European Journal of Haematology最新文献

{"title":"Treatment of Critical Bleeds in Patients With Immune Thrombocytopenia: A Systematic Review","authors":"Saifur R. Chowdhury,&nbsp;Emily Sirotich,&nbsp;Gordon Guyatt,&nbsp;Daya Gill,&nbsp;Dimpy Modi,&nbsp;Laura M. Venier,&nbsp;Syed Mahamad,&nbsp;Mahmudur Rahman Chowdhury,&nbsp;Kerolos Eisa,&nbsp;Carolyn E. Beck,&nbsp;Vicky R. Breakey,&nbsp;Kerstin de Wit,&nbsp;Stephen Porter,&nbsp;Kathryn E. Webert,&nbsp;Adam Cuker,&nbsp;Clare O'Connor,&nbsp;Jennifer MacWhirter -DiRaimo,&nbsp;Justin W. Yan,&nbsp;Charles Manski,&nbsp;John G. Kelton,&nbsp;Matthew Kang,&nbsp;Gail Strachan,&nbsp;Ziauddin Hassan,&nbsp;Barbara Pruitt,&nbsp;Menaka Pai,&nbsp;Rachael F. Grace,&nbsp;Dale Paynter,&nbsp;Jay Charness,&nbsp;Nichola Cooper,&nbsp;Steven Fein,&nbsp;Arnav Agarwal,&nbsp;Hasmik Nazaryan,&nbsp;Ishaq Siddiqui,&nbsp;Russell Leong,&nbsp;Sushmitha Pallapothu,&nbsp;Aaron Wen,&nbsp;Emily Xu,&nbsp;Bonnie Liu,&nbsp;Amirmohammad Shafiee,&nbsp;Preksha Rathod,&nbsp;Henry Kwon,&nbsp;Jared Dookie,&nbsp;Dena Zeraatkar,&nbsp;Lehana Thabane,&nbsp;Rachel Couban,&nbsp;Donald M. Arnold","doi":"10.1111/ejh.14351","DOIUrl":"10.1111/ejh.14351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 49 eligible studies reporting 112 critical bleed patients with ITP, including 66 children (median age, 10 years), 36 adults (median age, 41.5 years), and 10 patients with unreported age. Patients received corticosteroids (<i>n</i> = 67), IVIG (<i>n</i> = 49), platelet transfusions (<i>n</i> = 41), TPO-RAs (<i>n</i> = 17), and splenectomy (<i>n</i> = 28) either alone or in combination. Studies reported 29 different treatment combinations, the 5 most common were corticosteroids, platelet transfusion and splenectomy (<i>n</i> = 13), corticosteroids and IVIG (<i>n</i> = 13), or splenectomy alone (<i>n</i> = 13); IVIG alone (<i>n</i> = 11); and corticosteroids, IVIG and TPO-RA (<i>n</i> = 8). Mortality among patients with critical bleeds in ITP was 30.6% for adults and 19.7% for children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The effects of individual treatments on patient outcomes were uncertain due to very low-quality evidence. There is a need for a standardized approach to the treatment of ITP critical bleeds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Systematic Review Registration</h3>\u0000 \u0000 <p>CRD42020161206.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 3","pages":"458-468"},"PeriodicalIF":2.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Teclistamab in Patients With Relapsed or Refractory AL Amyloidosis","authors":"Margaret Stalker,&nbsp;Alfred Garfall,&nbsp;Adam Cohen,&nbsp;Dan T. Vogl,&nbsp;Mia Djulbegovic,&nbsp;Sandra Susanibar-Adaniya,&nbsp;Edward Stadtmauer,&nbsp;Oxana Megherea,&nbsp;Adam J. Waxman","doi":"10.1111/ejh.14348","DOIUrl":"10.1111/ejh.14348","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Teclistamab has demonstrated deep responses in patients with multiple myeloma in the MajesTEC-1 study. However, the safety and efficacy of teclistamab in patients with AL amyloidosis are unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed patients with biopsy-proven relapsed/refractory AL amyloidosis who were treated with teclistamab from December 2022 to February 2024 at the University of Pennsylvania. The data cutoff was 2/29/24. Adverse events (AE) were extracted from the electronic medical record. Patients were assessed for hematologic and organ response per consensus guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight patients were included in this case series: median age 63 (range 59–67), 75% female, 88% White. All eight patients achieved at least very good partial response (VGPR) and had normalization of free light chains (FLC), and six (75%) patients achieved undetectable FLC levels. Of the six patients with immunofixation completed, all six (100%) achieved hematologic complete response (hCR). The median time to hematologic VGPR and hCR was 13 days (range 12–18 days) and 88 days (range 32–150 days), respectively. The median duration of follow-up was 8.5 months (range 1–14 months). Of the five patients with cardiac involvement, four (80%) achieved a cardiac response. Of the seven patients with renal involvement, two patients already achieved renal response prior to teclistamab, and of the remaining five, three (60%) achieved renal response. Six patients (75%) developed low-grade cytokine release syndrome (CRS). No patients developed ICANS. Neutropenia and AKI both occurred in 25% of patients, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this series of patients, teclistamab showed outstanding depth of response and was well-tolerated. Teclistamab shows promise in treating patients with relapsed AL amyloidosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 3","pages":"443-447"},"PeriodicalIF":2.