American Journal of Hematology最新文献

{"title":"Multihit TP53 Mutations in Myeloproliferative Neoplasms and Acute Myeloid Leukemia: Comparative Analysis of Survival and Risk Factors in 142 Informative Cases","authors":"Saubia Fathima, Maymona Abdelmagid, Ali Alsugair, Kebede H. Begna, Aref Al-Kali, Abhishek A. Mangaonkar, Animesh D. Pardanani, Mrinal M. Patnaik, Cinthya J. Zepeda Mendoza, Rong He, Kaaren K. Reichard, Talha Badar, James M. Foran, Jeanne Palmer, Giuseppe G. Loscocco, Paola Guglielmelli, Alessandro M. Vannucchi, Attilio Orazi, Daniel A. Arber, Devendra Hiwase, Mithun V. Shah, Naseema Gangat, Ayalew Tefferi","doi":"10.1002/ajh.27670","DOIUrl":"https://doi.org/10.1002/ajh.27670","url":null,"abstract":"A total of 142 patients with myeloproliferative neoplasms (MPNs) or acute myeloid leukemia (AML) associated with multihit <i>TP53</i> mutations (m<i>TP53</i>^MUT) were accessed from the Mayo Clinic database and included (i) chronic phase MPN (MPN-CP; <i>N</i> = 19), (ii) accelerated phase MPN (MPN-AP; <i>N</i> = 14), (iii) blast phase MPN (MPN-BP; <i>N</i> = 28), and (iv) AML (<i>N</i> = 81). Concurrent <i>ASXL1</i>^MUT, <i>EZH2</i>^MUT, <i>IDH1</i>,^MUT and <i>IDH2</i>^MUT were more common in MPN-^MUTBP-mTP53 compared to AML-m<i>TP53</i>^MUT. At median of 11.6 months follow-up, 124 (87%) deaths and 19 (13%) allogeneic stem cell transplantations (ASCT) were documented. Overall survival (OS), calculated from the time of m<i>TP53</i>^MUT detection, was similar between MPN-BP-m<i>TP53</i>^MUT (median 4.6 months) and MPN-AP-m<i>TP53</i>^MUT (5.6 months; <i>p</i> = 0.5) but both were inferior to MPN-CP-m<i>TP53</i>^MUT (11.6 months, <i>p</i> &lt; 0.01). OS in MPN-CP-m<i>TP53</i>^MUT was similar to that of AML-m<i>TP53</i>^MUT (median 7.4 months, <i>p</i> = 0.07). In multivariable analysis, OS was favorably affected by ASCT (HR 0.4, <i>p</i> = 0.03) and disease stage (i.e., chronic phase disease) or achieving response to pre-transplant chemotherapy (HR 0.2, <i>p</i> &lt; 0.01) and unfavorably by the presence of concurrent <i>TET2</i>^MUT or <i>DNMT3A</i>^MUT (HR 2.7, <i>p</i> &lt; 0.01). Based on these risk factors, a 3-tiered risk model was constructed: low (no risk factors; <i>N</i> = 18; median OS 23.8 months); intermediate (one risk factor; <i>N</i> = 44; 11.1 months); and high (two or more risk factors; <i>N</i> = 80; 4 months; <i>p</i> &lt; 0.01). The current study highlights the equally detrimental impact of m<i>TP53</i>^MUT on long-term survival in MPN and AML and identifies predictors of short-term survival.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"89 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Stem Cell Transplant for Myelofibrosis and Myelodysplastic Syndromes: A Contemporary Review","authors":"Nico Gagelmann, Nicolaus Kröger","doi":"10.1002/ajh.27660","DOIUrl":"https://doi.org/10.1002/ajh.27660","url":null,"abstract":"Allogeneic hematopoietic stem‐cell transplantation (HCT) remains the only potentially curative therapy for patients with myelodysplastic neoplasms (MDS) and myelofibrosis (MF) and is the standard care for eligible patients with higher‐risk disease. Despite significant advancements, both diseases pose unique challenges due to their clinical and molecular heterogeneity, necessitating personalized approaches to patient selection, timing, and transplant management. For MDS, genomic profiling has revolutionized prognostic frameworks such as IPSS‐M, enabling tailored therapeutic decisions. In MF, driver mutations (e.g., <jats:italic>JAK2, CALR, MPL</jats:italic>) and additional high‐risk molecular markers provide critical insights into disease biology and transplant outcomes. Optimal timing of HCT is critical, and recent models might help personalize treatment approaches. Molecular measurable residual disease monitoring has demonstrated prognostic value in both diseases, guiding preemptive strategies to mitigate relapse risk. Harnessing molecular technologies, clinical expertise, patient‐centered decision‐making, and innovative pharmaceutical strategies offers an exciting opportunity to shape a transformative and curative treatment framework. Here, we provide a contemporary review on HCT for MDS and MF, highlighting up‐to‐date insights into disease biology, standard of care, and recommendations, as well as open avenues.