EJHaem最新文献

{"title":"Real-world outcomes of intensive induction approaches in core binding factor acute myeloid leukemia","authors":"Alexandra E. Rojek,&nbsp;Benjamin J. McCormick,&nbsp;Joanna Cwykiel,&nbsp;Oluwatobi Odetola,&nbsp;Yasmin Abaza,&nbsp;Nhi Nai,&nbsp;Charles E. Foucar,&nbsp;Rohan K. Achar,&nbsp;Rory M. Shallis,&nbsp;Danielle Bradshaw,&nbsp;Meaghan Standridge,&nbsp;Vamsi Kota,&nbsp;Guru Subramanian Guru Murthy,&nbsp;Talha Badar,&nbsp;Anand A. Patel","doi":"10.1002/jha2.981","DOIUrl":"10.1002/jha2.981","url":null,"abstract":"<p>Core-binding factor acute myeloid leukemia (CBF-AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as a favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. The CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin (GO), is commonly added to intensive chemotherapy (IC) in CBF-AML. We sought to compare outcomes in patients treated with IC with or without GO in CBF-AML. We included 200 patients with CBF-AML treated with IC across seven academic centers. Induction treatment regimens were categorized as IC alone, IC with GO, or IC with KIT inhibitor (dasatinib or midostaurin). Median follow-up for the whole cohort was 2.5 years. Three-year overall survival (OS) was 70% and 3-year event-free survival (EFS) was 51%. Patients treated with IC with GO experienced a 3-year EFS of 50% compared to those treated with IC alone who experienced a 3-year EFS of 47%, with no statistically significant difference (<i>p</i> = 0.62). Similarly, those treated with IC with GO did not experience an improved OS compared to those treated with IC alone (<i>p</i> = 0.67). Patients treated with IC with KIT inhibitor experienced a significantly improved 3-year EFS of 85% compared to those with IC with or without GO (<i>p</i> = 0.04). We find in our study that there is no survival benefit in patients treated with IC with the addition of GO; improved EFS was seen in patients with CBF-AML treated with IC plus KIT inhibitors, consistent with outcomes noted in prospective studies utilizing this approach.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"728-737"},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.981","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141809005","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":"Carfilzomib use in patients with relapsed/refractory multiple myeloma in France: A national retrospective cohort study","authors":"Cyrille Hulin,&nbsp;Nadia Quignot,&nbsp;Heng Jiang,&nbsp;Hakima Mechiche,&nbsp;Gaëlle Désaméricq","doi":"10.1002/jha2.946","DOIUrl":"10.1002/jha2.946","url":null,"abstract":"<p>Carfilzomib is a proteasome inhibitor that has been shown to improve progression-free survival and overall survival (OS) in patients with relapsed/refractory multiple myeloma (RRMM) [<span>1-3</span>]. In Europe, carfilzomib is approved for the treatment of patients with RRMM in combination with dexamethasone (Kd); lenalidomide and dexamethasone (KRd); and, since 2020, daratumumab and dexamethasone (D-Kd) [<span>4-6</span>]. A recent observational cohort study described the use of KRd and Kd across Europe and Israel [<span>7, 8</span>], but survival data in the real-world setting have not been reported for carfilzomib-treated patients in Europe. Using and expanding on a previous study of patients with RRMM from the Système Nationale des Données de Santé (SNDS) national claims database [<span>9</span>], this comprehensive real-world analysis describes the treatment patterns and outcomes of patients receiving carfilzomib (KRd and Kd) in France between 2016 and 2019.</p><p>Briefly, adults who were diagnosed with multiple myeloma and had received at least one dose of carfilzomib between 2014 and 2019 were included. The study design has previously been published [<span>9</span>]; this study extension had an end date of December 31, 2019. Carfilzomib became available in France in 2016 under an Authorization for Temporary Use, and then became fully available in July 2018. For each patient, data were collected on clinical characteristics and were analysed as a primary objective. Data on treatment patterns were also analysed. OS and time-to-next treatment (TTNT) were estimated in an exploratory analysis. OS was defined as the time from the start of carfilzomib treatment until death or the end of follow-up. TTNT was defined as the start of carfilzomib treatment until the initiation of the next line of treatment or death.