EJHaem最新文献

{"title":"Medical history and lifestyle factors have limited impact on time-to-first-treatment in patients with chronic lymphocytic leukemia","authors":"Ingrid Glimelius,&nbsp;Geffen Kleinstern,&nbsp;Dennis P. Robinson,&nbsp;Larry Mansouri,&nbsp;Klaus Rostgaard,&nbsp;Henrik Hjalgrim,&nbsp;Carsten Utoft Niemann,&nbsp;Mattias Mattsson,&nbsp;Kari G. Rabe,&nbsp;Paul J. Hampel,&nbsp;Sameer A. Parikh,&nbsp;Richard Rosenquist,&nbsp;James R. Cerhan,&nbsp;Susan L. Slager,&nbsp;Karin E. Smedby","doi":"10.1002/jha2.1000","DOIUrl":"https://doi.org/10.1002/jha2.1000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non-modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>In 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non-modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time-to-first-treatment (TTFT) and adjusted all results for the CLL-International Prognostic Index (CLL-IPI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TTFT was shorter for patients with high/very high-risk CLL-IPI than those with low/intermediate risk CLL-IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL-IPI from any environmental characteristics assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment naïve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"998-1004"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.1000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of intravenous vitamin C supplementation in allogeneic hematopoietic cell transplant recipients","authors":"Gary L. Simmons,&nbsp;Roy Sabo,&nbsp;Rehan Qayyum,&nbsp;May Aziz,&nbsp;Erika Martin,&nbsp;Robyn J. Bernard,&nbsp;Manjari Sriparna,&nbsp;Cody McIntire,&nbsp;Elizabeth Krieger,&nbsp;Donald F. Brophy,&nbsp;Ramesh Natarajan,&nbsp;Alpha Fowler III,&nbsp;Catherine H. Roberts,&nbsp;Amir Toor","doi":"10.1002/jha2.995","DOIUrl":"https://doi.org/10.1002/jha2.995","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intravenous vitamin C was administered following hematopoietic stem cell transplant to mitigate nonrelapse mortality (NRM) in a Phase II clinical trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with advanced hematologic malignancies received IV vitamin C, 50 mg/kg/day, in three divided doses on days 1–14 after HSCT, followed by 500 mg bid oral until 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients enrolled (55) were deficient in vitamin C at day 0 and had restoration to normal levels. Vitamin C recipients had a trend for lower nonrelapse mortality (NRM, 11% vs. 25%, <i>p</i>-value = 0.07) compared with propensity score-matched historical controls. A similar trend toward improved survival was observed (82% vs. 62% <i>p</i> = 0.06), with no attributable grade 3 and 4 toxicities to vitamin C.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients undergoing allogeneic HSCT, repletion of vitamin C is feasible and may reduce NRM and improve overall survival. Randomized trials in large uniform cohorts of patients are needed to confirm the utility of this easily available and inexpensive therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1043-1047"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-grade follicular lymphoma with interferon regulatory factor-4 rearrangement: Expanding the spectrum of interferon regulatory factor-4-rearranged lymphomas","authors":"Ali Sakhdari,&nbsp;Peter J. B. Sabatini,&nbsp;Tulasi Geevar,&nbsp;Tong Zhang,&nbsp;Jan M. A. Delabie","doi":"10.1002/jha2.992","DOIUrl":"https://doi.org/10.1002/jha2.992","url":null,"abstract":"<p>In recent years, the recognition of distinct lymphoma entities has expanded with advancements in molecular characterization. Large B-cell Lymphoma with interferon regulatory factor-4 (<i>IRF4</i>) rearrangement (LBCL-<i>IRF4</i>-R) is one such entity. We present a case of classic low-grade follicular lymphoma with <i>IRF4</i> rearrangement in a 50-year-old male, demonstrating an unusual immunophenotypic and genetic profile reminiscent of LBCL-<i>IRF4</i>-R. Molecular analysis revealed mutations in <i>CREBBP</i>, <i>KMT2D</i>, <i>IRF4</i>, and <i>CARD11</i>, with previously unreported variants identified in <i>IRF4</i> and <i>CREBBP</i>. This case broadens the spectrum of B-cell lymphomas associated with <i>IRF4</i> rearrangement by demonstrating a small B-cell lymphoma with this genetic feature.