Clinical Lymphoma, Myeloma & Leukemia最新文献_第3页

Survival Outcomes in Patients With Chronic Lymphocytic Leukemia: A SEER Analysis 慢性淋巴细胞白血病患者的生存结局：一项SEER分析

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.07.012

Shivani Modi , Srinishant Rajarajan , Hardik Jain , Claudia Dourado

Survival Outcomes

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia. CLL treatment has evolved dramatically from alkylator-based regimens to chemoimmunotherapy and targeted therapies. This study evaluated real-world survival outcomes across treatment eras using population-based data, focusing on patients who received active systemic therapy to assess treatment effectiveness rather than natural disease progression.

Methods

We conducted a retrospective cohort study using surveillance, epidemiology, and end results (SEER) data from 1995 to 2020, restricting analysis to CLL patients who received active systemic treatment. Patients were stratified into three treatment eras based on treatment initiation date: Pre-novel therapy era (1995-2004, alkylator-based regimens), Early novel therapy era (2005-2014, chemoimmunotherapy with anti-CD20 monoclonal antibodies), and modern novel therapy era (2015-2020, targeted therapies including BTK inhibitors and BCL-2 inhibitors). Era boundaries accounted for the lag between regulatory approval and community adoption. Overall survival was calculated from treatment initiation date, with era assignment based on first-line therapy to maintain temporal consistency.

Results

Among 49,056 CLL patients across three treatment eras, median overall survival improved significantly from 3.5 years (95% CI, 3.2-3.8) in the pre-novel therapy era (1995-2004) to 5.2 years (95% CI, 4.9-5.6) in the early novel therapy era (2005-2014), and 7.8 years (95% CI, 6.9-8.7) in the modern novel therapy era (2015-2020). Multivariable Cox regression analysis demonstrated progressive reductions in mortality risk, with adjusted hazard ratios of 0.75 (95% CI, 0.68-0.82, P < .001) for the Early Novel era and 0.45 (95% CI, 0.38-0.53, P < .001) for the Modern era compared to the Pre-Novel era. Complete response rates increased from 15% to20% in the Pre-Novel era to over 60% in the Modern era with targeted therapies.

Conclusions

This analysis demonstrates significant improvements in survival outcomes for CLL patients across treatment eras, with the most pronounced benefits observed in the modern targeted therapy era. By focusing on treated patients and calculating survival from treatment initiation, we isolated the impact of therapeutic advances from disease biology and patient selection factors. However, the COVID-19 pandemic's disproportionate impact on immunocompromised CLL patients, particularly affecting the modern therapy era, represents an important limitation that may underestimate the true survival benefits of contemporary targeted therapies. These findings support the continued development and adoption of novel therapeutic strategies in CLL management.

生存结果：慢性淋巴细胞白血病（CLL）是最常见的成人白血病。CLL治疗已经从基于烷基化剂的方案发展到化学免疫治疗和靶向治疗。本研究使用基于人群的数据评估了不同治疗时期的真实生存结果，重点关注接受主动全身治疗的患者，以评估治疗效果，而不是自然疾病进展。方法：我们使用1995年至2020年的监测、流行病学和最终结果（SEER）数据进行了一项回顾性队列研究，将分析限制在接受积极全身治疗的CLL患者。根据治疗开始日期，将患者分为三个治疗时代：新疗法前时代（1995-2004年，以烷基化剂为基础的方案），早期新疗法时代（2005-2014年，抗cd20单克隆抗体的化学免疫治疗）和现代新疗法时代（2015-2020年，包括BTK抑制剂和BCL-2抑制剂的靶向治疗）。时代界限解释了监管批准和社区采用之间的滞后。总生存期从治疗开始日期计算，时间分配基于一线治疗以保持时间一致性。结果：在三个治疗时代的49056名CLL患者中，中位总生存期从新疗法前时代（1995-2004）的3.5年（95% CI, 3.2-3.8）显著提高到早期新疗法时代（2005-2014）的5.2年（95% CI, 4.9-5.6），以及现代新疗法时代（2015-2020）的7.8年（95% CI, 6.9-8.7）。多变量Cox回归分析显示，与前小说时代相比，早期小说时代的校正风险比为0.75 (95% CI, 0.68-0.82, P < .001)，现代小说时代的校正风险比为0.45 （95% CI, 0.38-0.53, P < .001）。通过靶向治疗，完全缓解率从前小说时代的15% - 20%增加到现代时代的60%以上。结论：该分析表明，CLL患者在不同治疗时期的生存结果有显著改善，在现代靶向治疗时期观察到最明显的益处。通过关注治疗患者并从治疗开始计算生存率，我们将治疗进展的影响从疾病生物学和患者选择因素中分离出来。然而，COVID-19大流行对免疫功能低下的CLL患者的不成比例的影响，特别是对现代治疗时代的影响，代表了一个重要的限制，可能低估了当代靶向治疗的真正生存益处。这些发现支持在CLL治疗中持续发展和采用新的治疗策略。