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"5 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Donor Age and Donor Cytomegalovirus Serostatus on Outcomes After Related Donor Allogeneic Hematopoietic Stem Cell Transplantation","authors":"Rohtesh S. Mehta, Hannah Choe, Jennifer Saultz, Zimu Gong, Prashant Sharma, Taha Al-Juhaishi, Gabriela S. Petitto, Aleksandr Lazaryan, Anurag Singh, Elisabetta Xue, Dimana Dimitrova, Mustafa Hyder, Shannon McCurdy, Annie Im, Bryan Huber, Yosra M. Aljawai, Jennifer Kanakry, Filippo Milano, Christopher G. Kanakry","doi":"10.1002/ajh.27662","DOIUrl":"https://doi.org/10.1002/ajh.27662","url":null,"abstract":"Cytomegalovirus (CMV) infection post-hematopoietic cell transplantation (HCT) remains a significant cause of morbidity and mortality. While letermovir prophylaxis is available for CMV-seropositive recipients, optimal donor selection for CMV-seronegative recipients remains unclear, with donor age often prioritized over CMV serostatus. We investigated the relative impact of donor age and CMV serostatus in CMV-seronegative recipients (<i>n</i> = 1013) with either CMV-seropositive (<i>n</i> = 318) or CMV-seronegative donors (<i>n</i> = 695), who underwent HCT with HLA-matched sibling donors with calcineurin inhibitor-based or post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease prophylaxis, or haploidentical donors with PTCy. Multiple conventional and machine-learning approaches were employed to account for confounding factors. Across all analyses, CMV-seropositive donor status was consistently associated with significantly inferior overall survival (OS) and disease-free survival, primarily driven by increased non-relapse mortality (NRM). Older donor age showed a statistically significant association with OS and DFS in some but not all models, and its effect size was small (about 1% increased hazard per year in Cox proportional hazard model) compared to the substantial impact of CMV-seropositive donors (about 27%–33% increased hazards for worse OS, approximately 50%–60% higher NRM in Cox proportional hazard model). However, our machine learning model revealed a more nuanced and complex non-linear effect of donor age, further demonstrating the adverse impact of donor CMV serostatus. Our findings suggest that prioritizing a CMV-seronegative donor may be associated with improved outcomes in CMV-seronegative recipients. Further research is needed to validate these findings and explore underlying mechanisms.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"16 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53‐Mutated Myeloid Neoplasms: 2024 Update on Diagnosis, Risk‐Stratification, and Management","authors":"Mithun Vinod Shah, Daniel A. Arber, Devendra K. Hiwase","doi":"10.1002/ajh.27655","DOIUrl":"https://doi.org/10.1002/ajh.27655","url":null,"abstract":"Alterations in the tumor suppressor gene <jats:italic>TP53</jats:italic> are common in human cancers and are associated with an aggressive nature. Approximately 8%–12% of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) harbor <jats:italic>TP53</jats:italic> mutations (<jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup>) and present immense challenges due to inherent chemoresistance and poor outcomes. As <jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup> are more common in older individuals and those with secondary/therapy‐related myeloid neoplasms (MN), their incidence is expected to increase with an aging population and rising proportion of cancer survivors. Treatments used for other MN—intensive chemotherapy, hypomethylating agents, and the BCL‐2 inhibitor venetoclax—do not improve the survival of <jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup> MN patients meaningfully. Additionally, further development of many promising agents has been discontinued, highlighting the challenges. Widespread acknowledgment of these problems led to the recognition of <jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup> MN as a distinct entity in the 5th edition of the World Health Organization and International Consensus Classifications. However, critical discrepancies between the two classifications may lead to under‐ or overestimation of the prognostic risk. Here, we review