British Journal of Haematology最新文献

{"title":"Venetoclax plus hypomethylating agents in DDX41-mutated acute myeloid leukaemia and myelodysplastic syndrome: Mayo Clinic series on 12 patients","authors":"Ahmad Nanaa,&nbsp;Rong He,&nbsp;James M. Foran,&nbsp;Talha Badar,&nbsp;Naseema Gangat,&nbsp;Animesh Pardanani,&nbsp;William J. Hogan,&nbsp;Mark R. Litzow,&nbsp;Mrinal Patnaik,&nbsp;Aref Al-Kali,&nbsp;Hassan B. Alkhateeb","doi":"10.1111/bjh.19105","DOIUrl":"10.1111/bjh.19105","url":null,"abstract":"<p>Venetoclax (VEN) is an FDA-approved selective inhibitor of B-cell leukaemia/lymphoma-2 (BCL-2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high-risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating <i>DDX41</i>-mutated (m<i>DDX41</i>) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of m<i>DDX41</i> MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"204 1","pages":"171-176"},"PeriodicalIF":6.5,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10246584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma","authors":"Connor M. D. Williams,&nbsp;Jacqueline E. Noll,&nbsp;Alanah L. Bradey,&nbsp;Jvaughn Duggan,&nbsp;Vicki J. Wilczek,&nbsp;Makutiro G. Masavuli,&nbsp;Branka Grubor-Bauk,&nbsp;Romana A. Panagopoulos,&nbsp;Duncan R. Hewett,&nbsp;Krzysztof M. Mrozik,&nbsp;Andrew C. W. Zannettino,&nbsp;Kate Vandyke,&nbsp;Vasilios Panagopoulos","doi":"10.1111/bjh.19102","DOIUrl":"10.1111/bjh.19102","url":null,"abstract":"<p>Expression of myeloperoxidase (MPO), a key inflammatory enzyme restricted to myeloid cells, is negatively associated with the development of solid tumours. Activated myeloid cell populations are increased in multiple myeloma (MM); however, the functional consequences of myeloid-derived MPO within the myeloma microenvironment are unknown. Here, the role of MPO in MM pathogenesis was investigated, and the capacity for pharmacological inhibition of MPO to impede MM progression was evaluated. In the 5TGM1-KaLwRij mouse model of myeloma, the early stages of tumour development were associated with an increase in CD11b⁺ myeloid cell populations and an increase in <i>Mpo</i> expression within the bone marrow (BM). Interestingly, MM tumour cell homing was increased towards sites of elevated myeloid cell numbers and MPO activity within the BM. Mechanistically, MPO induced the expression of key MM growth factors, resulting in tumour cell proliferation and suppressed cytotoxic T-cell activity. Notably, tumour growth studies in mice treated with a small-molecule irreversible inhibitor of MPO (4-ABAH) demonstrated a significant reduction in overall MM tumour burden. Taken together, our data demonstrate that MPO contributes to MM tumour growth, and that MPO-specific inhibitors may provide a new therapeutic strategy to limit MM disease progression.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 4","pages":"614-624"},"PeriodicalIF":6.5,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10222806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study","authors":"Darina Ocadlikova,&nbsp;Federico Lussana,&nbsp;Nicola Fracchiolla,&nbsp;Massimiliano Bonifacio,&nbsp;Lidia Santoro,&nbsp;Mario Delia,&nbsp;Sabina Chiaretti,&nbsp;Crescenza Pasciolla,&nbsp;Alessandro Cignetti,&nbsp;Fabio Forghieri,&nbsp;Francesco Grimaldi,&nbsp;Giulia Corradi,&nbsp;Letizia Zannoni,&nbsp;Stefania De Propris,&nbsp;Gian Maria Borleri,&nbsp;Ilaria Tanasi,&nbsp;Jayakumar Vadakekolathu,&nbsp;Sergio Rutella,&nbsp;Anna Rita Guarini,&nbsp;Robin Foà,&nbsp;Antonio Curti,&nbsp;the Campus ALL","doi":"10.1111/bjh.19104","DOIUrl":"10.1111/bjh.19104","url":null,"abstract":"<p>Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 4","pages":"637-650"},"PeriodicalIF":6.5,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10221138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Danish national haemoglobinopathy screening programme: Report from 16 years of screening in a low-prevalence, non-endemic region","authors":"Esther Agnethe Ejskjær Gravholt,&nbsp;Jesper Petersen,&nbsp;Mathis Mottelson,&nbsp;Amina Nardo-Marino,&nbsp;Mathias Rathe,&nbsp;Marianne Olsen,&nbsp;Charlotte Holm,&nbsp;Finn Stener Jørgensen,&nbsp;Henrik Birgens,&nbsp;Andreas Glenthøj","doi":"10.1111/bjh.19103","DOIUrl":"10.1111/bjh.19103","url":null,"abstract":"<p>The Danish national haemoglobinopathy screening programme seeks to determine parental haemoglobinopathy carrier state antenatally. In this retrospective register-based