Keith W. Pratz, Courtney D. DiNardo, Martha Arellano, Michael J. Thirman, Vinod Pullarkat, Pamela S. Becker, B. Douglas Smith, Meng Zhang, Kaylee Miu, Jalaja Potluri, Daniel A. Pollyea
<p>Allogeneic hematopoietic stem cell transplantation (SCT) remains the most effective curative treatment for patients with intermediate- and poor-risk acute myeloid leukemia (AML). Patients ineligible for intensive chemotherapy due to age or comorbidities have historically not been candidates for SCT. Venetoclax in combination with hypomethylating agents (HMA) decitabine or azacitidine demonstrated rapid and durable remission in newly diagnosed AML patients ineligible for intensive chemotherapy and is approved globally for this indication [<span>1, 2</span>]. An increase in patients achieving remission with alternative induction therapies could allow more patients to proceed to SCT, since reduced intensity conditioning regimens used for older patients have similar post-SCT outcomes compared with myeloablative conditioning [<span>3</span>]. This analysis evaluates long-term clinical outcomes of patients receiving SCT after venetoclax plus HMA therapy.</p> <p>A combined cohort of patients enrolled to the randomized phase 3 trial VIALE-A (NCT02993523) and open-label phase 1b dose-escalation and expansion trial M14-358 (NCT02203773) was included. Study designs have been reported previously [<span>1, 2</span>]. Briefly, enrolled patients were ineligible for intensive chemotherapy due to age (≥ 75 years old) or comorbidities and had no prior AML-related therapy. Patients enrolled in VIALE-A were administered 400 mg oral venetoclax daily plus azacitidine, while patients in M14-358 were administered oral venetoclax at either 400 or 800 mg daily in combination with either azacitidine (75 mg/m<sup>2</sup> subcutaneously or intravenously on Days 1–7) or decitabine (20 mg/m<sup>2</sup> intravenously on Days 1–5) in 28-day cycles. The data cutoff was July 19, 2019, for M14-358 and December 1, 2021, for VIALE-A.</p> <p>Outcomes were assessed before and after allogeneic SCT. Overall survival (OS) was assessed from randomization or first dose of venetoclax. Best response was assessed per modified International Working Group criteria for AML [<span>4</span>]. A measurable residual disease (MRD)-negative response was defined as < 10<sup>−3</sup> leukemia cells/leukocyte. MRD was assessed by flow cytometry [<span>1, 2</span>]. Additional outcomes included time to best response, 2-year post-SCT remission, and 2-year post-SCT OS. Results are reported using descriptive statistics unless otherwise specified. Survival analyses and estimates were calculated using the Kaplan–Meier method. Patients who were lost to follow-up were censored at the date of the last study visit or the last known date alive, whichever was later.</p> <p>In total, 33 patients from VIALE-A (<i>n</i> = 2) and M14-358 (<i>n</i> = 31) received SCT after venetoclax plus HMA therapy. Patients were a median age of 69 years (range, 63–76). Most had <i>de novo</i> AML (69.7%) and adverse risk disease (54.5%) based on 2022 European LeukemiaNet categories (Table S1). Baseline mutations were identified w
{"title":"Long-Term Outcomes of Stem Cell Transplant in Older Patients With Acute Myeloid Leukemia Treated With Venetoclax-Based Therapies","authors":"Keith W. Pratz, Courtney D. DiNardo, Martha Arellano, Michael J. Thirman, Vinod Pullarkat, Pamela S. Becker, B. Douglas Smith, Meng Zhang, Kaylee Miu, Jalaja Potluri, Daniel A. Pollyea","doi":"10.1002/ajh.70204","DOIUrl":"https://doi.org/10.1002/ajh.70204","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (SCT) remains the most effective curative treatment for patients with intermediate- and poor-risk acute myeloid leukemia (AML). Patients ineligible for intensive chemotherapy due to age or comorbidities have historically not been candidates for SCT. Venetoclax in combination with hypomethylating agents (HMA) decitabine or azacitidine demonstrated rapid and durable remission in newly diagnosed AML patients ineligible for intensive chemotherapy and is approved globally for this indication [<span>1, 2</span>]. An increase in patients achieving remission with alternative induction therapies could allow more patients to proceed to SCT, since reduced intensity conditioning regimens used for older patients have similar post-SCT outcomes compared with myeloablative conditioning [<span>3</span>]. This analysis evaluates long-term clinical outcomes of patients receiving SCT after venetoclax plus HMA therapy.