European Journal of Haematology最新文献

{"title":"The impact of hematology electronic consultations on the management of iron deficiency","authors":"Hannah L. King,&nbsp;Genevieve B. Benedetti,&nbsp;Stefan Barisic,&nbsp;Virginia Tan,&nbsp;Marie E. Piatski,&nbsp;Jacob M. Berkowitz,&nbsp;Ashley E. Benson,&nbsp;Jamie O. Lo,&nbsp;Sven R. Olson,&nbsp;Thomas G. DeLoughery,&nbsp;Joseph J. Shatzel,&nbsp;Kylee L. Martens","doi":"10.1111/ejh.14276","DOIUrl":"10.1111/ejh.14276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Delays in the evaluation and treatment of iron deficiency can lead to increased disease-related morbidity and mortality. Electronic consultation (e-consult) is a referral modality that allows providers quicker access to recommendations from a specialist based on electronic chart review. While the use of e-consult is expanding in classical hematology, gaps exist in the understanding of patient outcomes related to its use for iron deficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We randomly selected 200 e-consults and 200 traditional referrals from 3,336 hematology referrals for iron deficiency at a single center. The primary outcomes of the retrospective analysis were: time to completion of the referral, and time to treatment with intravenous iron. Secondary outcomes included recurrence of iron deficiency, need for repeat e-consult, conversion to in-person evaluation, and assessment of whether the etiology of iron deficiency was addressed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>E-consults significantly reduced the time from referral to intravenous iron repletion (e-consult, 33 days; traditional referral, 68 days; <i>p</i> &lt; .05). Assessment of the underlying etiology occurred in 70.7% of the e-consult encounters compared to 92.5% of traditional referrals (<i>p</i> &lt; .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight advantages of e-consults in improving care delivery in iron deficiency, and identifying gaps that can be improved through practice standardization to ensure equitable, high-value care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 5","pages":"614-622"},"PeriodicalIF":2.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An open-label, first-in-human, single agent, dose escalation study for the evaluation of safety and efficacy of SAR442085 in patients with relapsed or refractory multiple myeloma","authors":"Prashant Kapoor,&nbsp;Nitya Nathwani,&nbsp;Tomas Jelinek,&nbsp;Ludek Pour,&nbsp;Aurore Perrot,&nbsp;Meletios-Athanasios Dimopoulos,&nbsp;Shang-Yi Huang,&nbsp;Ivan Spicka,&nbsp;Saurabh Chhabra,&nbsp;Eben Lichtman,&nbsp;Maria-Victoria Mateos,&nbsp;Dheepak Kanagavel,&nbsp;Liang Zhao,&nbsp;Helene Guillemin-Paveau,&nbsp;Sandrine Macé,&nbsp;Helgi van de Velde,&nbsp;Paul G. Richardson","doi":"10.1111/ejh.14270","DOIUrl":"10.1111/ejh.14270","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi-centre, Phase 1, single-agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)-modified anti-CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc-gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study comprised two parts: Part-A (dose-escalation involving anti-CD38 mAb pre-treated and naïve patients) and Part-B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-seven heavily pre-treated patients were treated in Part A. Part-B (dose-expansion) was not studied. Seven dose-limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5–7·5 mg/kg. Most common treatment-emergent adverse events were infusion-related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti-CD38 mAb naïve and 4% in anti-CD38 pre-treated patients, with a median progression-free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The efficacy of SAR442085 was promising in anti-CD38 mAb naïve patients but did not extend to the larger cohort of anti-CD38 mAb pre-treated patients. This observation, along with transient high-grade thrombocytopenia, could potentially limit its clinical use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 5","pages":"593-605"},"PeriodicalIF":2.