Therapeutic Advances in Hematology最新文献

{"title":"Prognostic value of patient-reported outcome thresholds on survival and adverse events in CLL/SLL: A pooled analysis of ibrutinib trials.","authors":"Ahmad Y Abuhelwa, Sara A Almansour, Humaid O Al-Shamsi, Ziad Abuhelwa, Mohamad A Ziade, Yasser Bustanji, Mohammad H Semreen, Mohammad A Y Alqudah, Ross A McKinnon, Karem H Alzoubi, Michael J Sorich, Ashley M Hopkins","doi":"10.1177/20406207261480380","DOIUrl":"10.1177/20406207261480380","url":null,"abstract":"<p><strong>Background: </strong>EORTC thresholds for clinical importance on the QLQ-C30 have been proposed to improve the interpretability of patient-reported outcomes (PROs), but their clinical relevance remains underexplored in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).</p><p><strong>Objectives: </strong>This study aimed to evaluate the frequency of clinically important baseline PRO domains and their associations with survival and adverse events in patients with CLL/SLL.</p><p><strong>Design: </strong>This was a pooled retrospective analysis of individual patient data from three randomized clinical trials of ibrutinib-based therapy.</p><p><strong>Methods: </strong>Data were pooled from RESONATE, RESONATE-2, and HELIOS. EORTC thresholds for clinical importance were applied to baseline QLQ-C30 scores to identify clinically important PRO domains. Cox proportional hazards models were used to examine associations between the number of clinically important PRO domains and overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events.</p><p><strong>Results: </strong>Among 1,238 patients, 920 (74%) reported at least one clinically important PRO domain and 395 (32%) reported five or more. Each additional clinically important domain was independently associated with worse OS (adjusted HR [95% CI]: 1.07 [1.04-1.11]; P < 0.001), worse PFS (1.03 [1.00-1.06]; P = 0.047), and increased risk of grade ≥3 adverse events (1.03 [1.01-1.06]; P = 0.006). Compared with patients reporting no clinically important PRO domains, those with ≥5 domains had worse OS (2.04 [1.42-2.94]; P < 0.001) and higher risk of grade ≥3 adverse events (1.47 [1.17-1.85]; P < 0.001). Physical function was the strongest individual prognostic domain for OS (C-index = 0.63).</p><p><strong>Conclusion: </strong>Clinically important PRO domains were common among patients with CLL/SLL initiating ibrutinib-based therapy and were independently associated with survival and toxicity outcomes. These findings support the clinical utility of EORTC QLQ-C30 thresholds for identifying patients with higher baseline PRO burden who may benefit from enhanced risk stratification, supportive care, and individualized treatment planning.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261480380"},"PeriodicalIF":2.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866788","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":"Treatment strategies for relapsed/refractory hemophagocytic lymphohistiocytosis in pediatric patients.","authors":"Man Wang, Lihui Wang, Cuiping Zhu, Zongxuan Huang, YanLing Tao","doi":"10.1177/20406207261484706","DOIUrl":"10.1177/20406207261484706","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of immune cells which leads to excessive cytokine discharge and systemic inflammation, had a mortality rate of as high as 60% when left untreated or not properly managed in the past, but the HLH-94 protocol was introduced and it brought about significant improvement in patient outcomes, however, nearly 30% of patients remain unresponsive to this initial therapy, either failing to achieve remission or relapsing after an initial response. Therefore, new chemotherapy regimens, such as those incorporating doxorubicin, PEG-asparaginase, or higher-intensity etoposide dosing, and biologically targeted therapies, including monoclonal antibodies against cytokines like interleukin-6 (IL-6) or interleukin-2 (IL-2), as well as Janus kinase (JAK) inhibitors, are being explored in relapsed or refractory patients. Nevertheless, data on their application in children remain limited. Pediatric HLH presents unique challenges due to differences in disease biology, drug metabolism, and long-term toxicity concerns. This article summarizes current treatment strategies for relapsed and refractory HLH in pediatric patients, aiming to provide evidence-based guidance for clinicians managing this complex and high-risk group.