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Clinical Validation of Liquid Chromatography–Tandem Mass Spectrometry for Measuring Ruxolitinib in Steroid-Refractory Graft-Versus-Host Disease: A First Step Towards Optimized Treatment","authors":"Sara Redondo,&nbsp;María Costa,&nbsp;Maria-Estela Moreno-Martinez,&nbsp;Miguel Arguello-Tomas,&nbsp;Mireia Riba,&nbsp;Olga Aso,&nbsp;Eva Iranzo,&nbsp;Albert Esquirol,&nbsp;Jorge Sierra,&nbsp;Javier Briones,&nbsp;Rodrigo Martino,&nbsp;Edgar Zapico,&nbsp;Irene García-Cadenas","doi":"10.1111/ejh.14349","DOIUrl":"10.1111/ejh.14349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This non-interventional, prospective, single-center study aimed to develop a technique to measure ruxolitinib (RUX) concentrations and provide preliminary data on the distribution of plasma drug levels in patients with steroid refractory (SR) GvHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Between April 2023 and May 2024, we analyzed 48 blood samples from 29 patients with SR-GvHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median individual plasma concentrations varied across different RUX doses and largely overlapped: 39.2 ng/mL at 10 mg b.i.d (range: 0–73), 13.1 ng/mL at 10–5 mg (range, 6.1–35.6), and 31.6 ng/mL at 5 mg b.i.d (range: 0.7–99.9). Samples taken under non-optimal temperature conditions showed a lower median concentration of 0.77 ng/mL (range: 0–7.4 ng/mL). The four patients who did not respond at days +28 and +180 after RUX initiation (3 with lower gastrointestinal aGvHD, and 1 with ocular, hepatic, and pulmonary cGvHD) showed a median concentration of only (7.4 ng/mL (range, 0–29) ng/mL) with full dosing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The introduction and validation of a liquid chromatography–tandem mass spectrometry method for quantifying plasma RUX concentrations was feasible in our center. Administering predetermined and fixed doses of RUX in patients with SR-GvHD showed highly variable and overlapping plasma drug concentrations. This underscores the potential importance of RUX- pharmacokinetics (PK) monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 3","pages":"436-442"},"PeriodicalIF":2.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Oral Anticoagulants Versus Warfarin in Patients With Isolated Heparin-Induced Thrombocytopenia or Heparin-Induced Thrombocytopenia With Thrombosis","authors":"Kaiya Hassan,&nbsp;Robert Kinan,&nbsp;Ashley Casey,&nbsp;Miranda Dermady,&nbsp;Britta Mizuki,&nbsp;Katerina Stanilova,&nbsp;Heather Savage,&nbsp;Helen Yuan,&nbsp;Emma Hillis,&nbsp;Connor Bertaut,&nbsp;Taylor Guillory,&nbsp;Eric Coons","doi":"10.1111/ejh.14350","DOIUrl":"10.1111/ejh.14350","url":null,"abstract":"<div>\u0000 \u0000 <p>No existing studies compare oral anticoagulants to treat heparin-induced thrombocytopenia with or without thrombosis (HIT/HITT). This retrospective study evaluated thrombotic and bleeding outcomes in adults treated for HIT/HITT with a direct oral anticoagulant (DOAC) or warfarin between 2012 and 2023 within the Ochsner Health System. Patients with mechanical heart valves, valvular atrial fibrillation, antiphospholipid syndrome, active malignancy, or venous thromboembolism (VTE) within the previous 6 months were excluded. The primary outcome was a composite of new or progressive VTE or arterial thromboembolism. Secondary outcomes included major and clinically relevant non-major bleeding, duration of hospitalization, time to platelet recovery, and incidence of skin necrosis, gangrene, and amputation. Forty-nine patients receiving a DOAC and 30 patients receiving warfarin were included. Baseline characteristics were similar between cohorts. There were non-statistically significant increased rates of both the primary outcome (8.9% vs. 4.3%, <i>p</i> = 0.65) and the composite bleeding outcome (32.7% vs. 23.3%, <i>p</i> = 0.37) in the DOAC cohort. Larger, prospective studies are needed to confirm these findings.