Hematological Oncology最新文献

The aim of our study was to analyze the incidence, co-mutation pattern, and prognostic impact of CEBPA gene mutations in a large multicenter consecutive series of 1367 adult patients AML patients treated with non-IT modalities. A total of 83 patients (6.1%) had mutations in CEBPA gene. Among these, 34 (2.5%) harbored mutations located in bZIP domain (bZIP in-frame N = 6) and 49 (3.6%) in other regions of the gene (other CEBPAmut). Genes most frequently co-mutated in these CEBPAmut patients were TET2 (45.8%, N = 38), SRSF2 (42.2%, N = 35), and ASXL1 (40.9%, N = 34). Using the Bradley-Terry model we identified that mutations in MDS-related genes, in TP53, and in epigenetic regulators appear to occur earlier. In contrast, genes involved in activating cell signaling appeared to occur later than CEBPAmut. Overall Survival (OS) of non-IT AML patients was analyzed according to the type of CEBPAmut. Median OS was 11.6 months in CEBPA-bZIP patients compared to 9.0 and 6.9 for patients with other CEBPAmut or CEBPAwt, respectively. When selecting 1129 AML patients treated with HMA or HMA-based combinations, CEBPA-bZIP patients had a median survival time of 11.6 months (range 9.6-NR) and 2.5 years survival probability of 20.1% which were outcomes comparable to remaining ELN2024 favorable patients. We concluded that our series of non-IT AML patients within the PETHEMA registry confirm a low percentage of CEBPA mutated cases which are frequently co-mutated with MDS related genes. Those CEBPA-bZIP cases harbor a similar median OS than those belonging to favorable ELN2024 risk category.

Programmed death-1 (PD-1) blockade offers a survival advantage over antibody-drug conjugate (ADC) treatment in classic Hodgkin lymphoma (cHL). As such, an updated pharmacoeconomic analysis of these different therapeutic strategies is indicated. This study therefore assessed the cost-effectiveness of nivolumab combined with doxorubicin, vinblastine, and dacarbazine (N-AVD) to that of brentuximab vedotin with AVD (BV-AVD). A three-state Markov model was developed to assess lifetime costs and efficacy for N-AVD and BV-ACVD regimens as treatments for adolescent and adult cHL patients from the perspectives of payers in China and the USA, using respective willingness to pay (WTP) thresholds of $37,608 and $150,000 per quality-adjusted life year (QALY). Primary analytical outcomes included direct medical costs, lifetime efficacy, incremental cost-effectiveness ratio (ICERs), and incremental net health benefit (INHB). Model stability was tested through sensitivity and subgroup analyses. N-AVD treatment yielded 1.41–2.01 and 1.06–1.39 QALYs over BV-AVD for cHL patients in the USA and China, respectively. Incremental healthcare costs for first-line N-AVD treatment were −$746,249 to $393,009 and −$109,358 to $292,324 compared to BV-AVD treatment, for corresponding ICERs of –$432,098/QALY to $288,541/QALY and −$79,173/QALY to $275,376/QALY in the USA and China, respectively. Sensitivity analyses suggested that the utility of progression-free survival had an influence on the results of these cost-effectiveness analyses. N-AVD and BV-AVD are cost-effective approaches to treating patients with cHL in both the USA and China. N-AVD and BV-AVD may respectively be best suited to use as treatments for adolescents and elderly individuals.

The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second-generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65 years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real-world practice. The cohort was characterized by advanced age (median 78.1 years, range 65.1–94.5), with over half of the patients presenting with Binet stage C disease. Two-thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow-up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56–0.73, p < 0.001). At 12 months, the discontinuation rate was significantly higher among patients with a CFS > 3 (29.2%) compared with those with a CFS ≤ 3 (8.8%) (p < 0.001); among conventional prognostic variables, only relapsed/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease-related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.