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261484706"},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851565","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":"Real-world experiences with subcutaneous therapy in adults with primary immune thrombocytopenia: A dual cross-sectional survey study of patients and clinicians in Italy.","authors":"Esther Natalie Oliva, Alessandra Borchiellini, Giuseppe Carli, Ugo Consoli, Alessandro Lucchesi, Mariasanta Napolitano, Alessandra Ricco, Elena Rossi, Cristina Santoro, Nicola Vianelli, Monica Carpenedo","doi":"10.1177/20406207261481214","DOIUrl":"10.1177/20406207261481214","url":null,"abstract":"<p><strong>Background: </strong>Thrombopoietin receptor agonists (TPO-RAs) are frequently prescribed as second-line therapy for immune thrombocytopenia (ITP). Approved TPO-RAs have different characteristics that can influence doctor-patient shared decision-making.</p><p><strong>Objectives: </strong>To gain insight into how ITP and its treatment with subcutaneous TPO-RA are perceived by Italian adults with ITP and by treating hematologists.</p><p><strong>Design: </strong>Observational, cross-sectional survey.</p><p><strong>Methods: </strong>Italian national surveys were conducted in adults with ITP receiving subcutaneous TPO-RA treatment for ≥ 3 months, and separately in hematologists with extensive experience treating ITP. The ITP-PAQ questionnaire captured the impact of ITP and treatments. The patient survey assessed self-reported treatment adherence, setting of TPO-RA administration, administration autonomy, and collected demographic and disease-related data. Methodologic limitations include potential selection bias, absence of a comparison group, and reliance on patient-reported adherence.</p><p><strong>Results: </strong>Between December 2023 and February 2024, the surveys were completed by 50 clinicians and 78 patients distributed across Italy; mean patient age 55.5 (±13.7) years, mean disease duration 2.4 (±2.1) years. Patients were receiving subcutaneous ITP treatment for median 7 (minimum 3-maximum 50) months. The mean total ITP-PAQ score was 70.1±8.5, with approximately 80% of patients reporting little or no impact of ITP on overall quality of life. Most patients (51%) self-administered subcutaneous therapy at home; 27% went to hospital. Overall self-reported adherence was 97%. After the first months of treatment, 90% of patients reported being \"extremely satisfied\"/\"satisfied\" (68%/22%). This was maintained at survey, when 95% patients were \"extremely satisfied\"/\"satisfied\" (72%/23%). Satisfaction was highest with home self-administration (p=0.09). There were no significant differences (90% confidence level) in patients' and clinicians' responses regarding the main advantages of weekly administration.</p><p><strong>Conclusion: </strong>Both patients and specialists indicated that the high satisfaction may be associated with perceived advantages of weekly TPO-RA subcutaneous administration, which may be associated with improved adherence to therapy and reduced medication burden.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261481214"},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841100","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":"Real-world efficacy and safety of the carfilzomib-pomalidomide-dexamethasone regimen in patients with relapsed/refractory multiple myeloma: A multicenter retrospective study.","authors":"Huishou Fan, XiangYan Feng, Rongxia Wei, Xin Zhang, Tianlan Li, Lu Liu, Hui Wang, Lingjie Sun, Xue Shi, Hongguo Zhao, Zhao Li, Jingying Cui, Junqing Xu, Junjie Ma, Xianqi Feng, Wei Wang","doi":"10.1177/20406207261481202","DOIUrl":"10.1177/20406207261481202","url":null,"abstract":"<p><strong>Background: </strong>Relapsed and refractory multiple myeloma (RRMM) is generally associated with a poor prognosis.