Alessandro Re

Spedali Civili di Brescia · Unità Operativa di Ematologia

Highlights This EHA–ESMO Clinical Practice Guideline provides key recommendations for managing HIV‐associated lymphomas. The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow‐up. The author group encompasses a multidisciplinary group of experts from different institutions and countries...

BACKGROUND The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. METHODS The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint w...

Treatment of HIV-associated lymphoma (HIV-Ly) with autologous stem cell transplantation (ASCT) has shown a surprisingly low relapse rate in several series. The aim of this study was to compare the clinical outcomes of HIV-Ly and lymphomas of the general population receiving ASCT. We compared two series of consecutive HIV-positive and HIV-negative p...

Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3–5 years. In recent years, Bruton's tyrosine kinase inhibitors (BTKi) have been introduced, demonstrating high therapeutic activity. However, the prognosis for MCL patients failing ibrutinib therapy is particularly poor, with a surviva...

Patients with mantle cell lymphoma (MCL) who experience first relapse/refractoriness can be categorized into early or late progression-of-disease (POD) groups, with a threshold of 24 months from the initial MCL diagnosis. Bruton tyrosine kinase inhibitors (BTKi) are established standard treatment at first relapse, but their effectiveness as compare...

Large B-cell lymphoma (LBCL) carrying MYC rearrangement, alone or together with BCL2 and/or BCL6 translocations, have shown a poor prognosis when treated with R-CHOP, in HIV- population. Scanty data are available on the prevalence and prognostic impact of MYC rearrangements in HIV-associated LBCL. We conducted a retrospective study to evaluate the...

Peripheral T‐cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell‐free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre‐treatment cfDNA was strongly associated with clinical r...

Introduction: The R-BAC regimen is considered among standard first-line treatments for elderly fit patients with mantle cell lymphoma (MCL). We previously reported (RBAC500 trial) a significantly inferior progression-free survival (PFS) for patients with high risk (HR) features, namely blastoid morphology and/or elevated Ki67 proliferative index, a...

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Although some risk factors associated with worse survival are known, there are no reliable predictive biomarkers of response. Considering the prognostic relevance of cell-free DNA (cfDNA) in B-cell lymphomas, in this work we aimed to explore...

Introduction. Primary Mediastinal B Lymphoma (PMBL) is a rare and aggressive neoplasia that typically occurs in young women and is primarily located in the mediastinum. Although the combination of anthracycline and rituximab immunochemotherapy, and PET-guided consolidation radiotherapy, results in a high cure rate, approximately 10-20% of patients...

Introduction and methods: Mediastinal gray zone lymphoma (GZL) emerged as a rare and challenging entity due to its high rate of pathological reclassification and heterogeneous clinical management. The bio-GZL2020 study was designed to centralize histological samples and clinical data of patients (pts) diagnosed with GZL between 2006 and 2020 in 16...

Background Chimeric antigen receptor T (CAR-T) cells are an effective therapy in Diffuse large B-cell Lymphoma (DLBCL). However, more than half of patients (pts) still relapse. CAR-T cells from T-lymphocytes (T-Ly) enriched for early lineage T-cells have shown higher replicative potential and better efficacy. Recent studies have also shown that NK...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

Background The COVID-19 pandemic has had a significant impact on the management and care of onco-hematological patients, particularly those with lymphoproliferative disorders who are at higher risk for COVID-19 associated bacterial and fungal superinfections. Case presentation We present the successful treatment of a 44-year-old male patient with...

The combination of rituximab, bendamustine, and low dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from the Fondazione Italiana Linfomi (FIL RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with complete remission rate of 91%, and 2-years progression fre...

In the FIL MCL0208 phase III trial, lenalidomide maintenance (LEN) after transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabol...

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite wid...

Simple Summary Hodgkin lymphoma (cHL) in older adults is typically characterized by a prognosis that is markedly worse than that of young patients, due to both greater difficulty in achieving adequate disease control and higher treatment-related toxicity. Although rarely included in clinical trials, older cHL patients represent an unmet clinical ch...