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 3","pages":"429-435"},"PeriodicalIF":2.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Window Prior to a Haematological Cancer Diagnosis and the Association With Patient Pathways: A Nationwide Register-Based Cohort Study on Healthcare Utilization in Denmark","authors":"Line Flytkjær Virgilsen,&nbsp;Peter Vedsted,&nbsp;Henry Jensen,&nbsp;Henrik Frederiksen,&nbsp;Tarec Christoffer El-Galaly,&nbsp;Linda Aagaard Rasmussen","doi":"10.1111/ejh.14315","DOIUrl":"10.1111/ejh.14315","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study investigated healthcare utilisation in general practice and hospitals in the 2 years preceding a diagnosis of haematological cancer and the association with patient pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The nationwide register-based cohort study included 12 994 patients diagnosed with leukaemia, multiple myeloma and lymphoma in 2014–2018 and 10 matched references. Patient pathways were analysed in unplanned routes (acute admission up to 1 month's prior diagnosis) and elective routes (other routes, e.g., cancer patient pathways).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Female patients in unplanned diagnostic pathways had more contacts to general practice from 19 months before the diagnosis compared to their matched references; with IRR increasing from 1.14 (95% confidence interval (CI) 1.05–1.24) to 2.27 (95% CI 2.13–2.41) at 30–60 days before the diagnosis. Female patients had more point-of-care tests, hospital contacts and radiological investigations at 17, 24 and 17 months, respectively, before diagnosis compared to their references. Similar patterns were seen for male patients, although with a later onset of increase. No healthcare use variations were seen between patients diagnosed in unplanned versus elective pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Increased healthcare utilisation was seen in general practice and hospitals up to 24 months preceding a diagnosis, which may indicate a diagnostic window for detecting haematological cancer earlier.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 2","pages":"353-364"},"PeriodicalIF":2.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Genetic and Clinical Differences of Acute Myeloid Leukemia (AML) in Obese Patients","authors":"Fevzi F. Yalniz,&nbsp;Anna Johnson,&nbsp;Yanal Alnimer,&nbsp;Zena Chahine,&nbsp;Trevor Morris,&nbsp;Rina Yadav,&nbsp;Hiffsa Taj,&nbsp;Chaitanya Iragavarapu,&nbsp;Reinhold Munker,&nbsp;Gregory Monohan,&nbsp;Sainan Wai,&nbsp;Shulin Zhang,&nbsp;Sahar Nozad,&nbsp;Ayman Qasrawi","doi":"10.1111/ejh.14338","DOIUrl":"10.1111/ejh.14338","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The molecular architecture of acute myeloid leukemia (AML) is heterogeneous. Obesity has been identified as a risk factor for the development of AML. There remains a scarcity of data elucidating the specific genetic profile of AML in obese patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a review of adult patients treated at our institution for newly diagnosed AML from January 1, 2017, to January 1, 2023. Obesity is defined as BMI &gt; 30 kg/m². Demographic, clinical, laboratory, and pathologic data were collected retrospectively. The primary outcome of interest was the molecular features of obese compared to non-obese AML patients. The secondary outcome was overall survival (OS). Inverse probability of treatment weights (IPTW) used to balance both groups on several confounding variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 185 patients were included in the analysis. 