</p><p>The database included 2471 patients treated with carfilzomib-based regimens. Clinical characteristics are presented by treatment group (KRd or Kd) and treatment line (second line [2L], third line [3L], and fourth or later lines [4L+]) in Table 1. Overall, 40% (<i>n</i> = 993) of patients received KRd. Half of patients (<i>n</i> = 497; 50%) receiving KRd initiated it as a 2L treatment, and 44%–60% had autologous stem cell transplantation (ASCT) at first line (1L). Most patients (<i>n</i> = 1478; 60%) received the Kd regimen, which was generally initiated as 4L+ (<i>n</i> = 1133; 77%). Among patients receiving Kd at 4L+, 40% had ASCT at 1L and most had previous exposure to bortezomib (98%), lenalidomide (91%), or daratumumab (60%) (Table 1).</p><p>Patients receiving KRd were followed up for a mean of 11–15 months. The median OS estimates for patients receiving KRd were 40, 39, and 16 months at 2L (<i>n</i> = 497), 3L (<i>n</i> = 203), and 4L+ (<i>n</i> = 293), respectively. For patients initiating KRd in 2018, the median TTNT was longer when carfilzomib was received at earlier lines than later lines (2L, 14 months; 3L, 11 months; 4L","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"887-891"},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810259","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":"Catastrophic venous and arterial thrombosis in a young female with cervical cancer","authors":"Jordan Burgess,&nbsp;Fraser Hendry,&nbsp;Catherine Bagot,&nbsp;Brian Doherty","doi":"10.1002/jha2.973","DOIUrl":"10.1002/jha2.973","url":null,"abstract":"<p>A 31-year-old woman presented with progressive left arm, and neck swelling 2 weeks after a blood transfusion via a cannula in her left antecubital fossa, for severe menorrhagia. Imaging (Figure 1) demonstrated extensive deep vein thrombosis of the left arm extending to the skull base (top left image), extensive bilateral pulmonary emboli, and prominent, subcentimeter para-aortic and bilateral pelvic lymph nodes. The D-dimer level was significantly elevated at 46,212 ng/mL (0‒230). She was immediately started on apixaban.</p><p>Two weeks later, she presented with progressive headache and visual loss and was diagnosed with a left sigmoid sinus thrombus, a short segment occlusion of the left middle cerebral artery (bottom left image) and bilateral parieto-occipital infarction (middle left image). The strokes manifested as cortical blindness and aphasia. There were no concerns regarding the patient's compliance with apixaban; an anti-Xa apixaban level confirmed that she had taken a recent dose. The patient was switched to twice daily enoxaparin, aiming for a peak anti-Xa level of 1.0‒1.2 U/mL. Aspirin 75 mg daily was also initiated.</p><p>She was urgently investigated for possible causes of this severe prothrombotic state, including catastrophic anti-phospholipid syndrome, thrombotic thrombocytopenic purpura, myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, and auto-immune heparin-induced thrombocytopenia, all of which were negative. A further total body computed tomography demonstrated no change in the lymph node features but revealed new splenic and renal infarcts. On transthoracic echocardiogram, a thrombus was visible on both the tricuspid and mitral valves. In the absence of an identifiable cause, positron emission tomography was performed, demonstrating uptake in the cervix (right-sided image), para-aortic lymph nodes and peritoneal deposits. A cervical biopsy confirmed a diagnosis of metastatic cervical adenocarcinoma that was positive for high-risk human papillomavirus (HPV)45. Interestingly, cervical screening was HPV negative 20 months prior to this presentation. The patient unfortunately died shortly after commencing palliative chemotherapy.</p><p>Cancer is a hypercoagulable state associated with a sevenfold increase in venous thromboembolism; however, the association with arterial thromboembolism is less well-established [<span>1</span>]. Mucin-producing adenocarcinomas are one of the most common tumours associated with venous thromboembolism (VTE) [<span>2</span>] since mucin directly stimulates platelet activation [<span>3</span>]. Patients with cervical cancer have a higher cumulative risk of VTE as compared to the general population [<span>4</span>]. The incidence of thromboembolism has been demonstrated to be highest during chemotherapy [<span>5</span>].