</p>\u0000<p>A combined cohort of patients enrolled to the randomized phase 3 trial VIALE-A (NCT02993523) and open-label phase 1b dose-escalation and expansion trial M14-358 (NCT02203773) was included. Study designs have been reported previously [<span>1, 2</span>]. Briefly, enrolled patients were ineligible for intensive chemotherapy due to age (≥ 75 years old) or comorbidities and had no prior AML-related therapy. Patients enrolled in VIALE-A were administered 400 mg oral venetoclax daily plus azacitidine, while patients in M14-358 were administered oral venetoclax at either 400 or 800 mg daily in combination with either azacitidine (75 mg/m<sup>2</sup> subcutaneously or intravenously on Days 1–7) or decitabine (20 mg/m<sup>2</sup> intravenously on Days 1–5) in 28-day cycles. The data cutoff was July 19, 2019, for M14-358 and December 1, 2021, for VIALE-A.</p>\u0000<p>Outcomes were assessed before and after allogeneic SCT. Overall survival (OS) was assessed from randomization or first dose of venetoclax. Best response was assessed per modified International Working Group criteria for AML [<span>4</span>]. A measurable residual disease (MRD)-negative response was defined as < 10<sup>−3</sup> leukemia cells/leukocyte. MRD was assessed by flow cytometry [<span>1, 2</span>]. Additional outcomes included time to best response, 2-year post-SCT remission, and 2-year post-SCT OS. Results are reported using descriptive statistics unless otherwise specified. Survival analyses and estimates were calculated using the Kaplan–Meier method. Patients who were lost to follow-up were censored at the date of the last study visit or the last known date alive, whichever was later.</p>\u0000<p>In total, 33 patients from VIALE-A (<i>n</i> = 2) and M14-358 (<i>n</i> = 31) received SCT after venetoclax plus HMA therapy. Patients were a median age of 69 years (range, 63–76). Most had <i>de novo</i> AML (69.7%) and adverse risk disease (54.5%) based on 2022 European LeukemiaNet categories (Table S1). Baseline mutations were identified w","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"186 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920326","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}
Asya Makhro, Rick Huisjes, Elena Seiler, Min Qiao, Marije Bartels, Inga Hegemann, Patrick Eppenberger, Nicole Bender, Isabel Dorn, Anna Bogdanova, Richard van Wijk, Lars Kaestner
<p>Hereditary xerocytosis (HX), also known as dehydrated hereditary stomatocytosis (DHS), is a rare red blood cell (RBC) disorder caused by gain-of-function (GOF) mutations in the <i>PIEZO1</i> gene [<span>1-3</span>], which encodes a mechanosensitive, nonselective cation channel. Activation of Piezo1 leads to, i.a., Ca<sup>2+</sup> influx, opening of the Gárdos-channel, K<sup>+</sup> efflux, and subsequent RBC dehydration [<span>4, 5</span>]. Patients with HX typically exhibit compensated hemolysis, elevated reticulocyte counts, and iron overload. Mechanistic links—such as the relationship between Piezo1 activity and altered RBC lifespan, or between reticulocyte counts and erythropoiesis rate—are hypothesized but remain unconfirmed [<span>6, 7</span>].</p> <p>We investigated a cohort of 12 genetically confirmed HX patients (see Table S1 and Figure S1 for details). Our objective was to determine how GOF variants in <i>PIEZO1</i> affect RBC physiology and erythropoietic regulation in HX. In contrast to sickle cell disease (SCD), where RBC lifespan is markedly shortened and highly variable (10–60 days) [<span>8</span>], much less is known about RBC survival in HX. Therefore, we first assessed the average lifespan of HX RBCs using the protein 4.1a/4.1b ratio, which functions as a molecular clock [<span>9</span>] and scales linearly with RBC age. Figure 1A,B depict this ratio for healthy controls, SCD patients, and HX patients, plotted against reticulocyte counts. HX patients exhibit elevated reticulocyte counts despite having a comparable RBC age to SCD patients, suggesting delayed reticulocyte maturation [<span>10</span>]. This “uncoupling” of reticulocyte count from RBC age accounts for its weak correlation with erythropoietin (EPO) levels (Figure 1C), indicating that here the reticulocyte count is not a reliable marker of erythropoiesis rate. Based on the established lifespan of SCD RBCs [<span>8</span>], HX RBCs appear to have similarly shortened lifespans (0.66 ± 0.16 vs. 0.62 ± 0.11 days; <i>p</i> = 0.5).</p> <figure><picture> <source media="(min-width: 1650px)" srcset="/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg"/><img alt="Details are in the caption following the image" data-lg-src="/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg" loading="lazy" src="/cms/asset/970e0275-9fa0-4097-b695-93c3ee28a88f/ajh70188-fig-0001-m.png" title="Details are in the caption following the image"/></picture><figcaption> <div><strong>FIGURE 1<span style="font-weight:normal"></span></strong><div>Open in figure viewer<i aria-hidden="true"></i><span>PowerPoint</span></div> </div> <div>Red blood cell age, oxygen binding, and erythropoietin levels in hereditary xerocytosis (HX) patients. Panel A shows a representative example of gel electrophoresis to determine the protein Band 4.1a to 4.1b ratio, which is known to be a molecular clock for RBC age. Both bands just differ by the deamidation of the Band 4.1 protein. Pa