90 (49%) were obese. Compared with non-obese patients, obese patients were younger and more likely to be females (55 vs. 63, <i>p</i> = 0.04, 55% vs. 38%, <i>p</i> value, <i>p</i> = 0.02, respectively). After matching on age, gender, and ethnicity, obese patients exhibit lower rates of total number of gene mutations (median 2.7 vs. 3.2, <i>p</i> = 0.05), significantly lower rates of mutations in transcriptional factor genes (15.7% vs. 33.2%, <i>p</i> = 0.01), and near-significant in spliceosome genes (12% vs. 22.3%, <i>p</i> = 0.08), and higher rates of NPM1 mutation (23.3% vs. 12.6%, <i>p</i> = 0.08). Median OS was not significantly different in the matched cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The molecular features of obese AML patients significantly differ from non-obese counterparts. These findings suggest distinct underlying mechanisms in leukemogenesis in obese patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 2","pages":"365-372"},"PeriodicalIF":2.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies","authors":"Alexander Röth,&nbsp;Rong Fu,&nbsp;Guangsheng He,&nbsp;Hazzaa Alzahrani,&nbsp;Sheng-Chieh Chou,&nbsp;Yosr Hicheri,&nbsp;Maciej Kaźmierczak,&nbsp;Viviane Lacorte Recova,&nbsp;Michihiro Uchiyama,&nbsp;Ana-Maria Vladareanu,&nbsp;Leigh Beveridge,&nbsp;Simon Buatois,&nbsp;Muriel Buri,&nbsp;Nicolo Compagno,&nbsp;Dayu Shi,&nbsp;Nadiesh Balachandran,&nbsp;Sasha Sreckovic,&nbsp;Phillip Scheinberg","doi":"10.1111/ejh.14339","DOIUrl":"10.1111/ejh.14339","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To evaluate the tolerability of crovalimab versus eculizumab in C5 inhibitor (C5i)-naive and -experienced patients with PNH from COMMODORE 2, 3 and 1 (NCT04434092, NCT04654468 and NCT04432584).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pooled safety data were assessed in the total crovalimab and eculizumab populations and by C5i-naive versus C5i-switched status in patients receiving crovalimab. Analyses include 6.5 months of additional follow-up from the COMMODORE 2 and 1 primary analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>COMMODORE safety data (crovalimab, 393 patients [naive, 192 patients; switched, 201 patients]; eculizumab, 111 patients) were analysed. The total patient years (PY) were 503.9 and 51.1 in the total crovalimab and eculizumab populations, respectively, with 471 and 581 adverse events (AEs) per 100 PY. Serious infection rates were 8.9 and 13.7 AEs per 100 PY, respectively; no meningococcal infections were reported. Fatal AEs occurred in eight (2%) patients receiving crovalimab (naive, six patients; switched, two patients) and one (1%) receiving eculizumab, all treatment unrelated. In C5i-switched patients, 39 (19%) had transient immune complex reactions (risk when switching between C5i and crovalimab); the majority were Grades 1–2 arthralgia and rash, and 16 (8%) had Grade 3 events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Crovalimab's safety profile was consistent with eculizumab's and was generally comparable between C5i-naive and C5i-switched patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 2","pages":"373-382"},"PeriodicalIF":2.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Hematopoietic Stem Cell Transplantation in Refractory Multiple Myeloma—A Retrospective Multicenter Analysis","authors":"T. Richardson,&nbsp;G. Kobbe,&nbsp;R. Fenk,&nbsp;T. Schroeder,&nbsp;M. Crysandt,&nbsp;C. Neuerburg,&nbsp;Tobias A.W. Holderried,&nbsp;D. Schütte,&nbsp;P. Gödel,&nbsp;M. Hallek,&nbsp;C. Scheid,&nbsp;U. Holtick","doi":"10.1111/ejh.14346","DOIUrl":"10.1111/ejh.14346","url":null,"abstract":"<p>A growing list of therapies available for patients with multiple myeloma (MM) results in deep response rates, but eventually almost all patients relapse. Allogeneic hematopoietic cell transplantation (allo-SCT) is a familiar approach for MM, but responses are often short and side effects burdensome. Simultaneously, allo-SCT provides a unique platform on which novel immune therapies can be employed to improve clinical outcomes. Our work describes the characteristics and outcomes of 128 refractory myeloma patients who underwent allo-SCT at five German centers between 2010 and 2021. The median number of therapies before the transplant was 6. With a median follow-up of 6, 4 years, the median progression-free survival and overall survival were 7 and 19 months, respectively. NRM was 28% after 6 years. OS and PFS were 61% and 45% at 1 year, 49% and 34% at 2 years, and 38% and 25% at 6 years. Achieving a CR before transplant was the single most significant variable before transplant. Allo-SCT yet remains an option for fit patient's refractory to all other treatments available. It is potentially curative for a subset of patients. Finding the characteristics of patients with durable remissions is key to sparing unnecessary toxicity for those unlikely to benefit.