Testing to discontinue imatinib already started some years after the advent of this new CML therapy. Since that time, despite many trials and studies in this field, there are still significant gaps, and many fundamental questions remain unanswered. Probably the most intriguing is the persistence of minimal residual disease, which does not lead to disease recurrence in all patients. Nevertheless, today's understanding enables TKI to be safely discontinued in eligible patients outside clinical trials. Notwithstanding, TKI cessation still has to be considered and indicated with caution, taking into account several important viewpoints, like: (i) why stop the therapy in a particular patient, and are all the eligible patients willing to cease the treatment? (ii) Will all the TKI-related side effects relieve upon stopping? (iii) are there any side effects after discontinuing treatment? This review covers extensively all aspects of treatment cessation, like history, theoretical background, eligible patients, monitoring after treatment discontinuation, trigger for retreatment, therapy restart, predictive factors for successful therapy cessation, immunological aspects, potential complications of TKI withdrawal, late molecular relapses, blast crisis development, kinetics of preexisting TKI-related side effects and laboratory values, and quality of life upon treatment cessation. The art of treatment cessation is to select the best candidate based on many diverse facts and information, and follow the patient in the most rational way with smartly anticipating the potential risks and side effects.
{"title":"Treatment Cessation in Chronic Myeloid Leukemia: Evidence and Uncertainties","authors":"Jiří Mayer","doi":"10.1002/hon.70155","DOIUrl":"10.1002/hon.70155","url":null,"abstract":"<p>Testing to discontinue imatinib already started some years after the advent of this new CML therapy. Since that time, despite many trials and studies in this field, there are still significant gaps, and many fundamental questions remain unanswered. Probably the most intriguing is the persistence of minimal residual disease, which does not lead to disease recurrence in all patients. Nevertheless, today's understanding enables TKI to be safely discontinued in eligible patients outside clinical trials. Notwithstanding, TKI cessation still has to be considered and indicated with caution, taking into account several important viewpoints, like: (i) why stop the therapy in a particular patient, and are all the eligible patients willing to cease the treatment? (ii) Will all the TKI-related side effects relieve upon stopping? (iii) are there any side effects after discontinuing treatment? This review covers extensively all aspects of treatment cessation, like history, theoretical background, eligible patients, monitoring after treatment discontinuation, trigger for retreatment, therapy restart, predictive factors for successful therapy cessation, immunological aspects, potential complications of TKI withdrawal, late molecular relapses, blast crisis development, kinetics of preexisting TKI-related side effects and laboratory values, and quality of life upon treatment cessation. The art of treatment cessation is to select the best candidate based on many diverse facts and information, and follow the patient in the most rational way with smartly anticipating the potential risks and side effects.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503500","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}
Suzanne I. M. Neppelenbroek, Afke Ekels, Marie José Kersten, Djamila E. Issa, Noortje Thielen, Lonneke V. van de Poll-Franse, Simone Oerlemans
We investigated the course of fatigue, neuropathy, psychological distress and their impact on HRQoL among diffuse large B-Cell Lymphoma (DLBCL) survivors up to 13 years after diagnosis, and compared it to an age- and sex-matched population. DLBCL survivors diagnosed between 2004 and 2011, who survived ≥ 1 year were selected from the Netherlands Cancer Registry. Survivors completed annual questionnaires 2009–2019, including EORTC QLQ-C30, EORTC CLL-17 and the Hospital Anxiety and Depression Scale. Linear mixed models were used to assess symptom trends and HRQoL associations over time. 302 survivors (response rate 84%) completed a median of three questionnaires. Fatigue improved slightly over time but neuropathy and psychological distress remained unchanged; persistent symptoms were reported by 25%, 28%, and 23% of survivors, respectively. Having two or more comorbidities was associated with higher symptom levels (βfatigue = 7.8, p-value < 0.001; βneuropathy = 6.7, p-value = 0.003; βpsychological distress = 2.2, p-value < 0.001). Having received seven to eight cycles of (R-)CHOP14 was associated with higher neuropathy levels (β = 14.5, p < 0.001) and non-(R-)CHOP treatments were associated to high fatigue levels (β = 14.0, p-value = 0.02) and psychological distress (β = 4.3, p-value = 0.01). Higher symptom levels were associated with poorer HRQoL. One in four DLBCL survivors reported persistent fatigue, neuropathy or psychological distress, negatively impacting their HRQoL. Routine symptom monitoring is essential to identify needs and guide supportive care referrals.