recent advances in the biology, diagnosis, and treatment of <jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup> MN. The development of <jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup> MN is positioned at the intersection of age, hereditary predisposition, and anti‐cancer therapies. Precursor <jats:italic>TP53</jats:italic><jats:sup>mut</jats:sup> clones can be detected years prior to the eventual leukemic transformation—raising the possibility of early intervention. We discuss the two classification systems and the bearing of the discrepancies between the two on timely and effective management. We provide novel evidence in the areas of discrepancies. Finally, we review the current therapeutic landscape and the obvious limitations of the currently used therapies.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"37 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives","authors":"Giuseppe G. Loscocco, Paola Guglielmelli","doi":"10.1002/ajh.27658","DOIUrl":"https://doi.org/10.1002/ajh.27658","url":null,"abstract":"Myelofibrosis (MF) is a myeloproliferative neoplasm that is accompanied by driver <i>JAK2</i>, <i>CALR</i>, or <i>MPL</i> mutations in more than 90% of cases, leading to constitutive activation of the JAK–STAT pathway. MF is a multifaceted disease characterized by trilineage myeloid proliferation with prominent megakaryocyte atypia and bone marrow fibrosis, as well as splenomegaly, constitutional symptoms, ineffective erythropoiesis, extramedullary hematopoiesis, and a risk of leukemic progression and shortened survival. Therapy can range from observation alone in lower-risk and asymptomatic patients to allogeneic hematopoietic stem cell transplantation, which is the only potentially curative treatment capable of prolonging survival, although burdened by significant morbidity and mortality. The discovery of the <i>JAK2</i> V617F mutation prompted the development of JAK inhibitors (JAKi) including the first-in-class JAK1/JAK2 inhibitor ruxolitinib and subsequent approval of fedratinib, pacritinib, and momelotinib. The latter has shown erythropoietic benefits by suppressing hepcidin expression via activin A receptor type 1 (ACVR1) inhibition, as well as reducing splenomegaly and symptoms. However, the current JAKi behave as anti-inflammatory drugs without a major impact on survival or disease progression. A better understanding of the genetics, mechanisms of fibrosis, cytopenia, and the role of inflammatory cytokines has led to the development of numerous therapeutic agents that target epigenetic regulation, signaling, telomerase, cell cycle, and apoptosis, nuclear export, and pro-fibrotic cytokines. Selective JAK2 V617F inhibitors and targeting of mutant CALR by immunotherapy are the most intriguing and promising approaches. This review focuses on approved and experimental treatments for MF, highlighting their biological background.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"30 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of Relapsed/Refractory Core-Binding Factor Acute Myeloid Leukemia: A COMMAND Registry Study","authors":"Alexandra E. Rojek, Benjamin J. McCormick, Joanna Cwykiel, Oluwatobi Odetola, Yasmin Abaza, Nhi Nai, Charles E. Foucar, Rohan K. Achar, Rory M. Shallis, Danielle Bradshaw, Meaghan Standridge, Vamsi Kota, Guru Subramanian Guru Murthy, Talha Badar, Anand A. Patel","doi":"10.1002/ajh.27664","DOIUrl":"https://doi.org/10.1002/ajh.27664","url":null,"abstract":"&lt;p&gt;Core-binding factor acute myeloid leukemia (CBF-AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as favorable risk by the 2022 European LeukemiaNet (ELN) guidelines [&lt;span&gt;1&lt;/span&gt;]. We have previously reported on outcomes of patients with newly diagnosed CBF-AML treated with intensive chemotherapy (IC) regimens [&lt;span&gt;2&lt;/span&gt;] and despite the favorable risk status, approximately 50% of patients experienced relapse. Prior analyses have shown limited survival after relapse [&lt;span&gt;3-5&lt;/span&gt;]. Khan et al. reported on 92 patients with relapsed/refractory (R/R) CBF-AML treated from 1990 to 2014 with a median overall survival (mOS) of 12 months; type of therapy and allogeneic stem cell transplant (alloSCT) did not impact survival [&lt;span&gt;3&lt;/span&gt;]. Hospital