EJHaem最新文献

Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real-world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia-Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow-up time of 29.5 months (interquartile range 13.3–54.3 months) were included in the analysis – 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in-situ hybridisation status, receive first-line myeloma treatment with immunomodulatory drugs or anti-CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow-up (adjusted hazard ratio 0.72, 95% CI 0.46–1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 10⁹/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure. Forty-three participants (18.8% of those eligible) were recruited, with 41 eligible for analysis. Post-procedure bleeding occurred in one of 22 (4.5%) in the placebo arm and zero of 19 in the desmopressin arm. Despite liberal inclusion criteria, there were significant feasibility challenges recruiting patients in the critical care setting prior to invasive procedures.

We present a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome who had a dramatic and sustained elevation in plasma vascular endothelial growth factor (VEGF) levels from 182 to 740 pg/mL while on lenalidomide-dexamethasone therapy. Given his biochemical evidence of progression, second-line daratumumab was added. In hindsight, a concurrent influenza A infection was the likely driver of his VEGF elevation rather than his underlying POEMS syndrome. Given the importance of longitudinal VEGF monitoring and the infectious risks of plasma cell therapies, our case highlights the need for caution with POEMS response assessments in the setting of a respiratory viral infection.

The incidence of multiple myeloma (MM) has surged globally, particularly in Latin American countries, and is attributable to an aging population and increased life expectancy. This systematic review analyzes the epidemiology, patient characteristics, and treatment outcomes for MM in selected Latin American countries: Brazil, Mexico, Colombia, Argentina, Chile, Peru, and Uruguay. PubMed and the Latin American and Caribbean Health Sciences Literature (LILACS), conference abstracts (between June 2019 and June 2022), and GLOBOCAN registry (January 2010 to June 2022) were electronically searched. Qualitative analysis employed the Joanna Briggs Institute's critical appraisal tool. Among the 586 screened articles, 26 met the inclusion criteria. The participants’ median age ranged from 54 to 67 years. GLOBOCAN data revealed that for MM, Brazil and Uruguay had the highest and lowest incidence, 5-year prevalence, and mortality, respectively. Immunoglobulin G was the most common subtype detected. Stage III was frequently diagnosed. Though many approved drugs are available and bispecific antibodies hold promise as a future therapy, limited access, especially for CAR-T cell-based therapy remains a concern. The incidence of MM is increasing in Latin America. Resource constraints and costs hinder access to novel drugs and regimens. Understanding disease patterns and patient characteristics is vital to improve MM management in these countries.

Caplacizumab reduces the need for therapeutic plasma exchange (TPE) during treatment for thrombotic thrombocytopenic purpura (TTP), associates with fewer required TPE, and shortens hospital stay. It is therefore recommended as part of standard care. However, the treatment effects on hemostasis may complicate initial management. We present a case of a woman with immune-mediated TTP who developed an intrathoracic hemorrhage on caplacizumab treatment after replacement of her central venous catheter. Reduced von Willebrand factor (vWF):glycoprotein Ib mutant (GPIbM) activity was reversed using vWF concentrate and the bleeding stopped. Unfortunately, vWF substitution in combination with caplacizumab discontinuation likely contributed to subsequent extensive venous thromboembolism. Risk-reducing strategies against both bleeding and thrombosis are crucial during caplacizumab treatment, and emergency vWF substitution increases the already high risk of thrombosis associated with TPE.