{"title":"Fatigue, Neuropathy and Psychological Distress and Their Association With Health-Related Quality of Life in Survivors of Diffuse Large B-Cell Lymphoma: A Prospective Cohort Study and Comparison With a Normative Population","authors":"Suzanne I. M. Neppelenbroek, Afke Ekels, Marie José Kersten, Djamila E. Issa, Noortje Thielen, Lonneke V. van de Poll-Franse, Simone Oerlemans","doi":"10.1002/hon.70151","DOIUrl":"https://doi.org/10.1002/hon.70151","url":null,"abstract":"<div>\u0000 \u0000 <p>We investigated the course of fatigue, neuropathy, psychological distress and their impact on HRQoL among diffuse large B-Cell Lymphoma (DLBCL) survivors up to 13 years after diagnosis, and compared it to an age- and sex-matched population. DLBCL survivors diagnosed between 2004 and 2011, who survived ≥ 1 year were selected from the Netherlands Cancer Registry. Survivors completed annual questionnaires 2009–2019, including EORTC QLQ-C30, EORTC CLL-17 and the Hospital Anxiety and Depression Scale. Linear mixed models were used to assess symptom trends and HRQoL associations over time. 302 survivors (response rate 84%) completed a median of three questionnaires. Fatigue improved slightly over time but neuropathy and psychological distress remained unchanged; persistent symptoms were reported by 25%, 28%, and 23% of survivors, respectively. Having two or more comorbidities was associated with higher symptom levels (β<sub>fatigue</sub> = 7.8, <i>p</i>-value < 0.001; β<sub>neuropathy</sub> = 6.7, <i>p</i>-value = 0.003; <i>β</i><sub>psychological distress</sub> = 2.2, <i>p</i>-value < 0.001). Having received seven to eight cycles of (R-)CHOP14 was associated with higher neuropathy levels (<i>β</i> = 14.5, <i>p</i> < 0.001) and non-(R-)CHOP treatments were associated to high fatigue levels (<i>β</i> = 14.0, <i>p</i>-value = 0.02) and psychological distress (<i>β</i> = 4.3, <i>p</i>-value = 0.01). Higher symptom levels were associated with poorer HRQoL. One in four DLBCL survivors reported persistent fatigue, neuropathy or psychological distress, negatively impacting their HRQoL. Routine symptom monitoring is essential to identify needs and guide supportive care referrals.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470007","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}
Xue Yang, Pu Wang, Tianhong Xu, Chenqi Yu, Yang Yang, Peng Liu
Despite the survival benefit observed in recent decades, early mortality (EM) remains critical in newly diagnosed multiple myeloma (NDMM) patients, with heterogeneous definitions and risk factors across studies. Besides, prognostic models for predicting EM are limited, especially in real-world scenarios. This single-center retrospective study performed comprehensive analyses as well as risk prediction models of 1093 NDMM patients diagnosed between 2007 and 2021 in China, finding the EM rate was 5.9% at 2 months, 8.8% at 6 months and 13.3% at 12 months. Infection and cardiac events were documented as the top two most common causes of early death. Risk factors that were independent predictors of both EM and OS mainly included cardiac amyloidosis, stroke, del (17p) and poor performance status. ISS stage, platelet count, treatment regimen and concomitant cardiac disease influenced OS rather than EM. Multivariate model-based nomograms were constructed to estimate 2-month, 6-month, 12-month mortality, plus OS, enabling individualized outcome prediction, validated via receiver operating characteristic (ROC) and calibration curves. EM is associated with multiple factors in MM patients, and early identification of patients with higher risk of EM may translate into tailored management in clinical practice.
