver disease. Inclusion of additional lab variables within the ISTH DIC score may aid in identifying DIC in patients with liver disease.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"220-225"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective Evaluation of Oral Glucose Tolerance Test in Young Patients with Transfusion-Dependent Beta-Thalassemia.","authors":"Maria Dritsa, Marina Economou, Vasilios Perifanis, Aikaterini Teli, Athanasios Christoforidis","doi":"10.1159/000523874","DOIUrl":"10.1159/000523874","url":null,"abstract":"<p><strong>Background: </strong>Current guidelines recommend yearly evaluation of glucose metabolism with oral glucose tolerance test (OGTT) in patients with thalassemia major (TM) from their 10th year onwards.</p><p><strong>Aims: </strong>The aim of the study was to retrospectively evaluate all the OGTT tests performed in a single pediatric center during the last decade and assess the necessity of yearly performed OGTT in patients with TM during the second decade of life.</p><p><strong>Results: </strong>One hundred and seventy tests performed on 39 patients (24 boys) were included in the analysis. Mean age at the time of each OGTT was 14.15 ± 2.79 years. Seventeen tests (10%) in 8 patients (5 boys) were characterized as impaired glucose tolerance (IGT), whereas in 2 tests (1.18%), fasting glucose values were above 200 mg/dL (diabetes mellitus). Acknowledging the fact that there could be sporadic technical errors, especially in fasting glucose abnormal values, we selectively separated patients with either IGT and abnormal HOMA, MATSUDA, or QUICKI indices or persistently impaired fasting glucose or IGT. With these criteria, 7 patients (4 boys) were identified. No significant differences were observed in demographic and anthropometric parameters, ferritin levels, and mean volume of blood transfused in patients with a definite abnormal glucose metabolism. In order to address selection criteria for performing OGTT without missing a single patient with a definite glucose intolerance, these criteria should include (i) a first OGTT test at the initiation of puberty, (ii) OGTT in any patient with a fasting glucose above 100 mg/dL, and (iii) OGTT in any patient with a ΗΟΜΑ-IR index above 1.85 and yearly onwards. By adopting these criteria, total OGTT tests performed could have been reduced from 170 to only 91, translating to a significant reduction of 46.47%.</p><p><strong>Conclusions: </strong>Only a small percentage of young patients with transfusion-dependent b-thalassemia exhibit abnormal glucose metabolism during their second decade of life. By adopting specific selection criteria, one may avoid performing this time- and money-consuming test in a significant proportion of patients, albeit without sacrificing timely detection and intervention.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"1 1","pages":"1-7"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43094096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Survival of Chronic Myelomonocytic Leukemia-Dysplastic over Proliferative Subtype after Allogeneic Hematopoietic Cell Transplant: A Tertiary Center Experience and Literature Review.","authors":"Hunter D Niehus, Jean Sabile, Richard T Maziarz, Gabrielle Meyers, Rachel Cook, Arpita P Gandhi, Jennifer N Saultz, Shauna Rakshe, Andy Kaempf, Theodore Braun, Yazan Migdady","doi":"10.1159/000539880","DOIUrl":"10.1159/000539880","url":null,"abstract":"<p><strong>Introduction: </strong>CMML is a rare neoplasm with overlapping myelodysplastic and myeloproliferative features whose only potential cure is allogeneic hematopoietic cell transplantation (allo-HCT).</p><p><strong>Methods: </strong>This retrospective study examined 27 CMML patients with high-risk clinical features who underwent first allo-HCT at our institution between 2004 and 2022.</p><p><strong>Results: </strong>Nineteen patients were diagnosed with the proliferative subtype (CMML-MPN) and 8 with the dysplastic subtype (CMML-MDS). Median OS was 15 months post-HCT (95% CI: 5-71); OS at 1, 3, and 5 years was 52%, 35%, and 35%, respectively. Compared to those with CMML-MPN, patients with CMML-MDS had longer OS (median, 8.6 vs. 0.9 years; p = 0.025), RFS (4.4 vs. 0.5 years; p = 0.021), and GVHD-free, relapse-free survival (GRFS, 9.4 vs. 3.4 months; p = 0.033) as well as lower 1-year NRM (13 vs. 47%; p = 0.043), with the statistical significance of this CMML subtype effect maintained in multivariable models. High-risk cytogenetics were associated with shorter GRFS in the univariable (median, 3.1 vs. 6.2 months; p = 0.013) and multivariable (HR = 4.88; p = 0.006) settings.