</p><p><strong>Objectives: </strong>This real-world study aims to evaluate the efficacy and safety of the carfilzomib-pomalidomide-dexamethasone (KPd) regimen in patients with RRMM.</p><p><strong>Design: </strong>A multicenter, retrospective study was conducted in four centers in China.</p><p><strong>Methods: </strong>RRMM patients who received at least 1 cycle of KPd across four centers were retrospectively included and stratified by prior lines of treatment, survival outcomes and safety profile were analyzed.</p><p><strong>Results: </strong>A total of 82 patients were enrolled. Based on the lines of treatment (LOT) at KPd initiation, patients were stratified into second-line (2L, n=39), third-line (3L, n=26), and fourth-line or beyond (4L+, n=17) groups. Among 72 response-evaluable patients, the overall response rate (ORR) was 69.4%, with ORRs of 79.4%, 73.9%, and 40.0% in the 2L, 3L, and 4L+ groups, respectively. After a median follow-up of 10.8 months, the median progression-free survival (mPFS) for the entire cohort was 22.5 months, while the median overall survival (mOS) was not reached (NR). The mPFS was NR, 22.5, and 10.1 months (P=0.178), and the mOS was NR, NR, and 11.6 months (P=0.019) for patients receiving KPd in the 2L, 3L, and 4L+ settings, respectively. Multivariable analysis identified elevated lactate dehydrogenase (LDH) level (HR=3.489, 95% CI: 1.557-7.823) and LOT ≥4 (HR=2.791, 95% CI: 1.086-7.177) as independent predictors of inferior PFS (P<0.05), while LOT ≥4 (HR=3.917, 95% CI: 1.258-12.200) was also associated with worse OS (P=0.019). Grade ≥3 adverse events (AEs) occurred in 12.8%, 50.0%, and 47.1% of patients in the 2L, 3L, and 4L+ groups, respectively.</p><p><strong>Conclusion: </strong>The KPd regimen demonstrated favorable clinical efficacy and manageable toxicity in RRMM, particularly in those with early-line relapse.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261481202"},"PeriodicalIF":2.8,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841106","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":"Venetoclax with azacitidine and dexamethasone: Non-cytotoxic induction therapy for T-cell leukemia and mixed-phenotype leukemia.","authors":"Yutian Lei, Xiaoli Zhao, Huijun Huang, Limin Duan, Ji Xu, Kourong Miao, Huihui Zhao, Chun Qiao, Ming Hong, Sixuan Qian, Lei Fan, Yu Zhu","doi":"10.1177/20406207261480378","DOIUrl":"10.1177/20406207261480378","url":null,"abstract":"<p><strong>Background: </strong>T-lineage acute leukemias are aggressive malignancies for which treatment options are limited.</p><p><strong>Objectives: </strong>This study evaluated the efficacy and safety of a non-cytotoxic regimen combining venetoclax, azacitidine, and dexamethasone (VAD) as first-line induction therapy for T-cell acute lymphoblastic leukemia (T-ALL) and T/myeloid mixed-phenotype acute leukemia (T-Myeloid MPAL).</p><p><strong>Design: </strong>We retrospectively analyzed the clinical parameters and survival data of 11 patients with newly-diagnosed T-ALL or T-Myeloid MPAL who received the VAD regimen.</p><p><strong>Methods: </strong>The complete remission (CR) rate and adverse events were assessed. Kaplan-Meier curves were constructed to evaluate survival outcomes.</p><p><strong>Results: </strong>Among 11 patients (7 with early T-cell precursor [ETP] ALL, 2 with T-Myeloid MPAL, and 2 with non-ETP T-ALL), the overall CR rate after one cycle of VAD therapy was 90.9%, with 45.5% achieving measurable residual disease (MRD) negativity by flow cytometry. The historically poor-prognosis ETP-ALL subgroup showed an 85.7% CR rate (6/7), while both T-Myeloid MPAL cases attained MRD negativity. No tumor lysis syndrome or treatment-related mortality occurred. Over a median follow-up of 358 days, all 5 patients who received transplantations remained relapse-free.