</p><p>Jordan Burgess wrote the paper. Fraser Hendry supplied images and performed interpretation of radiological findings. Catherine Bagot helped in writing the ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"879-880"},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141813039","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":"Treatment comparison of hydroxyurea versus ruxolitinib in essential thrombocythaemia: A matched-cohort analysis","authors":"Michael R. Grunwald,&nbsp;Ellen K. Ritchie,&nbsp;Elisa Rumi,&nbsp;Albert Assad,&nbsp;J. E. Hamer-Maansson,&nbsp;Jingbo Yu,&nbsp;Tricia Kalafut,&nbsp;Evan Braunstein,&nbsp;Francesco Passamonti","doi":"10.1002/jha2.954","DOIUrl":"10.1002/jha2.954","url":null,"abstract":"<p>Hydroxyurea is the preferred first-line cytoreductive treatment for high-risk essential thrombocythaemia (ET), but many patients are intolerant or refractory to hydroxyurea. Ruxolitinib has been shown to improve symptoms in patients with ET. This post hoc analysis compared the clinical outcomes of patients with ET who received hydroxyurea only with those who switched from hydroxyurea to ruxolitinib due to intolerance/resistance to hydroxyurea. Patients with ET refractory/intolerant to hydroxyurea treated with ruxolitinib in a completed phase 2 study (HU-RUX) were propensity score matched with patients who received hydroxyurea only in an observational study (HU). Changes in leukocyte and platelet counts were reported at 6-month intervals during the 48-month follow-up. Following propensity score matching, 37 patients were included for analysis in each cohort. Mean (standard deviation [SD]) leukocyte and platelet counts at index were higher for HU-RUX versus HU (leukocyte: 9.3 [5.1] vs. 6.8 [3.1] × 10⁹/L; platelet: 1027.4 [497.8] vs. 513.9 [154.7] × 10⁹/L), both of which decreased significantly from index to 6 months through to 48 months in HU-RUX (mean [SD] change from index at 6 months—leukocyte: −1.8 [4.6] × 10⁹/L; platelet: −391.7 [472.9] × 10⁹/L; at 48 months—leukocyte: −3.8 [5.3] × 10⁹/L; platelet: −539.0 [521.8] × 10⁹/L), but remained relatively stable in HU (mean [SD] change from index at 6 months—leukocyte: 0 [1.8] × 10⁹/L; platelet: −5.7 [175.3] × 10⁹/L; at 48 months—leukocyte: −0.1 [2.7] × 10⁹/L; platelet: −6.9 [105.1] × 10⁹/L). In conclusion, these results demonstrate that switching from hydroxyurea to ruxolitinib in patients with ET who are intolerant or refractory to hydroxyurea could improve abnormal haematologic values similar to those who receive first-line hydroxyurea.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"778-783"},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.954","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141822784","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":"Successful management with urgent haploidentical-peripheral blood stem cell transplantation for a patient with severe aplastic anaemia who developed disseminated fungal infection following immunosuppressive therapy","authors":"Norihito Ikenobe,&nbsp;Kentaro Fujimori,&nbsp;Yoshihiro Gocho,&nbsp;Shota Myojin,&nbsp;Masaki Yamada,&nbsp;Kenichi Imadome,&nbsp;Mikiko Miyasaka,&nbsp;Osamu Miyazaki,&nbsp;Akihiro Yoneda,&nbsp;Shotaro Matsumoto,&nbsp;Satoshi Nakagawa,&nbsp;Takao Deguchi,&nbsp;Akihiro Iguchi,&nbsp;Daisuke Tomizawa,&nbsp;Chikara Ogimi,&nbsp;Kimikazu Matsumoto,&nbsp;Hirotoshi Sakaguchi","doi":"10.1002/jha2.917","DOIUrl":"10.1002/jha2.917","url":null,"abstract":"<p>Urgent haploidentical haematopoietic cell transplantation may be considered in cases of severe aplastic anaemia (SAA) without a human leukocyte antigen-matched donor and suffering from severe infection. However, deciding on allogeneic transplantation in the setting of active systemic infection is challenging due to poor outcomes. This report presents a case of disseminated <i>Magnusiomyces capitatus</i> infection in a 5-year-old male who underwent immunosuppressive therapy for hepatitis-associated SAA. To address the critical situation, granulocyte transfusion was promptly administered from the patient's mother, followed by unmanipulated haploidentical peripheral blood stem cell transplantation from the patient's father with posttransplant cyclophosphamide, ultimately resulting in successful rescue.