</p><p><strong>Conclusions: </strong>Patients who underwent transplant for CMML-MDS experienced substantially better outcomes than those transplanted for CMML-MPN. Future studies are needed for transplantation optimization in CMML, especially CMML-MPN.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"198-207"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusions in Ugandan Children with Sickle Cell Anemia: Study Design of the Alternative Dosing And Prevention of Transfusions Trial.","authors":"Alexandra Power-Hays, Ruth Namazzi, Charles Kato, Kathryn E McElhinney, Andrea L Conroy, Heather Hume, Chandy John, Sara M O'Hara, Susan E Stuber, Adam Lane, Teresa S Latham, Robert O Opoka, Russell E Ware","doi":"10.1159/000539541","DOIUrl":"10.1159/000539541","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;People with sickle cell anemia (SCA) may require frequent blood transfusions to treat acute and chronic complications. Hydroxyurea is a life-saving treatment for SCA that could also decrease the need for blood transfusions. Inadequate medication access and challenges in dose optimization limit the widespread use of hydroxyurea in Africa. If feasible, pharmacokinetic (PK) dosing might improve dose determination to minimize toxicities and maximize clinical benefits. The Alternative Dosing And Prevention of Transfusions (ADAPT, NCT05662098) trial will analyze the impact of hydroxyurea on transfusion rate and serve as a pilot study to evaluate the feasibility of PK-guided hydroxyurea dosing in Uganda.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Herein we describe the rationale and design of ADAPT, a prospective cohort study of ∼100 children with SCA in Jinja, Uganda. The primary hypothesis is that hydroxyurea will decrease blood transfusion use by ≥ 50%, comparing the transfusion incidence rate ratio between a 3-month pretreatment and a 12-month treatment period. A key secondary hypothesis is that our PK-dosing approach will generate a suitable hydroxyurea dose for ≥80% of participants. Every ADAPT participant will undergo hydroxyurea PK testing, and if a dose is generated within 15-35 mg/kg/day, participants will start on their individualized dose. If not, they will start on a default dose of 20 mg/kg/day. Hydroxyurea dose optimization will occur with periodic dose adjustments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, demonstrating the reduction in blood transfusion utilization with hydroxyurea treatment would provide leverage to increase hydroxyurea access, and PK-guided hydroxyurea dosing should optimize the safe and effective treatment of SCA across sub-Saharan Africa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;People with sickle cell anemia (SCA) may require frequent blood transfusions to treat acute and chronic complications. Hydroxyurea is a life-saving treatment for SCA that could also decrease the need for blood transfusions. Inadequate medication access and challenges in dose optimization limit the widespread use of hydroxyurea in Africa. If feasible, pharmacokinetic (PK) dosing might improve dose determination to minimize toxicities and maximize clinical benefits. The Alternative Dosing And Prevention of Transfusions (ADAPT, NCT05662098) trial will analyze the impact of hydroxyurea on transfusion rate and serve as a pilot study to evaluate the feasibility of PK-guided hydroxyurea dosing in Uganda.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Herein we describe the rationale and design of ADAPT, a prospective cohort study of ∼100 children with SCA in Jinja, Uganda. The primary hypothesis is that hydroxyurea will decrease blood transfusion use by ≥ 50%, comparing the transfusion incidence rate ratio between a 3-month pretreatment and a 12-month treatment period. A key secondary hypothesis is that our PK-dosing approach will generate a ","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"208-219"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Digital Health Coaching on Self-Efficacy and Patient-Reported Outcomes in Individuals with Acute Myeloid and Chronic Lymphocytic Leukemia: A Pilot Randomized Controlled Trial.","authors":"Jennifer Marvin-Peek, Valerie Shelton, Kelly Brassil, Bryan Fellman, Austin Barr, Kelly Sharon Chien, Danielle Hammond, Mahesh Swaminathan, Nitin Jain, William Wierda, Alessandra Ferrajoli, Courtney DiNardo","doi":"10.1159/000539756","DOIUrl":"10.1159/000539756","url":null,"abstract":"<p><strong>Introduction: </strong>Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy.