11 research outputs found
ABS0671 IgG4-RELATED DISEASE IN OVERLAP WITH IDIOPATHIC MULTICENTRIC CASTLEMAN DISEASE: CLINICAL-PATHOLOGICAL CHARACTERISTICS AND THERAPEUTIC IMPLICATIONS OF AN ORPHAN DISEASE
No full textRadiomics-Based Machine Learning Model for Predicting Overall and Progression-Free Survival in Rare Cancer: A Case Study for Primary CNS Lymphoma Patients
No full textPrimary Central Nervous System Lymphoma (PCNSL) is an aggressive neoplasm with a poor prognosis. Although therapeutic progresses have significantly improved Overall Survival (OS), a number of patients do not respond to HD–MTX-based chemotherapy (15–25%) or experience relapse (25–50%) after an initial response. The reasons underlying this poor response to therapy are unknown. Thus, there is an urgent need to develop improved predictive models for PCNSL. In this study, we investigated whether radiomics features can improve outcome prediction in patients with PCNSL. A total of 80 patients diagnosed with PCNSL were enrolled. A patient sub-group, with complete Magnetic Resonance Imaging (MRI) series, were selected for the stratification analysis. Following radiomics feature extraction and selection, different Machine Learning (ML) models were tested for OS and Progression-free Survival (PFS) prediction. To assess the stability of the selected features, images from 23 patients scanned at three different time points were used to compute the Interclass Correlation Coefficient (ICC) and to evaluate the reproducibility of each feature for both original and normalized images. Features extracted from Z-score normalized images were significantly more stable than those extracted from non-normalized images with an improvement of about 38% on average (p-value < (Formula presented.)). The area under the ROC curve (AUC) showed that radiomics-based prediction overcame prediction based on current clinical prognostic factors with an improvement of 23% for OS and 50% for PFS, respectively. These results indicate that radiomics features extracted from normalized MR images can improve prognosis stratification of PCNSL patients and pave the way for further study on its potential role to drive treatment choice
Deep learning-based overall survival prediction model in patients with rare cancer: a case study for primary central nervous system lymphoma
No full textPurpose: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive form of extranodal non-Hodgkin lymphoma. To predict the overall survival (OS) in advance is of utmost importance as it has the potential to aid clinical decision-making. Though radiomics-based machine learning (ML) has demonstrated the promising performance in PCNSL, it demands large amounts of manual feature extraction efforts from magnetic resonance images beforehand. deep learning (DL) overcomes this limitation. Methods: In this paper, we tailored the 3D ResNet to predict the OS of patients with PCNSL. To overcome the limitation of data sparsity, we introduced data augmentation and transfer learning, and we evaluated the results using r stratified k-fold cross-validation. To explain the results of our model, gradient-weighted class activation mapping was applied. Results: We obtained the best performance (the standard error) on post-contrast T1-weighted (T1Gd)—area under curve = 0.81 (0.03) , accuracy = 0.87 (0.07) , precision = 0.88 (0.07) , recall = 0.88 (0.07) and F1-score = 0.87 (0.07) , while compared with ML-based models on clinical data and radiomics data, respectively, further confirming the