et al. evaluated 145 patients with CBF-AML from 1994 to 2011 who underwent IC on a variety of French AML Intergroup studies and reported a second complete remission (CR2) rate of 88% with 5-year disease-free survival of 50% for the entire cohort [&lt;span&gt;5&lt;/span&gt;]. Additionally, 53% of the patients included in this study proceeded to undergo alloSCT in CR2, with the study noting a survival benefit for patients with inv(16) but not for t(8;21). Finally, Kurosawa et al. analyzed 139 patients treated from 1999 to 2006 with R/R CBF-AML and reported a 3-year overall survival (OS) of 48% along with a survival benefit seen with alloSCT in those with t(8;21) [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;While these prior studies offer valuable insight into the outcomes of R/R CBF-AML, the therapeutic armamentarium for AML has greatly expanded since 2017 with the re-approval of the CD33-directed antibody drug conjugate gemtuzumab ozogamicin (GO) and guideline recommendations for its frontline use in intensive IC-eligible patients with CBF-AML, and the incorporation of targeted therapeutics and the BCL2 inhibitor venetoclax into management [&lt;span&gt;6&lt;/span&gt;]. Furthermore, access to alloSCT has expanded given the increasing utilization of haplo-identical as well as mismatched donors when appropriate. Given these advances, we sought to characterize the treatment patterns and outcomes of R/R CBF-AML patients in a timeframe inclusive of these advances.&lt;/p&gt;\u0000&lt;p&gt;Here we report on 68 patients with CBF-AML who experienced relapse or were refractory to frontline IC from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND) registry and received treatment for their R/R disease. Patients with AML harboring inv(16)/t(16;16) or t(8;21) who were treated with IC from January 2010 through April 2023, across the seven participating institutions, were included. The study was approved by the institutional review boards at institution participating in the COMMAND registry. Survival analysis was done using Kaplan–Meier survival estimates and log-rank tests of significance, with additional modifications as noted below.&lt;/p&gt;\u0000&lt;p&gt;The median age of patients at diagnosis with CBF-AML was 48.5 years (ra","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"15 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia With Myelodysplasia-Related Genetic Features: Relevance of the Genetic Underlying Category. A Retrospective Analysis on Behalf of the Acute Leukemia Working Party of the EBMT","authors":"Jordi Esteve, Arnon Nagler, Myriam Labopin, Jurjen Versluis, Jaime Sanz, Tobias Gedde-Dahl, David Burns, Mieke Roeven, Hélène Labussière-Wallet, Peter Von Dem Borne, Gwendolyn Van Gorkom, Nathalie Contentin, Andreas Neubauer, Eva Maria Wagner-Drouet, Nicolaus Kröger, Mohamad Mohty, Fabio Ciceri","doi":"10.1002/ajh.27647","DOIUrl":"https://doi.org/10.1002/ajh.27647","url":null,"abstract":"Patients (pts) with myelodysplasia-related AML (MR-AML) are now genetically recategorized, with three different groups in the International Consensus Classification: AML with mutated TP53 (TP53-AML), with myelodysplasia-related gene mutations (MR-GM AML), and with myelodysplasia-related cytogenetic abnormalities (MR-CG AML). Moreover, TP53-AML is determined by the presence of an additional complex karyotype (TP53-mut CK and non-CK AML, respectively). Nonetheless, the relevance of this classification to transplantation outcomes is largely unknown. We analyzed the outcomes of pts. with MR-AML undergoing allogeneic hematopoietic cell transplantation in first complete remission between 2010 and 2022 according to these genetic categories. Overall, 1152 patients were identified: 379 (33%), 328 (28%), 246 (21%), and 199 (17%) with MR-GM, TP53-mut CK, MR-CG, and TP53-mut non-CK AML, respectively. Median age was 60 years; median year of transplant was 2020. Unrelated donors and reduced-intensity conditioning were used in 65% and 61% of cases, respectively. Outcomes differed markedly among genetic categories, with an increasing relapse incidence (20.2%, 29.2%, 44.6%, and 57.6% at 2 years), and decreasing LFS (60%, 55.3%, 40.6%, and 20.2% at 2 years), overall survival (65.7%, 60.1%, 47.1%, and 24.5% at 2 years), and graft-versus-host disease-free, relapse-free survival (46.9%, 39.5%, 31.9%, and 13.2% at 2 years) in MR-GM, MR-CG, TP53-mut non-CK, and TP53-mut CK AML, respectively. These differences were confirmed in the multivariate analysis (hazard ratio for LFS: 0.21, 0.33 and 0.61 in MR-GM, MR-CG, and TP53-mut non-CK, with respect to reference TP53-mut CK AML group). This study confirms the strong impact of genetic grouping of MR-AML on transplant outcomes.