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引用次数: 0

Management of Chronic Myeloid Leukemia During Pregnancy: Review of Evidence and Treatment Algorithm 妊娠期慢性髓性白血病的管理：证据和治疗算法的回顾。

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.07.017

Fadi G. Haddad, Jennifer Croden, Koji Sasaki, Ghayas C. Issa, Naveen Pemmaraju, Hagop Kantarjian, Elias Jabbour

Philadelphia chromosome-positive chronic myeloid leukemia (CML) during pregnancy is rare, with an annual incidence of 1 per 100,000 pregnancies. Managing CML in pregnancy is challenging due to concerns about the teratogenicity of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). While some pregnant patients with chronic-phase CML may be managed with close monitoring and no therapy, others, particularly those diagnosed in the first trimester, may require treatment to prevent disease progression and maternal complications. Imatinib has been associated with an increased risk of congenital malformations when used in the first trimester; however, growing evidence support its safety later in the second and third trimesters. Similar to imatinib, nilotinib has limited placental transfer with no congenital malformations reported to date in women who received it later in pregnancy. Dasatinib, however, is contraindicated due to its high association with congenital abnormalities and hydrops fetalis. Ponatinib exposure has been linked to a higher incidence of Hirschsprung’s disease and should be avoided in pregnancy. Although no congenital malformations have been reported with bosutinib or asciminib, data remains limited, and their use is not recommended. Interferon-α is a safer alternative during pregnancy but is slower in achieving cytoreduction, and less effective compared to TKIs. Hydroxyurea, while not teratogenic, may increase the risk of miscarriage and low birth weight. If a male patient is receiving TKI therapy, the female partner can safely become pregnant without an increased risk for the fetus. Shared decision-making and thorough counseling on the risks and benefits of different treatment options are essential. This review examines the potential fetotoxicity of CML therapies, focusing on TKIs and alternative treatments for pregnant women.

妊娠期费城染色体阳性慢性髓性白血病（CML）是罕见的，年发病率为10万分之一。由于担心BCR::ABL1酪氨酸激酶抑制剂（TKIs）的致畸性，妊娠期CML的治疗具有挑战性。虽然一些患有慢性粒细胞白血病的妊娠患者可以通过密切监测而不进行治疗，但其他患者，特别是在妊娠早期诊断出的患者，可能需要治疗以防止疾病进展和产妇并发症。伊马替尼与妊娠早期使用的先天性畸形风险增加有关；然而，越来越多的证据支持其在妊娠中期和晚期的安全性。与伊马替尼类似，尼洛替尼的胎盘移植有限，迄今为止在怀孕后期接受尼洛替尼的妇女中没有先天性畸形的报道。然而，达沙替尼是禁忌症，因为它与先天性异常和胎儿水肿高度相关。波纳替尼暴露与Hirschsprung病的高发病率有关，在怀孕期间应避免使用。虽然博舒替尼或阿西米尼没有先天性畸形的报道，但数据仍然有限，不建议使用它们。干扰素-α在妊娠期间是一种更安全的选择，但在实现细胞减少方面较慢，与TKIs相比效果较差。羟基脲虽然没有致畸性，但可能会增加流产和低出生体重的风险。如果男性患者正在接受TKI治疗，女性伴侣可以安全地怀孕，而不会增加胎儿的风险。对不同治疗方案的风险和益处进行共同决策和全面咨询是必不可少的。这篇综述探讨了CML治疗的潜在胎儿毒性，重点是TKIs和孕妇的替代治疗。

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引用次数: 0

Dermatologic Adverse Events Following CD19-Directed CAR T-Cell Therapy in Hematologic Malignancies cd19靶向CAR - t细胞治疗血液恶性肿瘤后皮肤不良事件。

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.09.012

Ryan Storgard , Rachel E. Reingold , Rose Parisi , Stephen W. Dusza , Sarah J. Noor , Jae H. Park , Craig S. Sauter , Kevin J. Curran , M. Lia Palomba , Gunjan Shah , Roni Shouval , Miguel-Angel Perales , Michael Scordo , Alina Markova

Background

CD19 CAR T-cell therapy is a significant advance in B-NHL and ALL. This study describes the incidence, onset, and factors of dermatologic adverse events (dAE) post-therapy.

Methods

A retrospective analysis at Memorial Sloan Kettering Cancer Center (4/2013-8/2020) identified 193 patients undergoing CD19 CAR T-cell therapy. We aimed to characterize dAEs post CAR T-cell therapy including the 100-day cumulative incidence, time to dAE onset, and associations with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Results

Eighty-two patients experienced 94 dAEs within the first 100 days (incidence: 0.42 (95% CI: 0.36-0.51) post CAR T-cell therapy. Common dAEs were rash (30.9%, n = 29) including maculopapular rash, inflammatory papules, and local erythema; infection (23.4%, n = 22) including cellulitis and folliculitis; and xerosis (16.0%, n = 15). Specific early onset dAEs included rash and chemotherapy-related events, eg, alopecia, mucositis (median 12- and 17-days postinfusion, respectively). Thrombocytopenic purpura and xerosis presented later (median 22-and 25-days). CRS and dAEs occurred in 33.5% of patients, with CRS preceding dAEs in 86% of cases. Among 15% with ICANS and dAEs, ICANS was antecedent in 67%.