</p><p><strong>Conclusion: </strong>The VAD regimen demonstrated a high response rate and favorable safety, enabling effective transplantation bridging with avoidance of conventional cytotoxic therapy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261480378"},"PeriodicalIF":2.8,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841161","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":"Targeting CD38 in relapsed /refractory T-cell acute lymphoblastic leukemia/lymphoma: A systematic review of daratumumab-based therapy.","authors":"Abdulrahman F Al-Mashdali, Mujahid O Abdelraof, Monia Ibrahim, Mohammed Abdulgayoom, Shehab F Mohamed, Honar Cherif","doi":"10.1177/20406207261484097","DOIUrl":"10.1177/20406207261484097","url":null,"abstract":"<p><strong>Background: </strong>Relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) has poor outcomes and limited salvage options. Objectives: To evaluate the efficacy and safety of daratumumab-based therapy in R/R T-ALL/T-LBL.</p><p><strong>Design: </strong>Systematic review of observational reports.</p><p><strong>Methods: </strong>Sixteen reports including 34 patients treated with daratumumab-based regimens were reviewed. Baseline characteristics, treatment patterns, response, MRD status, survival, allogeneic HSCT, and safety were descriptively synthesized.</p><p><strong>Results: </strong>Complete remission was reported in 30/34 patients (88.2%), partial remission in 2/34 (5.9%), and no response in 2/34 (5.9%). Among complete responders with reported MRD status, 24/29 (82.8%) achieved MRD negativity. Median PFS was 10 months (range, 0.4-45), and median OS was 10 months (range, 1.5-45), although many values reflected last follow-up. Eighteen patients (52.9%) proceeded to allogeneic HSCT; 13/18 (72.2%) were alive at last follow-up. Infusion reactions occurred in 10 patients, mostly grade 1-2.</p><p><strong>Conclusion: </strong>Daratumumab-based therapy may induce remission and facilitate HSCT bridging in selected patients, but findings remain hypothesis-generating because evidence is mainly from case reports and small series.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261484097"},"PeriodicalIF":2.8,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841125","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":"Favorable response to second-line sirolimus regardless of <i>STAT3/5b</i> status in acquired pure red cell aplasia: A retrospective study from a single center.","authors":"Zexing Sun, Xinru Jia, Yingying Shen, Xiawan Yang, Qi Liu, Hangping Ge, Yun Zhang, Zhiyin Zheng, Yiping Shen, Yuhong Zhou, Dijiong Wu","doi":"10.1177/20406207261483341","DOIUrl":"10.1177/20406207261483341","url":null,"abstract":"<p><strong>Background: </strong>Cyclosporine A (CsA) is the standard first-line treatment for acquired pure red cell aplasia (PRCA), but outcomes vary. Effective salvage strategies for CsA-refractory patients, particularly those with complex secondary subtypes, remain inadequately defined. Additionally, the clinical utility of <i>STAT3/5b</i> mutations in guiding treatment selection remains unclear.</p><p><strong>Objectives: </strong>To evaluate the efficacy of second-line sirolimus for the treatment of PRCA and explore the possible genetic predictors for the response.</p><p><strong>Design: </strong>This study was a retrospective, single center, comparative study.</p><p><strong>Methods: </strong>Patients with acquired PRCA treated between 2021 and 2025, including 36 patients who received first-line CsA and 22 patients who switched to sirolimus due to lack of response or intolerance. Clinical outcomes, including overall response rate (ORR) and time to response (TTR), were compared between primary and secondary PRCA. <i>STAT3/5b</i> mutation status was also analyzed to assess its predictive value for treatment response.</p><p><strong>Results: </strong>The ORR for first-line CsA was 25.0% (9/36), with significantly higher efficacy observed in primary cases (42.1%, 8/19) than in secondary cases (5.9%, 1/17; <i>p =</i> 0.015). In the salvage sirolimus group, the ORR was 54.5%, demonstrating efficacy in both primary (37.5%, 3/8) and secondary cases (64.3%, 9/14). The median TTR did not differ significantly between sirolimus and CsA (3.0 vs. 1.5 months, <i>p =</i> 0.150), and both agents achieved sustained remission in responders. Regarding genetic predictors, no responses to CsA were observed in patients harboring <i>STAT3/5b</i> mutations (0/6). In contrast, sirolimus elicited responses in both mutated (3/6) and wild-type (4/5) patients, indicating efficacy irrespective of <i>STAT3/5b</i> status.