Background Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, hematological toxicity has been increasingly reported...

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added wi...

Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late o...

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.gov: NCT05366569) is to improve our un...

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa+Cemi) in patients wi...

The T‐cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T‐cell and NK‐cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy‐four institutions from 14 countries in North A...

Therapy-related myeloid neoplasm (t-MN) is a threatening complication of autologous stem cell transplantation (ASCT). Detecting clonal hematopoiesis (CH) mutations in cryopreserved cells before ASCT has been associated with a higher risk of t-MN, but the evolution of molecular abnormalities from pre-ASCT to t-MN, within the same patient, remains to...

Patients with aggressive B-cell lymphoma and MYC rearrangement at FISH exhibit poor outcome after R-CHOP. In the last decade, 68 patients with Burkitt lymphoma (BL; n=46) or high-grade B-cell lymphoma (single, double or triple hit; HGBCL; n=22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen", at five Italian Centers. Fort...

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare lymphoid malignancies that mostly have poor prognoses with currently available treatments. Upfront consolidation with autologous stem cell transplantation (ASCT) is frequently carried out, but its efficacy has never been investigated in randomized trials. We designed a multicente...

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor veneto...

PURPOSE Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study...

Background: Hepatitis C virus (HCV) chronic infection has been associated with increased risk of non-Hodgkin lymphoma (NHL) in people living with human immunodeficiency virus (HIV) as well as with a trend of inferior overall survival (OS) in HIV-associated NHL in the modern antiretroviral therapy (ART) era (Besson 2020). The recent introduction of...

Introduction: Immune checkpoint blockade of programmed death-1 (PD-1) receptor and its ligand (PD-L1) has contributed to efficacy in many tumor types, with clinical responses observed in a proportion of patients (pts) with Hodgkin lymphoma and rare non-Hodgkin lymphoma subtypes. A recent study demonstrated that combination treatment with anti-PD-L1...

Introduction: In the general HIV negative population, patients (pts) with diffuse large B cell lymphoma (DLBCL) or high grade B cell lymphoma (HGBCL) carrying MYC rearrangements and BCL2 and/or BCL-6 translocations [double hit (DHL) or triple hit lymphomas (THL)] have shown a dismal prognosis when treated with standard R-CHOP and are frequently can...

Introduction: Peripheral T-cell lymphomas (PTCL) have a 40-50% cure rate when treated with cyclophosphamide-doxorubicin-etoposide-vincristine-prednisone (CHOEP) and hematopoietic stem cell transplantation (HSCT). Romidepsin, a histone deacetylase inhibitor, showed promising activity in relapsed or refractory PTCLs. Methods: On these premises, we de...

Introduction: We recently demonstrated in a large multicentre study that sGA can identify fit older patients with aggressive lymphoma able to tolerate first-line intensive treatment with curative intent and to obtain similar results than younger people (Merli at al JCO 2021). Regardless of age, about 40% of patients with aggressive lymphoma are eit...

The activity of the combination of rituximab, bendamustine, and low dose cytarabine (R-BAC) was evaluated in a phase 2 multicentre trial from the Fondazione Italiana Linfomi (FIL RBAC500) in previously untreated patients with mantle cell lymphoma (MCL) who were not eligible to stem cell transplant. Maintenance treatment was not planned after induct...

Introduction Non-pegylated liposomal doxorubicin (NPLD) is considered a good alternative to conventional doxorubicin for the treatment of older patients (pts) with aggressive lymphomas and/or at high risk for cardiological toxicity. The use of R-COMP for the treatment of older pts with DLBCL has been supported by several small retrospective studies...

The R-BAC regimen is considered among standard first-line treatment for elderly fit patients with mantle cell lymphoma (MCL). In the previous R-BAC500 FIL trial, patients with the blastoid variant and/or high Ki67 proliferative index (High Risk - HR-) had a significantly higher risk of progression (2-years PFS of 40%), as compared to classical hist...

The role of consolidation radiotherapy (RT) to bulky lesions is controversial for advanced-stage Hodgkin's lymphoma (HL) patients achieving complete metabolic response (CMR) after ABVD-based chemotherapy. Herein we present the final results of the Fondazione Italiana Linfomi HD0801 trial, investigating the potential benefit of RT in that particular...