{"title":"Mechanistic Consequences of Piezo1 Gain-of-Function Variants for Decreased Red Cell Survival in Hereditary Xerocytosis","authors":"Asya Makhro, Rick Huisjes, Elena Seiler, Min Qiao, Marije Bartels, Inga Hegemann, Patrick Eppenberger, Nicole Bender, Isabel Dorn, Anna Bogdanova, Richard van Wijk, Lars Kaestner","doi":"10.1002/ajh.70188","DOIUrl":"https://doi.org/10.1002/ajh.70188","url":null,"abstract":"<p>Hereditary xerocytosis (HX), also known as dehydrated hereditary stomatocytosis (DHS), is a rare red blood cell (RBC) disorder caused by gain-of-function (GOF) mutations in the <i>PIEZO1</i> gene [<span>1-3</span>], which encodes a mechanosensitive, nonselective cation channel. Activation of Piezo1 leads to, i.a., Ca<sup>2+</sup> influx, opening of the Gárdos-channel, K<sup>+</sup> efflux, and subsequent RBC dehydration [<span>4, 5</span>]. Patients with HX typically exhibit compensated hemolysis, elevated reticulocyte counts, and iron overload. Mechanistic links—such as the relationship between Piezo1 activity and altered RBC lifespan, or between reticulocyte counts and erythropoiesis rate—are hypothesized but remain unconfirmed [<span>6, 7</span>].</p>\u0000<p>We investigated a cohort of 12 genetically confirmed HX patients (see Table S1 and Figure S1 for details). Our objective was to determine how GOF variants in <i>PIEZO1</i> affect RBC physiology and erythropoietic regulation in HX. In contrast to sickle cell disease (SCD), where RBC lifespan is markedly shortened and highly variable (10–60 days) [<span>8</span>], much less is known about RBC survival in HX. Therefore, we first assessed the average lifespan of HX RBCs using the protein 4.1a/4.1b ratio, which functions as a molecular clock [<span>9</span>] and scales linearly with RBC age. Figure 1A,B depict this ratio for healthy controls, SCD patients, and HX patients, plotted against reticulocyte counts. HX patients exhibit elevated reticulocyte counts despite having a comparable RBC age to SCD patients, suggesting delayed reticulocyte maturation [<span>10</span>]. This “uncoupling” of reticulocyte count from RBC age accounts for its weak correlation with erythropoietin (EPO) levels (Figure 1C), indicating that here the reticulocyte count is not a reliable marker of erythropoiesis rate. Based on the established lifespan of SCD RBCs [<span>8</span>], HX RBCs appear to have similarly shortened lifespans (0.66 ± 0.16 vs. 0.62 ± 0.11 days; <i>p</i> = 0.5).</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/970e0275-9fa0-4097-b695-93c3ee28a88f/ajh70188-fig-0001-m.png\" title=\"Details are in the caption following the image\"/></picture><figcaption>\u0000<div><strong>FIGURE 1<span style=\"font-weight:normal\"></span></strong><div>Open in figure viewer<i aria-hidden=\"true\"></i><span>PowerPoint</span></div>\u0000</div>\u0000<div>Red blood cell age, oxygen binding, and erythropoietin levels in hereditary xerocytosis (HX) patients. Panel A shows a representative example of gel electrophoresis to determine the protein Band 4.1a to 4.1b ratio, which is known to be a molecular clock for RBC age. Both bands just differ by the deamidation of the Band 4.1 protein. Pa","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"167 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919789","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}
Guillaume Moulis, Matthieu Mahévas, Jean-François Viallard, Stéphane Chèze, Louis Terriou, Sylvain Audia, Thomas Moulinet, Mikael Ebbo, Delphine Gobert, Ailsa Robbins, Clément Gourguechon, Julie Graveleau, Thibault Comont, Aurélie Saunier, Jehanne Faldlallah, Miguel Carreiro, Philippe Guilpain, Helder Gil, Marc Ruivard, Nadine Magy-Bertrand, Antoine Dossier, Yann Leveneur, Xavier Delbrel, Bernard Anthony, François Lifermann, Mikaël Martin, Marie-Pierre Ledoux, Frédérique Roy-Péaud, Laurie Chabbert, Maryse Lapeyre-Mestre, Agnès Sommet, Yoann Zadro, Bernard Bonnotte, Marc Michel, Bertrand Godeau