</p><p><strong>Conclusions: </strong>CsA is effective in primary PRCA, whereas sirolimus demonstrates efficacy in both primary and secondary cases regardless of <i>STAT3/5b</i> status. Early genetic profiling may facilitate the identification of patients who may not fully response to CsA and potentially earlier transition to sirolimus salvage therapy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261483341"},"PeriodicalIF":2.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819562","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":"Successful treatment of relapsed <i>KMT2A</i> rearranged AML with central nervous system involvement using revumenib in combination with venetoclax and azacitidine: A case report.","authors":"Jialiang Xu, Yangpeng Chen, Yan Zhang, Fuhua Zhang, Yu Zhang, Jing Sun, Na Xu","doi":"10.1177/20406207261484015","DOIUrl":"10.1177/20406207261484015","url":null,"abstract":"<p><p>This case report describes the successful treatment of a patient with acute monocytic leukemia (AML-M5), positive for the <i>KMT2A::AFDN</i> fusion gene, who relapsed and developed central nervous system involvement after allogeneic hematopoietic stem cell transplantation. The patient was a 32-year-old male initially treated with conventional chemotherapy followed by transplantation; however, he experienced relapse with AML infiltration of the CNS. Based on the MLL abnormality, salvage therapy was administered using the menin inhibitor Revumenib combined with venetoclax and azacitidine, followed by donor lymphocyte infusion (DLI). After one course of treatment, he achieved minimal residual disease (MRD)-negative status in both bone marrow and cerebrospinal fluid, with sustained complete remission. The main adverse effects observed were grade IV myelosuppression and grade II gastrointestinal symptoms. This case indicates that the salvage strategy incorporating Revumenib, venetoclax, azacitidine, and DLI not only exhibits potential for achieving deep remission in <i>KMT2A</i>-rearranged AML but also aids in controlling central nervous system infiltration, thereby providing a novel therapeutic direction for patients with relapsed AML. Further studies involving larger sample sizes are required to assess the long-term survival benefits of this strategy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261484015"},"PeriodicalIF":2.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819578","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":"Factors associated with longitudinal hydroxyurea adherence trajectories among individuals with sickle cell disease in Texas Medicaid: A group-based trajectory modeling study.","authors":"Blessing I Okoye, Godwin Okoye, Jamie C Barner","doi":"10.1177/20406207261481884","DOIUrl":"10.1177/20406207261481884","url":null,"abstract":"<p><strong>Background: </strong>Hydroxyurea, first-line therapy in sickle cell disease (SCD), has suboptimal adherence ranging from 10%-36%. Thus, examining longitudinal adherence trajectories may help identify critical timepoints and individual subgroups for targeted interventions.</p><p><strong>Objectives: </strong>To identify distinct longitudinal hydroxyurea adherence trajectories among individuals with SCD enrolled in Texas Medicaid and to examine sociodemographic and clinical factors associated with trajectory group membership.</p><p><strong>Design: </strong>Retrospective, longitudinal cohort study.</p><p><strong>Methods: </strong>A retrospective analysis of Texas Medicaid data (01/01/2016-08/31/2023) included individuals with ≥3 medical claims for SCD, ≥1 prescription claim for hydroxyurea without a claim in the pre-index period, aged 2-63 years on the index date (first hydroxyurea claim), and continuously enrolled in Texas Medicaid for 6 months pre- and 12 months post-index. Proportion of days covered (PDC) was used to estimate adherence. Group-based trajectory modeling (GBTM) was used to identify hydroxyurea adherence trajectories. Multinomial logistic regression was used to examine factors associated with hydroxyurea adherence trajectory group membership.