A 26-year-old man was diagnosed with B/T-type mixed-phenotype acute leukemia (MPAL-B/T) based on blasts being positive for CD19, cytoplasmic CD3, and cyCD79a, but negative for myeloperoxidase. Acute lymphoblastic leukemia-based chemotherapy was started, but the leukemia was refractory. He underwent cord blood transplantation with the conditioning regimen of total body irradiation plus cyclophosphamide and cytarabine with granulocyte-colony stimulating factor priming. Prophylaxis for graft versus host disease was performed with short-term methotrexate and cyclosporin. The leukemia relapsed in bone marrow 20 months later. At that time, he was treated with inotuzumab ozogamicin because the blasts expressed CD22 (75.4%), but this was ineffective. He was next administered blinatumomab with dexamethasone pretreatment, resulting in a complete remission (CR). He subsequently underwent human leukocyte antigen-haploidentical peripheral blood stem cell transplantation. He has still maintained a CR for 12 months. Blinatumomab might be a promising treatment and a bridge to stem cell transplantation even in relapsed/refractory CD19-expressing MPAL-B/T.

Several non-coding RNAs are known to be associated with the pathobiology and progression of multiple myeloma (MM). ciRS-7 (also known as CDR1-AS), a key oncogenic circular RNA (circRNA) that sponges miR-7-5p and other cancer-related microRNAs, was recently found to be downregulated in malignant plasma cells resistant to immunomodulatory drugs. Considering that various circRNAs have a strong potential as molecular biomarkers, we aimed to investigate the expression of ciRS-7 in plasma cell disorders, assess its prognostic importance in MM, and compare these findings with those of individuals with smoldering MM (SMM) and monoclonal gammopathy of unknown significance (MGUS). This study included 171 patients (110 newly diagnosed MM, 34 SMM, and 27 MGUS cases), from which bone marrow aspirate samples were collected for CD138+ plasma cell selection. Total RNA was reversely transcribed using random hexamer primers, and the expression levels of ciRS-7 were quantified using an in-house-developed protocol that includes pre-amplification and real-time quantitative polymerase chain reaction. ciRS-7 levels were found to significantly differ among CD138+ plasma cells of MM, SMM, and MGUS patients. ROC analysis indicated that ciRS-7 expression effectively distinguishes between MM and SMM patients. Moreover, high levels of ciRS-7 were associated with unfavorable prognosis in MM, independently of MM patients’ age and Revised International Staging System stage. Additionally, in silico analysis predicted the binding of 85 microRNAs to ciRS-7. In conclusion, this study provides novel insights into the role of ciRS-7 as a promising molecular marker able to distinguish MM from SMM and predict prognosis in MM.

Ashouri K, Chennapan K, Martynova A, Nazaretyan S, Ali A, Ginosyan AA, et al. “Post-stem cell transplant maintenance in FLT3^mut acute myeloid leukemia – A retrospective analysis: Outcomes are improved with midostaurin but not with gilteritinib.” Eur J Haematol. 2024;5(2):423–27. https://doi.org/10.1002/jha2.885

The title of the letter should read “Post-hematopoietic stem cell transplant FLT3 inhibitor maintenance therapy improves outcomes in acute myeloid leukemia: Real-world insights and clinical implications.”

We apologize for this error.

Novel treatments in multiple myeloma (MM) could influence the incidence of skeletal-related events (SREs). We aimed to examine the incidence of SRE and the preventive use of osteoclast inhibitors (OIs) in a cohort of MM patients in the era of modern treatment. In this real-world retrospective study, we included 199 patients with a diagnosis of MM between January 1, 2010, and December 31, 2019, with follow-up at St. Olavs University Hospital. Data was extracted from The Myeloma Registry of Central Norway. SREs occurred in 46% of patients at baseline and 55.8% during follow-up. Excluding baseline SREs, the incidence rate was 29 (95% confidence interval: 26–33) per 100 person years. 48% experienced > 1 SRE. The incidence of SREs was highest at baseline followed by a gradual increase in each subsequent line of treatment. The first two years after diagnosis 80% received bisphosphonates (BPs). The proportion of recommended dosage was 46%. Only two cases (1.2%) of symptomatic hypocalcemia and one case (0.6%) of osteonecrosis of the jaw were identified. SREs are still a common problem in an era of novel treatment. Cumulative dosage of BPs was lower than recommended, and treatment with BPs was safe in this population.

Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen-specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA-1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023–2024 COVID-19 vaccination campaign.