{"title":"Real-World Data Analysis on Early Mortality in Chinese Multiple Myeloma Patients: Analysis of 1093 Patients During a 15-Year Period","authors":"Xue Yang, Pu Wang, Tianhong Xu, Chenqi Yu, Yang Yang, Peng Liu","doi":"10.1002/hon.70156","DOIUrl":"https://doi.org/10.1002/hon.70156","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite the survival benefit observed in recent decades, early mortality (EM) remains critical in newly diagnosed multiple myeloma (NDMM) patients, with heterogeneous definitions and risk factors across studies. Besides, prognostic models for predicting EM are limited, especially in real-world scenarios. This single-center retrospective study performed comprehensive analyses as well as risk prediction models of 1093 NDMM patients diagnosed between 2007 and 2021 in China, finding the EM rate was 5.9% at 2 months, 8.8% at 6 months and 13.3% at 12 months. Infection and cardiac events were documented as the top two most common causes of early death. Risk factors that were independent predictors of both EM and OS mainly included cardiac amyloidosis, stroke, del (17p) and poor performance status. ISS stage, platelet count, treatment regimen and concomitant cardiac disease influenced OS rather than EM. Multivariate model-based nomograms were constructed to estimate 2-month, 6-month, 12-month mortality, plus OS, enabling individualized outcome prediction, validated via receiver operating characteristic (ROC) and calibration curves. EM is associated with multiple factors in MM patients, and early identification of patients with higher risk of EM may translate into tailored management in clinical practice.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470001","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}
Charlotte Nørregaard Grønset, Mary Jarden, Jan Christensen, Casper Simonsen, Anders Tolver, Charlotte Suetta, Martin Hutchings
Lymphomas are common cancers affecting the lymphatic system. Chemotherapy is a standard treatment, yet its impact on patient's physical capacity remains understudied. This study aimed to evaluate changes in body composition, muscle strength, and physical performance in patients diagnosed with lymphoma undergoing chemotherapy and to explore the potential association between muscle function and treatment tolerability. This single-center prospective cohort study included participants aged ≥ 18 years scheduled for first-line anthracycline-based chemotherapy for aggressive lymphoma. Patients were recruited and tested before treatment and after 6 months. Body composition (DXA), hand-grip strength, 30 s Sit-To-Stand test, 10-m gait speed and Quality of Life (EORTC-QLQ-C30) were assessed. Low muscle strength, lean mass and gait speed were defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2). Fifty-eight patients (42 males) with a median age of 62 years (range 18–87) completed both test points and were included in the analysis. From baseline to follow-up, total lean mass decreased by 1.70 kg (95% CI −2.55 to −0.85, p = 0.0002), body fat percentage increased by 2.3% (95% CI 1.19 to 3.41, p = 0.0001), handgrip strength decreased by 1.93 kg (95% CI −3.15 to −0.71, p = 0.002), whereas Sit-To-Stand performance increased by 1.4 repetitions (95% CI 0.15 to 2.69, p = 0.03). No changes were observed in appendicular lean mass, body weight, or gait speed. Further, there was no association between changes in muscle function and treatment tolerability. Significant declines in total lean body mass and muscle strength were observed from the start of chemotherapy to 6 months post treatment. These findings underscore the importance of routine muscle function screening and rehabilitation during and after chemotherapy for patients with lymphoma.
