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The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC rituximab maintenance in patients with extranodal marginal zone lymphoma (MZL) who received front-line treatment with chlorambucil plus rituximab. Study treatment was an induction phase with oral chlorambucil 6 mg/m2/day on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and intravenous rituximab 375 mg/m2 on day 1 of weeks 1-4, and 1,400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1,400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI: 78-92), 84% (95% CI: 75-89), and 93% (95% CI: 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that SC rituximab did not improve the CR rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC rituximab maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.

Background: Kaposi Sarcoma (KS) has been historically associated with HIV, especially in people with advanced immunosuppression. Its prevalence decreased over time, but management remains difficult especially when the diagnosis is late and there is a visceral involvement. Bone localization, and particularly the vertebral one, is rare. We herein present a case of vertebral localizations of KS and performed a review literature to assess demographic, clinical characteristics and treatment outcomes in people with HIV., Methods: The systematic review was carried out by following the PRISMA guidelines and registering the protocol in PROSPERO database (n. registration: CRD42024548626). We included all cases of vertebral localizations of KS from January 1rst 1981 to December 31rst, 2023., Results: Twenty-two cases, including ours, were ever reported in people with HIV, mostly males (95.4%), with a median age of 35 years (IQR: 32-44), median CD4+ T cell count of 80 cell/mm 3 (IQR 13-111), 31.8% with high HIV viral load. Five people received HIV and KS diagnosis simultaneously. In all cases, but one, there were multiple sites involved. Most spine lesions were localized at thoracic and lumbar levels (59.1%), causing pathological fractures in 2 cases. Chemotherapy and radiotherapy were performed in 50% and 18.2% cases, respectively. 22.7% persons died, stability and improvement/disease regression were reported for 13.6% and 22.7% persons, respectively, while 9.9% had a significant disease progression and a person was lost to follow-up., Conclusions: Despite progresses in treatment, late presentation of KS, especially with spine involvement may have a poor prognosis. More efforts are needed to promote access to HIV testing, especially when indicating conditions are present.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical-epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan-Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.

Treatment of diffuse large B-cell lymphoma (DLBCL) in older patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a 2-stage single-arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2) in ≥70-year-old untreated frail patients with DLBCL. Frailty was prospectively defined using a simplified geriatric assessment tool. Patients were administered a maximum of 6 28-day cycles of 20 mg oral lenalidomide from days 2 to 22 and IV rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients with partial response or complete response (CR) at cycle 6 were administered lenalidomide 10 mg/d from days 1 to 21 for every 28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary end point was the overall response rate (ORR) after cycle 6; the coprimary end point was the rate of grade 3 or 4 extrahematological toxicity. The ORR was 50.8%, with 27.7% CR. After a median follow-up of 24 months, the median progression-free survival was 14 months, and the 2-year duration of response was 64%. Thirty-four patients experienced extrahematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3. The activity of the R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach in frail older patients with DLBCL. This trial was registered at EudraCT as #2015-003371-29 and clinicaltrials.gov as #NCT02955823., (© 2023 by The American Society of Hematology.)

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most commonly used regimen for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with cardiotoxicity, especially in older patients. Substituting doxorubicin with non-PEGylated liposomal doxorubicin (R-COMP) may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials. We describe the characteristics and outcome of patients with DLBCL aged ≥65 years prospectively enrolled in the Elderly Project by the Fondazione Italiana Linfomi and treated with full doses of R-CHOP or R-COMP per local practice. Starting from 1163 patients, 383 (55%) were treated with R-CHOP and 308 (45%) with R-COMP. Patients treated with R-COMP were older (median age, 76 vs 71 years), less frequently fit at simplified geriatric assessment (61% vs 88%; P < .001), and had a more frequent baseline cardiac disorders (grade >1, 32% vs 8%; P < .001). Three-year progression-free survival (PFS) was similar between R-CHOP and R-COMP (70% and 64%); 3-year overall survival was 77%, and 71% respectively. R-CHOP was associated with better PFS vs R-COMP only in the Elderly Prognostic Index (EPI) low-risk group. The two groups had similar rates of treatment interruptions due to toxicities or of cardiac events (P = 1.00). We suggest R-COMP is a potentially curative treatment for older patients with intermediate- or high-risk EPI, even in the presence of a baseline cardiopathy. R-CHOP is confirmed as the standard therapy for low risk patients., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Up to 10%-15% of diffuse large B-cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the 'Elderly Project', on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV-) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell-of-origin determination by Nanostring showed that HCV+ cases less frequently had an activated B-cell profile compared to HCV- patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab-cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R-CHOP)-like immunochemotherapy. Grade 3-4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3-year overall survival of HCV+ patients was very similar to HCV- (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct-acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3-year progression-free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

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 octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.