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment","authors":"Mandee Lines,&nbsp;Ryan M. Kemper,&nbsp;Jordan Wallace,&nbsp;Thomas Alexander,&nbsp;Carmen Echols,&nbsp;Lauren M. Garner,&nbsp;Jenna Bognaski Kaplan,&nbsp;Patrick Thompson,&nbsp;Daniel J. Crona,&nbsp;Kynlon Phillips","doi":"10.1111/ejh.14273","DOIUrl":"10.1111/ejh.14273","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/μL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed “skewed metabolism.” Allopurinol may potentially correct skewed 6MP metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Procedure</h3>\u0000 \u0000 <p>Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; <i>p</i> = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; <i>p</i> &lt; .0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 5","pages":"584-592"},"PeriodicalIF":2.3,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of large granular lymphocyte leukemia associated with variable common immunodeficiency disorders: A study of 12 cases","authors":"C. Gueuning,&nbsp;E. Lazaro,&nbsp;H. Dupuy,&nbsp;C. Leonard,&nbsp;C. Greib,&nbsp;C. Prot-Leurent,&nbsp;E. Riviere,&nbsp;J. F. Viallard","doi":"10.1111/ejh.14265","DOIUrl":"10.1111/ejh.14265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Common Variable Immunodeficiency Disorders (CVID) and Large Granular Lymphocytes leukemia (LGLL) exhibit diverse clinical manifestations including infections, dysimmunity, and lymphoproliferation. Recent decades have seen the discovery of new genes in the lymphopoiesis pathway, such as JAK–STAT. This case series supplemented by a literature review aims to describe clinical and biological characteristics of patients with both CIVD and LGLL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Patients were included through a call for comments to French and Belgian centers and through a literature review via PubMed. Clinical characteristics were compared to two large French cohort involving CVID and LGLL patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve patients were included. In all cases, CVID precedes LLGL (median diagnosis delay for LLGL was 7 years). Most cases presented with splenomegaly and autoimmune cytopenia. Ten out of 12 patients underwent splenectomy during follow up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with LGLL and CVID differ from patients without immune deficiency in term of clinical presentation and prognosis. We suggest CVID may act as a trigger of LGL lymphocytosis, due to endogenous and exogenous antigenic pressure leading to the selection of a dominant LGL clone and stimulation of the JAK–STAT pathway. The role of splenomegaly and splenectomy in LGLL onset warrant further investigation in future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 4","pages":"550-557"},"PeriodicalIF":2.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRP and sCD25 help distinguish between adult-onset Still's disease and HLH","authors":"Madelaine Beckett,&nbsp;Caroline Spaner,&nbsp;Mariam Goubran,&nbsp;John Wade,&nbsp;Juan Antonio Avina-Zubieta,&nbsp;Audi Setiadi,&nbsp;Lori Tucker,&nbsp;Kam Shojania,&nbsp;Sheila Au,&nbsp;Andre Mattman,&nbsp;Agnes Y. Y. Lee,&nbsp;David C. Fajgenbaum,&nbsp;Luke Y. C. Chen","doi":"10.1111/ejh.14267","DOIUrl":"10.1111/ejh.14267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Adult-onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D-dimer, C-reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D-dimer); interleukin-1/interleukin-6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a single-center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 μg/L vs. 29 020 μg/L, <i>p</i> = .01) while D-dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, <i>p</i> = .3). CRP was higher (median 168 mg/L vs. 71 mg/L, <i>p</i> &lt;.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, <i>p</i> = .004) in AOSD compared to HLH. The combined ROC curve using CRP &gt;130 mg/L and sCD25&lt; 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93–0.97) with sensitivity 91% and specificity 93%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 5","pages":"576-583"},"PeriodicalIF":2.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes with low dose anti-thymocyte globulin based graft versus host disease prophylaxis after mismatched unrelated donor allogeneic hematopoietic cell transplantation","authors":"Hafsah Chalchal,&nbsp;Vinita Dhir,&nbsp;Ashish Masurekar,&nbsp;Harold Atkins,&nbsp;Christopher Bredeson,&nbsp;Michael Kennah,&nbsp;Natasha Kekre,&nbsp;David Allan,&nbsp;Ram Vasudevan Nampoothiri","doi":"10.1111/ejh.14274","DOIUrl":"10.1111/ejh.14274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anti-thymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis is widely used for mismatched unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Although recent literature suggested improved outcomes with PTCy-based regimens when compared to ATG-based regimens these studies used doses of ATG ≥5 mg/kg. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower-dose ATG-based regimens at our center.