Conclusion

dAEs following CAR T-cell therapy are common but mostly low-grade and often manifest within the initial month postinfusion.

背景：CD19 CAR - t细胞治疗是治疗B-NHL和ALL的重要进展。本研究描述了治疗后皮肤不良事件（dAE）的发生率、发病和因素。方法：对纪念斯隆-凯特琳癌症中心（2013年4月- 2020年8月）193例接受CD19 CAR - t细胞治疗的患者进行回顾性分析。我们的目的是表征CAR - t细胞治疗后dAEs的特征，包括100天累积发病率、dAE发病时间以及与细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的相关性。结果：82例患者在CAR -t细胞治疗后的前100天内经历了94次dAEs（发生率：0.42 (95% CI: 0.36-0.51)）。常见的dAEs为皮疹（30.9%,n = 29），包括斑疹丘疹、炎性丘疹和局部红斑；感染（23.4%,n = 22）包括蜂窝织炎和毛囊炎；干枯病（16.0%,n = 15）。特异性早发性dAEs包括皮疹和化疗相关事件，如脱发、粘膜炎（中位分别为输注后12天和17天）。血小板减少性紫癜和干燥症出现较晚（中位22天和25天）。33.5%的患者发生CRS和dAEs， 86%的患者CRS先于dAEs。在15%的ICANS和dAEs患者中，有67%的人有ICANS。结论：CAR - t细胞治疗后的dAEs是常见的，但大多是低级别的，通常在输注后的第一个月内出现。

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引用次数: 0

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients Aged 65 Years and Above With Myelofibrosis 同种异体造血干细胞移植治疗65岁及以上老年骨髓纤维化患者的疗效。

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.08.012

Moazzam Shahzad , Muhammad Kashif Amin , Sohaib Irfan , Rania Ahsan , Hana Qasim , Muhammad Jawad Javed , Matthew McGuirk , Sibgha Gull Chaudhary , Iqra Anwar , Abdulraheem Yacoub , Anurag K. Singh , Mehdi Hamadani , Joseph P. Mcguirk , Muhammad Umair Mushtaq

Background

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only curative option for myelofibrosis (MF) but is often underutilized in patients aged ≥ 65 due to concerns about treatment-related toxicity.

Methods

We conducted a retrospective analysis of chronic-phase MF allo-HCT recipients using the publicly available CIBMTR P-5640 dataset (2008-2019). Key endpoints included overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), and graft-vs-host disease (GVHD)-related outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. Statistical analysis was performed using R (v4.3.2), with statistical significance defined as P < .05.

Results

We included 856 MF allo-HCT recipients (aged ≥ 65: n = 259, aged < 65: n = 597). The 2-year OS, DFS, and GVHD-free, relapse-free survival (GRFS) for patients ≥ 65 years were 62%, 33%, and 12%, respectively. Rates of relapse, NRM, grade II–IV acute GVHD, and chronic GVHD were 43%, 27%, 46%, and 42%, respectively. In multivariable analysis, age ≥ 65 years was independently associated with inferior DFS (HR 1.26, 95% CI 1.03-1.55, P = .025); however, there was no impact on other post-transplant outcomes. Independent predictors of worse outcomes in older patients included splenic radiation and ATG use, secondary MF, higher comorbidities (HCT-CI ≥ 3), mismatched donor type, and bone marrow graft.

Conclusions

In myelofibrosis patients aged 65 years and above undergoing allogeneic HCT, a favorable 2-year overall survival of 62% was noted with an inferior DFS compared to younger patients, while other post-transplant outcomes remained comparable. These findings support allo-HCT as a viable option in selected elderly MF patients using tailored transplant strategies.