Fostamatinib is available in France since October 2021 for the treatment of adult chronic immune thrombocytopenia (ITP). French health authorities requested a 3-year, prospective, multicenter registry to provide real-world evidence about the effectiveness and safety of fostamatinib. Patients' characteristics, treatment response (ongoing exposure to fostamatinib and a platelet count ≥ 30 × 109/L with no rescue in the previous 4 weeks) after 3, 6, 12, and 24 months (M); bleeding; fostamatinib discontinuation; adverse drug reactions (ADRs) and other events of interest have been analyzed. In total, 164 patients were included (median age: 59 years; 55.5% women; 84.1% had previous bleeding; 30 had secondary ITP; 89.0% had chronic ITP). The median ITP duration was 7.2 years and the median number of previous ITP treatments was 6. The response rate was 44.0% (70/159) at M3, 41.9% (62/148) at M6, 32.4% (44/136) at M12 and 20.0% (21/105) at M24. Concomitant treatment (mostly TPO-RA) was used in > 60.0% of responders at each endpoint. The cumulative discontinuation rate at each endpoint was, respectively, 27.0%, 44.6%, 55.9%, and 76.2%. Seventy-one (43.3%) patients experienced at least one bleeding during fostamatinib exposure; none was fatal. One hundred adverse drug reactions (8 serious) were observed in 61 (36.7%) patients, including diarrhea in 28 (17.1%) patients, arterial hypertension in 17 (10.4%). Seven thrombosis (4.3%) and 40 infections (12 serious) were reported in 25 patients (15.2%), mostly in patients with known risk factors. In conclusion, fostamatinib in combination with TPO-RA should be considered in difficult-to-treat ITP patients. No new safety signal was observed.
{"title":"Real-World Effectiveness and Safety of Fostamatinib in Difficult-to-Treat Immune Thrombocytopenia Patients. A Prospective, Multicenter Registry in France","authors":"Guillaume Moulis, Matthieu Mahévas, Jean-François Viallard, Stéphane Chèze, Louis Terriou, Sylvain Audia, Thomas Moulinet, Mikael Ebbo, Delphine Gobert, Ailsa Robbins, Clément Gourguechon, Julie Graveleau, Thibault Comont, Aurélie Saunier, Jehanne Faldlallah, Miguel Carreiro, Philippe Guilpain, Helder Gil, Marc Ruivard, Nadine Magy-Bertrand, Antoine Dossier, Yann Leveneur, Xavier Delbrel, Bernard Anthony, François Lifermann, Mikaël Martin, Marie-Pierre Ledoux, Frédérique Roy-Péaud, Laurie Chabbert, Maryse Lapeyre-Mestre, Agnès Sommet, Yoann Zadro, Bernard Bonnotte, Marc Michel, Bertrand Godeau","doi":"10.1002/ajh.70194","DOIUrl":"https://doi.org/10.1002/ajh.70194","url":null,"abstract":"Fostamatinib is available in France since October 2021 for the treatment of adult chronic immune thrombocytopenia (ITP). French health authorities requested a 3-year, prospective, multicenter registry to provide real-world evidence about the effectiveness and safety of fostamatinib. Patients' characteristics, treatment response (ongoing exposure to fostamatinib and a platelet count ≥ 30 × 10<sup>9</sup>/L with no rescue in the previous 4 weeks) after 3, 6, 12, and 24 months (M); bleeding; fostamatinib discontinuation; adverse drug reactions (ADRs) and other events of interest have been analyzed. In total, 164 patients were included (median age: 59 years; 55.5% women; 84.1% had previous bleeding; 30 had secondary ITP; 89.0% had chronic ITP). The median ITP duration was 7.2 years and the median number of previous ITP treatments was 6. The response rate was 44.0% (70/159) at M3, 41.9% (62/148) at M6, 32.4% (44/136) at M12 and 20.0% (21/105) at M24. Concomitant treatment (mostly TPO-RA) was used in > 60.0% of responders at each endpoint. The cumulative discontinuation rate at each endpoint was, respectively, 27.0%, 44.6%, 55.9%, and 76.2%. Seventy-one (43.3%) patients experienced at least one bleeding during fostamatinib exposure; none was fatal. One hundred adverse drug reactions (8 serious) were observed in 61 (36.7%) patients, including diarrhea in 28 (17.1%) patients, arterial hypertension in 17 (10.4%). Seven thrombosis (4.3%) and 40 infections (12 serious) were reported in 25 patients (15.2%), mostly in patients with known risk factors. In conclusion, fostamatinib in combination with TPO-RA should be considered in difficult-to-treat ITP patients. No new safety signal was observed.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"5 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919788","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}
Ayalew Tefferi, Maymona Abdelmagid, Jeanne M. Palmer, Aref Al-Kali, Cecilia Y. Arana Yi, Aasiya Matin, Hassan B. Alkhateeb, Talha Badar, Yassin Bashir, Kaaren K. Reichard, Rong He, Animesh Pardanani, Naseema Gangat
Real-world experience using momelotinib as first-line JAK2 inhibitor therapy in myelofibrosis. Anemia response was moderate (23%) while treatment-emergent adverse events included nephropathy (29%) and peripheral neuropathy (20%).