</p><p><strong>Methods: </strong>Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score.</p><p><strong>Results: </strong>A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p = 0.219). There were no significant associations between the intervention and other patient-reported outcomes for patients with CLL.</p><p><strong>Conclusion: </strong>There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.</p><p><strong>Introduction: </strong>Promotion of self-efficacy can enhance engagement with health care and treatment adherence in patients with cancer. We report the outcomes of a pilot trial of a digital health coach intervention in patients with leukemia with the aim of improving self-efficacy.</p><p><strong>Methods: </strong>Adult patients with newly diagnosed acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) were randomized 1:1 to a digital health coach intervention or standard of care. The primary outcome of self-efficacy was measured by the Cancer Behavior Inventory (CBI) score.</p><p><strong>Results: </strong>A total of 147 patients (37 AML, 110 CLL) were enrolled from July 2020 to December 2022. In the AML cohort, there was a mean increase in CBI score of 7.03 in the digital health coaching arm compared to a mean decrease of -3.57 in the control arm at 30 days (p = 0.219). There were no significant associations between the intervention and other patient-reported outcomes for patients with CLL.</p><p><strong>Conclusion: </strong>There were numerical, but not statistically significant increases in self-efficacy metrics in AML patients who received digital health coaching. Although this trial was underpowered due to enrollment limitations during a pandemic, digital health coaching may provide benefit to patients with hematologic malignancy and warrants further investigation.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"233-243"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Center Experience of Patients with Plasma Cell Leukemia in the Era of New Therapeutics.","authors":"Maria Dampmann, Sarah Flossdorf, Julius Keyl, Hans Christian Reinhardt, Christine Hanoun","doi":"10.1159/000539223","DOIUrl":"10.1159/000539223","url":null,"abstract":"<p><strong>Introduction: </strong>Plasma cell leukemia (PCL) can occur de novo as primary PCL (pPCL), or in patients with prior diagnosis of multiple myeloma (MM) as secondary PCL (sPCL). In 2021, the diagnostic criteria have been revised, establishing a new cut-off of ≥5% plasma cells in the peripheral blood. Lacking specific clinical trials, PCL is treated similarly to MM; however, outcome for patients with PCL remains poor. Here, we report outcomes for patients with pPCL and sPCL in the era of novel agents.</p><p><strong>Methods: </strong>We performed a retrospective analysis and identified 19 patients (11 pPCL, 8 sPCL) who have been treated for PCL between 2010 and 2022 at University Hospital Essen.</p><p><strong>Results: </strong>Patients with pPCL had a median overall survival (OS) of 37.8 months (95% CI: [15.4; 52.3] months) from diagnosis, with a median time to next treatment (TTNT) of 18.4 (2.0; 22.9) months. All patients were treated with a proteasome-inhibitor (PI)-based induction therapy, and the majority was consolidated with an autologous stem cell transplantation (SCT). Five of these patients received a tandem transplantation. Patients with sPCL had a median OS of only 1.5 months after diagnosis of PCL. Only 1 patient achieved a remission with daratumumab and subsequent allogenic SCT.</p><p><strong>Conclusion: </strong>With our study, we add evidence for a PI-based induction therapy followed by a consolidating autologous SCT for patients with pPCL and give further evidence that a tandem transplant concept might be beneficial. The diagnosis of sPCL remains devastating and needs new therapeutic approaches.