背景：同种异体造血干细胞移植（Allogeneic hematopoietic stem cell transplantation, allo-HCT）仍然是治疗骨髓纤维化（MF）的唯一选择，但由于担心治疗相关的毒性，在年龄≥65岁的患者中往往未得到充分利用。方法：我们使用公开的CIBMTR P-5640数据集（2008-2019）对慢性期MF - all - hct受体进行了回顾性分析。关键终点包括总生存期（OS）、无病生存期（DFS）、复发、非复发死亡率（NRM）和移植物抗宿主病（GVHD）相关结局。采用Cox回归模型计算风险比（HR）和95%置信区间（CI）。采用R （v4.3.2）进行统计学分析，P < 0.05为差异有统计学意义。结果：我们纳入了856名MF异位hct受体（年龄≥65岁：n = 259，年龄< 65岁：n = 597）。≥65岁患者的2年OS、DFS和无gvhd、无复发生存率（GRFS）分别为62%、33%和12%。复发率、NRM、II-IV级急性GVHD和慢性GVHD分别为43%、27%、46%和42%。在多变量分析中，年龄≥65岁与较差的DFS独立相关（HR 1.26, 95% CI 1.03-1.55, P = 0.025）；然而，对移植后的其他结果没有影响。老年患者预后较差的独立预测因素包括脾放疗和ATG使用、继发性MF、较高的合并症（HCT-CI≥3）、供体类型不匹配和骨髓移植。结论：在接受同种异体HCT的65岁及以上骨髓纤维化患者中，与年轻患者相比，DFS较差的2年总生存率为62%，而其他移植后结果保持可比性。这些发现支持allo-HCT作为选择老年MF患者的可行选择，使用量身定制的移植策略。

{"title":"Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Older Patients Aged 65 Years and Above With Myelofibrosis","authors":"Moazzam Shahzad , Muhammad Kashif Amin , Sohaib Irfan , Rania Ahsan , Hana Qasim , Muhammad Jawad Javed , Matthew McGuirk , Sibgha Gull Chaudhary , Iqra Anwar , Abdulraheem Yacoub , Anurag K. Singh , Mehdi Hamadani , Joseph P. Mcguirk , Muhammad Umair Mushtaq","doi":"10.1016/j.clml.2025.08.012","DOIUrl":"10.1016/j.clml.2025.08.012","url":null,"abstract":"<div><h3>Background</h3><div>Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only curative option for myelofibrosis (MF) but is often underutilized in patients aged ≥ 65 due to concerns about treatment-related toxicity.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of chronic-phase MF allo-HCT recipients using the publicly available CIBMTR P-5640 dataset (2008-2019). Key endpoints included overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), and graft-vs-host disease (GVHD)-related outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. Statistical analysis was performed using R (v4.3.2), with statistical significance defined as <em>P</em> < .05.</div></div><div><h3>Results</h3><div>We included 856 MF allo-HCT recipients (aged ≥ 65: n = 259, aged < 65: n = 597). The 2-year OS, DFS, and GVHD-free, relapse-free survival (GRFS) for patients ≥ 65 years were 62%, 33%, and 12%, respectively. Rates of relapse, NRM, grade II–IV acute GVHD, and chronic GVHD were 43%, 27%, 46%, and 42%, respectively. In multivariable analysis, age ≥ 65 years was independently associated with inferior DFS (HR 1.26, 95% CI 1.03-1.55, <em>P</em> = .025); however, there was no impact on other post-transplant outcomes. Independent predictors of worse outcomes in older patients included splenic radiation and ATG use, secondary MF, higher comorbidities (HCT-CI ≥ 3), mismatched donor type, and bone marrow graft.</div></div><div><h3>Conclusions</h3><div>In myelofibrosis patients aged 65 years and above undergoing allogeneic HCT, a favorable 2-year overall survival of 62% was noted with an inferior DFS compared to younger patients, while other post-transplant outcomes remained comparable. These findings support allo-HCT as a viable option in selected elderly MF patients using tailored transplant strategies.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"26 1","pages":"Pages e32-e40"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032651","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}

引用次数: 0

Comparative Outcomes of Intensive Chemotherapy Versus Venetoclax Plus Hypomethylating Agents in Acute Myeloid Leukemia Patients Aged 60-75 Years: A Propensity Score–Adjusted Cohort Study 60-75岁急性髓系白血病患者强化化疗与Venetoclax加低甲基化药物的比较结果：一项倾向评分调整的队列研究

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.08.016

Moath Albliwi , Emily C. Zabor , John Hanna , Jessica El-Asmar , Daniel P. Nurse , Ameed Bawwab , Hasan Abuamsha , Yomna Abu-Farsakh , Asad Rauf , Heya Batah , Ahmed Mohamed , Muaz Alsabbagh Alchirazi , Akriti G. Jain , John C Molina , Sophia Balderman , Abhay Singh , Aaron T. Gerds , Sudipto Mukherjee , Ronald M. Sobecks , Betty Hamilton , Moaath K. Mustafa Ali

Background

Venetoclax (VEN) combined with hypomethylating agents (HMA) is established as standard of care for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML). While emerging evidence supports its use in fit, younger patients, data on its comparative efficacy versus intensive chemotherapy (IC) remain limited.

Methods

We conducted a retrospective cohort study to compare composite complete response (CCR), overall survival (OS), and event-free survival (EFS) in patients with AML who received 7 + 3 IC vs. HMA+VEN. All AML patients aged 60–75 years treated between 1/2015 and 9/2023 were included. Propensity score (PS) adjustment and multivariable regression were used to adjust outcomes.

