American Journal of Hematology最新文献

{"title":"Reversal of Glomerular Hyperfiltration Following Hematopoietic Stem Cell Transplantation in Children With Sickle-Cell Anemia","authors":"Stella Huet, Annie Kamdem, Valentine Beaufront, Karima Yakouben, Nathalie Dhedin, Catherine Paillard, Isabelle Hau, Claire Falguière, Aoufa Dahmani, Bassem Khazem, Ekaterina Belozertsteva, Céline Delestrain, Stéphane Bechet, Cécile Arnaud, Corinne Pondarré","doi":"10.1002/ajh.70004","DOIUrl":"10.1002/ajh.70004","url":null,"abstract":"<p>Glomerular hyperfiltration is one of the earliest manifestations of sickle nephropathy, preceding the development of albuminuria and, ultimately, renal failure [<span>1</span>]. Among sickle genotypes, the sickle cell anemia (SCA) subgroup (HbSS and HbSβ<sup>0</sup> thalassemia) is associated with a higher estimated glomerular filtration rate (eGFR) [<span>2</span>], that may begin in infancy, as described in the BABY-HUG trial [<span>3</span>]. The pathogenesis of glomerular hyperfiltration in SCA remains unclear, but it involves chronic hemolysis and anemia resulting in a high renal plasma flow, with sickling of the red blood cells in the hypertonic, hypoxic, and acidic environment of the renal medulla leading to vaso-occlusion (VO), ischemia, and infarction of the vasa recta.</p><p>In our recently published regional newborn sickle cell disease (SCD) cohort study, we described substantial persistent morbidity due to acute complications and chronic organ damage in the SCA subgroup, providing a rationale for the earlier introduction of disease-modifying therapies (DMTs) [<span>4</span>]. However, there have been few investigations of the ability of DMTs to normalize eGFR in children with SCA [<span>3, 5</span>].</p><p>Our main objective was to study the impact of therapeutic intensification, such as hydroxyurea (HU), chronic transfusion program (TP) and hematopoietic stem cell transplantation (HSCT), on eGFR, using prospectively collected longitudinal data from our sickle cell disease (SCD) cohort.</p><p>This study was approved by our institutional ethics committee (no. 2021-07-09). We included only children diagnosed with SCD by newborn screening. Serum creatinine concentration and height data were collected prospectively during complete annual check-ups as part of standard patient management and were recorded in our database, allowing longitudinal GFR estimation. We used the pediatric under-25 formula, a method derived from the CKiD Schwartz formula for use in children and young adults up to 25 years old, to provide an estimate of kidney function adjusted for age and sex. In addition, patient and treatment characteristics such as age, DMT, routine blood count, hemoglobin (Hb), HbF, and HbS levels and hemolytic parameters were also monitored, making it possible to assess eGFR changes following DMT.</p><p>In accordance with national guidelines, at our regional center, HU is introduced after the recurrence of VO complications and/or low Hb levels, and TP, mainly for stroke prevention. Our center also specifically offers HSCT to patients with cerebral vasculopathy or frequent VO complications with a human leukocyte antigen-identical sibling [<span>4</span>].</p><p>Statistical analysis was conducted with STATA v17. The eGFR values (mL/min/1.73 m<sup>2</sup>) were described with mean, standard deviation (SD), median, interquartile range (IQR) and comparisons between sickle genotype groups were performed with non-parametric Wilcoxon–Mann–Whitney te","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1886-1890"},"PeriodicalIF":9.