{"title":"Post-FDA Approval Experience With Momelotinib in JAK Inhibitor-Naïve Myelofibrosis: Focus on Anemia Response and Treatment-Emergent Nephropathy and Peripheral Neuropathy","authors":"Ayalew Tefferi, Maymona Abdelmagid, Jeanne M. Palmer, Aref Al-Kali, Cecilia Y. Arana Yi, Aasiya Matin, Hassan B. Alkhateeb, Talha Badar, Yassin Bashir, Kaaren K. Reichard, Rong He, Animesh Pardanani, Naseema Gangat","doi":"10.1002/ajh.70203","DOIUrl":"https://doi.org/10.1002/ajh.70203","url":null,"abstract":"Real-world experience using momelotinib as first-line JAK2 inhibitor therapy in myelofibrosis. Anemia response was moderate (23%) while treatment-emergent adverse events included nephropathy (29%) and peripheral neuropathy (20%).","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919877","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}
François Therme, Jean Francois Viallard, Manuela Rueter, Thibault Comont, Stephane Cheze, Sylvain Audia, Mikael Ebbo, Matthieu Mahevas, Louis Terriou, Quitterie Reynaud, Pierre-Yves Jeandel, Thomas Moulinet, Delphine Gobert, Philippe Guilpain, Clément Gourguechon, Ailsa Robbins, Marc Ruivard, Laurie Chabbert, Bernard Bonnotte, Bertrand Godeau, Maryse Lapeyre-Mestre, Yoann Zadro, Marc Michel, Guillaume Moulis
Adult patients with immune thrombocytopenia (ITP) have an increased risk of venous thrombosis as compared to the general population. The management of ITP in the context of anticoagulation is challenging. We conducted an observational study in the prospective, multicenter, national CARMEN-France registry. Adult patients with newly diagnosed ITP between June 2013 and May 2022 were selected. We assessed the cumulative incidence of venous thrombosis during follow-up with death as a competing event, described these events, and assessed patient outcomes depending on management strategies, with a focus on thromboses that occurred during treatment with thrombopoietin receptor agonists (TPO-RA). Among the 1303 patients selected for this study, 53 experienced venous thrombosis. The cumulative incidence of venous thrombosis was 2.6% (95% CI: 1.8-3.7) at 1 year and 8.6% (95% CI: 5.8-12.0) at 5 years. In patients exposed to TPO-RA, the cumulative incidence was 9.3% (95% CI: 6.2-13.2) and 13.4% (95% CI: 8.6-19.2) at 1 and 5 years of exposure, respectively. Patients who experienced thrombosis were older, had more frequently a history of venous thrombosis and secondary ITP, a more severe ITP, and were more frequently treated with TPO-RAs. Twenty (37.7%) of the 53 events were atypical, including five cerebral venous thromboses. Four patients died, and seven experienced major bleeding. The analysis of different managements of ITP after the thrombotic event suggested that the safest strategy was to promptly control ITP to enable early anticoagulation, including using TPO-RAs. Long-term anticoagulation therapy should be considered in patients treated with TPO-RAs and persistent risk factors for thrombosis.
{"title":"Incidence, Characteristics, and Management of Venous Thrombosis in Adult Patients With Immune Thrombocytopenia: Results From the Multicenter, Prospective Registry CARMEN-France.","authors":"François Therme, Jean Francois Viallard, Manuela Rueter, Thibault Comont, Stephane Cheze, Sylvain Audia, Mikael Ebbo, Matthieu Mahevas, Louis Terriou, Quitterie Reynaud, Pierre-Yves Jeandel, Thomas Moulinet, Delphine Gobert, Philippe Guilpain, Clément Gourguechon, Ailsa Robbins, Marc Ruivard, Laurie Chabbert, Bernard Bonnotte, Bertrand Godeau, Maryse Lapeyre-Mestre, Yoann Zadro, Marc Michel, Guillaume Moulis","doi":"10.1002/ajh.70192","DOIUrl":"https://doi.org/10.1002/ajh.70192","url":null,"abstract":"<p><p>Adult patients with immune thrombocytopenia (ITP) have an increased risk of venous thrombosis as compared to the general population. The management of ITP in the context of anticoagulation is challenging. We conducted an observational study in the prospective, multicenter, national CARMEN-France registry. Adult patients with newly diagnosed ITP between June 2013 and May 2022 were selected. We assessed the cumulative incidence of venous thrombosis during follow-up with death as a competing event, described these events, and assessed patient outcomes depending on management strategies, with a focus on thromboses that occurred during treatment with thrombopoietin receptor agonists (TPO-RA). Among the 1303 patients selected for this study, 53 experienced venous thrombosis. The cumulative incidence of venous thrombosis was 2.6% (95% CI: 1.8-3.7) at 1 year and 8.6% (95% CI: 5.8-12.0) at 5 years. In patients exposed to TPO-RA, the cumulative incidence was 9.3% (95% CI: 6.2-13.2) and 13.4% (95% CI: 8.6-19.2) at 1 and 5 years of exposure, respectively. Patients who experienced thrombosis were older, had more frequently a history of venous thrombosis and secondary ITP, a more severe ITP, and were more frequently treated with TPO-RAs. Twenty (37.7%) of the 53 events were atypical, including five cerebral venous thromboses. Four patients died, and seven experienced major bleeding. The analysis of different managements of ITP after the thrombotic event suggested that the safest strategy was to promptly control ITP to enable early anticoagulation, including using TPO-RAs. Long-term anticoagulation therapy should be considered in patients treated with TPO-RAs and persistent risk factors for thrombosis.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931490","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}
Abhishek A Mangaonkar, Kelly L Bolton, Mrinal M Patnaik
Condition overview: Clonal hematopoiesis (CH) refers to the presence of somatic variants in hematopoietic stem and progenitor cells (HSPC) that result in expansion over time.
