Annals of Hematology最新文献

{"title":"Genital graft versus host disease in women after allogeneic hematopoietic stem cell transplantation - a single center experience.","authors":"Yulia Wilk Goldsher, Bina Cohen Sacher, May Cohen, Moshe Yeshurun, Gad Sabah, Ram Eitan, Haim Krissi","doi":"10.1007/s00277-025-06224-1","DOIUrl":"https://doi.org/10.1007/s00277-025-06224-1","url":null,"abstract":"<p><p>Chronic Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), affecting the female genital tract in 25-66% of the patients. This condition, referred to as Genital GVHD is an underdiagnosed gynecologic comorbidity, that can significantly impair quality of life. We aimed to describe the prevalence and management of genital GVHD following HSCT. This retrospective analysis included women who underwent allogeneic HSCT at a single Bone Marrow Transplantation Unit between 2015 and 2020 and were evaluated at a specialized Vulvo-Vaginal Clinic. Diagnosis and severity of genital GVHD were based on the recommendations by the National Institute of Health (NIH), therapeutic options included topical treatments and surgical interventions. Of the thirty-six patients evaluated, 19.4% were diagnosed with genital GVHD. Patients with genital GVHD were older than those with no-genital GVHD (58.42 vs 47.48 years, p = 0.02), and most of them had concurrent multi-organ chronic GVHD (85.71%). Genital GVHD was mostly symptomatic in our cohort (71.42%), clinical findings at the time of diagnosis corresponded with NIH grade 3 (severe disease) in 57.1% of cases. Topical treatments were initiated for all patients with genital GVHD, one required surgical intervention. Genitourinary syndrome of menopause (GSM) was diagnosed among 100% of patients with genital GVHD and among 58.62% of patients without genital GVHD (p = 0.08). In the genital GVHD group, adherence to clinical follow up was limited (43.85%). Genital GVHD should be considered as part of chronic GVHD evaluation after allogeneic HSCT. It is associated with advanced age and the presence of chronic systemic GVHD. Impaired quality of life and limited follow-up within this population emphasize the need for increased awareness and early evaluations.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051413","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":"Hematopoietic stem cell transplantation and immunosuppressive therapy: implications of clonal haematopoiesis.","authors":"Zhengwei Tan, Xinhe Zhang, Jia Feng, Yuechao Zhao, Huijin Hu, Dijiong Wu, Qinghong Yu, Yu Zhang, Liqiang Wu, Tonglin Hu, Zhengsong Yan, Baodong Ye, Wenbin Liu","doi":"10.1007/s00277-024-06152-6","DOIUrl":"https://doi.org/10.1007/s00277-024-06152-6","url":null,"abstract":"<p><p>Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome. The advent of next-generation sequencing (NGS) has shed light on the link between somatic mutations (SM) and the efficacy of immunosuppressive therapy (IST) in AA patients. However, the relationship between SM and hematopoietic stem cell transplantation (HSCT) has not been extensively explored. In this retrospective analysis, we examined 166 AA patients who received HSCT or IST at our institution between May 2019 and December 2023. NGS was conducted on 66 genes within bone marrow cells to investigate the correlation between SM and the prognosis and therapeutic response in AA patients, as well as to assess the impact of mutation types on HSCT outcomes. Clinical data were gathered from 166 AA patients, comprising 84 males and 82 females, with a median age of 32 years (ranging from 9 to 75 years). In our study, a total of 151 somatic mutations were identified across 84 patients (50.6%), with 42 patients (25.3%) presenting a single mutation and 26 patients (15.7%) harboring two mutations. The top five genes with the highest mutation frequency were BCOR/BCORL1 (12.6%), ASXL1 (8.6%), TET2 (6.6%), CEBPA (5.3%), and GATA2 (4.6%). We stratified patients into SM and No-SM groups based on the presence of mutations and further divided them into HSCT and IST groups to assess the influence of mutation types on treatment response and survival within and between these groups. The findings were as follows: 1.Patients in the HSCT group exhibited a higher treatment response (OR 85.9% vs. 68.4%, p < 0.05), although there was no significant difference in survival. 