</p><p><strong>Results: </strong>Of included individuals (N=1,246; mean age=18.1±12.7, 50.8% female), GBTM revealed five membership groups: consistent adherence (16.1%; mean PDC=89.2±8.5%), fluctuating adherence (28.7%; mean PDC=52.6±12.8), sharp decline and fluctuating adherence (16.5%; mean PDC=26.2±8.8), rapidly decreasing adherence (22.2%; mean PDC=25.6±10.3), and early and consistent nonadherence (16.5%; mean PDC=8.4±1.3). Potential intervention timepoints were identified at months 2, 3, and 5, when adherence declined markedly. Age groups 16-21, 22-34, and ≥35 years (reference: 2-15 years), and an increasing number of vaso-occlusive crises (VOC) in the pre-index period were significantly associated with higher odds of being in the less-adherent trajectory groups compared to the consistent adherence trajectory group: adjusted odds ratio (aORs) range: age groups=2.2-8.7; VOC=1.2-1.4.</p><p><strong>Conclusion: </strong>Unique adherence trajectory patterns with critical timepoints for intervention were observed. Individualized and timely interventions should be tailored to adults, especially those who are transitioning to adult care (22-34 years), and those experiencing frequent VOC.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261481884"},"PeriodicalIF":2.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819580","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":"The impact of chemotherapy relative dose intensity on survival in elderly patients with extranodal NK/T-cell lymphoma: A retrospective cohort study.","authors":"Wanyue Zhao, Siyu Qian, Yuxiao Chang, Wenjie Gu, Shuchang Li, Shifeng Hao, Xiang Gao, Suxiao Li, Meng Dong, Qingjiang Chen, Lu Zhao, Xudong Zhang","doi":"10.1177/20406207261480376","DOIUrl":"10.1177/20406207261480376","url":null,"abstract":"<p><strong>Background: </strong>Optimizing chemotherapy for elderly patients with extranodal natural killer/T-cell lymphoma (ENKTL) represents a significant clinical challenge, requiring a balance between effective relative dose intensity (RDI) and treatment tolerance. The prognostic impact of RDI in this population remains unclear.</p><p><strong>Objectives: </strong>To investigate the relationship between RDI and survival outcomes and to establish a clinically meaningful RDI threshold for elderly ENKTL patients.</p><p><strong>Design: </strong>A retrospective observational single-center cohort study.</p><p><strong>Methods: </strong>The study analyzed treatment-naïve ENKTL patients aged ≥60 years who received DDGP-like regimens or P-GEMOX regimen between May 2016 and December 2023. The optimal RDI cutoff was determined by receiver operating characteristic curve analysis. Variable selection for multivariable Cox regression was performed using least absolute shrinkage and selection operator (LASSO) regression to mitigate overfitting and adjust for potential confounders. The primary endpoints were progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>A total of 79 patients were enrolled. The median number of chemotherapy cycles was 3 (IQR: 3-5), with a median treatment interval of 26 days (IQR: 23-31). Treatment delays exceeding one week occurred in 55.7% of patients (n = 44), and only 2.5% (n = 2) received full dose intensity (RDI = 1). An average RDI ≥ 0.62 was significantly associated with prolonged PFS (<i>p</i> = 0.010) and OS (<i>p</i> = 0.012). Multivariable analysis confirmed higher RDI as an independent predictor of superior PFS (HR = 0.385, 95% CI: 0.186-0.801, <i>p</i> = 0.011) and OS (HR = 0.433, 95% CI: 0.194-0.968, <i>p</i> = 0.041). Furthermore, age≥70 years (vs.60-70 years; p = 0.007), diabetes (p = 0.039), and adverse events including infection (p = 0.033), rash (p = 0.043), and diarrhea (p = 0.017) were significant predictors of reduced RDI.</p><p><strong>Conclusion: </strong>An ARDI ≥ 0.62 may represent a critical threshold associated with improved prognosis in elderly ENKTL. However, this observation is preliminary and warrants further validation in prospective studies.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261480376"},"PeriodicalIF":2.8,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798207","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}