The optimal second-line chemotherapy regimen for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains uncertain. We retrospectively compared efficacy and safety between gemcitabine, carboplatin, dexamethasone, and rituximab (GCD-R) and cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) as second-line treatments for R/R DLBCL. We evaluated 68 R/R DLBCL patients receiving either GCD-R (n = 42) or CHASER (n = 26) as second-line treatment between 2004 and 2020. The primary endpoint was the complete response rate (CRR). Secondary endpoints included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events. CRR (43% vs. 42%; p = 1.00) and ORR (60% vs. 50%; p = 0.46) were comparable between GCD-R and CHASER groups. Median OS (GCD-R 18.6 months, CHASER 11.2 months; p = 0.93) and median PFS (GCD-R 10.0 months, CHASER 4.6 months; p = 0.47) showed no significant differences between groups. Further, among patients who subsequently underwent autologous stem cell transplantation, OS was also comparable between groups (p = 0.44). However, febrile neutropenia was significantly less frequent with GCD-R (33%) than with CHASER (92%; p < 0.001). As GCD-R predominantly uses peripheral intravenous catheters, whereas CHASER frequently requires central venous access, catheter management was significantly simpler with GCD-R (p < 0.001). GCD-R demonstrated equivalent efficacy to CHASER with significantly reduced toxicity and improved patient management, supporting its use as an effective and well-tolerated salvage therapy for R/R DLBCL. GCD-R represents a feasible treatment option not only for elderly patients, but also for patients eligible for subsequent stem cell transplantation.

Conditioning regimens are critical for patients with relapsed/refractory (R/R) malignant hematologic diseases. Thiotepa, an alkylating agent with excellent cytotoxicity and blood‒brain barrier permeability, has been widely used in conditioning regimens for lymphoma and has recently been used in patients with acute leukemia with central nervous system involvement. The aim of this retrospective study was to observe the efficacy and safety of a conditioning regimen comprising thiotepa, busulfan, and cyclophosphamide (TBC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with R/R hematologic diseases. Between July 2022 and December 2023, 27 patients were selected. With a median follow-up of 609 (243–954) days, the 1-year and estimated 2-year overall survival (OS) rates were 85.2% ± 6.8% and 76.5% ± 8.5%, respectively. The 1-year and estimated 2-year disease-free survival (DFS) rates were 81.5% ± 7.5% and 62.8% ± 12.2%, respectively. Six patients experienced relapse, and the 1-year and estimated 2-year cumulative incidence of relapse (CIR) rates were 14.8% ± 6.8% and 31.0% ± 12.6%, respectively. Two patients died from graft-versus-host disease (GVHD) or infection. The 1-year and estimated 2-year nonrelapse mortality (NRM) rates were 4.2% ± 4.1% and 8.5% ± 5.8%, respectively. 14 (51.9%) patients received maintenance therapy after allo-HSCT. Regimen-related toxicities were mostly well tolerated. Multivariate analysis revealed that failure to achieve first complete remission (CR1) before HSCT and previous treatment with CAR-T cell were predictors of poor DFS. This study suggests that the TBC conditioning regimen may be a promising option for patients with R/R hematologic diseases undergoing allo-HSCT.

The introduction of pediatric-inspired chemotherapy protocols for acute lymphoblastic leukemia (ALL) in the setting of adult patients affected by lymphoblastic lymphoma (LL) has improved the results in terms of outcomes. Within the Campus ALL network, we retrospectively collected data on 50 LL-patients from 23 hematology centers in Italy treated according to the GIMEMA LAL1913 protocol, with the aim of confirming the ALL results and of testing the effectiveness of an approach based on higher cumulative doses of the non-myelosuppressive components such as steroids and pegylated asparaginase, in addition to earlier and more intensive central nervous system prophylaxis. After cycle 3 (high dose methotrexate and cytarabine, C3), the cumulative incidence (CI) of PET-based complete response (CR) was of 83% (median time to response from protocol start: 3.7 months; CI95%: 3.1–4.2). With a median follow-up of 27.5 months, the 2-year overall survival (OS), disease free survival (DFS) ed event free survival rates were of 77%, 76% and 69%, respectively. The 2-year CI of relapse was of 26%. Multivariable analysis identified ECOG ≥ 2 as an independent prognostic factor for OS (HR = 3.279; CI95% 1.035–10.389, p = 0.044) and DFS (HR = 13.00, ICI95%: 3.383–57.909, p < 0.001), respectively. No significant impact was observed for pegylated asparaginase dose (reduced and/or omitted versus (vs.) full doses), age (≥ 55 vs. < 55), stage (0–I vs. II–IV), CD1a (negativity vs. other than CD1a negativity), bone marrow involvement (absent vs. ≤ 20%), or allotransplantation. The results of this study show the appropriateness of the LAL1913 protocol for the management of LL patients. Survival outcomes reflect those expected, although this drug combination was never tested before in a real-life setting. Taken together, these results suggest that LAL1913 might be considered as a reference protocol for the frontline treatment of adult LL patients.