study, we evaluated the 16-year trajectory of this programme, utilising the Danish Red Blood Cell Centre's laboratory database, covering approximately 77% of the Danish population. During the study period, we observed a substantial increase in annual diagnostic examinations performed, from 389 in 2007 to 3030 in 2022. Women constituted 88% of these cases, aligning with the emphasis of the screening programme. Of these, 54% of women of reproductive age (15–40 years) and 10% of women &gt;40 years were specified as pregnant. During our study period, 61 children were born with a severe haemoglobinopathy, out of which 23 children were born from mothers not residing in Denmark during their first trimester thus not included in the screening programme. Prenatal invasive testing was performed for 60 fetuses, identifying 12 with homozygous or compound heterozygous haemoglobinopathy. The Danish haemoglobinopathy screening programme has provided screening, information and reproductive choices for numerous families. During the study period, screening for haemoglobinopathies has been steadily increasing and is expected to continue to increase. Awareness of and adherence to the screening programme is subject of further investigation and optimisation.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"204 1","pages":"329-336"},"PeriodicalIF":6.5,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First description of bone marrow failure syndrome in Spain caused by mutations in the ERCC6L2 gene","authors":"Perla Bandini,&nbsp;Nina Borràs,&nbsp;Eugenia Fernandez Mellid,&nbsp;Laura Martin-Fernandez,&nbsp;Paula Melero Valentín,&nbsp;Natalia Comes,&nbsp;Lorena Ramírez,&nbsp;Patricia Cadahia Fernández,&nbsp;Matilde Rodríguez Ruiz,&nbsp;Manuel Mateo Perez Encinas,&nbsp;Francisco Vidal,&nbsp;Irene Corrales","doi":"10.1111/bjh.19050","DOIUrl":"10.1111/bjh.19050","url":null,"abstract":"&lt;p&gt;Inherited bone marrow failure syndromes (BMFS) are a heterogeneous group of disorders characterized by trilineage peripheral blood cytopenias, often presenting during infancy.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Currently, more than 100 genes, including &lt;i&gt;ERCC6L2&lt;/i&gt;, have been associated with BMFS.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; &lt;i&gt;ERCC6L2&lt;/i&gt; encodes a DNA repair protein of the Snf2 family of helicases called ERCC excision repair 6-like 2 protein. Consequently, variants affecting &lt;i&gt;ERCC6L2&lt;/i&gt; cause BMFS-2 and result in genome instability and a predisposition to bone marrow failure (BMF).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In 2014, Tummala et al.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; described the first &lt;i&gt;ERCC6L2&lt;/i&gt; homozygous variants in two consanguineous families who presented with trilineage BMF with developmental delay and microcephaly.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; To our knowledge, only 24 families have been diagnosed with BMFS-2 worldwide and 18 different &lt;i&gt;ERCC6L2&lt;/i&gt; variants have been reported (Table 1).&lt;span&gt;&lt;sup&gt;2-11&lt;/sup&gt;&lt;/span&gt; Herein, we describe the first case of BMFS-2 in Spain, reporting two siblings with pathogenic variants in &lt;i&gt;ERCC6L2&lt;/i&gt; with no extra-haematopoietic symptoms and comparing them with the previously reported patients.&lt;/p&gt;&lt;p&gt;Two siblings were referred to a haematologist in 2013 at the ages of 13 and 7 years old after a blood test performed for tonsillitis revealed thrombocytopenia and leukopenia in the older brother (33 × 10&lt;sup&gt;9&lt;/sup&gt; platelets/L, 3.6 × 10&lt;sup&gt;9&lt;/sup&gt; leukocytes/L, 1.3 × 10&lt;sup&gt;9&lt;/sup&gt; lymphocytes/L; Figure 1A). The younger brother also presented with thrombocytopenia (82 × 10&lt;sup&gt;9&lt;/sup&gt; platelets/L). Based on these findings, a bone marrow (BM) biopsy was conducted for both, detecting BM hypoplasia with no evidence of myelodysplastic syndromes (MDS). Further molecular tests were performed, showing no alterations: karyotype (46, XY), chromosome breakage studies for Fanconi anaemia, and analysis by fluorescence in situ hybridization (FISH) of 20q21, 5q33, 7q35 and the centromeric region of chromosome 8.