A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64–2.87), with >1 comorbidity (2.44, 1.85–3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19–2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2–0.37) or BA.4/BA.5 (0.13, 0.08–0.19) periods and among patients vaccinated with one or two (0.51, 0.34–0.75) or three or four (0.22, 0.16–0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03–3.25) and Omicron (3.19, 95% CI 1.59–6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

Background: Patients with B-lymphocyte malignancies (BCMs) receiving B-lymphocyte-targeted therapies have increased risk of severe COVID-19 outcomes and impaired antibody response to SARS-CoV-2 mRNA vaccination in comparison to non-hematologic oncologic patients or general population. Consequently, it is vital to explore vaccine-induced T-lymphocyte responses in patients referred for the understanding of immune protection against SARS-CoV2 infections. The objective of the present study was to analyze the recall immune responses carried out by T lymphocytes after two COVID-19 mRNA vaccine doses. Methods: We enrolled 40 patients with BCMs and 10 healthy controls (HCs) after 4 weeks from the second mRNA vaccine dose. Spike (S)-specific T-lymphocyte responses were assessed in peripheral blood mononuclear lymphocytes (PBMCs) by intracellular IFN-γ staining combined with flow cytometry. Furthermore, the humoral response was assessed with the measurement of anti-spike antibodies. Results: From March to July 2021, 40 patients (median age 68) received mRNA vaccines. The overall antibody response for BCMs was 52.5% versus 100% for the healthy controls (p = 0.008). The antibody response was different across BCMs: 18.75% for non-Hodgkin lymphoma, 54.5% for chronic lymphocytic leukemia, and 92.3% for multiple myeloma. Responses varied by malignancy type and treatment, with anti-CD20 therapies showing the lowest response (6.7%). T-lymphocyte analysis revealed reduced numbers and altered differentiation stages in patients compared to the controls. However, the vaccine-induced T response was generally robust, with variations in specific T subpopulations. Conclusions: mRNA vaccines induced significant humoral and cellular immune responses in B-cell lymphoid malignancy patients, although responses varied by treatment type and malignancy. Further research is needed to optimize vaccination strategies in this population.

Background: Human metapneumovirus (hMPV) is an increasingly recognized respiratory pathogen in immunocompromised patients, but its impact in haematological malignancies is poorly defined. Unlike influenza or SARS-CoV-2, hMPV has no specific treatment or vaccine, contributing to underdiagnosis and underestimation of its clinical relevance. Method: We performed a multicentre retrospective cohort study within the Epidemiology of COVID-19 in patients with hematological malignancies: A European Haematology Association Survey/ Epidemiology of respiratory viral infections in patients with hematological malignancies: A European Haematology Association Survey registry of haematological patients with hMPV (January 2023–December 2024), comparing clinical features and outcomes with matched influenza and SARS-CoV-2 cohorts. Results: The study included 130 patients with hMPV. Median age was 58.5 years; 57% were male. Plasma cell neoplasms (25%), lymphoma (23%), and acute myeloid leukemia (20%) were the most common hematological malignancies. Hospitalization occurred in 64%, intensive care unit (ICU) admission in 19%, and 30-day mortality was 8%. Most cases (73%) received supportive care only. Secondary infections were common (24%). Chronic renal disease significantly increased mortality risk (hazard ratio 20.9 11.05, P = .014). Compared with influenza and SARS-CoV-2, hMPV patients had comparable severity and outcomes, with 18.5% ICU admission rates versus 25.9% for influenza (P = .316) and 20.9% versus 4.7% for SARS-CoV-2 (P = .006), and 30-day mortality of 5.6% versus 11.1% for influenza (P = .489) and 7.0% versus 2.3% for SARS-CoV-2 (P = .277), yet received fewer targeted interventions. Conclusions: hMPV causes clinically significant disease in patients with hematological malignancy, often necessitating hospital and ICU care, and leading to mortality. In the absence of specific treatments or vaccines, this virus remains an underrecognized pathogen in patients with hematological malignancy. Enhanced clinical awareness and investment in diagnostics, prevention, and therapeutics are needed.

The familial occurrence of hematological malignancies has been underappreciated. Recent studies suggest that up to 15% of adults with myeloid neoplasms carry germline pathogenic variants in cancer-predisposing genes. This study aimed to identify the underlying germline predisposition variant in patients with a strong family or personal onco-hematological history using whole exome sequencing on sixteen uncharacterized individuals. It was carried out in two groups of patients, one with samples available from two affected relatives (Cohort A) and one with available samples from the index case (Cohort B). In Cohort A, six families were characterized. Two families shared variants in genes associated with DNA damage response and involved in cancer development (CHEK2 and RAD54L). Pathogenic or likely pathogenic germline variants were also found in novel candidate genes (NFATC2 and TC2N). In two families, any relevant pathogenic or likely pathogenic genomic variants were identified. In Cohort B, four additional index cases were analyzed. Three of them harbor clinically relevant variants in genes with a probable role in the development of inherited forms of hematological malignancies (GATA1, MSH4 and PRF1). Overall, whole exome sequencing is a useful approach to achieve a further characterization of these patients and their mutational spectra. Moreover, further investigations may help improve optimization for disease management of affected patients and their families.

To describe the impact of adding a tyrosine kinase inhibitor (TKI) to intensive chemotherapy (IC) on the outcome of de novo BCR::ABL1+ acute myeloid leukemia (AML), we retrospectively analyzed the data of 212 adult AML with ≥20% bone marrow blasts, BCR::ABL1+ or t(9;22)(q34.1;q11.2), no history of previous chronic myeloid leukemia and no prior exposure to BCR-ABL1 TKI. Eighty-nine patients were treated with IC alone and 123 with IC+TKI between 1999 and 2024. Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 52/77 patients (68%) with IC and 110/123 patients (89%) with IC+TKI (P<0.0001). With a median follow-up of 66.7 months, the median overall survival (OS) was 20.5 months with IC and not reached with IC+TKI. The 3-year and 5-year OS rates were 42.1% and 38.5% with IC and 70.9% and 62.9% with IC+TKI (P<0.0001) respectively. In multivariate analyses, the addition of TKI to IC was significantly and independently associated with an improved CR/CRi rate (odds ratio: 4.74 [95% confidence interval: 2.17-10.35]; P<0.001) and OS (hazard ratio: 0.40 [0.27-0.62]; P<0.001). Also, adding TKI to IC and alloHSCT in CR1 were independent prognostic factors for relapse-free survival (HR: 0.42; 95% CI: 0.23-0.75; P=0.004 and HR: 0.31; 95% CI: 0.17-0.55; P<0.0001). The outcome of de novo BCR::ABL1+ AML is strongly improved by the addition of a TKI to IC and should become the standard of care. The classification as adverse-risk should be reconsidered in the future ELN classification.