淋巴瘤是影响淋巴系统的常见癌症。化疗是一种标准的治疗方法，但其对患者体能的影响仍未得到充分研究。本研究旨在评估接受化疗的淋巴瘤患者的身体组成、肌肉力量和身体表现的变化，并探讨肌肉功能与治疗耐受性之间的潜在关联。这项单中心前瞻性队列研究纳入了年龄≥18岁的患者，计划接受基于蒽环类药物的一线化疗治疗侵袭性淋巴瘤。在治疗前和6个月后招募患者并进行测试。评估身体组成（DXA）、手握力量、30 s坐立测试、10 m步速和生活质量（EORTC-QLQ-C30）。根据欧洲老年人肌肉减少症工作组（EWGSOP2）的定义，肌肉力量、瘦质量和步态速度低。58名患者（42名男性）完成了这两个测试点，中位年龄为62岁（范围18-87岁），并被纳入分析。从基线到随访，总瘦体重减少了1.70 kg (95% CI -2.55至-0.85,p = 0.0002)，体脂率增加了2.3% (95% CI - 1.19至3.41,p = 0.0001)，握力减少了1.93 kg (95% CI -3.15至-0.71,p = 0.002)，而坐立训练增加了1.4次（95% CI - 0.15至2.69,p = 0.03）。未观察到阑尾瘦质量、体重或步态速度的变化。此外，肌肉功能的改变与治疗耐受性之间没有关联。从化疗开始到治疗后6个月，观察到总瘦体重和肌肉力量显著下降。这些发现强调了常规肌肉功能筛查和化疗期间和化疗后淋巴瘤患者康复的重要性。
{"title":"Changes in Lean Muscle Mass, Muscle Strength, and Physical Performance Following First-Line Chemotherapy in Patients With Lymphoma","authors":"Charlotte Nørregaard Grønset, Mary Jarden, Jan Christensen, Casper Simonsen, Anders Tolver, Charlotte Suetta, Martin Hutchings","doi":"10.1002/hon.70154","DOIUrl":"10.1002/hon.70154","url":null,"abstract":"<div>\u0000 \u0000 <p>Lymphomas are common cancers affecting the lymphatic system. Chemotherapy is a standard treatment, yet its impact on patient's physical capacity remains understudied. This study aimed to evaluate changes in body composition, muscle strength, and physical performance in patients diagnosed with lymphoma undergoing chemotherapy and to explore the potential association between muscle function and treatment tolerability. This single-center prospective cohort study included participants aged ≥ 18 years scheduled for first-line anthracycline-based chemotherapy for aggressive lymphoma. Patients were recruited and tested before treatment and after 6 months. Body composition (DXA), hand-grip strength, 30 s Sit-To-Stand test, 10-m gait speed and Quality of Life (EORTC-QLQ-C30) were assessed. Low muscle strength, lean mass and gait speed were defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2). Fifty-eight patients (42 males) with a median age of 62 years (range 18–87) completed both test points and were included in the analysis. From baseline to follow-up, total lean mass decreased by 1.70 kg (95% CI −2.55 to −0.85, <i>p</i> = 0.0002), body fat percentage increased by 2.3% (95% CI 1.19 to 3.41, <i>p</i> = 0.0001), handgrip strength decreased by 1.93 kg (95% CI −3.15 to −0.71, <i>p</i> = 0.002), whereas Sit-To-Stand performance increased by 1.4 repetitions (95% CI 0.15 to 2.69, <i>p</i> = 0.03). No changes were observed in appendicular lean mass, body weight, or gait speed. Further, there was no association between changes in muscle function and treatment tolerability. Significant declines in total lean body mass and muscle strength were observed from the start of chemotherapy to 6 months post treatment. These findings underscore the importance of routine muscle function screening and rehabilitation during and after chemotherapy for patients with lymphoma.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437935","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}
Antonio Pinto, Carmelo Carlo-Stella, Monia Marchetti, Caterina Patti, Annalisa Arcari, Nicola Di Renzo, Marco Laddetto, Maurizio Martelli, Pier Luigi Zinzani
Aggressive large B-cell lymphomas (LBCL) include a range of disease types characterized by heterogenous histopathologic, molecular, and genetic features. In this review, we summarize the main standardized disease assessments, treatments and patient journey and we discuss some of the questions that we will face in interpreting and applying their results in clinical practice in the next few years. Specific methodologies borrowed from FDA clinical trials indications to settle the more important goals (both for fit and unfit patients) - key aspects to be considered in clinical management—were used. The Expert Panel was conceived to reach a consensus on defining unsettled and controversial issues while envisioning possible solutions for current challenges in treating newly diagnosed patients with advanced-stage LBCL not only in the Italian context but also for other Countries sharing similar health care system. The fast-evolving treatment scenario for LBCL holds promise of improving outcomes in these high-risk setting, and we eagerly await new treatment regimens to further optimize patient outcomes.