&lt;/p&gt;&lt;p&gt;In January 2021 (20 and 14 years old), the siblings were recruited in a research project aimed at unravelling the molecular basis of inherited bleeding disorders or thrombocytopenia by whole-exome sequencing (WES). Written informed consent was provided by their legal guardians, and the study was approved by the research ethics committee of Hospital Universitari Vall d'Hebron in accordance with the guidelines of the Declaration of Helsinki. WES was performed using the DNA Prep with Enrichment protocol (Illumina) in a NextSeq500 system (Illumina). The variants obtained were filtered using a virtual 352-gene panel related to inherited platelet and/or bleeding disorders, but no candidate variants were initially identified.&lt;/p&gt;&lt;p&gt;In December 2021, the younger brother was admitted to the hospital with fever and upper respiratory infection due to SARS-CoV-2 and severe cytopenia (17 × 10&lt;sup&gt;9&lt;/sup&gt; platelets/L, 0.71 × 10&lt;sup&gt;9&lt;/","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 4","pages":"e102-e107"},"PeriodicalIF":6.5,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10213383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphoplasmacytic lymphoma presenting cold agglutinin syndrome: Clonal expansion of KMT2D and IGHV4-34 mutations after COVID-19","authors":"Kiyohito Hayashi,&nbsp;Daisuke Koyama,&nbsp;Yuki Sato,&nbsp;Masahiko Fukatsu,&nbsp;Takayuki Ikezoe","doi":"10.1111/bjh.19106","DOIUrl":"10.1111/bjh.19106","url":null,"abstract":"&lt;p&gt;Cold agglutinin disease (CAD) is an autoimmune haemolytic anaemia (AIHA) mediated by monoclonal IgM anti-I autoantibodies without significant lymphoproliferative disease (LPD). Cold agglutinin syndrome (CAS) is associated with various LPDs.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; CAD is categorized as an independent disease according to the fifth edition of the World Health Organization (WHO) classification of haematolymphoid tumours&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and the International Consensus Classification (ICC) of mature lymphoid neoplasms.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Recurrent somatic mutations in &lt;i&gt;KMT2D&lt;/i&gt; and &lt;i&gt;CARD11&lt;/i&gt; have been detected in CAD, whereas mutations in &lt;i&gt;MYD88&lt;/i&gt; L265P and &lt;i&gt;CXCR4&lt;/i&gt; and very rarely &lt;i&gt;KMT2D&lt;/i&gt; mutations are detected in patients with lymphoplasmacytic lymphoma (LPL).&lt;span&gt;&lt;sup&gt;2, 5-8&lt;/sup&gt;&lt;/span&gt; The cold agglutinins (CAs) encoded by &lt;i&gt;IGH&lt;/i&gt; gene segment &lt;i&gt;V4-34&lt;/i&gt; can bind to the I/i carbohydrate antigen on the surface of erythrocytes.&lt;span&gt;&lt;sup&gt;2, 9&lt;/sup&gt;&lt;/span&gt; However, the mutational status of &lt;i&gt;IGH&lt;/i&gt; gene in LPL with CAS is still unclear. Furthermore, previous reports have indicated an association between CAS and coronavirus disease 2019 (COVID-19).&lt;span&gt;&lt;sup&gt;10-12&lt;/sup&gt;&lt;/span&gt; The mechanism underlying CA production in COVID-19 remains to be elucidated. Here, we present a crucial case that sheds light on the pathophysiology of LPL with CAS associated with COVID-19.&lt;/p&gt;&lt;p&gt;A 58-year-old Japanese male consulted an ophthalmologist owing to sudden onset of a visual field defect in his right eye. Subsequently, his immunoglobulin IgM was markedly elevated at 9094 mg/dL, while IgG and IgA were within normal limits. Serum immunofixation electrophoresis (IFE) showed the IgM-kappa type. His serum concentration of the kappa chain was 75.2 mg/dL, and that of the lambda chain was 7.2 mg/dL, resulting in a kappa/lambda ratio of 10.44. Urinalysis revealed the presence of kappa type Bence Jones proteins, suggesting IgM monoclonal gammopathy. Laboratory tests revealed a white blood cell count (WBC) of 8700/μL (with neutrophils accounting for 45% and lymphocytes for 38%), a haemoglobin concentration (Hb) of 8.2 g/dL, platelet count of 121 000/μL, total bilirubin of 1.6 mg/dL, indirect bilirubin of 0.8 mg/dL, lactate dehydrogenase (LDH) of 180 U/L and haptoglobin &lt;1.0 mg/dL. Moreover, the patient exhibited a positive result for CA (titre &gt;2048-fold) and C3 in a direct globulin test. All antibodies for infections that cause CAS, such as anti-&lt;i&gt;Mycoplasma pneumoniae&lt;/i&gt; antibodies, human immunodeficiency virus (HIV) antigen/antibodies, hepatitis B virus (HBV) surface antigen and hepatitis C virus (HCV) antibodies, were negative. Cryoglobulin was also not detected. Additionally, BM aspirate revealed monotonous proliferation of small- to medium-sized lymphocytes; plasmacytoid lymphocytes