Results

The study included 172 patients who received 7 + 3 and 74 who received HMA+VEN. After adjustment, the average age was –68 years in both groups. The CCR was significantly lower with HMA+VEN (51.4%) than with 7 + 3 (66.9%; P = .025), but this was not significant in the weighted logistic regression model (OR: 0.65, 95% CI: 0.32-1.32, P = .2). PS-adjusted median OS was 18.0 months for 7 + 3 vs. 9.5 months for HMA+VEN (P = .14). VEN+HMA was associated with similar PS-adjusted median EFS (7.2 vs. 7 months, P = .91) compared to 7 + 3. Allogeneic transplant was not different between 7 + 3 and HMA+VEN (48% vs. 24%, log-rank P = .6).

Conclusions

In AML patients aged 60–75 years, HMA + VEN achieved CCR, OS, and EFS comparable to those of the 7 + 3 regimen, consistent with previous reports. However, our analysis may be underpowered or confounded, and a sufficiently powered randomized trial is needed to definitively assess the efficacy, toxicity, and cost-effectiveness of HMA + VEN vs. 7 + 3.

背景：Venetoclax （VEN）联合低甲基化药物（HMA）被确立为老年或新诊断的急性髓性白血病（AML）患者的标准治疗。虽然新出现的证据支持其用于健康的年轻患者，但其与强化化疗（IC）的比较疗效数据仍然有限。方法：我们进行了一项回顾性队列研究，比较接受7 + 3 IC与HMA+VEN治疗的AML患者的综合完全缓解（CCR）、总生存期（OS）和无事件生存期（EFS）。所有在2015年1月至2023年9月期间接受治疗的60-75岁AML患者均被纳入研究。倾向得分（PS）调整和多变量回归对结果进行调整。结果：172例患者接受7 + 3治疗，74例患者接受HMA+VEN治疗。调整后两组患者平均年龄均为-68岁。HMA+VEN组的CCR（51.4%）显著低于7 + 3组（66.9%,P = 0.025），但在加权logistic回归模型中，这一差异无统计学意义（OR: 0.65, 95% CI: 0.32-1.32, P = 0.2）。7 + 3组经ps调整的中位生存期为18.0个月，HMA+VEN组为9.5个月（P = 0.14）。与7 + 3相比，VEN+HMA与ps调整后的中位EFS相似（7.2 vs. 7个月，P = 0.91）。同种异体移植在7 + 3和HMA+VEN之间没有差异（48% vs 24%, log-rank P = .6）。结论：在60-75岁的AML患者中，HMA + VEN获得的CCR、OS和EFS与7 + 3方案相当，与先前的报道一致。然而，我们的分析可能不够有力或存在混淆，需要一项足够有力的随机试验来明确评估HMA + VEN与7 + 3的疗效、毒性和成本效益。

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引用次数: 0

Advanced Multicolor Flow Cytometry Method for Multiple Myeloma 多发性骨髓瘤的先进多色流式细胞术。

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2026-01-01 DOI: 10.1016/j.clml.2025.09.014

Noa Ofir , Ety Rozenberg , Omri Sharabi , Miri Zektser , Ory Rouvio , Roi Gazit

Background

Multiple myeloma (MM) is a bone marrow plasma cells malignancy. Despite impressive advancements of treatments, MM remains incurable due to complex clonality. Here, we present a novel 14-color flow cytometry (FACS) protocol for robust detection and visualization of MM clonality.

Method

We developed a single-tube 14-color FACS protocol to analyze fresh bone marrow samples, tested on 8 MM patients. A premixed, stable antibody cocktail was used to enhance reproducibility and streamline workflow. Dimensionality reduction technique (t-SNE) was applied to visualize plasma cell clonality.

Results

Our panel shown CD38⁺ CD138⁺ plasma cells, and their clonality. As expected, MM patients had unique clonal patterns with significant heterogeneity at primary diagnosis. Advanced t-SNE analysis provides a convenient visualization of multi-parameter heterogeneity in a unified 2-D plot. Importantly, our data presents some similarities among patients, and further differences between primary analysis and secondary relapse.

Conclusions

Taken together, our protocol provides a robust and efficient method for improving MM diagnosis using commercially available antibodies and a standard FACS machine. Concise visualization of multi-parameter FACS will help therapeutic decisions and advance the personalized treatment strategies with emerging antigen-specific drugs.

背景：多发性骨髓瘤是一种骨髓浆细胞恶性肿瘤。尽管治疗取得了令人印象深刻的进步，但由于复杂的克隆性，MM仍然无法治愈。在这里，我们提出了一种新的14色流式细胞术（FACS）方案，用于MM克隆的强大检测和可视化。方法：采用单管14色流式细胞仪对8例MM患者的新鲜骨髓样本进行分析。预先混合，稳定的抗体鸡尾酒用于提高重现性和简化工作流程。采用降维技术（t-SNE）可视化浆细胞克隆。结果：我们的小组显示CD38+ CD138+浆细胞及其克隆性。正如预期的那样，MM患者在初次诊断时具有独特的克隆模式和显著的异质性。先进的t-SNE分析在统一的二维图中提供了方便的多参数异质性可视化。重要的是，我们的数据显示了患者之间的一些相似之处，以及原发性分析和继发性复发之间的进一步差异。结论：综上所述，我们的方案提供了一种强大而有效的方法来改善MM的诊断，使用市售抗体和标准的FACS机器。多参数FACS的简明可视化将有助于制定治疗决策，并推进新出现的抗原特异性药物的个性化治疗策略。