2.Patients with favorable mutations, such as PIGA and BCOR/BCORL1, experienced significantly improved response and survival compared to those with unfavorable mutations like ASXL1, DNMT3A, and TET2 (OR 93.7% vs. 72%, p < 0.05) (3-year OS 93.7% vs. 80%, p > 0.05). 3.The HSCT-Favorable group demonstrated superior response rates (OR 100% vs. 67.7%, p < 0.05) and longer survival (3-year OS 100% vs. 67.7%, p < 0.05) compared to the IST-Favorable group. This study underscores that AA patients carrying favorable mutations, particularly BCOR/BCORL1, tend to have a more robust response and better prognosis than those without mutations or those with unfavorable mutations, such as ASXL1/DNMT3A. These findings are especially pertinent to HSCT, highlighting the importance of NGS prior to initiating treatment.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051414","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":"Time-dependent recovery of renal impairment in patients with newly diagnosed multiple myeloma.","authors":"Yoshikazu Utsu, Yuki Isono, Shin-Ichi Masuda, Hironori Arai, Sonoko Shimoji, Rena Matsumoto, Takafumi Tsushima, Kazusuke Tanaka, Kosuke Matsuo, Chiharu Kimeda, Shiho Konno, Yudai Yano, Nobuhiko Kuramoto, Nobuyuki Aotsuka","doi":"10.1007/s00277-025-06201-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06201-8","url":null,"abstract":"<p><p>Renal impairment is reported in 20%-50% of patients with newly diagnosed multiple myeloma and is known as a poor prognostic factor. Although several studies have demonstrated that treatment with novel antimyeloma agents improves renal impairment and myeloma itself, the time-dependent clinical course of recovery of renal function has not been extensively studied. We retrospectively collected the data of characteristics and outcomes in consecutive unselected patients diagnosed with and treated for symptomatic multiple myeloma between January 2015 and December 2022, and extracted and analyzed the cases with renal impairment. Among 234 patients with multiple myeloma, 67 (28.6%) had renal impairment (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m²) at the time of diagnosis. The median eGFR at diagnosis was 28 ml/min/1.73m², and the eGFR significantly improved to 41.5 ml/min/1.73m², which corresponds to a 42.9% increase, at 3 months after the initiation of treatment for myeloma (p < 0.0001). Further improvement in renal function was not observed at 6 months (eGFR 46 ml/min/1.73m²) and 1 year (eGFR 43.5 ml/min/1.73m²) after treatment initiation. The primary treatment was a bortezomib-containing regimen in approximately 90% of patients. A post hoc analysis revealed a positive correlation between the serum calcium concentration at diagnosis and improvement in renal function. In conclusion, renal function can partially recover through the treatment of multiple myeloma, and the treatment response during the first 3 months may predict the renal function prognosis. Further accumulation of cases is needed to identify the predictive factors for renal recovery.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051415","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":"TGFBI regulates the TGF-β pathway to affect the malignant progression and cisplatin sensitivity in diffuse large B-cell lymphoma.","authors":"Lili Wu, Lei Jiang, Yulei Zhou, Weie Zheng, Aimei Feng, Haifei Guo","doi":"10.1007/s00277-025-06208-1","DOIUrl":"https://doi.org/10.1007/s00277-025-06208-1","url":null,"abstract":"<p><p>Despite the association between aberrant TGFBI expression and tumors development found in various cancer types, the role of TGFBI in diffuse large B-cell lymphoma (DLBCL) progression is not clear. This study attempted to reveal how TGFBI impacts malignant progression and cisplatin sensitivity in DLBCL. Bioinformatics and qRT-PCR were used to analyze expression of TGFBI. To investigate the effect of TGFBI on malignant progression and cisplatin sensitivity in DLBCL cells, cell viability and IC50 values were assessed by CCK-8. Cell proliferation ability was detected by colony formation assay. Cell apoptosis rate was detected by flow cytometry. The degree of DNA damage in cells from different treatment groups was detected by comet assay. Protein expression of TGF-β pathway-related