{"title":"Defining and Addressing the Current Unmet Medical Needs for the Frontline Treatment of Advanced Stage Aggressive Large B-Cell Lymphoma: A Perspective From an Ad Hoc Panel of Italian Experts","authors":"Antonio Pinto, Carmelo Carlo-Stella, Monia Marchetti, Caterina Patti, Annalisa Arcari, Nicola Di Renzo, Marco Laddetto, Maurizio Martelli, Pier Luigi Zinzani","doi":"10.1002/hon.70152","DOIUrl":"10.1002/hon.70152","url":null,"abstract":"<p>Aggressive large B-cell lymphomas (LBCL) include a range of disease types characterized by heterogenous histopathologic, molecular, and genetic features. In this review, we summarize the main standardized disease assessments, treatments and patient journey and we discuss some of the questions that we will face in interpreting and applying their results in clinical practice in the next few years. Specific methodologies borrowed from FDA clinical trials indications to settle the more important goals (both for fit and unfit patients) - key aspects to be considered in clinical management—were used. The Expert Panel was conceived to reach a consensus on defining unsettled and controversial issues while envisioning possible solutions for current challenges in treating newly diagnosed patients with advanced-stage LBCL not only in the Italian context but also for other Countries sharing similar health care system. The fast-evolving treatment scenario for LBCL holds promise of improving outcomes in these high-risk setting, and we eagerly await new treatment regimens to further optimize patient outcomes.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12583570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437903","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}
Muhamad Oum, Ahmad Nanaa, Yazan Jabban, David Viswanatha, Rong He, Dragan Jevremovic, James M. Foran, Talha Badar, Cecilia Arana Yi, Patricia T. Greipp, Aasiya Matin, Mehrdad Hefazi, William J. Hogan, Antoine N. Saliba, Mrinal Patnaik, Abhishek A. Mangaonkar, Mithun Shah, Hassan B. Alkhateeb, Aref Al-Kali
{"title":"Clinical and Prognostic Impact of Allelic Status in EZH2-Mutated Myeloid Neoplasms","authors":"Muhamad Oum, Ahmad Nanaa, Yazan Jabban, David Viswanatha, Rong He, Dragan Jevremovic, James M. Foran, Talha Badar, Cecilia Arana Yi, Patricia T. Greipp, Aasiya Matin, Mehrdad Hefazi, William J. Hogan, Antoine N. Saliba, Mrinal Patnaik, Abhishek A. Mangaonkar, Mithun Shah, Hassan B. Alkhateeb, Aref Al-Kali","doi":"10.1002/hon.70148","DOIUrl":"10.1002/hon.70148","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344996","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}
Jiali Li, Shaobing Gao, Zhenling Li, Yuexin Cheng, Jun Rao, Xixi Xiang, Yunjng Zeng, Xi Zhang, Li Gao
Multiple myeloma (MM) is a malignant neoplasm of plasma cells leading to bone destruction and marrow failure. Prognosis and management of MM rely on cytogenetic determination of copy number alterations (CNAs). Nevertheless, karyotype analysis difficult due to the presence of few plasma cells and their low proliferative activity. A shallow whole-genome sequencing (sWGS) technology named LeukoPrint was used to detect genome-wide CNAs in MM patients (n = 128), which can cover the entire genome without involving cell culture. Compared with karyotyping and fluorescent in situ hybridization (FISH), LeukoPrint demonstrated a significantly higher detection rate of copy number alterations (CNAs), increasing from 8.0% (karyotyping) and 44.2% (FISH) to 75.0% (n = 96), provided new CNA information and redefined the prognostic stratification in 20.3% of patients according to mSMART guidelines. Hyperdiploidy was the most common CNA feature (39.6%) in this cohort. A high concordance of 90.7% was observed in CNA between matched bone marrow and peripheral blood samples. LeukoPrint can be regarded as an automated, convenient and cost-effective approach to describe genomic CNA profiles. With the advantage of detecting CNAs of short segments and incorporating routine diagnostic methods, LeukoPrint can add value to conventional karyotyping with improved prognostic stratification.