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphocyte Kinetics and Outcomes of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma With Out of Specification Products","authors":"Sarah Dingli, Paul Rothweiler, Moritz Binder, Joselle Cook, Morie A. Gertz, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Shaji K. Kumar, Mustaqeem Siddiqui, Rahma Warsame, Yi Lin, Arthur G. Erdman, David Dingli","doi":"10.1002/ajh.70001","DOIUrl":"10.1002/ajh.70001","url":null,"abstract":"<p>The treatment of multiple myeloma has changed dramatically over the last two decades, fueled by a better understanding of disease biology and the identification of novel targets that led to the development of highly active therapeutics including monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T) [<span>1-6</span>]. Except for CAR-T cells, all other therapeutics are manufactured and ready for use when the patient needs them. In contrast, the current state of CAR-T cells requires leukapheresis of the patient's own lymphocytes for manufacturing of a personalized product over the course of several weeks. Although the process for manufacturing is standardized and highly regulated, the state of the cells collected for manufacturing may vary and this can lead to the production of CAR-T cells that do not meet specification criteria as required by the Food and Drug Administration (FDA). The reasons for these out of specification (OOS) products may vary. However, often the patient and physician are compelled to proceed with the use of the product since therapeutic options may be limited. Therefore, it is important to determine whether the use of these OOS products is associated with any difference in outcomes, even though the data from the clinical trials that led to the approval of both idecabtagene vicleucel (Ide-cel, brand name Abecma) and ciltacabtagene autoleucel (Cilta-cel, brand name Carvykti) showed that patients may experience responses at doses considered to be “suboptimal” and below the thresholds required by the FDA [<span>1-3</span>]. We have compared the outcomes of patients who received products that were both according to specifications as well as OOS at our institution. The kinetics of lymphocyte recovery and various metrics that have been shown to impact response and durability are reported.</p><p>In the interval between June 2021 and September 2024, 134 patients have been treated with commercially approved CAR-T for multiple myeloma after their FDA approval. Only two patients treated with Ide-cel had an OOS product infused and therefore, this analysis is restricted to patients treated with Cilta-cel. We identified 22 (30.1%) patients who received OOS ciltacabtagene and 51 patients who received the in-spec product. The baseline demographic, clinical, and laboratory characteristics of these patients are summarized in Table S1. There were no significant differences in the patients' demographics, age, number of lines of therapy, cytogenetically (FISH defined high-risk disease), the presence of extramedullary disease (EMD), baseline serum ferritin, or CRP obtained prior to the start of LD chemotherapy. We also found no difference in the brain to liver glucose ratio (B2LR) determined by PET/CT before the start of LD chemotherapy of patients treated with in-spec or OOS product (<i>p</i> = 0.3324). Similarly, the fraction of patients with a B2LR ≤ 2.5 was similar (<i>p</i> = 0.2631), suggesting that the","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 9","pages":"1705-1708"},"PeriodicalIF":9.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the ELN2024 and Mayo Genetic Risk Models in an External Cohort of 352 Patients With Newly Diagnosed AML Receiving Less-Intensive Therapies","authors":"Marco Roncador, Maddalena Marconato, Jeremy Werner Deuel, Stefan Balabanov","doi":"10.1002/ajh.70003","DOIUrl":"10.1002/ajh.70003","url":null,"abstract":"<p>Risk stratification is critical for guiding therapeutic decisions and predicting outcomes in acute myeloid leukemia (AML). Current widely used risk models, such as the European LeukemiaNet (ELN) genetic risk classification, were predominantly developed based on cohorts treated with intensive chemotherapy [<span>1</span>]. However, when applied to patients receiving less-intensive regimens, these systems have often demonstrated limited discriminatory power, frequently skewing patients toward adverse-risk categories [<span>2</span>].