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"15 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombosis-Driven Disease Progression in JAK2-Mutant Polycythemia Vera and Essential Thrombocythemia: Reassessing Risk-Based Management","authors":"Tiziano Barbui, Valerio De Stefano, Elena Rossi, Arianna Ghirardi, Alessandra Carobbio, Giuseppe Gaetano Loscocco, Annalisa Condorelli, Paola Guglielmelli","doi":"10.1002/ajh.27657","DOIUrl":"https://doi.org/10.1002/ajh.27657","url":null,"abstract":"This paper explores emerging therapies in polycythemia vera and essential thrombocythemia, focusing on thrombosis as a driver of disease progression leading to myelofibrosis, blast phase, second cancers, and mortality. While the thrombosis rate in high-risk patients has declined, it remains persistently high in low-risk individuals, with most events being arterial. Inflammation driven by JAK2 V617F mutation plays a primary role in pathogenesis, and mounting evidence suggests arterial thrombosis itself can fuel a self-sustaining cycle of inflammation, thereby accelerating hematologic and systemic complications. Early intervention with cytoreductive and anti-inflammatory drugs may not only prevent incidental thrombosis but also disrupt this inflammatory circuit.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"41 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depth of Response From Fixed-Duration Treatment Is Associated With Superior Survival in Waldenstrom Macroglobulinemia","authors":"Jonas Paludo, Jithma P. Abeykoon, Nirosha D. Perera, Shayna Sarosiek, Joshua Gustine, Andres Ramirez-Gamero, Marzia Varettoni, Alessandra Tedeschi, Chiara Cavalloni, Anna Maria Frustaci, Levi D. Pederson, Saurabh S. Zanwar, Prashant Kapoor, Thomas M. Habermann, Thomas E. Witzig, Robert A. Kyle, Morie A. Gertz, Susan M. Geyer, Steven P. Treon, Jorge J. Castillo, Stephen M. Ansell","doi":"10.1002/ajh.27663","DOIUrl":"https://doi.org/10.1002/ajh.27663","url":null,"abstract":"As the treatment paradigm for Waldenström macroglobulinemia (WM) continues to evolve, the debate surrounding the prioritization of depth of response versus disease control as therapeutic goals gains significant relevance. However, the impact of depth of response from fixed-duration therapy on overall survival (OS) was unclear. This multicenter study evaluated the prognostic impact of depth of response using a landmark survival analysis. A total of 440 patients with WM treated with frontline fixed-duration regimens were included. Attaining a major response (MaR) was associated with superior outcomes, including significantly longer OS. The estimated 5-year PFS rates for patients with MaR at 6 months versus not were 50% versus 32%, respectively, <i>p</i> &lt; 0.001, and the estimated 5-year OS rates for patients with MaR at 6 months versus not were 89% versus 70%, respectively, <i>p</i> &lt; 0.001. In a multivariable analysis, MaR at 6 months was independently associated with superior PFS (HR 0.66, <i>p</i> = 0.007) and OS (HR 0.28, <i>p</i> &lt; 0.001). Similar results were seen when considering deeper responses (CR + VGPR vs. PR). Depth of response at 6 months is an important prognostic marker in WM and an independent predictor of PFS and OS. These results support its utilization as a suitable endpoint in clinical studies in WM.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"53 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukemia Cutis in the Setting of Indolent Chronic Lymphocytic Leukemia","authors":"Kelly S. Chien, Jonathan L. Curry, Naveen Pemmaraju, Nitin Jain","doi":"10.1002/ajh.27654","DOIUrl":"https://doi.org/10.1002/ajh.27654","url":null,"abstract":"<h2> Conflicts of Interest</h2>\u0000<p>The authors declare no conflicts of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 144 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}