Corrado Girmenia

Background: Pre-exposure passive immune prophylaxis (PrEP) might contribute to improve hematologic malignancy (HM) outcomes; however, there are currently no specific guidelines to inform patient selection. Methods: A literature review and a Delphi consensus process were used to identify COVID-19 risk factors, critical COVID-19 outcomes, and efficacy of PrEP against SARS-CoV-2 in HMs. An analytic hierarchy process was used to assign a priority score to candidate outcomes and to determine the PrEP indications. For these decisions, the experts assumed adequate compliance with anti-COVID-19 vaccination and acknowledged the effectiveness of PrEP in reducing SARS-CoV-2-related mortality and hospital admissions. Results: Based on the literature review, the expert panel identified 80 risk categories among patients with HM and prioritized eight clinical outcomes related to SARS-CoV-2 PrEP. The highest mean priority scores were observed for HM-related mortality (7.0), intensive care unit admission (6.7), and delays in anti-HM treatment (6.6). Based on such a framework, the experts deemed that if there was a variant-specific PrEP promptly available, it would be considered mandatory for all candidates receiving allogeneic hematopoietic cell transplantation, CAR-T therapy, or bispecific antibodies, regardless of local viral epidemiology. During epidemiological waves, variant-specific PrEP would also be recommended for patients with HMs at high risk of unfavorable COVID-19 clinical outcomes. Conclusions: This study identified PrEP indications for patients with HM receiving appropriate active immunization against COVID-19.

New options for prevention and therapy of cytomegalovirus (CMV) infection and new tests for antiviral immune reconstitution are leading to increased complexity in the management of CMV after allogeneic hematopoietic stem cell (allo‐HSCT) and solid organ transplantation (SOT) recipients. To inform the optimal care of these patients, under the auspices of the Italian GITMO, SITO, SIMIT, and AMCLI transplant, infectious, and clinical microbiology societies, we updated the guidelines published in 2019. New recommendations were produced using a consensus‐building methodology after a comprehensive review of articles released from 2019 to 2025 (March). Five domains and 31 key questions were selected through a series of questionnaires using a Delphi process. The recommendations on CMV management in transplant recipients were related to diagnostics, prevention, and treatment. Key recommendations include: in both allo‐HSCT and SOT, donor and recipient should be evaluated for anti‐CMV serological status before transplant for risk stratification; monitoring of CMV infection after transplant should be performed by assaying CMV DNAemia with real time PCR; CMV‐specific cell mediated immunity should be monitored after transplantation in allo‐HSCT and SOT; in CMV seropositive adult allo‐HSCT recipients with negative CMV DNAemia, letermovir prophylaxis is recommended; there is no mandatory indication to universal prophylaxis in SOT recipients; preemptive antiviral therapy is recommended in patients with clinically significant CMV infection (CS‐CMV‐i); in patients with resistant or refractory CMV infection or disease after first‐line antiviral therapy, oral maribavir is recommended as second line antiviral therapy. In conclusion, these recommendations aim to guide clinical practice and improve outcomes in this high‐risk population.

Background: In the letermovir primary prophylaxis (LET-PP) era, the epidemiology of human cytomegalovirus infection (HCMV-i) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients has changed. Methods: We prospectively evaluated incidence and risk factors for clinically significant (CS) HCMV-i at 180 days from transplant and 1-year overall survival in 1310 allo-HSCTs performed from January 2021 to March 2022 according to LET-PP use. Results: The cumulative incidence of CS-HCMV-i at 100 and 180 days from transplant was 3.8% and 16%, respectively, in patients who received LET-PP, and 14% and 17% in patients who did not. Variables associated with increased risk of CS-HCMV-i in patients who received LET-PP included transplant from an HCMV-seronegative donor, transplant from a donor other than matched related, >20 days to engraftment, and acute graft-versus-host disease (GVHD). Transplant in HCMV-seropositive recipients was associated with increased risk of CS-HCMV-i in patients who did not receive LET-PP. One-year overall survival after transplant was 81.1%. Acute leukemia, disease not in remission at transplant, Eastern Cooperative Oncology Group performance status >1, >20 days to engraftment, acute GVHD, CS Epstein-Barr virus DNAemia, gram-negative bacteremia, and invasive fungal disease were associated with increased mortality in patients who received LET-PP. HCMV recipient seropositivity, Hematopoietic Cell Transplantation Comorbidity Index score ≥3, and gram-negative bacteremia were associated with increased mortality in patients who did not receive LET-PP. Conclusions: In patients who received LET-PP, recipient/donor serology no longer correlates with early CS-HCMV-i whereas it still predicts late CS-HCMV-i as well as risk of CS-HCMV-i in patients who did not receive LET-PP. Donor serology, CS-HCMV-i and HCMV disease no longer impact survival in allo-HSCT recipients who receive LET-PP. Clinical Trials Registration. NCT04412811.

Purpose: This study aimed to investigate the prevalence and viral reactivations of clinical interest in the immunocompromised patient with particular focus on hematologic and solid organ transplant recipients. Methods: Molecular screening data of CMV, EBV, JCV and BKV from 2011 to 2023 were analyzed. This extensive time span allowed the access to more than 100,000 samples from over 20,000 patients treated at Policlinico Umberto I. It was possible to temporally investigate patient attendance patterns, average age distribution, seasonality of infections, and positivity rates of the analyzed viruses. Results: Between 2019 and 2022 a significant reduction in organ transplants performed and in the positive molecular detection of EBV, JCV and BKV was observed. Additionally, there has been a noteworthy decrease in CMV reactivations, with a reduction of up to 50% starting in 2019. A remarkable reduction of 39% in the rate of CMV viral reactivation has been also achieved in SOT between 2016 and 2023. Conclusion: The years following 2019 were profoundly impacted by the COVID-19 pandemic era. This period resulted in a substantial reduction in healthcare services and hospital visits. Furthermore, the introduction of the drug Letermovir in Italy in 2019 demonstrated remarkable efficacy, evidenced by a reduction in CMV reactivations. Additionally, the adoption of a novel clinical approach centered on personalized therapy facilitated improved management of immunocompromised patients.

The identification of patients at high risk of Herpes zoster (HZ) requiring a preventive strategy with antiviral prophylaxis and anti-HZ vaccine is a clinically relevant issue in patients with immunological impairment. The absence of trials comparing vaccination to pharmacological prophylaxis or defining their sequential use makes the optimal preventive strategy uncertain. This article presents the results of group discussion among a panel of experts convened ad hoc to review the literature regarding antiviral prophylaxis and vaccine efficacy and safety in populations with malignant and non-malignant hematologic diseases, and in subjects submitted to hematopoietic stem cell transplantation. The expert panel used consensus methodology and proposed solutions for preventive strategies, producing advice for the management of the most relevant unmet clinical needs. This comprehensive overview aims to support the practice of pharmacological and vaccination-based HZ prevention and inform the design and conduct of new studies in the field.

High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients.

Reduced Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-KP) colonization in a hematological-emergency setting during Sars-CoV-2 pandemic period