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple m...

Background immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT. Methods we performed a systematic review of current literature...

Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous disease, including one-third of cases overexpressing MYC and BCL2 proteins (Double Expressor Lymphoma, DEL) and 5-10% of patients with chromosomal rearrangements of MYC, BCL2 and/or BCL-6 (Double/Triple-Hit Lymphomas, DH/TH). TP53 mutations are detected in 20-25% of DEL. We report the efficac...

Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) w...

A Correction to this paper has been published: https://doi.org/10.1038/s41375-020-01119-8

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linf...

Background Secondary CNS lymphoma is a rare but potentially lethal event in patients with diffuse large B-cell lymphoma. We aimed to assess the activity and safety of an intensive, CNS-directed chemoimmunotherapy consolidated by autologous haematopoietic stem-cell transplantation (HSCT) in patients with secondary CNS lymphoma. Methods This interna...

Simple Summary Mantle Cell Lymphoma (MCL) is a lymphoproliferative disorder which represents less than 10% of all non-Hodgkin Lymphomas. The typical course of MCL is characterized by several relapses (“remitting-relapsing” course), and since its identification it has been considered an incurable disease. Allogeneic stem cell transplantation (allo-S...

In the article entitled “The classic prognostic factors in advanced Hodgkin’s lymphoma patients are losing their meaning at the time of Pet-guided treatments”, the affiliation of Armando Santoro should be corrected as follows:

Background Fit patients with mantle cell lymphoma aged 18–65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population. Methods This...

Introduction: We have previously reported short-term efficacy of six courses of R-DA-EPOCH in patients with aggressive B cell lymphomas carrying concomitant MYC and BCL-2 and/or BCL-6 rearrangement (DHL/THL) or gene increase copy number (ICN) (Tucci et al. Blood S1: 4154, 2017). Further experience with the same program has been described in the mea...

Background: Peripheral T-cell lymphoma (PTCL) is an aggressive form of non-Hodgkin lymphoma (NHL) that is typically associated with a poor prognosis. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with PTCL who have received at least 1 prior therapy (J Clin Oncol. 2012;30:631). Presented h...

Background and Aims. Prediction of treatment efficacy is an active and growing field of pharmacology. In the Fondazione Italiana Linfomi (FIL) MCL0208 phase III trial (NCT02354313), a 24 months lenalidomide maintenance (LM, 15 mg days 1-21 every 28 days) after high-dose immuno-chemotherapy followed by autologous transplantation (ASCT) in 300 frontl...

A few prospective trials in HIV‐positive patients with Burkitt lymphoma (BL) or high‐grade B‐cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicen...

Background Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID‐19) pandemic. However, there are still few data on COVID‐19 occurring in hematologic patients. Methods One hundred two patients with COVID‐19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2...

Although the incidence of HIV-associated lymphomas decreased after the introduction of effective combination antiretroviral therapy, they became the most common AIDS-related cancer in high-income countries. Moreover, as people living with HIV live longer, a wide range of non-AIDS-related cancer has emerged, including other haematological malignanci...

Hodgkin lymphoma (HL) has a bimodal age distribution curve, with a second peak in people aged more than 60 years. Interim PET/CT (iPET/CT) is highly predictive for PFS and OS in young HL, but it has not been sufficiently studied in the elderly. In this retrospective dual-center study, 82 patients with HL and aged 65 or more who performed iPET/CT we...

We report final results of a phase II trial addressing efficacy and feasibility of lenalidomide maintenance in patients with chemo‐sensitive relapse of diffuse large B‐cell lymphoma (DLBCL) not eligible for or failed after autologous stem cell transplantation (ASCT). Patients with relapsed DLBCL who achieved at least a partial response to salvage c...

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the develo...

FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of pa...

The complete remission (CR) rate achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). By inducing a CR rate of 75%, the bendamustine, gemcitabine, vinorelbine (BEGEV) regimen represents an optimal chemothera...