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引用次数: 0

Relative Effectiveness of Talquetamab Versus Real-World Physician's Choice Treatment Regimens in Patients With Relapsed/Refractory Multiple Myeloma: Updated Results From an Indirect Treatment Comparison. 在复发/难治性多发性骨髓瘤患者中，Talquetamab与现实世界医生选择的治疗方案的相对有效性：来自间接治疗比较的最新结果

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2025-12-19 DOI: 10.1016/j.clml.2025.12.009

Jing Christine Ye, Noa Biran, Sandhya Nair, Xiwu Lin, Keqin Qi, Eric M Ammann, Thomas Renaud, Bonnie W Lau, Jenny Zhang, Trilok Parekh, Kathleen S Gray, Xinke Zhang, Luciano J Costa

Background: Talquetamab is approved for treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM) based on the MonumenTAL-1 study (NCT03399799/NCT04634552). Previous indirect treatment comparisons (ITCs) demonstrated superiority of talquetamab over real-world physician's choice (RW) treatment regimens. Here, we report an updated ITC with an additional ∼ 8 and 15 months of follow-up in MonumenTAL-1 and the Flatiron Health Research Database, respectively.

Patients and methods: The research database was used to develop an external control arm for patients who met key MonumenTAL-1 eligibility criteria (n = 629; 1169 eligible lines of therapy [LOT]). Patient-level data from MonumenTAL-1 were included for patients who received talquetamab 0.4 mg/kg QW (n = 143) or 0.8 mg/kg Q2W (n = 154). After adjusting for baseline imbalances, the relative effectiveness of talquetamab versus RW treatment regimens was assessed for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS).

Results: Talquetamab 0.4 mg/kg QW and 0.8 mg/kg Q2W, respectively, demonstrated significant improvements over RW treatment regimens for all outcomes, including PFS (HR, 0.66 [95% CI, 0.53-0.82] and 0.54 [0.44-0.68]), TTNT (HR, 0.57 [0.47-0.69] and 0.49 [0.40-0.60]), and OS (HR, 0.56 [0.42-0.74] and 0.42 [0.31-0.57]); superiority was maintained in the United States Prescribing Information-aligned subgroup of patients with ≥ 4 prior LOT. Results from sensitivity analyses were generally similar.

Conclusion: Talquetamab demonstrated continued superiority over RW treatment regimens in RRMM for PFS, TTNT, and OS, including in patients with ≥ 4 prior LOT. These data suggest talquetamab is an effective treatment option in eligible patients.

背景：基于MonumenTAL-1研究（NCT03399799/NCT04634552）， Talquetamab被批准用于治疗三级暴露性复发/难治性多发性骨髓瘤（RRMM）。先前的间接治疗比较（ITCs）证明了talquetamab优于现实世界的医生选择（RW）治疗方案。在这里，我们报告了一个更新的ITC，分别在monument -1和Flatiron健康研究数据库中进行了额外的8个月和15个月的随访。患者和方法：研究数据库用于为符合monument -1关键资格标准的患者（n = 629； 1169个符合条件的治疗线[LOT]）开发外部对照臂。来自MonumenTAL-1的患者水平数据包括接受talquetamab 0.4 mg/kg QW （n = 143）或0.8 mg/kg Q2W （n = 154）的患者。在调整基线不平衡后，评估了talquetamab与RW治疗方案的相对有效性，包括无进展生存期（PFS）、到下一次治疗的时间（TTNT）和总生存期（OS）。结果：与RW治疗方案相比，Talquetamab分别为0.4 mg/kg QW和0.8 mg/kg Q2W治疗方案的所有结果均有显著改善，包括PFS （HR, 0.66 [95% CI, 0.53-0.82]和0.54[0.44-0.68]）、TTNT （HR, 0.57[0.47-0.69]和0.49[0.40-0.60]）和OS (HR, 0.56[0.42-0.74]和0.42 [0.31-0.57])；在美国处方信息一致的既往LOT≥4的患者亚组中保持优势。敏感性分析的结果大致相似。结论：在治疗PFS、TTNT和OS的RRMM中，包括既往LOT≥4次的患者，Talquetamab表现出持续优于RW治疗方案。这些数据表明，在符合条件的患者中，talquetamab是一种有效的治疗选择。

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引用次数: 0

Clinical Characteristics, Molecular Analysis and Survival Outcomes of Patients With Extramedullary Acute Myeloid Leukemia: A Retrospective Single-Center Study. 髓外急性髓性白血病患者的临床特征、分子分析和生存结局：一项回顾性单中心研究。

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2025-12-19 DOI: 10.1016/j.clml.2025.12.011

Jingyu Song, Xiaoli Lv, Qi Li, Yanqiu Zhao, Dan Guo, Jie Liu, Peiwen Ding, Jiajuan Ji, Yuting Zhu, Dan Luo, Huibo Li, Shengjin Fan

Background: Extramedullary acute myeloid leukemia (eAML) is a rare subtype of AML. The clinical features, molecular mechanisms and prognosis of eAML remain controversial. This study aimed to systematically analyze the differences in clinical and molecular characteristics between eAML patients and AML patients, and evaluate the impact of this disease subtype on survival outcomes.