stability of our model. Also, we observed that PCNSL is a whole-brain disease and in the cases where the OS is less than 1 year, it is more difficult to distinguish the tumor boundary from the normal part of the brain, which is consistent with the clinical outcome. Conclusions: All these findings indicate that T1Gd can improve prognosis predictions of patients with PCNSL. To the best of our knowledge, this is the first time to use DL to explain model patterns in OS classification of patients with PCNSL. Future work would involve collecting more data of patients with PCNSL, or additional retrospective studies on different patient populations with rare diseases, to further promote the clinical role of our model
Impact of Levofloxacin for Prophylaxis of Pre-engraftment Bloodstream Infections after Allogeneic HSCT: A single-center Matched Analysis in an Endemic Country for Carbapenem-resistant Gram-negative Bacteria
No full textSHORT-TERM DOSE-DENSE “CARMEN” THERAPY IS BETTER TOLERATED AND EVENLY EFFECTIVE THAN OTHER INTENSIFIED REGIMENS IN HIV- AND HIV+ PATIENTS WITH BURKITT LYMHOMA
No full textP036 | A-AVD VERSUS ABVD IN FIRST-LINE STAGE IV CLASSICAL HODGKIN LYMPHOMA: EFFICACY AND TOXICITY IN A SINGLE CENTER EXPERIENCE
No full textBrentuximab Vedotin combined with AVD (A-AVD) is the new standard for first-line advanced-stage Hodgkin Lymphoma (HL). The ECHELON-1 trial showed improved 7-year PFS (82.3% vs 74.5%) and OS (93.5% vs 88.8%) with A-AVD compared to ABVD. Nevertheless, the enhanced survival outcomes may be accompanied by an increased incidence of toxicities, notably peripheral neuropathy and neutropenia, and a more challenging management of treatment-related complications. Furthermore, in Italy, its use is restricted to stage IV disease. We reviewed our single-center experience with A-AVD and compared it to ABVD-treated HL cases.
Since 2022, we treated 13 patients (pts) with A-AVD. We selected all consecutive stage-IV HL pts treated with an ABVD-like regimen (including ABVD and MBVD), from 2010 onward, for a total of 34 pts. Among the 47 pts, the median age was 41 years (17-82), with 28 male pts (60%).
With a median follow-up of 41 months (range: 4–122 months), the PFS and OS for the entire cohort were 89% [95% CI: 75–95] and 93% [CI: 79–98], respectively. In the A-AVD cohort specifically, the median PFS was 92% [CI: 57–99], with a single case of disease progression, while the median OS was 97% [CI: 81–99], with one recorded death. The ABVD cohort presented comparable survival outcomes, with a median PFS of 84% [CI: 65–93], corresponding to 7 cases of progression, and a median OS of 90% [CI: 70–97], with 3 deaths reported. Statistical comparison of the cohorts utilizing the Kaplan-Meier method revealed no significant differences. The p-values for PFS and OS were 0.89 and 0.57, respectively.
Regarding toxicity and management, the registration trial showed higher neurological complications in the A-AVD group (19% vs 9%), confirmed by our clinical data (8% vs 3%). Supportive therapies and doses adjustment mitigate these adverse effects, improving treatment consistency and pts quality of life.
PET2 analysis revealed deeper responses in A-AVD (CR: 92% vs 65%), though sample size limited statistical significance.
In conclusion, A-AVD demonstrated therapeutic efficacy comparable to ABVD at end-of-treatment (EoT) evaluation. A-AVD is associated with a less favorable toxicity profile; therefore, supportive care and dose modification play a crucial role in mitigating its impact.