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1072-1075"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141830435","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":"Implications of acute coronavirus disease 2019 during haematopoietic stem cell transplantation—Experience from real-world clinical practice","authors":"Christopher Shwei Wen Tham,&nbsp;Jeffrey Quek,&nbsp;Yeh Ching Linn,&nbsp;Lawrence Ng,&nbsp;Aloysius Ho,&nbsp;Francesca Lim,&nbsp;Yunxin Chen,&nbsp;Chandramouli Nagarajan,&nbsp;William Hwang,&nbsp;Jing Jing Lee,&nbsp;Gina Gan,&nbsp;Shimin Jasmine Chung,&nbsp;Ban Hock Tan,&nbsp;Thuan Tong Tan,&nbsp;Hein Than","doi":"10.1002/jha2.978","DOIUrl":"10.1002/jha2.978","url":null,"abstract":"<p>The impact of community-acquired respiratory viral infections (CARVIs) in the transplant population has been highlighted by the recent coronavirus disease 2019 (COVID-19) pandemic. Patients undergoing haematopoietic stem cell transplantation (HCT) following acute COVID-19 experienced significant morbidity and mortality. Few guidelines and reports suggest that HCT is deferred during persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity during and after infection, and is feasible only in fully recovered patients [<span>1, 2</span>]. However, those with high-risk haematological malignancies often progress and succumb to their disease without timely HCT. These two opposing pressures must therefore be reconciled, yet data are sparse on the optimal timing and safety of HCT that needs be performed during or immediately following acute COVID-19 infection.</p><p>In this study at Singapore General Hospital, the largest tertiary transplant centre in Singapore, the outcome of patients who underwent HCT following COVID-19 in the preceding 120 days or with active COVID-19 infection during transplant was analysed. A retrospective analysis of transplant-related outcomes in consecutive patients admitted for planned HCT between September 2021 and April 2022 was conducted. COVID-19 was detected by SARS-CoV-2 RNA by polymerase chain reaction (PCR) on nasopharyngeal swab. Patients diagnosed with COVID-19 within 120 days prior to stem cell infusion were included in the study.</p><p>We identified 10 allogeneic and 1 autologous HCT patients. Median interval between diagnosis of COVID-19 to HCT infusion was 53 days (range 1–118). Median duration of COVID-19 infection (defined by time to negative PCR) was 20 days. Six patients tested negative by PCR and 2 were prolonged low-level viral shedders, prior to HCT. Two patients were diagnosed with COVID-19 while receiving conditioning chemotherapy prior to HCT infusion, at days −1 and −3, respectively.</p><p>All allogeneic HCT patients were fully vaccinated with two doses of mRNA vaccines (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) prior to infection. Median receptor binding domain IgG serology titre (Abbott assay) in vaccinated patients was 1301 AU/mL at the time of COVID-19 diagnosis. COVID-19 disease severity by National Institutes of Health (NIH) guidelines [<span>3</span>] was mild in nine patients, moderate in one patient and critical in one patient. Eight patients received antivirals with or without concurrent monoclonal antibodies (mab; sotrovimab, <i>n</i> = 4; casirivimab–imdevimab, <i>n</i> = 1).</p><p>Patient characteristics and outcomes are summarised in Table 1, and transplant-related details are provided in Supporting Information Table 1. Two patients died of non-relapse pulmonary complications on days +43 and +50 post-HCT. There were no instances of grade III–IV acute graft versus host disease and no evidence of SARS-CoV-2 reinfection or late complications, or increase in vira","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"907-910"},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.978","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141653604","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":"Comment on “Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients”","authors":"Hinpetch Daungsupawong,&nbsp;Viroj Wiwanitkit","doi":"10.1002/jha2.976","DOIUrl":"10.1002/jha2.976","url":null,"abstract":"<p>Dear Editor,</p><p>We would like to share ideas on the publication “Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients [<span>1</span>].” Researchers compared patients based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology in order to examine the outcomes of hematologic malignancy (HM) patients with SARS-CoV-2 infection from January 2022 to March 2023 in this retrospective single-center analysis. Of the 112 patients in the research, 39% had a negative serology for SARS-CoV-2. Comparing seronegative individuals to seropositive patients, the findings showed that the former were older, had a higher likelihood of a lymphoid neoplasm, had anti-CD20 medication, and had a more severe illness. Additionally, a Kaplan–Meier study revealed that patients who tested negative for COVID-19 were more likely to experience respiratory failure, require mechanical ventilation, and die from the virus.