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG-based regimens for all adults undergoing allogeneic HCT at The Ottawa Hospital from 2015 to 2022. Data regarding demographics, conditioning regimen, dose of ATG, rates of GVHD, duration of remission, and survival, were collected and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-seven (<i>n</i> = 77) patients (males 62.3%; median age 50 years) underwent allogeneic HCT from MMUD. Majority(81%; <i>n</i> = 63) received 2.5 mg/kg of rabbit ATG and remaining 18.2% (<i>n</i> = 14) received 4.5 mg/kg. Grade II-IV acute GVHD occurred in 24.7% (<i>n</i> = 19) while any chronic GVHD occurred in 32.5% (<i>n</i> = 25) patients. After a median follow-up of 21 months, relapse occurred in 28.6% of patients. Two-year OS, GRFS, CIR, and NRM were 60.6%, 45.3%, 16.9%, and 18.2% respectively. Dose of ATG (2.5 mg/kg vs. 4.5 mg/kg) was not associated with outcomes in either univariate or multivariate analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>When compared to published studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG may potentially lead to improved outcomes in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy-based regimens to determine ideal GVHD prophylaxis for these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 4","pages":"543-549"},"PeriodicalIF":2.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman–Diamond syndrome","authors":"Alejandra Lagos-Monzon,&nbsp;Stephanie Ng,&nbsp;Alice M. Luca,&nbsp;Hongbing Li,&nbsp;Mathura Sabanayagam,&nbsp;Mariana Benicio,&nbsp;Houtan Moshiri,&nbsp;Richard Armstrong,&nbsp;Chetan Tailor,&nbsp;Marion Kennedy,&nbsp;Eyal Grunebaum,&nbsp;Gordon Keller,&nbsp;Yigal Dror","doi":"10.1111/ejh.14260","DOIUrl":"10.1111/ejh.14260","url":null,"abstract":"<p>Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (<i>SBDS</i> and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human-derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of <i>SBDS</i> in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation-related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., <i>CHCHD2</i>) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 4","pages":"530-542"},"PeriodicalIF":2.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel biomarkers to identify complicated course of febrile neutropenia in hematological patients receiving intensive chemotherapy","authors":"Esa Jantunen,&nbsp;Sari Hämäläinen,&nbsp;Kari Pulkki,&nbsp;Auni Juutilainen","doi":"10.1111/ejh.14264","DOIUrl":"10.1111/ejh.14264","url":null,"abstract":"<p>Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%–10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C-reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow-up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q-SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 4","pages":"392-399"},"PeriodicalIF":2.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies","authors":"Eric Wenlong Li,&nbsp;Esther Jones,&nbsp;Christian Bryant,&nbsp;Tracy King,&nbsp;Dipti Talaulikar,&nbsp;Jun Yen Ng,&nbsp;Adam Bryant,&nbsp;Zainab Ridha,&nbsp;Nicole Wong Doo,&nbsp;Anna Menzies,&nbsp;Silvia Ling,&nbsp;Shir Jing Ho,&nbsp;Edward Abadir,&nbsp;Vinay Vanguru,&nbsp;Douglas Joshua,&nbsp;P. Joy Ho","doi":"10.1111/ejh.14266","DOIUrl":"10.1111/ejh.14266","url":null,"abstract":"<p>PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37–80), with a median of four (1–8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5–6.7) and 7.4 months (95% CI 6.4–10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6–13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4–39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 4","pages":"521-529"},"PeriodicalIF":2.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejh.14266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors of death or chronic renal replacement therapy requirements in patients with thrombotic microangiopathies without ADAMTS-13 deficiency","authors":"Miguel G. Uriol-Rivera,&nbsp;Bernardo López Andrade,&nbsp;Antonio Mas Bonet,&nbsp;Aina Obrador Mulet,&nbsp;Carmen Ballester Ruiz,&nbsp;Leonor Periañez Parraga,&nbsp;Javier Lumbreras,&nbsp;José Ignacio Ayestarán Rota,&nbsp;Mireia Ferreruela Servalos,&nbsp;Joana Ferrer Balaguer,&nbsp;Lucio Pallares Ferreres,&nbsp;María Jose Picado Valles,&nbsp;Rosa María Ruíz de Gopegui Valero,&nbsp;Susana Tarongi Sanchez,&nbsp;Ana Garcia Martin,&nbsp;Juan Rodríguez Garcia,&nbsp;Cristina Gomez Cobo,&nbsp;Daniel Ramis-Cabrer,&nbsp;the Son Espases Multidisciplinary Team for the management of Thrombotic Microangiopathy","doi":"10.1111/ejh.14261","DOIUrl":"10.1111/ejh.14261","url":null,"abstract":"<p>Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0–19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02–0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12–39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18–46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"113 4","pages":"510-520"},"PeriodicalIF":2.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}