</p><p>Recently, Gangat et al. [<span>3</span>] proposed a new Mayo Genetic Risk Model in the <i>American Journal of Hematology</i>, specifically designed to predict outcomes in newly diagnosed AML patients treated with venetoclax combined with hypomethylating agents (Ven-HMA). Alongside the updated ELN2024 classification, which was adapted to better stratify patients receiving non-intensive therapies, these models represent a new generation of tools tailored for patients ineligible for intensive chemotherapy. Nevertheless, their applicability to other non-intensive treatment regimens, such as low-dose cytarabine, remains unclear.</p><p>In the present study, we conducted an independent validation of the Mayo Genetic Risk Model and the ELN2024 classification outside the context of hypomethylating agent (HMA)-based treatments, using a publicly available dataset from Tazi et al. [<span>1</span>], and compared their prognostic performance with that of the established ELN2022 model.</p><p>We analyzed a cohort of 352 AML patients treated with non-intensive regimens, enrolled across several UK-based NCRI clinical trials, including AML11, AML12, AML14, AML15, AML16, and AML LI1. Specifically, the cohort comprised 162 patients from the AML16 trial and 190 from the remaining studies, with the majority of the latter originating from AML15 and AML LI1 (exact numbers unavailable). Available data included age, sex, complete blood counts, bone marrow blast percentage, genetic and cytogenetic profiles, and WHO 2016 [<span>4</span>] diagnostic classifications. Treatment details at the individual level were not accessible. All patients in the AML16 trial (<i>n</i> = 162, 46%) and AML LI1 received low-dose cytarabine [<span>5</span>], either alone or in combination with investigational agents. Non-intensively treated participants in AML15 received gemtuzumab ozogamicin monotherapy. Risk scores were reconstructed using R software (v4.3.1), and survival differences between groups were assessed with Cox proportional hazards models and visualized via Kaplan–Meier plots.</p><p>Table 1 summarizes the patient characteristics: the median age was 75.6 years, with a slight male predominance (57.1%) and a modestly decreased ability to perform activities of daily living (ECOG 1 in 52.6% of patients). The most frequent diagnoses (WHO 2016 classification) were AML not otherwise specified (AML NOS; 37.8%), AML with <i>NPM1</i> mutation (23.0%), and A","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1861-1864"},"PeriodicalIF":9.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-ADAMTS13 Antibodies Trajectory is Associated With ADAMTS13 Recovery in Immune-Mediated TTP","authors":"Marie Robert,&nbsp;Arthur Mageau,&nbsp;Ygal Benhamou,&nbsp;François Provôt,&nbsp;Jehane Fadlallah,&nbsp;Lionel Galicier,&nbsp;Elie Azoulay,&nbsp;Hafid Ait-Oufella,&nbsp;Tomas Urbina,&nbsp;Pascale Poullin,&nbsp;Alain Wynckel,&nbsp;Coralie Poulain,&nbsp;Nihal Martis,&nbsp;Pierre Perez,&nbsp;Virginie Rieu,&nbsp;Yahsou Delmas,&nbsp;Jean-Michel Halimi,&nbsp;Christelle Barbet,&nbsp;Amélie Seguin,&nbsp;Valérie Chatelet,&nbsp;Jean-François Augusto,&nbsp;Mathieu Legendre,&nbsp;Olivier Moranne,&nbsp;Carole Philipponnet,&nbsp;Bérengère Cador,&nbsp;Raïda Bouzid,&nbsp;Bérangère S. Joly,&nbsp;Agnès Veyradier,&nbsp;Paul Coppo,&nbsp;the French Reference Center for Thrombotic Microangiopathies","doi":"10.1002/ajh.70005","DOIUrl":"10.1002/ajh.70005","url":null,"abstract":"<p>Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e., &gt; 30 days) due to persistent ADAMTS13 deficiency, raising cost and tolerance concerns. Therefore, we investigated whether anti-ADAMTS13 antibodies titer and their trajectory during the acute phase of the disease could predict ADAMTS13 improvement (i.e., activity ≥ 20% before day-30 post-TPE). From a cohort of 286 patients receiving the triplet regimen, we identified on diagnosis a cut-off value for anti-ADAMTS13 IgG antibodies of 90.5 U/mL, with a modest discriminating ability (AUC: 0.57) for predicting long-term response, precluding its use to guide therapeutic strategies. Nonetheless, the analysis of anti-ADAMTS13 IgG antibodies titer trajectory from diagnosis revealed that the proportion of iTTP patients with ADAMTS13 activity improvement was higher in patients who decreased (Dec+) their antibodies titer within the 7–14 days interval post-TPE compared to those without decrease (Dec−) (65% vs. 25% of cases, respectively, <i>p</i> &lt; 0.001), a finding confirmed in a validation cohort (<i>N</i> = 51). These results highlight the possibility of intensifying immunosuppression in an early period post-TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti-ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B-cell depleting agents when appropriate.