</p><p>This study's retrospective approach, which can create biases and restrictions in data collection and analysis, is one of its drawbacks. Furthermore, the research was carried out at a single facility, which can restrict how broadly the results can be applied to other demographics. Additionally, it is possible that the sample size of 112 patients was insufficient to make firm conclusions, particularly when comparing the outcomes of HM patients who were seronegative and those who were seropositive. Furthermore, the study did not look into any confounding factors that might have affected the patients' results.</p><p>Conducting a bigger multicenter prospective study to validate the results of this study and improve the generalizability of the results could be one of the next directions for this area of research. Furthermore, analyzing the effects of various treatment modalities on outcomes in SARS-CoV-2-infected HM patients may offer insightful information for clinical practice. Furthermore, investigating the immune response and its impact on illness outcomes and progression in seronegative HM patients may aid in deciphering the underlying processes of COVID-19 in this particular cohort. Last but not least, examining the long-term consequences of COVID-19 for HM patients, such as the likelihood of relapse and late sequelae, may yield crucial data for patient management and post-treatment care.</p><p><i>Ideas, writing, analyzing, and approval (50%)</i>: Hinpetch Daungsupawong. <i>Ideas, supervision, and approval (50%)</i>: Viroj Wiwanitkit.</p><p>The authors declare no conflicts of interest.</p><p>The authors received no specific funding for this work.</p><p>The authors have confirmed that ethical approval statement is not needed for this submission.</p><p>The authors have confirmed that patient consent statement is not needed for this submission.</p><p>The authors h","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"905-906"},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141654991","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":"Targeted management of coexistent severe thrombophilias—A case report of a successful pregnancy despite paroxysmal nocturnal hemoglobinuria and hereditary protein C deficiency","authors":"Julien Dereme,&nbsp;Matthew Goodyer,&nbsp;David Baud,&nbsp;Lorenzo Alberio,&nbsp;Francesco Grandoni,&nbsp;Mathilde Gavillet","doi":"10.1002/jha2.972","DOIUrl":"10.1002/jha2.972","url":null,"abstract":"<p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by the absence of complement regulatory proteins on the surface of erythrocytes, leading to intravascular hemolysis and thrombosis. Managing PNH during pregnancy poses significant challenges due to increased risks of morbidity and mortality. This case report describes the detailed obstetric course of a 44-year-old woman with PNH and additional hereditary protein C deficiency who had previously experienced multiple thrombotic events and adverse pregnancy outcomes (two early miscarriages and one stillbirth at 25 weeks gestation [WG]), treated with eculizumab (terminal C5 inhibitor) and optimal anticoagulation management. Close monitoring of hemolysis and hemostasis parameters was conducted throughout the gestation period together with increased obstetrical surveillance. The pregnancy progressed without thrombotic complications or breakthrough hemolysis, and the patient delivered a healthy newborn at 36 WG after induction of labor due to restricted fetal growth. To the best of our knowledge, this is the first reported case of a positive pregnancy outcome despite PNH in conjunction with hereditary thrombophilia. This case report highlights the importance of a multidisciplinary approach involving hematologists and obstetricians in the management of pregnant women with PNH. Tailored therapy, close monitoring, and comprehensive care are crucial to minimize risks and optimize outcomes.