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1068-1071"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Routine hemostasis profile in steady state sickle cell disease adult patients compared to laboratory values, between phenotypes and during pregnancy: A retrospective, descriptive study","authors":"Comlan Affo,&nbsp;Carine Schmidt,&nbsp;Antoine Bosquet,&nbsp;Bénédicte Dumont,&nbsp;Isabelle Mahé","doi":"10.1002/jha2.876","DOIUrl":"https://doi.org/10.1002/jha2.876","url":null,"abstract":"<p>Sickle cell disease is a rare genetic disease resulting from an abnormality in hemoglobin. Hemostasis in the steady state, defined as ≥2 months without vaso-occlusive crises, is poorly described in the literature. We report the routine hemostasis profile in steady state patients with sickle cell disease (SCD), including during pregnancy and according to phenotype. This retrospective study collected data over the period 2010 to 2021. Data on routine hemostasis parameters (prothrombin time [PT] activated partial thromboplastin time [aPTT], and platelets) were collected from medical records and were compared with laboratory norms including during pregnancy; the HbSS phenotype was compared with the HbSC, HbSB°thalassemia, and HbSB+thalassemia phenotypes. we included 119 adults (representing 190 day-hospitals) with SCD who had attended at least one checkup in the steady state. Seven patients (15 day-hospitals) on anticoagulants were excluded. Eleven (17 day-hospitals) were pregnant. Mean routine hemostasis parameters were within normal values regardless of pregnancy. Mean PT was lower during pregnancy (12.3 ± 0.6 s vs. 13.2 ± 1.0 s; <i>P</i> = .01). PT and platelet counts were higher (<i>P</i> = .01) and aPTT was lower (<i>P</i> = .03) in men and nonpregnant women in the HbSS group compared with those in the HbSC group. routinely collected hemostasis parameters in steady state patients were within normal laboratory values, including in pregnant women. PT values differed significantly between pregnant women and nonpregnant women, and PT, aPTT, and platelet counts differed between HbSS, HbSC, and HbSB+thalassemia phenotypes.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"920-928"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53 variants underlying pediatric low-hypodiploidy B-cell acute lymphoblastic leukemia demonstrate diverse origins and may persist as a hematopoietic clone in remission","authors":"Albert Itov,&nbsp;Karina Ilyasova,&nbsp;Olga Soldatkina,&nbsp;Anna Kazakova,&nbsp;Vladimir Kozeev,&nbsp;Alexandra Semchenkova,&nbsp;Elena Osipova,&nbsp;Elmira Boichenko,&nbsp;Egor Volchkov,&nbsp;Alexander Popov,&nbsp;Elena Zerkalenkova,&nbsp;Julia Roumiantseva,&nbsp;Galina Novichkova,&nbsp;Alexander Karachunskiy,&nbsp;Yulia Olshanskaya","doi":"10.1002/jha2.986","DOIUrl":"https://doi.org/10.1002/jha2.986","url":null,"abstract":"<p>Pediatric low-hypodiploidy B-cell acute lymphoblastic leukemia (LH-ALL) with <i>TP53</i> variants has been proposed to be considered a manifestation of Li-Fraumeni syndrome (LFS). However, our study demonstrates that of the majority the pathogenic variants in the TP53 gene are somatic (70.5%), and only 12.5% of patients with germline fulfilled the criteria of LFS. We also describe the first case of hypodiploid BCP-ALL with a mosaic pathogenic mutation in <i>TP53</i> and the first case of the persistence of clonal hematopoiesis with the <i>TР53</i> gene mutation in the child during 3-year minimal residual disease-negative remission, similar to what has been described in adults.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1010-1013"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.986","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutant NPM1 marginally impacts ribosome footprint in acute myeloid leukemia cells","authors":"Lorenzo Brunetti,&nbsp;Giulia Pianigiani,&nbsp;Michael C. Gundry,&nbsp;Margaret A. Goodell,&nbsp;Brunangelo Falini","doi":"10.1002/jha2.996","DOIUrl":"https://doi.org/10.1002/jha2.996","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>NPM1</i>-mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild-type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in <i>NPM1</i>-mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we performed ribosome footprint profiling (Ribo-seq) and bulk messenger RNA (mRNA) sequencing in two <i>NPM1</i>-mutated cell lines engineered to express endogenous NPM1c fused to the FKBP (F36V) degron tag (degron cells).