proteins like TGF-β1, Smad2, and p-Smad2 was detected by western blot. Bioinformatics and molecular experiments results revealed substantial upregulation of TGFBI in DCBCL. Cell experiment results indicated that high TGFBI expression expedited DCBCL progression and reduced cisplatin sensitivity. Further rescue experiments revealed that SB525334, a TGF-β pathway inhibitor, could weaken the acceleration of DCBCL progression and restore reduced cisplatin sensitivity both induced by high TGFBI expression. TGFBI could promote malignant progression and inhibit the cisplatin sensitivity of DLBCL cells by regulating the TGF-β pathway. In brief, TGFBI has the potential to be a target in DLBCL treatment.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036159","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":"The impact of Mycoplasma pneumoniae infection on platelets in children with immune thrombocytopenia: a real-world study from China.","authors":"Nan Wang, Zhifa Wang, Juntao Ouyang, Jingyao Ma, Yunyun Wei, Yu Hu, Jingjing Liu, Shuyue Dong, Jinxi Meng, Xiaoling Cheng, Runhui Wu","doi":"10.1007/s00277-024-06179-9","DOIUrl":"https://doi.org/10.1007/s00277-024-06179-9","url":null,"abstract":"<p><p>Mycoplasma pneumoniae (M. pneumoniae), as one of the susceptible pathogens during childhood, may lead to severe mycoplasmal pneumonia and affect platelet fluctuations. We prospectively collected data on persistent/chronic ITP children who were infected with M. pneumoniae infection from August 2023 to December 2023. There were 64 patients (40 males) with a median age of 7.08 years (range 4.30 to 9.76) enrolled in this study. Overall, 33 (51.6%) children received TPO-RAs therapy and 31 (48.4%) received other treatments. The impact of M. pneumoniae infection on platelet count is bidirectional, but thrombocytopenia remains predominant. During M. pneumoniae infection, platelet changes in the TPO-RA group were higher than in the non-TPO-RA group. Thrombocytosis was observed in 6 patients (5 in the TPO-RA group vs. 1 in the non-TPO-RA group). Rescue treatment was implemented in 18 patients (7 in the TPO-RA group vs. 11 in the non-TPO-RA group). Monitoring platelets should be strengthened during M. pneumoniae infection.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036165","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":"Income and education affect prognosis and treatment in symptomatic myeloma : A population-based study on 8672 multiple myeloma patients diagnosed 2008-2021 from the Swedish myeloma registry.","authors":"Gunnar Larfors, Kristina Carlson, Christopher Day, Sigrun Einarsdottir, Gunnar Juliusson, Moshtaak Karma, Dorota Knut-Bojanowska, Ingigerður Sólveig Sverrisdóttir, Ingemar Turesson, Mariana Villegas-Scivetti, Cecilie Hveding Blimark","doi":"10.1007/s00277-025-06214-3","DOIUrl":"https://doi.org/10.1007/s00277-025-06214-3","url":null,"abstract":"<p><p>Despite advancements in multiple myeloma treatment, prognostic variability persists. We investigated the impact of income and education on treatment and survival in a country with publicly funded healthcare. We analysed data from the Swedish Myeloma Registry (2008-2021) linked to national registers. Cox models assessed survival, adjusting for demographics and comorbidities. Treatment patterns were compared using cumulative incidence functions. Among 8,672 patients, higher education and income correlated with prolonged survival. Adjusted hazard ratios (HRs) for low income were 1.4 (95% CI 1.3-1.5) and for low education were 1.3 (95% CI 1.2-1.4). Higher income patients were more likely to receive lenalidomide (HR 1.5, 95% CI 1.3-1.6) and pomalidomide (HR 1.7, 95% CI 1.4-2.0), and less likely to receive melphalan tablets (HR 0.8, 95% CI 0.7-0.9). Low-income patients were less likely to undergo stem cell transplant (HR 0.8, 95% CI 0.7-0.9). Immigrant status or biological sex did not influence outcomes. Even in a tax-funded system, socioeconomic disparities impact myeloma survival and treatment. Lower socioeconomic status correlates with inferior outcome and more conservative treatment. Attitudinal biases may contribute to these disparities. Better treatment for the less privileged patients could significantly improve myeloma survival, advocating for efforts to overcome the influence of socioeconomic status.