Methods: We retrospectively included 96 patients with eAML and 144 patients with AML from our center between 2015 and 2024.

Results: eAML patients had a higher tumor burden than AML patients, with significantly elevated white blood cells (P < .001), platelets (P < .001), LDH (P < .001), peripheral blood blasts (P < .001) and bone marrow blasts (P = .005). In terms of molecular genetics, the eAML group was enriched for TET2, DNMT3A, ASXL1, PTPN11 and KMT2A mutations, while NPM1 and U2AF1 mutations were uncommon. The median overall survival (20.1 months vs. 38.8 months, P = .0021) and median relapse-free survival (7.6 months vs. 20.8 months, P = .00027) were significantly shorter for eAML patients. KRAS mutations and chromosomal abnormalities of t(9;11) were associated with poor prognosis. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) could improve the prognosis of eAML patients. In subgroup analysis, we found that patients with multiple extramedullary involvements, synchronous eAML, skin infiltration, and soft tissue involvement had a worse prognosis, while patients with central nervous system (CNS) infiltration had a better prognosis.

Conclusion: Our study demonstrates that patients with eAML subtype have a worse prognosis, unique molecular features and higher tumor burden. Allo-HSCT might be an effective way to improve prognosis. This study provides evidence critical for risk stratification and treatment optimization in eAML.

背景：髓外急性髓性白血病（eAML）是一种罕见的AML亚型。eAML的临床特点、分子机制及预后仍有争议。本研究旨在系统分析eAML患者与AML患者在临床和分子特征上的差异，评估该疾病亚型对生存结局的影响。方法：我们回顾性地纳入了2015年至2024年间本中心96例eAML患者和144例AML患者。结果：eAML患者肿瘤负荷高于AML患者，白细胞（P < 0.001）、血小板（P < 0.001）、LDH （P < 0.001）、外周血母细胞（P < 0.001）、骨髓母细胞（P = 0.005）明显升高。分子遗传学方面，eAML组富集TET2、DNMT3A、ASXL1、PTPN11和KMT2A突变，而NPM1和U2AF1突变不常见。eAML患者的中位总生存期（20.1个月vs. 38.8个月，P = 0.0021）和中位无复发生存期（7.6个月vs. 20.8个月，P = 0.0027）显著缩短。KRAS突变和t染色体异常与预后不良相关（9;11）。同种异体造血干细胞移植（alloo - hsct）可改善急性髓细胞白血病患者的预后。在亚组分析中，我们发现多发性髓外受累、同步eAML、皮肤浸润和软组织受累的患者预后较差，而中枢神经系统（CNS）浸润的患者预后较好。结论：我们的研究表明eAML亚型患者预后较差，具有独特的分子特征和较高的肿瘤负担。同种异体造血干细胞移植可能是改善预后的有效方法。该研究为eAML的风险分层和治疗优化提供了关键证据。

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引用次数: 0

Real-World Evidence on Ibrutinib in First-Line Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma: A Comprehensive Review. 伊鲁替尼治疗一线慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的真实世界证据：全面回顾。

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2025-12-19 DOI: 10.1016/j.clml.2025.12.012

Nilanjan Ghosh, John N Allan, Sabyasachi Ghosh, Zaina P Qureshi, Alex Bokun, Susan O'Brien

Ibrutinib, a Bruton tyrosine kinase inhibitor, is a cornerstone of first-line treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). While generally well tolerated, dose adjustments may be used in some patients to manage adverse events or tolerability issues. This review examines the real-world outcomes such as the effectiveness and duration of therapy of first-line ibrutinib treatment in patients with CLL/SLL, including those with high-risk genomic features. The role of flexible dosing strategies, including dose adjustments or interruptions, and their role in optimizing ibrutinib treatment duration and outcomes are explored. Consistent with results from clinical trials, real-world evidence supports the effectiveness of ibrutinib dosing flexibility in managing adverse events while maintaining long-term clinical benefits. Ibrutinib dose adjustments help optimize treatment persistence and reduce treatment discontinuations, thereby enabling continuous ibrutinib treatment. Furthermore, real-world evidence suggests that ibrutinib dose flexibility contributes to reduced healthcare resource utilization, including fewer hospitalizations and outpatient visits, thus lowering the economic burden of CLL/SLL treatment. Long-term effectiveness, together with lower costs and the ability to tailor ibrutinib dosing to individual patients, supports ibrutinib as a pivotal agent in the management of CLL/SLL.