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and discussion</h3>\u0000 \u0000 <p>Incubation of degron cells with the small compound dTAG-13 enables highly specific degradation of NPM1c within 4 hours. As expected, RNA-sequencing data showed early loss of homeobox gene expression following NPM1c degradation, confirming the reliability of our model. In contrast, Ribo-seq data showed negligible changes in the ribosome footprint in both cell lines, implying that the presence of NPM1c does not influence ribosome abundance and positioning on mRNA. While it is predictable that NPM1c exerts its leukemogenic activity at multiple levels, ribosome footprint does not seem influenced by the presence of mutant NPM1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1028-1032"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.996","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of melphalan 140 mg/m2 followed by autologous stem cell transplantation in multiple myeloma patients with co-morbidities: Single-centre experience","authors":"Dario Melotti,&nbsp;Samir Asher,&nbsp;Ethan Troy-Barnes,&nbsp;George Nesr,&nbsp;William Wilson,&nbsp;Marquita Camilleri,&nbsp;Rakesh Popat,&nbsp;Ke Xu,&nbsp;Neil Rabin,&nbsp;Jonathan Sive,&nbsp;Xenofon Papanikolaou,&nbsp;Lydia Lee,&nbsp;Annabel McMillan,&nbsp;Kwee Yong,&nbsp;Chara Kyriakou","doi":"10.1002/jha2.977","DOIUrl":"https://doi.org/10.1002/jha2.977","url":null,"abstract":"<p>High-dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant-eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m² (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single-centre UK-based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced-intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant-related death within the initial autograft admission. The progression-free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose-reduced melphalan conditioning is safe and effective in patients deemed unfit for standard-intensity conditioning.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1102-1106"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dasatinib in core-binding factor acute myeloid leukemia: A promising therapeutic approach","authors":"Shyam Srinivasan","doi":"10.1002/jha2.994","DOIUrl":"https://doi.org/10.1002/jha2.994","url":null,"abstract":"&lt;p&gt;In the present issue of eJHaem, Rojek et al. [&lt;span&gt;1&lt;/span&gt;] have published on the real-world outcomes of 200 patients with core-binding factor acute myeloid leukemia (CBF-AML) treated between 2010 and 2023. First and foremost, I commend the authors for their work. Of several aspects discussed in this paper on real-world outcomes of CBF-AML, one thing stands out: the benefit of adding &lt;i&gt;KIT&lt;/i&gt; inhibitors (dasatinib or midostaruin) to intensive chemotherapy in CBF-AML. The use of tyrosine kinase inhibitors (TKI), especially dasatinib, has recently garnered interest in AML, following its remarkable success in other hematolymphoid neoplasms including CML and Ph&lt;sup&gt;+&lt;/sup&gt; acute lymphoblastic leukemia (ALL). Dasatinib, a multikinase inhibitor with activity on &lt;i&gt;KIT&lt;/i&gt; and &lt;i&gt;SRC&lt;/i&gt; activated proteins, has recently shown benefit in two other phase II studies in CBF-AML [&lt;span&gt;2, 3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In the present study, 14 days of &lt;i&gt;KIT&lt;/i&gt; inhibitors (majority receiving dasatinib) along with induction chemotherapy produced significantly superior remission rates among 21 patients with CBF-AML compared to patients who did not receive &lt;i&gt;KIT&lt;/i&gt; inhibitors during induction (95% vs. 83%, &lt;i&gt;p&lt;/i&gt; = 0.01). Subsequently, patients continued to receive &lt;i&gt;KIT&lt;/i&gt; inhibitors during consolidation phase, which was followed by 1-year of maintenance therapy. The survival of these patients in the study was phenomenal, with a 3-year event-free survival (EFS) and overall survival (OS) of 85% and 95%, respectively. These outcomes are similar or even slightly better to the 90% remission rates and 3-year OS of 77% reported by the CALGB group with the use of dasatinib in CBF-AML [&lt;span&gt;3&lt;/span&gt;]. It is noteworthy that only six of 21 patients who received a &lt;i&gt;KIT&lt;/i&gt; inhibitor in the study by Rojek et al. had a &lt;i&gt;KIT&lt;/i&gt; mutation. Dasatinib mainly acts by inhibiting &lt;i&gt;KIT&lt;/i&gt; kinase activity, and is effective on mutations involving either the activation or the juxtamembrane loop, which are commonly seen in