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1736-1746"},"PeriodicalIF":9.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardization of Terminology, Definitions, and Outcome Criteria for Bleeding in Hereditary Hemorrhagic Telangiectasia: International Consensus Report","authors":"Hanny Al-Samkari,&nbsp;Raj S. Kasthuri,&nbsp;Hans-Jurgen Mager,&nbsp;Jenny Y. Zhou,&nbsp;Marcelo M. Serra,&nbsp;Bethany T. Samuelson-Bannow,&nbsp;Layla N. Van Doren,&nbsp;Jay F. Piccirillo,&nbsp;Marianne S. Clancy,&nbsp;Keith R. McCrae,&nbsp;Sonia M. Thomas,&nbsp;Antoni Riera-Mestre,&nbsp;Allyson M. Pishko,&nbsp;Sarah Sewaralthahab,&nbsp;James R. Gossage,&nbsp;Vivek N. Iyer,&nbsp;Cedric Hermans,&nbsp;Adrienne Hammill,&nbsp;Ingrid Winship,&nbsp;Meir Mei-Zahav,&nbsp;Annette von Drygalski,&nbsp;Scott Olitsky,&nbsp;Marie E. Faughnan","doi":"10.1002/ajh.70011","DOIUrl":"10.1002/ajh.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is the second most common inherited bleeding disorder worldwide, affecting approximately 1 in 5000 people. Development of disease-modifying and efficacious hemostatic agents to treat HHT has finally begun after decades without such medical therapies. However, the lack of consensus on standardized severity definitions, outcome criteria, and terminology remains a major obstacle to clinical investigation and therapeutic development in HHT. Additionally, with the ongoing repurposing of antiangiogenic agents and emerging development of novel HHT-specific therapies, comparative clinical trials are expected in the future. Therefore, to end the problematic heterogeneity hindering these efforts, the Global Research and Medical Advisory Board (GRMAB) of the Cure HHT Foundation, an international group of recognized HHT experts, convened a conference of expert HHT clinician-investigators from within GRMAB as well as invited external experts in HHT and bleeding disorders generally, patients with HHT, and patient advocates to define standard terminology and definitions for outcomes and severity classification for bleeding and anemia in HHT. These criteria and definitions should be adopted by regulators, investigators, and the pharmaceutical industry in the development and performance of interventional clinical trials and cohort studies to allow improved comparability between clinical trials, facilitate communication between clinicians and investigators, improve therapeutic guideline development, and provide a standardized framework for regulatory agencies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Search Strategy and Selection Criteria</h3>\u0000 \u0000 <p>Evidence for this report was systematically identified and evaluated utilizing two search strategies in Ovid MEDLINE, described in full detail in the Appendix, pp.4–13. The searches were conducted on January 7, 2025. The titles and abstracts of each record were reviewed, and the inclusion criteria were applied to all search results to identify full text articles to be retrieved for further review. All retrieved full texts were then reviewed to reach a final determination if a study met the inclusion criteria. Included references were then compiled into evidence tables, which were then utilized by the International Consensus Report Working Group throughout the development of report recommendations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1813-1827"},"PeriodicalIF":9.