Brentuximab vedotin (BV) plus doxorubicin, vinblastine and dacarbazine (AVD) demonstrated to improve survival compared to ABVD as frontline treatment of advanced stage Hodgkin Lymphoma (HL). We retrospectively collected data of 99 stage IV HL patients treated off-protocol with BV-AVD to evaluate the predictive role of interim-PET. Median age was 36 years (range: 18-82); 83.
View Article and Find Full Text PDFChronic lymphocytic leukemia (CLL) is characterized by an extremely variable clinical course. Although several parameters have been shown to be associated with clinical outcomes in patients with CLL, there remains substantial intragroup clinical heterogeneity in otherwise molecularly and staging homogeneous CLL subgroups. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course and that higher CAT expression is associated with the presence of the rs1001179 single nucleotide polymorphism (SNP) T allele in the CAT promoter.
View Article and Find Full Text PDFWe present the case of a 43-year-old Caucasian man who developed visceral leishmaniasis (VL) following treatment with a combination of brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine (A+AVD) for advanced-stage classical Hodgkin's lymphoma (cHL). The patient initially showed a favorable response to the treatment, but shortly after completing six cycles, he experienced recurrent fever, splenomegaly, and severe anemia. Extensive infectious disease evaluations led to a diagnosis of VL, confirmed by PCR testing.
View Article and Find Full Text PDFMantle 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 survival expectation of a few months.
View Article and Find Full Text PDFBackground: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT.
View Article and Find Full Text PDFMantle cell lymphoma (MCL) pathogenesis is strongly related to the role of the tumor immune microenvironment (TIME) in which MCL cells proliferate. TIME cells can produce growth signals influencing MCL cells' survival and exert an antitumoral immune response suppression. The activity of TIME cells might be mirrored by some ratios of peripheral blood cell subpopulations, such as the monocyte-to-platelet ratio (MPR).
View Article and Find Full Text PDFShear wave elastography (SWE) is an emerging and promising ultrasound modality, and is more recently employed in the diagnosis of musculoskeletal (MSK) pathologies. SWE evaluates tissue stiffness by measuring the speed of propagating acoustic waves through body tissue structures. Knowing the variations in stiffness of MSK soft tissue can provide helpful diagnostic insight for the evaluation of pathology in muscles, tendons, ligaments, nerves, and other soft tissues.
View Article and Find Full Text PDFMantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention.
View Article and Find Full Text PDFPrecise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66bCD10CD16CD11b PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments.
View Article and Find Full Text PDFMantle cell lymphoma is a rare disease that attracts the curiosity of clinicians and scientists due to its heterogeneous clinical behaviour, that can vary from indolent forms to the most aggressive presentations among non-Hodgkin lymphomas. The report by Eyre and colleagues describes the current treatment strategies available in most countries, and offers insights to clinicians for several intriguing difficult-to-treat scenarios. Commentary on: Eyre et al.
View Article and Find Full Text PDFThe transcriptional factor ETS1 is upregulated in 25% of diffuse large B cell lymphoma (DLBCL). Here, we studied the role of ETS1 phosphorylation at threonine 38, a marker for ETS1 activation, in DLBCL cellular models and clinical specimens. p-ETS1 was detected in activated B cell-like DLBCL (ABC), not in germinal centre B-cell-like DLBCL (GCB) cell lines and, accordingly, it was more common in ABC than GCB DLBCL diagnostic biopsies.
View Article and Find Full Text PDFResistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR's tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance.
View Article and Find Full Text PDFTime to progression of disease (POD) after first-line (1L) therapy is prognostic in mantle cell lymphoma (MCL), although studies have included a broad range of 1L, second-line (2L), and subsequent lines of therapy. The purpose of this study was to evaluate the factors predicting outcomes in patients with relapsed/refractory (R/R) MCL exclusively initiating 2L Bruton's tyrosine kinase inhibitors (BTKis) after 1L rituximab-containing therapy. Patients were accrued from 8 international centers (7 main, 1 validation cohort).
View Article and Find Full Text PDFLeuk Lymphoma
November 2023
Brexucabtagene autoleucel is a chimeric anti CD19 antigen receptor T-cell therapy that allows durable responses in relapsed/refractory (R/R) mantle cell lymphoma (MCL). The present study compared the clinical and economic outcomes of R/R MCL patients (pre-exposed to ibrutinib and chemoimmunotherapy) treated with brexucabtagene autoleucel versus Rituximab, bendamustine, cytarabine (R-BAC) in the Italian Healthcare System. A partitioned-survival model extrapolated survival and healthcare costs of R/R MCL patients over a lifetime horizon.
View Article and Find Full Text PDFThe combination of rituximab, bendamustine, and low-dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from Fondazione Italiana Linfomi (RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with a complete remission rate of 91% and 2-year progression-free survival (PFS) of 81% (95% confidence interval [CI], 68-89). Here, we report the long-term survival outcomes, late toxicities, and results of minimal residual disease (MRD) evaluation.
View Article and Find Full Text PDFMembranous glomerulonephritis (MGN) is a rare extra-hematological autoimmune complication of chronic lymphocytic leukemia (CLL), clinically characterized by nephrotic-range proteinuria and, less frequently, renal failure. Because of the rarity of this condition, there is no standardized treatment. Chlorambucil and fludarabine-based regimens, possibly combined with rituximab, have been historically the most frequent therapeutic approaches, with renal response obtained in about two-third of the patients.
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