@unica.it/unica
Medical science and public health
University of Cagliari
Hematology, Leukemia, lymphomas, chronic lymphocytic leukemia
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Roberta Murru, Andrea Galitzia, Luca Barabino, Roberta Presicci, Giorgio La Nasa, and Giovanni Caocci
Springer Science and Business Media LLC
AbstractChronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies. We retrospectively evaluated 210 unselected CLL patients diagnosed between 1988 and 2018. This evaluation encompassed demographics, Binet stage, immunoglobulin (Ig) levels, treatment history, comorbidities, and IGHV mutational status at diagnosis. The frequency and severity of infectious events were recorded. Analysis revealed that age, IGHV mutational status, Binet stage, and hypogammaglobulinemia were statistically associated with the Time to First Infection (TTFI) in univariate and multivariate analyses. Using hazard ratios from the multivariate analysis, we finally devised a risk scoring system that integrated age, IGHV mutational status, immunoglobulin levels, and Binet stage to stratify patients at diagnosis based on their specific infection risk. In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients.
Thomas Chatzikonstantinou, Lydia Scarfò, Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Gloria Iacoboni, Jana Kotaskova, Christos Demosthenous, Lukas Smolej, Stephen Mulligan,et al.
Elsevier BV
L. Barabino, A. Galitzia, R. Murru, G. Caocci, M. Greco, C. Targhetta, G. Angioni, A. Vacca, E. Piras, V. Frau,et al.
study
A. Galitzia, R. Murru, G. Caocci, L. Barabino, A. Azzena, V. Licheri, M. Greco and G. La Nasa
BACKGROUND
Persistent polyclonal B-cell lymphocytosis is a rare nonmalignant disorder characterized by mild persistent lymphocyte proliferation with possible evolution to aggressive lymphoma. Its biology is not well known, but it is characterized by a specific immunophenotype with rearrangement of the BCL-2/IGH gene, whereas amplification of the BCL-6 gene has rarely been reported. Given the paucity of reports, it has been hypothesized that this disorder is associated with poor pregnancy outcomes.
CASE REPORT
To our knowledge, only two successful pregnancies have been described in women with this condition. We report the third successful pregnancy in a patient with PPBL and the first with amplification of the BCL-6 gene.
CONCLUSIONS
PPBL is still a poorly understood clinical condition with insufficient data to demonstrate an adverse effect on pregnancy. The role of BCL-6 dysregulation in the pathogenesis of PPBL and its prognostic significance are still unknown. Evolution into aggressive clonal lymphoproliferative disorders is possible and prolonged hematologic follow-up is warranted in patients with this rare clinical disorder.
Andrea Galitzia, Luca Barabino, Roberta Murru, Giovanni Caocci, Marianna Greco, Giancarlo Angioni, Olga Mulas, Sara Oppi, Stefania Massidda, Alessandro Costa,et al.
MDPI AG
Patients with CLL have high rates of either severe disease or death from COVID-19 and a low response rate after COVID-19 vaccination has been reported. We conducted a single-center study with the main objective to evaluate the immunogenicity of the BNT1162b2 mRNA vaccines in 42 patients affected by CLL with the assessment of antibody response after the second and the third dose. After the second dose of vaccine, 13 patients (30%) showed an antibody response. The presence of hypogammaglobulinemia and the use of steroids or IVIG were the main factors associated with poor response. After the third dose, 5/27 (18%) patients showed an antibody response while in non-responders to the second dose, only 1 patient (4%) showed an elicitation of the immune response by the third dose, with no statistically significant difference. Our data, despite the small size of our cohort, demonstrate that patients with CLL have a low rate of effective response to the BNT162b2 vaccine. However, the effective role of a subsequent dose is still unclear, highlighting the need for alternative methods of immunization in this particularly fragile group of patients.
Giovanni Caocci, Olga Mulas, Daniela Mantovani, Alessandro Costa, Andrea Galizia, Luca Barabino, Marianna Greco, Roberta Murru, and Giorgio La Nasa
Springer Science and Business Media LLC
L. Barabino, A. Galitzia, R. Murru, G. Caocci, C. Targhetta, M. Greco, G. Angioni, O. Mulas, A. Vacca, E. Piras,et al.
OBJECTIVE
Due to the high mortality rate of COVID-19, the assessment of BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) efficacy in allogeneic hematopoietic stem cell transplant (HSCT) recipients is mandatory.