{"title":"Identification of Copy Number Alterations From Shallow Whole-Genome Sequencing in Multiple Myeloma","authors":"Jiali Li, Shaobing Gao, Zhenling Li, Yuexin Cheng, Jun Rao, Xixi Xiang, Yunjng Zeng, Xi Zhang, Li Gao","doi":"10.1002/hon.70150","DOIUrl":"10.1002/hon.70150","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple myeloma (MM) is a malignant neoplasm of plasma cells leading to bone destruction and marrow failure. Prognosis and management of MM rely on cytogenetic determination of copy number alterations (CNAs). Nevertheless, karyotype analysis difficult due to the presence of few plasma cells and their low proliferative activity. A shallow whole-genome sequencing (sWGS) technology named LeukoPrint was used to detect genome-wide CNAs in MM patients (<i>n</i> = 128), which can cover the entire genome without involving cell culture. Compared with karyotyping and fluorescent in situ hybridization (FISH), LeukoPrint demonstrated a significantly higher detection rate of copy number alterations (CNAs), increasing from 8.0% (karyotyping) and 44.2% (FISH) to 75.0% (<i>n</i> = 96), provided new CNA information and redefined the prognostic stratification in 20.3% of patients according to mSMART guidelines. Hyperdiploidy was the most common CNA feature (39.6%) in this cohort. A high concordance of 90.7% was observed in CNA between matched bone marrow and peripheral blood samples. LeukoPrint can be regarded as an automated, convenient and cost-effective approach to describe genomic CNA profiles. With the advantage of detecting CNAs of short segments and incorporating routine diagnostic methods, LeukoPrint can add value to conventional karyotyping with improved prognostic stratification.</p>\u0000 </div>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354713","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}
The aim of this study was to describe the initial 3-year experience in vein-to-vein time for axi-cel therapy and the role of pharmacists in the first recruiting French centers. Retrospective observational data were collected for vein-to-vein time for commercial axi-cel after ≥ 2 lines of systemic therapy between January 2019 and December 2021 in the first 12 authorized French centers. Hospital pharmacists used a circuit database to ensure the prospective traceability at all steps. Totally 501 of the 562 intention-to-treat registrations on the database for cytapheresis (89,1%) led to the infusion of axi-cel. Median vein-to-vein time was shortened by 4 days. This was mainly due to tightening the interval from apheresis to release. The 36-day median vein-to-vein time achieved after 3 years' experience should be compared to the 29–34 days reported in Canada, the USA and Israel, where manufacturing sites are geographically closer to hospital centers than they are in France. The top 5 recruiting centers had the shortest vein-to-vein times. This French experience may serve as a model for other European centers, notably as regards deployment of pharmacists to improve the patient pathway with CAR T-cells and other gene and cellular therapies.
{"title":"The French Experience of Pharmacists and CAR T-Cells: A Study of the French Society of Oncology Pharmacy (SFPO)","authors":"Vérane Schwiertz, Romain de Jorna, Adeline Quintard, Marie-Antoinette Lester, Marine Pinturaud, Nicolas Cormier, Elise D’Huart, Emmanuelle Fougereau, Muriel Carvalho, Benjamin Sourisseau, Pauline Gueneau, Mathieu Wasiak, Alexia Jouvance, Muriel Paul, Régine Chevrier, Bertrand Pourroy, Jean-Louis Cazin, Florence Ranchon, Isabelle Madelaine-Chambrin, Catherine Rioufol","doi":"10.1002/hon.70144","DOIUrl":"10.1002/hon.70144","url":null,"abstract":"<p>The aim of this study was to describe the initial 3-year experience in vein-to-vein time for axi-cel therapy and the role of pharmacists in the first recruiting French centers. Retrospective observational data were collected for vein-to-vein time for commercial axi-cel after ≥ 2 lines of systemic therapy between January 2019 and December 2021 in the first 12 authorized French centers. Hospital pharmacists used a circuit database to ensure the prospective traceability at all steps. Totally 501 of the 562 intention-to-treat registrations on the database for cytapheresis (89,1%) led to the infusion of axi-cel. Median vein-to-vein time was shortened by 4 days. This was mainly due to tightening the interval from apheresis to release. The 36-day median vein-to-vein time achieved after 3 years' experience should be compared to the 29–34 days reported in Canada, the USA and Israel, where manufacturing sites are geographically closer to hospital centers than they are in France. The top 5 recruiting centers had the shortest vein-to-vein times. This French experience may serve as a model for other European centers, notably as regards deployment of pharmacists to improve the patient pathway with CAR T-cells and other gene and cellular therapies.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345008","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}