AML [&lt;span&gt;4&lt;/span&gt;]. However, several studies, including the present one, show dasatinib to be effective in CBF-AML irrespective of the &lt;i&gt;KIT&lt;/i&gt; status, highlighting a mechanism of action beyond &lt;i&gt;KIT&lt;/i&gt; inhibition. One reason for this could be dasatinib's ability to enhance the sensitivity of blasts to cytotoxic agents and its ability to induce differentiation of AML cells, both of which can occur irrespective of the &lt;i&gt;KIT&lt;/i&gt; status [&lt;span&gt;5, 6&lt;/span&gt;]. Additionally, regardless of mutation status, &lt;i&gt;KIT&lt;/i&gt; is known to be highly expressed in CBF-AML blasts [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Several aspects of the present study warrant careful consideration. First, the study included patients treated over a period of 13 years. It would be worthwhile for the authors to specify when KIT inhibitors were adopted as a treatment strategy. Additionally, an analysis should consider the prolonged timeframe, as other treatment factors may have changed considerably during","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1100-1101"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.994","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimisation of the Danish national haemoglobinopathy screening programme – A prospective intervention study","authors":"E. Gravholt, Finn Stener Jørgensen, Charlotte Holm, Jesper Petersen, A. Nardo‐Marino, M. Mottelson, A. Glenthøj","doi":"10.1002/jha2.980","DOIUrl":"https://doi.org/10.1002/jha2.980","url":null,"abstract":"The Danish national haemoglobinopathy screening programme offers screening to at‐risk pregnant women. Despite efforts to increase awareness of the screening programme, most women in the target population remain unscreened. In contrast, > 90% of pregnant women in Denmark attend a screening for chromosomal abnormalities by combined first‐trimester screening (cFTS).This study aimed to improve adherence to the Danish national haemoglobinopathy screening programme by offering screening to at‐risk unscreened pregnant women in relation to their cFTS.During a 27‐week intervention period, 3254 women attended cFTS at Copenhagen University Hospital—Amager Hvidovre Hospital. Of these, 938 women (28.8%) were identified as at risk of carrying haemoglobinopathy variants based on their ethnic origins. Of the 938 women at risk, 539 (57.5%) were unscreened prior to their cFTS and were targeted for the intervention. These women were contacted with an offer of haemoglobinopathy screening. Subsequently, 253/539 (46.9%) of the at‐risk unscreened women were tested for haemoglobinopathies, of these 4/253 (1.6%) carried haemoglobinopathy variants necessitating partner screening. No partners carried haemoglobinopathy variants necessitating testing of the fetus.The study increased the proportion of at‐risk pregnant women tested for haemoglobinopathies from 42.5% to 69.5% and made haemoglobinopathy screening more readily available to women attending cFTS.","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"42 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B-cell or T-cell acute lymphoblastic leukemia: Results from the ECOG-ACRIN EA9152 protocol","authors":"Neil D. Palmisiano,&nbsp;Ju-Whei Lee,&nbsp;David F. Claxton,&nbsp;Elisabeth M. Paietta,&nbsp;Hassan Alkhateeb,&nbsp;Jae Park,&nbsp;Nikolai A. Podoltsev,&nbsp;Ehab L. Atallah,&nbsp;Dale G. Schaar,&nbsp;Shira N. Dinner,&nbsp;Jonathan A. Webster,&nbsp;Selina M. Luger,&nbsp;Mark R. Litzow","doi":"10.1002/jha2.991","DOIUrl":"10.1002/jha2.991","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B- and T-ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L-VCR and VEN for patients with r/r B-or T-cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a 3+3 dose escalation design, r/r ALL subjects were given single-agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L-VCR at 2.25 mg/m² IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 18 patients in phase I, grade ≥ 3 treatment-related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose-limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty-two percent of evaluable patients (<i>N</i> = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The combination of VEN and L-VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L-VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"951-956"},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}