Diagnosis: CH of indeterminate potential (CHIP) is operationally defined as pathogenic variants in oncogenic driver genes occurring in HSPCs at variant allele frequencies ≥ 2%.
Clinical associations: CH is associated with increased risk for progressive cytopenias (also called clonal cytopenia of undetermined significance), hematological (predominantly myeloid but also lymphoid) neoplasms, cytosis (including monocytosis), and nonhematological conditions such as atherosclerotic cardiovascular and cerebrovascular disease. CH is linked to numerous other diseases including venous thromboembolism, type 2 diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, and gout, with a potential protective impact in Alzheimer's disease (AD).
Management recommendations: CH detection is becoming increasingly common due to the ubiquitous use of somatic and germline sequencing in clinical practice, particularly, in oncology. The clinical implications of CH are most relevant in therapy-related myeloid neoplasms (t-MN), with antecedent CH clones in genes such as TP53, PPM1D, and/or CHEK2 having a clear selection advantage. Furthermore, genetic predisposition to CH has provided some clarity on the origin and evolution of CH. We are currently defining the role for CH assessment in individuals with persistent (≥ 4 months) unexplained cytopenias, in patients with malignancies prior to adjuvant cytotoxic chemotherapy and/or radiation or radionuclide therapy, screening prior to autologous hematopoietic stem cell transplantation or chimeric antigen receptor T cell (CAR-T) therapy, and to work-up potentially germline mosaic variants.
{"title":"Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenias of Undetermined Significance: 2026 Update on Clinical Associations and Management Recommendations.","authors":"Abhishek A Mangaonkar, Kelly L Bolton, Mrinal M Patnaik","doi":"10.1002/ajh.70205","DOIUrl":"https://doi.org/10.1002/ajh.70205","url":null,"abstract":"<p><strong>Condition overview: </strong>Clonal hematopoiesis (CH) refers to the presence of somatic variants in hematopoietic stem and progenitor cells (HSPC) that result in expansion over time.</p><p><strong>Diagnosis: </strong>CH of indeterminate potential (CHIP) is operationally defined as pathogenic variants in oncogenic driver genes occurring in HSPCs at variant allele frequencies ≥ 2%.</p><p><strong>Clinical associations: </strong>CH is associated with increased risk for progressive cytopenias (also called clonal cytopenia of undetermined significance), hematological (predominantly myeloid but also lymphoid) neoplasms, cytosis (including monocytosis), and nonhematological conditions such as atherosclerotic cardiovascular and cerebrovascular disease. CH is linked to numerous other diseases including venous thromboembolism, type 2 diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, and gout, with a potential protective impact in Alzheimer's disease (AD).</p><p><strong>Management recommendations: </strong>CH detection is becoming increasingly common due to the ubiquitous use of somatic and germline sequencing in clinical practice, particularly, in oncology. The clinical implications of CH are most relevant in therapy-related myeloid neoplasms (t-MN), with antecedent CH clones in genes such as TP53, PPM1D, and/or CHEK2 having a clear selection advantage. Furthermore, genetic predisposition to CH has provided some clarity on the origin and evolution of CH. We are currently defining the role for CH assessment in individuals with persistent (≥ 4 months) unexplained cytopenias, in patients with malignancies prior to adjuvant cytotoxic chemotherapy and/or radiation or radionuclide therapy, screening prior to autologous hematopoietic stem cell transplantation or chimeric antigen receptor T cell (CAR-T) therapy, and to work-up potentially germline mosaic variants.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931504","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}
Gian Luca Forni,Emanuela Stampone,Valeria Maria Pinto,Laura Silvestri,Debora Bencivenga,Sara Sarnelli,Marilena Di Finizio,Paolo Ricchi,Sabrina Quintino,Ugo Salvadori,Domenico Girelli,Fulvio Della Ragione,Adriana Borriello
{"title":"Iron Overload and Anemia in Transferrin Immune Complex Disease, an Overlooked Monoclonal Gammopathy of Clinical Significance.","authors":"Gian Luca Forni,Emanuela Stampone,Valeria Maria Pinto,Laura Silvestri,Debora Bencivenga,Sara Sarnelli,Marilena Di Finizio,Paolo Ricchi,Sabrina Quintino,Ugo Salvadori,Domenico Girelli,Fulvio Della Ragione,Adriana Borriello","doi":"10.1002/ajh.70187","DOIUrl":"https://doi.org/10.1002/ajh.70187","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"54 35 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907756","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}