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"77-84"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic Pleocytosis in the Cerebrospinal Fluid following CAR-T Cell Therapy for Central Nervous System Lymphoma: A Case for Warning?","authors":"Mayasa Abu Ata, Israel Henig, Dana Yehudai-Ofir, Inna Tzoran, Shimrit Ringelstein-Harlev, Tsofia Inbar, Ilana Slouzkey, Michal Karmona Fintuch, Anat Stern, Olesya Stanevsky, Michal Weiler-Sagie, Yaniv Zohar, Ido Livneh, Goni Merhav, Ayelet Eran, Tsila Zuckerman, Ofrat Beyar Katz","doi":"10.1159/000539354","DOIUrl":"10.1159/000539354","url":null,"abstract":"<p><strong>Introduction: </strong>Chimeric antigen receptor T (CAR-T) cell therapy, emerging as an efficient treatment option for patients with secondary central nervous system (CNS) lymphoma, is frequently complicated with immune effector cell-associated neurotoxicity syndrome (ICANS).</p><p><strong>Case presentation: </strong>We report a case of a 64-year-old woman with transformed follicular lymphoma, developing high-grade ICANS with eosinophilic pleocytosis following third-line therapy with CAR-T cells (tisagenlecleucel). During bridging therapy, she declined neurologically and was diagnosed with secondary CNS lymphoma. She received methotrexate-cytarabine-thiotepa-rituximab regimen with clinical and radiological improvement. Post-CAR-T cell infusion she developed cytokine release syndrome grade II and ICANS grade III. Given the lack of response to steroids, anakinra was initiated with complete ICANS resolution. Cerebrospinal fluid (CSF) analysis, performed only on day +10 due to thrombocytopenia, revealed eosinophils, while infections were excluded.</p><p><strong>Conclusion: </strong>This report emphasizes the importance of CSF analysis in individuals with CAR-T-related neurotoxicity for elucidating the role of specific immune cells in such complications.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"119-126"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlights from the 66th ASH Annual Meeting 2024.","authors":"Ine Schmale","doi":"10.1159/000544847","DOIUrl":"10.1159/000544847","url":null,"abstract":"","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"244-246"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.","authors":"Lindsey E Roeker, Catherine C Coombs, Nirav N Shah, Wojciech Jurczak, Jennifer A Woyach, Chan Y Cheah, Krish Patel, Kami Maddocks, Yucai Wang, Pier Luigi Zinzani, Talha Munir, Youngil Koh, Meghan C Thompson, Catherine E Muehlenbein, Chunxiao Wang, Richard Sizelove, Sarang Abhyankar, Safarulla Hasanabba, Donald E Tsai, Toby A Eyre, Michael Wang","doi":"10.1159/000539587","DOIUrl":"10.1159/000539587","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Here we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year ","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"180-197"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ratio of Serum Urea Nitrogen to Albumin Is a Better Predictor of Overall Survival in Multiple Myeloma Patients than Urea Nitrogen Alone.","authors":"Jiaqi Shao, Enfan Zhang, Haoguang Chen, Zhen Cai, Mengmeng Dong","doi":"10.1159/000538479","DOIUrl":"10.1159/000538479","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analyzed MM patients' clinical data to explore the role of sUN and sUN/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate-adjusted Cox regression analysis, Kaplan-Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with β2-microglobulin (β2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with overall survival (OS), although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate-adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. β2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost β2-MG and LDH's predictive value and sUAR had a higher predictive value.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with β2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analyzed MM patients' clinical data to explore the role of sUN and sUN/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate-adjusted Cox regression analysis, Kaplan-Meier (K-M) curve","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"36-47"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}