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027772","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":"The association between radiotherapy and the prognosis of follicular lymphoma patients with different characteristics in the rituximab era: a cohort study based on Surveillance, Epidemiology and End Results.","authors":"Liyin Li, Zhenxin He, Qiang Zhou, Bo Nie","doi":"10.1007/s00277-025-06209-0","DOIUrl":"https://doi.org/10.1007/s00277-025-06209-0","url":null,"abstract":"<p><p>This retrospective cohort study examined the association between radiotherapy and prognosis in follicular lymphoma (FL) patients, with stratification by age, Ann Arbor stage, primary tumor site, surgical status, and grade. Using data from the SEER database, we employed Cox proportional hazards and competing risk models to assess the impact of radiotherapy on overall survival (OS) and cancer-specific survival (CSS) in 7,551 FL patients. The association between radiotherapy and second primary cancer (SPC) was explored using Logistic regression model. At the end of the 60-month follow-up, 6,053 patients were alive, while 1,498 had died. The overall result showed that radiotherapy was associated with the better OS [hazard ratio (HR): 0.70, 95% confidence interval (95%CI): 0.59-0.83, P < 0.001] and CSS (HR: 0.67, 95% CI: 0.52-0.87, P = 0.002)) in FL patients. Radiotherapy was associated with improved OS and CSS in patients aged ≥ 60 years [OS: HR: 0.65, CI: 0.53-0.79; CSS: HR: 0.63, CI: 0.52-0.77], early Ann Arbor stage (OS HR: 0.51, CI: 0.40-0.65; CSS HR: 0.51, CI: 0.40-0.65), primary sites at lymph nodes (OS HR: 0.76, CI: 0.62-0.93; CSS HR: 0.76, CI: 0.62-0.93) and skin/soft tissue (OS HR: 0.35, CI: 0.16-0.81; CSS HR: 0.36, CI: 0.16-0.82), and in both surgical (OS HR: 0.70, CI: 0.52-0.93; CSS HR: 0.70, CI: 0.52-0.93) and non-surgical patients (OS HR: 0.71, CI: 0.56-0.89; CSS HR: 0.69, CI: 0.55-0.87). Radiotherapy showed no significant association with second primary cancer (SPC) risk. These findings suggest radiotherapy improves 5-year survival outcomes in FL patients during the rituximab era.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027781","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":"Total marrow irradiation as part of autologous stem cell transplantation for patients with multiple myeloma.","authors":"Qing-Xiu Zhong, Fan-Yi Meng, Hong-Yu Chen, Xin Li, Xiao-Guo Wang, Shun-Hua Huang, Ming-Yan Wu, Jian-Hua Yu, Ying Xue, Yi-Hong Wu, Da-Na Yao, Jia-Xin Long, Xiao-Hong He","doi":"10.1007/s00277-025-06219-y","DOIUrl":"https://doi.org/10.1007/s00277-025-06219-y","url":null,"abstract":"<p><p>The efficacy and safety of total marrow irradiation (TMI) plus a reduced dose of melphalan as autologous stem cell transplantation (ASCT) preconditioning for multiple myeloma (MM) patients were evaluated. The 11 patients with MM had a median age of 57 (range: 46-75) years; six of them were at standard risk and five of them were at high risk based on the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) standard risk factors. Before ASCT, three patients achieved stringent complete response (sCR), two patients achieved complete remission (CR), and the rest of the patients had either partial response (PR) or progressive disease. Most of the 11 patients were pretreated with melphalan 120-140 mg/m² and TMI 12 Gy. The intravenous infusion median mononuclear cell count (MNC) was 8.13 (4.16-11.84) × 10⁸/kg, and the median CD34⁺ count was 4.74 (2.51-21.98) × 10⁶/kg. The minimal residual disease (MRD) in the grafts as determined by flow cytometry (FCM) and fluorescence in situ hybridization (FISH) were negative in 10 patients but positive in the progressive patient. All patients stopped maintenance therapy after transplantation, and further observation focused on the efficacy and tolerability of the transplantation. The neutropenic and thrombocytopenia durations were 11 (7-28) and 14 (8-70) days, respectively. The primary acute non-hematological toxicities were mild oral and gastrointestinal mucositis; there were no transplant-related deaths or serious complications. Of the eight patients who did not achieve sCR before transplantation, seven converted to sCR and one converted to VGPR after transplantation. The median follow-up period was 24 (10-57.5) months. Only one patient relapsed, and the progression-free survival (PFS) was 90.9%, while the overall survival (OS) was 100%. Our preliminary results suggest that melphalan 120-140 mg/m² plus TMI 12 Gy/6f as a conditioning regimen is safe and efficient for patients with MM.