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"1048-1052"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141657097","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":"Fludarabine, busulfan, and melphalan conditioning regimen in allogeneic hematopoietic stem cell transplantation for adult patients with myeloid malignancies: A multicenter retrospective study","authors":"Jieling Jiang,&nbsp;Xiaofan Li,&nbsp;Dong Wu,&nbsp;Quanyi Lu,&nbsp;Kourong Miao,&nbsp;Houcai Wang,&nbsp;Xiaoping Li,&nbsp;Yingnian Chen,&nbsp;Shiyuan Zhou,&nbsp;Yali Zhou,&nbsp;Guiping Liao,&nbsp;Chuanhe Jiang,&nbsp;Xiaohong Yuan,&nbsp;Youshan Zhao,&nbsp;Chunkang Chang,&nbsp;Jie Chen,&nbsp;Han Zhu,&nbsp;Ruye Ma,&nbsp;Nainong Li,&nbsp;Xiaolin Yin,&nbsp;Xiaojin Wu,&nbsp;Sanbin Wang,&nbsp;Chun Wang,&nbsp;Jiong Hu","doi":"10.1002/jha2.947","DOIUrl":"10.1002/jha2.947","url":null,"abstract":"<p>Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m²), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m²) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML <i>n</i> = 171, MDS-IB-1 or 2 <i>n</i> = 44, CMML <i>n</i> = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; <i>p</i> = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; <i>p</i> = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; <i>p</i> = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, <i>p</i> = 0.045; HR = 3.64, 95%CI 1.40-9.44, <i>p</i> = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, <i>p</i> = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"757-767"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.947","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141669474","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":"“Fast but not so furious”: A condensed step-up dosing schedule of teclistamab for relapsed/refractory multiple myeloma","authors":"Kevin C. Graf,&nbsp;James A Davis,&nbsp;Alyssa Cendagorta,&nbsp;Katelynn Granger,&nbsp;Kelly J. Gaffney,&nbsp;Kimberly Green,&nbsp;Brian T Hess,&nbsp;Hamza Hashmi","doi":"10.1002/jha2.906","DOIUrl":"10.1002/jha2.906","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific T-cell engager approved for relapsed-refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) are well-documented treatment -related adverse events of teclistamab. The prescribing information recommends step-up dosing on days 1, 4, and 7 with 48–72 h of inpatient observation after each dose to monitor for CRS. This leads to a more than weeklong hospital stay, adding to the cost of therapy, resource utilization, and patient inconvenience. Here, we present a single center retrospective analysis addressing the safety and utility of a condensed step-up dosing schedule for teclistamab. All patients who were treated with teclistamab from November 2022 to August 2023 at the Medical University of South Carolina were included in the analysis. Patients received subcutaneous (SC) teclistamab with step-up doses (0.06 and 0.3 mg/kg) separated by either 2 or 3 (48–72 h) before the administration of the first full (1.5 mg/kg) dose (days 1, 3, and 5 ‘condensed’ schedule or days 1, 4, and 7 ‘standard’ schedule, respectively). All patients were hospitalized for the two step-up doses and first full dose of teclistamab and received pre-medications prior to each dose. Patients could be discharged after a minimum of 24 h following the full dose, if they did not have any CRS or ICANS. Relevant data regarding incidence, severity, and onset of CRS was collected. Statistical analysis was completed to assess the probability of fever with the first full dose of teclistamab based on incidence of fever with previous doses. A total of 25 patients were included in the analysis. Twenty-eight percent (7/25) of patients underwent the standard step up while the remaining 72% (18/25) underwent a condensed step up of teclistamab. More than half (53%, 13/25) of the patients experienced CRS during step up dosing. Grades 1 and 2 CRS occurred in 48% (12/25) and 4% (1/25) patients, respectively. Of the 13 patients that experienced CRS, 30% (4/13) fevered with the first dose, 84% (11/13) fevered with the second dose, and one patient developed fever after the third dose. The negative predictive value of being ‘fever free’ after doses 1 and 2 and remaining ‘fever free’ throughout hospitalization was 0.92. The median length of hospital stay among the 1, 3, and 5 step up group was 6 days (6–25) and 70% (14/20) of patients were discharged from the hospital within 7 days of treatment initiation. This report demonstrates the utility of a condensed step-up schedule for teclistamab initiation. The schedule was found to be safe and reduced hospital length of stay. These results should prompt consideration of shorter hospital stays for patients who do not experience CRS and raise the possibility of outpatient administration with close observation.</p>\u0000 </","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 4","pages":"793-797"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141667539","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}