Ibrutinib是一种布鲁顿酪氨酸激酶抑制剂，是慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）一线治疗的基石。虽然通常耐受性良好，但剂量调整可用于某些患者以控制不良事件或耐受性问题。本综述研究了现实世界的结果，如一线伊鲁替尼治疗CLL/SLL患者的有效性和治疗持续时间，包括那些具有高风险基因组特征的患者。灵活的给药策略的作用，包括剂量调整或中断，以及它们在优化伊鲁替尼治疗持续时间和结果中的作用。与临床试验结果一致，实际证据支持伊鲁替尼灵活剂量管理不良事件的有效性，同时保持长期临床获益。依鲁替尼剂量调整有助于优化治疗持久性，减少治疗中断，从而实现持续的依鲁替尼治疗。此外，现实证据表明，伊鲁替尼剂量的灵活性有助于减少医疗资源的利用，包括减少住院和门诊就诊，从而降低CLL/SLL治疗的经济负担。长期的有效性，加上较低的成本和针对个体患者量身定制伊鲁替尼剂量的能力，支持伊鲁替尼作为CLL/SLL治疗的关键药物。

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引用次数: 0

Real-World Outcomes of High Dose Melphalan and Autologous Stem Cell Transplantation in Patients With Multiple Myeloma Older and Younger Than 65 Years. 大剂量美法兰和自体干细胞移植治疗年龄大于65岁的多发性骨髓瘤患者的实际疗效

IF 2.7 4区医学 Q2 HEMATOLOGY

Clinical Lymphoma, Myeloma & Leukemia

Pub Date : 2025-12-18 DOI: 10.1016/j.clml.2025.12.007

Koen M Klomberg, Miriam Gelderloos, Hilde A M Kooistra, Marcel Nijland, Geertruida H de Bock, Gerwin A Huls, Mirian Brink, Wilfried W H Roeloffzen, Wouter J Plattel

Background: High dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) remains the preferred consolidation strategy for patients with newly diagnosed multiple myeloma (MM). While its use has expanded to patients over 65 years (> 65), few studies have compared real-world outcomes to younger patients.

Patients and methods: This retrospective cohort study included patients with MM who received first line HDT/ASCT between 2013 and 2022 at a large tertiary referral center in The Netherlands. We compared outcomes between patients > 65 years and 65 years or younger (≤ 65), assessing overall survival (OS), time to next treatment or MM-related death (TTNT-D), complications, and quality of life.

Results: Among 394 patients, 109 were > 65 years (range 66-72, 11 patients > 70) and 285 ≤ 65 years (range 34-65). Distributions in baseline characteristics were comparable. Median OS and TTNT-D were 101 and 41 months, respectively, in patients > 65 years compared to 116 (P = .56) and 38 (P = .78) months for patients ≤ 65 years. Age was not a significant predictor. HDT/ASCT was feasible, illustrated by a low serious complications incidence rate and a transplantation-related mortality of 1%. Quality of life data show a stable to increasing trend in the long term.

Conclusion: Survival, treatment response, complication rates, and long-term quality of life were comparable between age groups. Our real-world data confirm the safety and efficacy of HDT/ASCT in fit patients with MM over 65 years. These findings support the broader application of HDT/ASCT in selected older patients and reinforce its role.

背景：大剂量化疗后自体干细胞移植（HDT/ASCT）仍然是新诊断多发性骨髓瘤（MM）患者首选的巩固策略。虽然它的使用已经扩展到65岁以上的患者，但很少有研究将现实世界的结果与年轻患者进行比较。患者和方法：这项回顾性队列研究纳入了2013年至2022年间在荷兰一家大型三级转诊中心接受一线HDT/ASCT治疗的MM患者。我们比较了bbb65岁和65岁以下（≤65岁）患者的结局，评估了总生存期（OS）、到下一次治疗的时间或mm相关死亡（TTNT-D）、并发症和生活质量。结果：在394例患者中，109例> 65岁（范围66-72），11例> 70)，285例≤65岁（范围34-65）。基线特征的分布具有可比性。bb0 ~ 65岁患者的中位OS和TTNT-D分别为101和41个月，而≤65岁患者的中位OS和TTNT-D分别为116 （P = 0.56）和38 （P = 0.78）个月。年龄不是一个显著的预测因子。HDT/ASCT是可行的，其严重并发症发生率低，移植相关死亡率为1%。从长期来看，生活质量数据显示出稳定到上升的趋势。结论：两组患者的生存、治疗反应、并发症发生率和长期生活质量具有可比性。我们的真实数据证实了HDT/ASCT在65岁以上MM患者中的安全性和有效性。这些发现支持了HDT/ASCT在特定老年患者中的广泛应用，并强化了其作用。

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引用次数: 0