Responses with A-AVD appear deeper and more rapid. This does not result in a difference in survival between the two cohorts; however, an increased sample size could reveal a survival benefit with A-AVD regimen
P082 | THERAPY-RELATED MYELOID NEOPLASMS FOLLOWING TREATMENT FOR HEMATOLOGIC MALIGNANCIES: A SINGLE-CENTER RETROSPECTIVE ANALYSIS
No full textBackground: Therapy-related myeloid neoplasms (t-MNs) represent a subgroup of myeloid malignancies arising after exposure to chemotherapy (CT) and/or radiotherapy (RT) for prior malignancies and are associated with poor prognosis. This study aims to analyze clinical characteristics, risk factors, and outcomes of patients who developed t-MN following treatment for prior hematological malignancies (pHM). t-MNs are a significant long-term complication of pHM treatment and are associated with poor prognosis despite aggressive therapeutic interventions. At present, allo-SCT remains the only potentially curative approach, offering improved survival in selected cases. Methods: We conducted a retrospective analysis on 42 t-MN cases diagnosed at our Centre (2012-2025) after CT/RT for pHM. Collected variables included pHM type, treatment of t-MN, cytogenetics/molecular data and survival. Results: Median age at t-MN diagnosis was 67 yr (IQR 10.5 yr); median latency of t-MN onset from completion of pHM therapy was 35 mo (IQR 90.8 mo). pHM were mainly non-Hodgkin lymphoma (N=22, 52%) and multiple myeloma (N=5; 12%). At presentation 32 pts (76.2 %) had myelodysplastic neoplasm (MDS) and 10 pts (23.8 %) acute myeloid leukemia (AML); 7 MDS (21.9 %) evolved to AML during follow up. High-risk disease at diagnosis was recorded in 15 MDS pts (35.7 %, IPSS-R ≥ 3.5) and 6 AML pts (60 %, ELN-2017 ≥ intermediate). 23 patients (54.8 %) received intensive treatment, including allogeneic stem cell transplant (allo-SCT) in 17 cases (40.5%); 19 patients received lower-intensity therapy or supportive care. Median overall survival (mOS) for the whole cohort was 15 mo; mOS was longer in allo-SCT recipients (18 mo vs 6 mo). 38.5% of patients who underwent alloHSCT were alive at 2 yrs follow up. Deaths were mainly due to disease progression. Multivariate analysis on our data suggested complex karyotype as predictor of mortality, although not reaching statistical significance due to the limited sample size (OR ≈ 3.9, p = 0.13). Conclusion: Allo-SCT is confirmed as a potentially curative approach on a long-term follow-up, offering improved survival in eligible patients. The considerable variability in t-MN onset latency emphasizes the necessity for sustained surveillance and personalized follow-up strategies. The development of frontline therapies with lower leukemogenic potential is envisaged to improve the long-term prognosis of patients treated for HMs.
DP076 | TOLERABILITY AND EFFICACY OF “CARMEN” AND OTHER INTENSIFIED REGIMENS USED IN HIV-NEGATIVE AND HIV-POSITIVE PATIENTS WITH BURKITT LYMPHOMA: REAL-LIFE DATA FROM A MULTICENTER SERIES OF 153 PATIENTS
No full textIntroduction: Treatment for sporadic and HIV-associated BL involves resource-heavy regimens, with long delivery times, often dose-limiting toxicity, and increased TRM. Over the last decades, BL pts have been successfully treated with the dose-dense, short-term “CARMEN” therapy in Italian Centres. CARMEN is a 36-day HDMTX-based regimen including single doses of cyclophosphamide, etoposide, and doxorubicin (Ferreri et al. Blood Adv 2022), with potentially better feasibility and tolerability than other used regimens. In a situation where comparative prospective trials are impractical, we analysed toxicity and efficacy of CARMEN and other regimens in BL pts treated at the 6 Italian centres that have developed the CARMEN program.
Methods: Consecutive pts ≤70 y with BL treated with curative intent between 2009 and 2024 were included. Pts treated with intensified regimens other than CARMEN served as controls. Toxic deaths, interruptions/dose reductions, G≥3 non-hematol toxicity, and G≥3 infections were used to define feasibility and tolerability.
Results: 153 pts (median 48 y, 19-69; 116 males) were considered: 57 received CARMEN and 96 received other regimens (GMALL, R-HyperCVAD, R-daEPOCH, CODOXM-IVAC). Fifty-seven pts had HIV. There were no differences between CARMEN and controls in age (median: 43 vs 48 y), PS 2-4 (41% vs 44%), advanced stage (86% vs 78%), extranodal disease (86% vs 77%), CNS involvement (14% vs 11%), high LDH serum level (74% vs 79%), and bulky disease (44% vs 32%). CARMEN was better tolerated than controls, with significantly lower rates of dose reductions, interruptions, G ≥3 non-hematol toxicities, and severe infections (Table). At a median follow-up of 84 (10-189) months, 7 pts had a second tumor: 2 (3%) after CARMEN and 5 (5%) after others. CARMEN was equally effective than other used regimens, with a 5-yr PFS of 68% (95%CI 66-70) and 66% (95%CI 64-68), respectively, and a 5-yr OS of 74% (95%CI 73-75) and 69% (95%CI 68-70) respectively. HIV status did not alter efficacy of CARMEN; this combination showed better efficacy in pts with CNS involvement.