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemolysis and Acquired Pyruvate Kinase Deficiency in a Child With a Malignant Myeloid Disorder","authors":"Wendy B. Wong,&nbsp;Michael Jeng,&nbsp;Louise Lo,&nbsp;Bertil Glader","doi":"10.1002/ajh.70009","DOIUrl":"10.1002/ajh.70009","url":null,"abstract":"&lt;p&gt;Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder characterized by chronic hemolytic anemia. It results as a consequence of homozygous or double heterozygous pathologic mutations of the PKLR gene. Non-genetic or acquired PKD is rare, but has been reported in adults with a variety of blood disorders, particularly in association with myeloid leukemia or myelodysplastic syndrome (MDS) [&lt;span&gt;1&lt;/span&gt;]. Usually, this is a clinically insignificant finding, not associated with hemolysis. However, in this letter, we report a child with acute myeloid leukemia (AML) who initially presented with hemolytic anemia and associated PKD.&lt;/p&gt;&lt;p&gt;A previously healthy 8-year-old Chinese boy presented to the emergency department with vomiting, a month of worsening jaundice, and tea-colored urine. He had a several months history of intermittent vomiting and fevers, occurring as often as every 2 weeks, attributed to frequent viral illnesses. His laboratory studies revealed a severe macrocytic anemia with evidence of hemolysis (Table 1A). The direct antiglobulin test (DAT) was positive for C3 and negative for IgG. He was admitted to the hospital for presumed cold agglutinin disease or paroxysmal cold hemoglobinuria. Extensive infectious workup included SAR-COV-2, Flu A/B, HIV, Mycoplasma, CMV, EBV, VZV, and Syphilis, which was negative. His exam was notable for jaundice and scleral icterus, but no splenomegaly was noted by exam or by abdominal ultrasound. Peripheral smear review did not show any specific RBC morphology that would allow characterization of hemolytic anemia. He was transfused with warmed packed red blood cells (PRBC). Repeat DAT was negative on hospital day 4, and his Donath Landsteiner study was negative. Workup for a functional enzyme or membrane disorder was not attempted because he had been transfused with PRBC. However, a next-generation sequencing panel for 51 red blood cell genes (including PKLR) was negative. Despite a good response to red blood cell transfusions, he had a persistence of excess nucleated RBC (250/100 WBC), and small numbers of immature WBC in the form of myelocytes, metamyelocytes, promyelocytes, and blasts, as well as a worsening thrombocytopenia down to a nadir of 68k. Peripheral blood flow cytometry demonstrated 12% myeloblasts. Bone marrow aspirate and biopsy morphology revealed erythroid hyperplasia (M:E ratio 1:3) with erythroid dysplasia (multinuclearity and irregular nuclear budding). Myeloid elements were decreased with a left shift, but no significant dysplasia. Megakaryocytes manifested frequent small size with hypolobulated forms. Bone marrow aspirate flow cytometry revealed increased myeloid blasts (19.9%), but this was considered an overestimation secondary to erythroid hyperplasia from concurrent hemolytic anemia. This was further supported by only mildly increased blasts by morphology and CD34 immunohistochemical stain (3%–4%). Iron stain did not reveal ringed sideroblasts. No cytogenetic abnor","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1895-1897"},"PeriodicalIF":9.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superior GVHD-Free, Relapse-Free Survival for Haploidentical Transplant With PTCy Than Matched Unrelated Donor for AML Patients Transplanted in Second Complete Remission: A Study From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation","authors":"Yishan Ye,&nbsp;Myriam Labopin,&nbsp;Ibrahim Yakoub-Agha,&nbsp;Gérard Socié,&nbsp;Didier Blaise,&nbsp;Tobias Gedde-Dahl,&nbsp;Igor Wolfgang Blau,&nbsp;Anna Maria Raiola,&nbsp;Jennifer Byrne,&nbsp;Etienne Daguindau,&nbsp;Hélène Labussière-Wallet,&nbsp;Anne Huynh,&nbsp;Ali Bazarbachi,&nbsp;Arnon Nagler,&nbsp;Eolia Brissot,&nbsp;Lin Li,&nbsp;Yi Luo,&nbsp;Jimin Shi,&nbsp;Mohamad Mohty,&nbsp;He Huang,&nbsp;Fabio Ciceri","doi":"10.1002/ajh.70008","DOIUrl":"10.1002/ajh.