Nicolas Lecornec,Flore Sicre de Fontbrune,Edouard Forcade,Loïc Garçon,Louis Terriou,Pierre Cougoul,Karen Delavigne,Isabelle Marie,Isabelle Brindel,Éric Deconinck,Étienne Daguindau,Shanti Amé,Marie-Pierre Ledoux,Laurence Sanhes,Stanislas Nimubona,Guy Leverger,Marianne de Montalembert,Régis Peffault de Latour,Jean-Hugues Dalle,Pierre Fenaux,Lydie Da Costa,Thierry Leblanc
Information about Diamond-Blackfan anemia syndrome (DBAS), a ribosomopathy associated with anemia, congenital anomalies and cancer predisposition is limited in adults. Using the French DBAS registry, 235 adult patients with DBAS were analyzed for hematological outcomes. At last follow-up, anemia, neutropenia, thrombocytopenia, and pancytopenia affected respectively 78%, 31%, 15%, and 11% of the patients. There was no severe aplastic anemia outside of clonal evolution. Among patients without DBAS-specific treatment (e.g., steroids or red blood cell transfusions), the incidence of anemia, neutropenia, and thrombocytopenia was 52%, 35%, and 10%, highlighting that treatment independence does not mean hematologic remission. Four patients developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), all associated with poor-risk features and dismal outcomes. Observed to expected ratios were 155 for MDS and 55.4 for AML, confirming a major risk-excess despite stringent criteria for MDS diagnosis. With a median follow-up of 32.2 years (IQR 26-44), overall survival (OS) was 98.0% (95% CI, 95.8-100), 90.6% (95% CI, 84.2-97.5), and 70.7% (95% CI, 57.3-87.2) at 30, 40, and 50 years respectively. Solid and hematologic cancers were the main cause of death. This study demonstrates, in a large cohort of adults with DBAS, that cytopenias beyond anemia are frequent and persistent. Myeloid neoplasms occur with a high incidence and dismal outcomes. These findings highlight the need for risk stratification, tailored surveillance, and optimized therapeutic strategies in this vulnerable population.
{"title":"Hematologic Landscape of Adult Patients With Diamond-Blackfan Anemia Syndrome.","authors":"Nicolas Lecornec,Flore Sicre de Fontbrune,Edouard Forcade,Loïc Garçon,Louis Terriou,Pierre Cougoul,Karen Delavigne,Isabelle Marie,Isabelle Brindel,Éric Deconinck,Étienne Daguindau,Shanti Amé,Marie-Pierre Ledoux,Laurence Sanhes,Stanislas Nimubona,Guy Leverger,Marianne de Montalembert,Régis Peffault de Latour,Jean-Hugues Dalle,Pierre Fenaux,Lydie Da Costa,Thierry Leblanc","doi":"10.1002/ajh.70197","DOIUrl":"https://doi.org/10.1002/ajh.70197","url":null,"abstract":"Information about Diamond-Blackfan anemia syndrome (DBAS), a ribosomopathy associated with anemia, congenital anomalies and cancer predisposition is limited in adults. Using the French DBAS registry, 235 adult patients with DBAS were analyzed for hematological outcomes. At last follow-up, anemia, neutropenia, thrombocytopenia, and pancytopenia affected respectively 78%, 31%, 15%, and 11% of the patients. There was no severe aplastic anemia outside of clonal evolution. Among patients without DBAS-specific treatment (e.g., steroids or red blood cell transfusions), the incidence of anemia, neutropenia, and thrombocytopenia was 52%, 35%, and 10%, highlighting that treatment independence does not mean hematologic remission. Four patients developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), all associated with poor-risk features and dismal outcomes. Observed to expected ratios were 155 for MDS and 55.4 for AML, confirming a major risk-excess despite stringent criteria for MDS diagnosis. With a median follow-up of 32.2 years (IQR 26-44), overall survival (OS) was 98.0% (95% CI, 95.8-100), 90.6% (95% CI, 84.2-97.5), and 70.7% (95% CI, 57.3-87.2) at 30, 40, and 50 years respectively. Solid and hematologic cancers were the main cause of death. This study demonstrates, in a large cohort of adults with DBAS, that cytopenias beyond anemia are frequent and persistent. Myeloid neoplasms occur with a high incidence and dismal outcomes. These findings highlight the need for risk stratification, tailored surveillance, and optimized therapeutic strategies in this vulnerable population.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"39 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907676","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}