Conclusions: With intrinsic limitations, this real-life study shows that CARMEN achieves comparable outcomes to other standard therapies, with significantly better tolerability in both HIV- and HIV+ BL pts. In addition to its short duration and good tolerability, CARMEN may be associated with reduced risk of chronic toxicity and second tumors due to the use of single doses of cytotoxic agents.
P006 | THE SHORT-TERM DOSE-DENSE CARMEN PROGRAM IS ASSOCIATED WITH BETTER TOLERABILITY AND SIMILAR EFFICACY THAN OTHER INTENSIFIED REGIMENS IN PATIENTS WITH HIGH-GRADE B-CELL LYMPHOMAS
No full textIntroduction. High-grade B-cell lymphoma (HGBCL) patients (pts) exhibits poor outcomes after RCHOP and used intensified regimens need long delivery time and show relevant dose-limiting toxicities and treatment-related mortality (TRM). The “CARMEN” program showed encouraging safety and efficacy results in MYC-rearranged lymphomas. Herein, we retrospectively analyzed toxicity and efficacy of RCHOP, CARMEN and other four intensified regimens in HGBCLs treated at the six Italian centers where CARMEN was developed. Methods. Consecutive HGBCL pts (18-75 years) treated between 2010 and 2024 who received at least one dose of chemotherapy were considered. Inclusion criteria were concomitant: diagnosis performed by local expert pathologists according to ICC/WHO5 classifications as well as availability of FISH for MYC, BCL-2, and BCL-6. CARMEN details were previously reported [Ferreri et al. Blood Adv 2022]. Results. 156 pts were analyzed: 57 (37%) pts had DHL-BCL2 lymphoma, 21 (13%) had DHL-BCL6, and 78 (50%) had HGBCL not otherwise specified (HGBCL NOS). 28 (18%) pts had HIV infection. Treatment consisted of RCHOP in 25 pts, R-daEPOCH in 55, CODOXM/IVAC or HyperCVAD in 17, GMALL in 20, and CARMEN in 39. Pts features were balanced among therapeutic subgroups (Table). CARMEN compared well with the other intensified regimens in terms of toxic deaths (10% vs. 12%), dose reductions/interruptions (31% vs. 34%), grade 3-4 non-hematological toxicity (33% vs. 32%), grade 3-4 infections (36% vs. 42%), and grade 3-4 opportunistic infections (8% vs. 7%). CARMEN showed more favorable tolerability profiles in HIV-positive pts, where TRM was 0% vs. 27% (p= 0.03), with dose reductions/interruptions in 14% vs. 55% (p= 0.03). At a median follow-up of 48 months (IQR 26-71), 78 (50%) pts experienced a PFS event and 68 (44%) died, with a 5-year PFS of 48% (95%CI=43-52) and OS of 52% (95%CI= 48-56). OS was similar after RCHOP and intensified regimens (5-year OS: 56%; 95%CI= 49-53 and 51%; 95%CI= 47-55) and after the latter group and CARMEN (5-year: 56%; 95%CI= 52-59 and 48%; 95%CI= 39-57) (figure). In multivariate analysis, age, PS, and transformation from indolent lymphomas, were independent predictors of PFS and OS. Conclusions. Exploiting its limited exposition to cytostatics and short duration, CARMEN regimen shows similar tolerability and efficacy than other intensified regimens. This cost-benefit treatment may be the backbone for future combinations to treat HGBCLS.