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>Donor preference for acute myeloid leukemia (AML) patients transplanted in second complete remission (CR2) remains unclear, and hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) from a haploidentical donor (HAPLO) merits attention. Data of 3878 adult AML patients receiving a first allo-HCT in CR2 from the European Society of Blood and Marrow Transplantation registry between 2010 and 2022 were analyzed. Univariate analyses and Cox regression models were used. Results of HCTs from 803 HAPLO PTCy, 1271 matched sibling donor (MSD), and 1804 matched unrelated donor (MUD) were analyzed. A higher proportion (80.7%) of patients with European LeukemiaNet (ELN2022) intermediate−/adverse-risk cytogenetics received an allo-HCT from HAPLO PTCy than from either MUD (79.6%) or MSD (70.2%). On multivariate analysis, HAPLO PTCy grafts (hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.51–0.82; <i>p</i> &lt; 0.001) were associated with a lower relapse incidence (RI) compared with MSD HCTs, although non-relapse mortality was higher (HR = 1.77, 95% CI 1.34–2.34; <i>p</i> &lt; 0.001). No difference was observed with respect to leukemia-free survival and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) for HAPLO PTCy compared to MSD grafts. Notably, HAPLO PTCy HCT was associated with significantly lower RI (HR = 0.64, 95% CI 0.48–0.82; <i>p</i> &lt; 0.001), chronic GVHD (cGVHD) (HR = 0.64, 95% CI 0.51–0.81; <i>p</i> &lt; 0.001) and extensive cGVHD (HR = 0.47, 95% CI 0.34–0.66; <i>p</i> &lt; 0.001) incidences compared to MUD HCTs. Collectively, HAPLO PTCy HCT was associated with superior GRFS (HR = 0.81, 95% CI 0.68–0.95; <i>p</i> = 0.013) than MUD HCT. For AML patients in CR2, HAPLO PTCy HCT is associated with lower RI and cGVHD, leading to superior GRFS compared with MUD HCTs.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 10","pages":"1760-1771"},"PeriodicalIF":9.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611121","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 Cytogenetic Response to Therapy on Long-Term Survival in Acute Myeloid Leukemia","authors":"John Hanna,&nbsp;Emily C. Zabor,&nbsp;Moath Albliwi,&nbsp;Jessica El-Asmar,&nbsp;Daniel P. Nurse,&nbsp;Ameed Bawwab,&nbsp;Hasan Abuamsha,&nbsp;Yomna Abu-Farsakh,&nbsp;Heya Batah,&nbsp;Asad Rauf,&nbsp;Joy Nakitandwe,&nbsp;David S. Bosler,&nbsp;Akriti G. Jain,&nbsp;John C. Molina,&nbsp;Sophia Balderman,&nbsp;Abhay Singh,&nbsp;Aaron T. Gerds,&nbsp;Sudipto Mukherjee,&nbsp;Ronald M. Sobecks,&nbsp;Anjali S. Advani,&nbsp;Hetty E. Carraway,&nbsp;Caroline Astbury,&nbsp;Moaath K. Mustafa Ali","doi":"10.1002/ajh.70000","DOIUrl":"10.1002/ajh.70000","url":null,"abstract":"<p>Prognostication in acute myeloid leukemia (AML) relies on clinical, molecular, and cytogenetic factors. In this retrospective study, we examined the impact of different levels of cytogenetic response on overall survival (OS) and event-free survival (EFS) in AML. Among 973 adult AML patients treated at Cleveland Clinic (5/2017–9/2023), 563 patients had baseline cytogenetic data and post-treatment response assessment available. Based on baseline and response cytogenetic status, patients were categorized into: normal to normal (NL-Cy to NL-Cy, <i>n</i> = 221, 39%), normal or abnormal to gain (NL/Abnl-Cy to Gain-Cy, <i>n</i> = 46, 8.2%), abnormal to persistent (Abnl-Cy to Persistent-Cy, <i>n</i> = 81, 14%), abnormal to partial response (Abnl-Cy to Partial-Cy, <i>n</i> = 20, 3.6%), and abnormal to complete response (Abnl-Cy to NL-Cy, <i>n</i> = 195, 35%). Landmark analysis was used to account for post-treatment assessments. The cohort had a median age of 62 years (interquartile range: 52–69), 256 females (45%), 90% were White, and median follow-up of 45.8 months (range: 0.73–191.3). The median OS and hazard ratios (HRs) from multivariable regression analysis were as follows: NL-Cy to NL-Cy: 37 months (95% CI: 27–91), HR = reference; NL/Abnl-Cy to Gain-Cy: 14 months (95% CI: 8.6–30), HR = 1.5 (95% CI: 0.99–2.39); Abnl-Cy to Persistent-Cy: 13 months (95% CI: 12–18), HR = 1.61 (95% CI: 1.13–2.31); Abnl-Cy to Partial-Cy: 25 months (95% CI: 14-NC), HR = 0.76 (95% CI: 0.39–1.49); and Abnl-Cy to NL-Cy: 27 months (95% CI: 19–101), HR = 1.25 (95% CI: 0.93–1.68) (<i>p</i> = 0.038). Achieving cytogenetic remission, complete or partial, was associated with better survival outcomes. These findings highlight the importance of monitoring cytogenetic responses to inform treatment decisions and support integrating cytogenetic response into risk-adapted, personalized AML management strategies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 9","pages":"1577-1589"},"PeriodicalIF":9.