Peter N. Benotti, G. Craig Wood, Jila Kaberi‐Otarod, Christopher D. Still, Glenn S. Gerhard, Bruce R. Bistrian
Iron deficiency (ID) is the most common nutritional deficiency following metabolic and bariatric surgery. Preoperative anemia and/or low serum levels of ferritin, which are common among candidates for metabolic and bariatric surgery (MBS), are associated with increased risk of developing severe postoperative ID. This study investigates iron status among candidates for MBS and its relationship to the development of severe postoperative anemia. From an established bariatric surgery registry, surgery candidates with iron assessment as well as longitudinal anemia follow‐up were identified. The relationship between ferritin levels < 30 ng/mL stratified by levels of transferrin saturation < 20% and < 15% was analyzed to identify risk factors associated with the onset of severe postoperative anemia (hemoglobin level < 8 g/dL). Four thousand seven hundred and nine patients were studied. 14.6% had ferritin concentrations < 30 ng/mL and another 20% 30–99 ng/dL coupled with transferrin saturations (TSATs) < 20% to indicate absolute ID and functional ID. The overall prevalence of ID was 35%. The overall risk of severe postoperative anemia was 10.5% at 5 years and 19.8% at 10 years. Ferritin levels of < 30 ng/mL and TSAT < 20% were each associated with greater risk of developing severe anemia ( p < 0.0001). Patients with ferritins < 30 ng/mL and TSATs < 15% had the most severe ID with the greatest risk of developing earlier and more severe anemia which was confirmed after adjusted analysis ( p < 0.0001). A preoperative ferritin level < 30 ng/mL with TSAT < 15% is an excellent predictor for severe postoperative anemia.
{"title":"Preoperative Iron Status and the Risk of Severe Postoperative Anemia After Metabolic and Bariatric Surgery","authors":"Peter N. Benotti, G. Craig Wood, Jila Kaberi‐Otarod, Christopher D. Still, Glenn S. Gerhard, Bruce R. Bistrian","doi":"10.1002/ajh.70191","DOIUrl":"https://doi.org/10.1002/ajh.70191","url":null,"abstract":"Iron deficiency (ID) is the most common nutritional deficiency following metabolic and bariatric surgery. Preoperative anemia and/or low serum levels of ferritin, which are common among candidates for metabolic and bariatric surgery (MBS), are associated with increased risk of developing severe postoperative ID. This study investigates iron status among candidates for MBS and its relationship to the development of severe postoperative anemia. From an established bariatric surgery registry, surgery candidates with iron assessment as well as longitudinal anemia follow‐up were identified. The relationship between ferritin levels < 30 ng/mL stratified by levels of transferrin saturation < 20% and < 15% was analyzed to identify risk factors associated with the onset of severe postoperative anemia (hemoglobin level < 8 g/dL). Four thousand seven hundred and nine patients were studied. 14.6% had ferritin concentrations < 30 ng/mL and another 20% 30–99 ng/dL coupled with transferrin saturations (TSATs) < 20% to indicate absolute ID and functional ID. The overall prevalence of ID was 35%. The overall risk of severe postoperative anemia was 10.5% at 5 years and 19.8% at 10 years. Ferritin levels of < 30 ng/mL and TSAT < 20% were each associated with greater risk of developing severe anemia ( <jats:italic>p</jats:italic> < 0.0001). Patients with ferritins < 30 ng/mL and TSATs < 15% had the most severe ID with the greatest risk of developing earlier and more severe anemia which was confirmed after adjusted analysis ( <jats:italic>p</jats:italic> < 0.0001). A preoperative ferritin level < 30 ng/mL with TSAT < 15% is an excellent predictor for severe postoperative anemia.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"14 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902505","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}
Marina Konopleva, Courtney D. DiNardo, Yan Sun, Paul Jung, Sanam Loghavi, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A. Pollyea
{"title":"Analysis of Patients With Monocytic and Monocytic‐Like Acute Myeloid Leukemia, Including AML ‐ M4 and AML ‐ M5 , Treated With Venetoclax Plus Azacitidine","authors":"Marina Konopleva, Courtney D. DiNardo, Yan Sun, Paul Jung, Sanam Loghavi, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A. Pollyea","doi":"10.1002/ajh.70161","DOIUrl":"https://doi.org/10.1002/ajh.70161","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903572","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}
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