Christian Rausch, Ulrike Bacher, Manuela Rabaglio, Corinne Vorburger, Anke Klingenberg, Yara Banz, Michael Daskalakis, Thomas Pabst
Patients with Hodgkin lymphoma (HL) or peripheral T-cell lymphoma (PTCL) who relapse after high-dose chemotherapy (HDCT) have a dismal prognosis. Brentuximab-vedotin (BV) is a CD30-targeting antibody-drug-conjugate (ADC) used in first-line-, salvage-, and maintenance-therapy of HL, as well as first-line- and salvage-therapy of PTCL. In phase I of this trial, we could show that BV can safely be added to BeEAM-HDCT (bendamustine, etoposide, cytarabine and melphalan). Here, we report the randomized phase II part of the trial comparing BV-BeEAM to BeEAM alone (ClinicalTrials.gov: NCT03187210). Primary endpoint was 1-year disease-free survival. Inclusion of 42 patients was planned but the study was terminated early, after a futility analysis showed lack of benefit. Twenty-five patients (HL: 11, PTCL: 14) who were planned to undergo HDCT were included. Median age was 60 years. Patients had a median of two prior therapies, and 11 were previously exposed to BV. Patients in the standard-arm had higher disease stage and (PTCL only) higher IPI. Duration of hospitalization, recovery of neutrophils/platelets, and infections were not significantly different between arms. No treatment related death occurred. However, two patients in the BV-arm developed grade 3 pneumonitis. After 22 months median follow-up, overall response-rate, complete remission-rate, disease-free survival and overall survival did not differ between groups. Pre-planned subgroup-analyses (HL-only, PTCL-only, only those achieving CR) did not show benefit in any subgroup. In conclusion, adding BV to BeEAM does not improve outcomes after HDCT, and may increase pulmonary toxicity. Frequent prior exposure to BV may have limited the potential benefit of the combination.
{"title":"Randomized Phase II Study of Brentuximab-Vedotin With High-Dose Chemotherapy in CD30 Positive Lymphoma","authors":"Christian Rausch, Ulrike Bacher, Manuela Rabaglio, Corinne Vorburger, Anke Klingenberg, Yara Banz, Michael Daskalakis, Thomas Pabst","doi":"10.1002/hon.70143","DOIUrl":"10.1002/hon.70143","url":null,"abstract":"<p>Patients with Hodgkin lymphoma (HL) or peripheral T-cell lymphoma (PTCL) who relapse after high-dose chemotherapy (HDCT) have a dismal prognosis. Brentuximab-vedotin (BV) is a CD30-targeting antibody-drug-conjugate (ADC) used in first-line-, salvage-, and maintenance-therapy of HL, as well as first-line- and salvage-therapy of PTCL. In phase I of this trial, we could show that BV can safely be added to BeEAM-HDCT (bendamustine, etoposide, cytarabine and melphalan). Here, we report the randomized phase II part of the trial comparing BV-BeEAM to BeEAM alone (ClinicalTrials.gov: NCT03187210). Primary endpoint was 1-year disease-free survival. Inclusion of 42 patients was planned but the study was terminated early, after a futility analysis showed lack of benefit. Twenty-five patients (HL: 11, PTCL: 14) who were planned to undergo HDCT were included. Median age was 60 years. Patients had a median of two prior therapies, and 11 were previously exposed to BV. Patients in the standard-arm had higher disease stage and (PTCL only) higher IPI. Duration of hospitalization, recovery of neutrophils/platelets, and infections were not significantly different between arms. No treatment related death occurred. However, two patients in the BV-arm developed grade 3 pneumonitis. After 22 months median follow-up, overall response-rate, complete remission-rate, disease-free survival and overall survival did not differ between groups. Pre-planned subgroup-analyses (HL-only, PTCL-only, only those achieving CR) did not show benefit in any subgroup. In conclusion, adding BV to BeEAM does not improve outcomes after HDCT, and may increase pulmonary toxicity. Frequent prior exposure to BV may have limited the potential benefit of the combination.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336573","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}
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