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel ADAMTS13 Mutation in a Patient With Congenital TTP Diagnosed in Pregnancy","authors":"William Frank Mawalla, Clara Chamba, Ahlam Nasser, Irene Jonathan, Emmanuel Josephat, Mbonea Yonazi, Zainab Yusuph, Elena Bresin, Giuseppe Remuzzi, Lucio Luzzatto","doi":"10.1002/ajh.70007","DOIUrl":"https://doi.org/10.1002/ajh.70007","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"697 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602890","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":"Maintenance Therapy in the Era of Quadruplets for Multiple Myeloma: When, What, and for How Long?","authors":"Hira Mian,&nbsp;Luciano J. Costa","doi":"10.1002/ajh.70002","DOIUrl":"10.1002/ajh.70002","url":null,"abstract":"&lt;p&gt;Quadruplet therapy—combining a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody—has redefined frontline treatment for newly diagnosed multiple myeloma (NDMM) and is now the standard of care. Given the deep and durable responses seen with these regimens, it is time to reconsider the role of continuous maintenance therapy. In this commentary, we argue that indefinite maintenance lacks solid evidence in the quadruplet era and may pose unnecessary toxicity risks.&lt;/p&gt;&lt;p&gt;The current paradigm of continuous therapy was established with lenalidomide after large phase III trials showed (vs. placebo or observation) improvement in progression-free survival (PFS) [&lt;span&gt;1, 2&lt;/span&gt;] and overall survival (OS) [&lt;span&gt;1&lt;/span&gt;]. In those trials (Table 1), the vast majority of patients received a doublet induction or even chemotherapy-based therapy with no PI or IMiD. The magnitude of the unmet need is highlighted by the PFS in the control arm, 22% at 4 years in one study [&lt;span&gt;2&lt;/span&gt;], and 39% at 3 years in another [&lt;span&gt;1&lt;/span&gt;]. With so much territory to conquer, the continuous use of an active drug showed meaningful improvement in outcomes, yet stained by increased risk of second malignancies and frequent treatment discontinuation for toxicity. Even with this meaningful improvement, the optimal duration of maintenance remained unknown, ranging anywhere between 1 year fixed duration [&lt;span&gt;5&lt;/span&gt;] to continuous therapy [&lt;span&gt;6&lt;/span&gt;] with likely diminishing benefit with increasing time [&lt;span&gt;7&lt;/span&gt;]. As upfront therapies have improved with the widespread adoption of triplets and subsequently quadruplets, it becomes crucial to critically revisit the merit of continuous therapy.&lt;/p&gt;&lt;p&gt;The CASSIOPEIA trial evaluated daratumumab added to bortezomib, thalidomide, and dexamethasone (D-VTd), with a second randomization to either daratumumab maintenance or observation [&lt;span&gt;8&lt;/span&gt;]. In this trial, 2 years of fixed maintenance therapy with daratumumab was found to be beneficial compared to observation, including among patients who received D-VTd induction (HR 0.76; &lt;i&gt;p&lt;/i&gt; = 0·048). Yet, a much larger effect size of daratumumab maintenance was seen among patients who received VTd induction (HR 0.34, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). This is the only trial with direct randomized evidence for any maintenance therapy with quadruplet induction and brings forth a few important considerations. First, there is a strong interaction between induction therapy and maintenance therapy, an element not well studied previously, casting doubt on the extent of benefit of even lenalidomide continuous therapy in the era of quadruplets. Second, as illustrated by the median PFS of 72.1 months for patients treated with Dara-VTd and no maintenance, with more effective upfront therapy, there is far less territory to be conquered by maintenance. Lastly, no OS benefit has been demonstrated with daratumumab maintenance thus far, including in the ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 9","pages":"1483-1485"},"PeriodicalIF":9.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}