PATIENTS AND METHODS
We conducted a single-center pilot study with the main objective of evaluating the immunogenicity of the BNT162b2 mRNA vaccine in 31 hematological patients who underwent hematopoietic stem cell transplantation within the previous 12 months and/or were affected by chronic graft-vs.-host-disease (cGVHD), by the assessment of antibody levels at 30-45 days after the second dose of vaccine.
RESULTS
After the second dose of vaccine, 23 out of 31 patients (74%) showed a positive immune response. The presence of severe cGVHD or Ig deficiency identified 7 out of 8 (85%) of non-responders. The median absolute cluster of differentiation 19 (CD19) count was significantly lower in non-responders vs. responders (109/µl vs. 351/µl). Underlying pathology, comorbidities, type of donor, time intervals from transplant and cluster of differentiation 3/cluster of differentiation 4/cluster of differentiation 8 (CD3/CD4/CD8) subsets were not significantly associated with an effective immune response to vaccination.
CONCLUSIONS
Despite the limited sample of patients enrolled, our findings suggest that hypogammaglobulinemia and cGVHD could be associated with poor humoral response to the BNT162b2.
Anna Maria Frustaci, Giovanni Del Poeta, Andrea Visentin, Paolo Sportoletti, Alberto Fresa, Candida Vitale, Roberta Murru, Annalisa Chiarenza, Alessandro Sanna, Francesca Romana Mauro,et al.
SAGE Publications
Background: The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia (CLL) is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events. Objectives: This study was aimed to evaluate whether age, fitness status, patients’/disease characteristics, or concomitant medications may predict outcomes in CLL patients receiving venetoclax. Design: Retrospective observational study. Methods: Impact of age, presence of Cumulative Illness Rating Scale (CIRS) >6 or severe organ impairment (CIRS3+), Eastern Cooperative Oncology Group–Performance Status (ECOG-PS), renal function, and concomitant medications were retrospectively analyzed on treatment management (definitive discontinuation due to toxicity, discontinuation due to toxicity, Tox-DTD; permanent dose reduction, PDR) and survival [progression free survival (PFS), event free survival (EFS), overall survival (OS)] in unselected patients receiving venetoclax monotherapy in common practice. Results: A total of 221 relapsed/refractory patients were included. Tox-DTD and PDR were reported in 5.9% and 21.7%, respectively, and were not influenced by any fitness parameter, age, number or type of concomitant medication, baseline neutropenia, or impaired renal function. None of these factors were associated with tumor lysis syndrome (TLS) development. Age and coexisting conditions had no influence on PFS and EFS. At univariate analysis, OS was significantly shorter only in patients with ECOG-PS >1 ( p < 0.0001) and elderly (⩾65 years) with CIRS >6 ( p = 0.014) or CIRS3+ ( p = 0.031). ECOG-PS >1 retained an independent role only for EFS and OS. While Tox-DTD affected all survival outcomes, no differences in PFS were reported among patients permanently reducing dose or interrupting venetoclax for > 7 days. Conclusion: Clinical outcome with venetoclax is not influenced by comorbidities, patients’ clinical characteristics, or concomitant medications. Differently from other targeted therapies, this demonstrates that, except ECOG-PS, none of the parameters generally considered for treatment choice, including baseline neutropenia or impaired renal function, should rule the decision process with this agent. Anyway, if clinically needed, a correct drug management does not compromise treatment efficacy and may avoid toxicity-driven discontinuations. Plain Language Summary Chapter 1: Why was this study done? Chapter 2: Which are the main findings of the study? Chapter 3: How these findings may impact on clinical practice? Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia • The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events (e.g. compromised renal function or baseline neutropenia). • In our large series of patients treated outside of clinical trials, we demonstrated that neither age, fitness, comorbidities nor concomitant medications impact on venetoclax management and survival. Importantly, patients presenting with baseline neutropenia or impaired renal function did not have a higher rate of dose reductions or toxicity-driven discontinuations, thus further underlining that venetoclax may be safely administered even in those categories with no preclusions. • Differently from other targeted agents, our data demonstrate that none of the baseline factors commonly considered in treatment decision process retains a role with venetoclax. Finally, permanent dose reductions and temporary interruptions did not adversely impact PFS suggesting that, if clinically needed, a correct drug management should be adopted with no risk of compromising venetoclax efficacy.