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027720","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":"Incidence trends and prognostic factors in head and neck MALT lymphoma.","authors":"Yaobin Lin, Shan Liu, Jianzhen Shen","doi":"10.1007/s00277-024-06161-5","DOIUrl":"https://doi.org/10.1007/s00277-024-06161-5","url":null,"abstract":"<p><p>Primary head and neck mucosa-associated lymphoid tissue lymphoma (HN-MALT) is a rare lymphoma with unknown incidence and prognosis. We allocated HN-MALT data from the Self-Surveillance, Epidemiology, and End Results database (2000-2021) into training and validation cohorts at a 7:3 ratio. A joinpoint regression analysis was used to examine sex-specific and age-group morbidities, and independent prognostic factors were identified through multivariate Cox analysis to construct a nomogram prediction model and verify the accuracy of prediction. A total of 2,517 patients with HN-MALT were randomly divided into training (1,762) and validation (755) groups. The incidence of HN-MALT in men and women decreased from 2007 to 2021, with an annual percent change (APC) of -3.04% (95%: -4.4 - -1.6, P < 0.05), while in the ≥ 60 years old group, the incidence decreased significantly from 2016 to 2021, with an APC of -8.20 (95%: -13.9 - -2.1, P < 0.05). The multivariate Cox analysis revealed that male, ≥ 60 years old, white, and divorced/separated/widowed were independent risk factors of the overall survival and lymphoma-specific survival. A nomogram prediction model was constructed based on the Cox regression results for multiple factors, the areas under the curve, the calibration curve, and decision curve analysis results of which indicated that the nomogram prediction model performed very well. HN-MALT cells exhibit distinctive clinical and pathological characteristics. Furthermore, we developed a nomogram model for the prognostic assessment to offer valuable guidance for clinical decision-making.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027757","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":"Multiplex digital PCR enables sensitive detection of resistance to BTK inhibitors.","authors":"Manon Garcia, Carolyne Croizier, Grégory Lazarian, Anne Quinquenel, Thomas Tassin, Céline Bourgne, Olivier Tournilhac, Jacques-Olivier Bay, Marc G Berger, Andréi Tchirkov, Lauren Véronèse, Romain Guièze","doi":"10.1007/s00277-025-06200-9","DOIUrl":"https://doi.org/10.1007/s00277-025-06200-9","url":null,"abstract":"<p><p>The advent of BTK inhibitors has been transformative in the management of patients with chronic lymphocytic leukemia or other B-cell lymphoproliferative disorders. However, emergence of BTK or PLCG2 mutations lead to resistance to these compounds and are now a growing concern in clinical practice. Assessing BTK mutations is now becoming a priority to guide the therapeutic decision at further relapse. To this end, targeted next-generation sequencing (NGS) is a valid tool, but lack of sensitivity and the required time for delivering results remain major challenges. Digital PCR could be more sensitive but is also limited by the number of mutations that can be screened. We here overcame these challenges by multiplexing digital PCR (mdPCR) in three assays that can cover 96% of ibrutinib-resistant cases. We investigated a cohort of 28 patients progressing on ibrutinib and for whom NGS revealed BTK mutations (C481S, C481F and C481R) and/or PLCG2 R665W mutation. Overall, 49 mutations were detected by NGS and 68 by mdPCR. We found mdPCR to bemore sensitive than NGS, particularly at low allelic frequencies, making it more suitable for the detection and quantification of small mutated clones. Thus, mdPCR offers high sensitivity, is expected to be more rapid and cost-effective than NGS in detecting resistance mutations to improve the therapeutic choice at relapse after exposure to BTK inhibitors.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027777","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}