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 3","pages":"423-428"},"PeriodicalIF":2.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating Notch1 and Notch2: Receptor-Specific Significance and Therapeutic Importance of Pinpoint Targeting Strategies for Hematological Malignancies","authors":"Priyadharshini Tamizhmani,&nbsp;Banumathi Balamurugan,&nbsp;Kishore Thirunavukarasu,&nbsp;Velayuthaprabhu Shanmugam,&nbsp;Selvakumar Subramaniam,&nbsp;Thirunavukkarasu Velusamy","doi":"10.1111/ejh.14312","DOIUrl":"10.1111/ejh.14312","url":null,"abstract":"<p>Notch1 and Notch2, transmembrane receptors belonging to the Notch family, are pivotal mediators of intercellular communication and have profound implications including cell fate determination, embryonic development, and tissue homeostasis in various cellular processes. Despite their structural homology, Notch1 and Notch2 exhibit discrete phenotypic characteristics and functional nuances that necessitate their individualized targeting in specific medical scenarios. Aberrant Notch signaling, often driven by the dysregulated activity of one receptor over the other, is implicated under various pathological conditions. Notch1 dysregulation is frequently associated with T-cell acute lymphoblastic leukemia, whereas Notch2 perturbations are linked to B-cell malignancies and solid tumors, including breast cancer. Hence, tailored therapeutic interventions that selectively inhibit the relevant Notch receptor need to be devised to disrupt the signaling pathways driving the specific disease phenotype. In this review, we emphasize the importance of distinct tissue-specific expression patterns, functional divergence, disease-specific considerations, and the necessity to minimize off-target effects that collectively underscore the significance of “individualized” targeting for Notch1 and Notch2. This comprehensive review sheds light on the receptor-specific characteristics of Notch1 and Notch2, providing insights into their roles in cellular processes and offering opportunities for developing tailored therapeutic interventions in the fields of biomedical research and clinical practice.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 2","pages":"213-230"},"PeriodicalIF":2.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss in Overall and Quality-Adjusted Life Expectancy for Patients With Chronic-Phase Chronic Myeloid Leukemia","authors":"Enoch Yi-Tung Chen,&nbsp;Torsten Dahlén,&nbsp;Leif Stenke,&nbsp;Magnus Björkholm,&nbsp;Shuang Hao,&nbsp;Paul W. Dickman,&nbsp;Mark S. Clements","doi":"10.1111/ejh.14328","DOIUrl":"10.1111/ejh.14328","url":null,"abstract":"<p>The introduction of tyrosine kinase inhibitors has considerably improved the life expectancy (LE) for patients with chronic myeloid leukemia (CML). Evaluating health-related quality of life within the treatment pathway remains crucial. Using the Swedish CML register, we included 991 adult patients with chronic-phase (CP) CML diagnosed 2007 to 2017, with follow-up until 2018. We developed a multistate model to estimate the loss in LE (LLE) and loss in quality-adjusted life expectancy (LQALE) for the patient population compared to the general population, along with the respective proportions of losses relative to the general population. All patients with CP-CML had a relatively low reduced LE but with larger LQALE. The maximum LLE within age/sex subgroups was 5.7 years (general population LE: 43.2 years vs. CP-CML LE: 37.5 years) for females diagnosed at age 45 years, with LQALE of 12.0 quality-adjusted life years (QALYs) (general population QALE: 38.2 QALYs vs. CP-CML QALE: 26.3 QALYs). Across all ages, the proportions of LLE ranged from 9% to 15%, and the proportions of LQALE were 29% to 33%. Despite a low LLE, our findings reveal a greater LQALE for patients with CP-CML. Further improvements in management of CP-CML are thus warranted to successfully address the prevailing medical needs.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 2","pages":"334-342"},"PeriodicalIF":2.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}