accounted for 38%, and plasma cells accounted for 4%, along with erythrocyte hyperplasia with severe haemagglutination (Figures 1A an","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 5","pages":"e110-e113"},"PeriodicalIF":6.5,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10212558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment-free remission after failing the first attempt with imatinib: Treatment-free Remission Accomplished by Dasatinib (TRAD) study","authors":"Maria Agustina Perusini,&nbsp;Igor Novitzky-Basso,&nbsp;Eshetu G. Atenafu,&nbsp;Donna Forrest,&nbsp;Isabelle Bence-Bruckler,&nbsp;Lynn Savoie,&nbsp;Mary-Margaret Keating,&nbsp;Lambert Busque,&nbsp;Robert Delage,&nbsp;Anargyros Xenocostas,&nbsp;Elena Liew,&nbsp;Pierre Laneuville,&nbsp;Kristjan Paulson,&nbsp;Tracy Stockley,&nbsp;Jeffrey H. Lipton,&nbsp;Brian Leber,&nbsp;Dennis Dong Hwan Kim","doi":"10.1111/bjh.19058","DOIUrl":"10.1111/bjh.19058","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple studies have reported a significant treatment-free remission (TFR) rate of 50%–60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re-initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re-therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post-imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of <i>BCR::ABL1</i> transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable <i>BCR::ABL1</i> transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach.</p>\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 5","pages":"781-791"},"PeriodicalIF":6.5,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10267825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disseminated invasive aspergillosis in a patient treated with ibrutinib for chronic lymphocytic leukaemia","authors":"Emily Booth,&nbsp;Matthijs Backx,&nbsp;Anurag Joshi,&nbsp;Hasan Nizami,&nbsp;Nagah Elmusharaf","doi":"10.1111/bjh.19045","DOIUrl":"10.1111/bjh.19045","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 4","pages":"499-500"},"PeriodicalIF":6.5,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Provider prescription of hydroxyurea in youth and adults with sickle cell disease: A review of prescription barriers and facilitators","authors":"Alex Pizzo,&nbsp;Jerlym S. Porter,&nbsp;Yvonne Carroll,&nbsp;Adam Burcheri,&nbsp;Matthew P. Smeltzer,&nbsp;Molly Beestrum,&nbsp;Chinonyelum Nwosu,&nbsp;Sherif M. Badawy,&nbsp;Jane S. Hankins,&nbsp;Lisa M. Klesges,&nbsp;Nicole M. Alberts","doi":"10.1111/bjh.19099","DOIUrl":"10.1111/bjh.19099","url":null,"abstract":"<p>Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence-based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow-up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 5","pages":"712-721"},"PeriodicalIF":6.5,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10179642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyclonal immunoglobulin recovery in patients with newly diagnosed myeloma receiving maintenance therapy after autologous haematopoietic stem cell transplantation with either carfilzomib, lenalidomide and dexamethasone or lenalidomide alone: Subanalysis of the randomized phase 3 ATLAS trial","authors":"Tadeusz Kubicki,&nbsp;Dominik Dytfeld,&nbsp;Tomasz Wróbel,&nbsp;Krzysztof Jamroziak,&nbsp;Paweł Robak,&nbsp;Jarosław Czyż,&nbsp;Agata Tyczyńska,&nbsp;Agnieszka Druzd-Sitek,&nbsp;Krzysztof Giannopoulos,&nbsp;Tomasz Szczepaniak,&nbsp;Anna Łojko-Dankowska,&nbsp;Magdalena Matuszak,&nbsp;Lidia Gil,&nbsp;Bartosz Puła,&nbsp;Justyna Rybka,&nbsp;Maciej Majcherek,&nbsp;Lidia Usnarska-Zubkiewicz,&nbsp;Łukasz Szukalski,&nbsp;Jan Maciej Zaucha,&nbsp;Damian Mikulski,&nbsp;Olga Czabak,&nbsp;Oscar B. Lahoud,&nbsp;Andrew Stefka,&nbsp;Benjamin A. Derman,&nbsp;Andrzej J. Jakubowiak","doi":"10.1111/bjh.19097","DOIUrl":"10.1111/bjh.19097","url":null,"abstract":"<p>Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B-cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard-risk patients with minimal residual disease negativity after six cycles de-escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, <i>p</i> &lt; 0.001) and in those who de-escalated from KRd to R (27/38, <i>p</i> &lt; 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B-cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression-free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"203 5","pages":"792-802"},"PeriodicalIF":6.5,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}