The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment, hemoglobin levels and International Prognostic Index and has been validated to predict overall survival in older patients with diffuse large B-cell lymphoma (DLBCL). In this study, we evaluated the ability of EPI to predict the risk of early mortality. This study included all patients registered in the Elderly Project for whom treatment details and a minimum follow-up of 3 months were available. Three main treatment groups were identified based on the anthracycline amount administered: cases receiving >70% of the theoretical anthracyclines dose (Full Dose [FD] group), ≤70% (Reduced Dose [RD]) and palliative therapy (PT; no anthracyclines). The primary endpoint was early mortality rate, defined as death for any cause occurring within 90 days from diagnosis. We identified 1150 patients with a median age of 76 years (range 65-94). Overall, 69 early deaths were observed, accounting for 19% of all reported deaths. The cumulative rate of early mortality at 90 days was 6.0%. Comparing early with delayed deaths, we observed a lower frequency of deaths due to lymphoma progression (42% vs. 75%; p < 0.001) and a higher frequency due to toxicity and infections (22% vs. 4%, p < 0.001, and 22% vs. 3%, p < 0.001, respectively) for early events. A multivariable logistic analysis on 931 patients (excluding PT) confirmed an independent association of high-risk EPI (odds ratio [OR] 3.60; 95% confidence interval [CI] 1.15-11.2) and bulky disease (OR 2.08; 95% CI 1.09-3.97) with the risk of early mortality. The cumulative incidence of early mortality for older patients with DLBCL is not negligible and is mainly associated with non-lymphoma related events. For patients receiving anthracyclines, high-risk EPI and bulky disease are associated with a higher probability of early mortality., (© 2022 John Wiley & Sons Ltd.)

Background: Early activation of palliative care for patients with advanced cancer is central in the treatment trajectory. At the Veneto Institute of Oncology, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients are evaluated by an oncologist together with a palliative care team. Recently, we reported on consecutive patients admitted at SCOC from 2018 to 2021 in terms of appropriateness, process, and outcome indicators. Here, we report further analysis in the same group of 753 patients, evaluating other parameters and the correlation between symptom intensity, gender, age, and survival., Methods: SCOC data were retrieved from a prospectively maintained database., Results: Among the patients, 42.2% were women, and the median age was 68 years, with 46.7% of patients aged ≥70 years. The most prevalent disease type was gastrointestinal cancer (75.2%), and 90.9% of the patients had metastatic disease. The median score for the distress thermometer was 4; the vast majority of the patients (98.6%) reported physical problems, and 69.4% presented emotional issues. Younger women demonstrated a significantly greater median distress than other patients (p=0.0018). Almost all symptoms had a higher prevalence on the 0-3 Edmonton Symptom Assessment Scale (ESAS) score, except for fatigue. About 43.8% of the patients received systemic anticancer treatment (SAT) in the last 60 days of life, 15.0% of whom received SAT in the last month and 3.1% in the last 2 weeks. For some symptoms, women frequently had more ESAS >3. Pain and nausea were significantly less reported by older patients compared with younger adults. Men had a lower risk of having MUST score ≥ 2 (p=0.0311). Men and older patients showed a lower prognosis awareness (p=0.0011 and p=0.0049, respectively). Older patients received less SAT within the last 30 days of life (p=0.0006) and had death risk decreased by 20.0%., Conclusion: Our study identified two subgroups of patients with advanced cancer who require special attention and support due to important symptoms' burden detected by Patient Reported Outcome Measures tests: women and younger adults. These categories of patients require special attention and should be provided early access at SCOC. The role of an oncologist remains crucial to intercept all patients in need of early palliative care and balancing trade-offs of anticancer treatment in advanced metastatic disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Galiano, Schiavon, Nardi, Guglieri, Pambuku, Martino, Bolshinsky, Murgioni, Intini, Soldà, Marino, Daniel, De Toni, Pittarello, Chiusole, Prete, Bimbatti, Nappo, Caccese, Bergamo, Brunello, Lonardi and Zagonel.)

Purpose: The SARS-CoV-2 spread has impacted Healthcare systems. COVID-19 pandemic has had consequences for patients with cancer, being associated with delays in diagnosis, in treatment And follow-up care, increase in overall infection rates and higher mortality. A survey on COVID-19 and a vaccination-questionnaire were developed at different times of the outbreak, to evaluate cancer patient-reported experience measures (PREMs) on the policies implemented to reduce the infection from SARS-CoV-2 and on the timing and methods of COVID-19 vaccination., Patients and Methods: The survey was distributed to all patients accessing the Institute during the "first-wave" Of the pandemic, evaluating patients' concerns about the pandemic, the pandemics' consequences on their cancer care, and their perception Of the measures adopted to limit the infection spread. The vaccination-questionnaire was proposed to 10% of the first 5297 cancer patients vaccinated with two doses of the Pfizer-BioNTechCOVID-19 vaccine. This questionnaire aimed at assessing the degree Of satisfaction with the Institutional vaccination campaign and vaccination-related adverse events., Results: From May 18th 2020 to June 15th 2020 the survey was completed by 3238 patients. Most of the responders expressed concern on the pandemic yet acknowledging their oncological disease as a priority. Measures implemented were appreciated by patients. Telemedicine was positively evaluated and the absence of the caregiver during the visit did not determine discomfort for two thirds of patients. From March 6th 2021 to May 8th 2021 the vaccination-questionnaire was completed by 357 patients. The 98.8% were satisfied with the vaccination campaign. No serious vaccination-correlated adverse events were reported. No patient had to delay/discontinue chemotherapy due to vaccination., Conclusion: PREMs during COVID-19 pandemic and related vaccination can provide important information to help reorganization of the health care systems for cancer care. Patients' feedback on the organizational changes implemented in the emergency period are essential for healthcare improvement and to help informed choices that are consistent with patients' needs., Competing Interests: Dr Sara Lonardi reports grants and personal fees from Amgen, Merck Serono Roche, Lilly, Astra Zeneca, and Bristol-Myers Squibb, grants from Bayer, and personal fees from Incyte, Daiichi-Sankyo, Servier, MSD, Pierre-Fabre, and GSK, outside the submitted work. Dr Antonella Brunello reports personal fees and travel expenses from and advisory board for Pharmamar, and personal fees from Glaxo Smith Kline, outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2022 Caccese et al.)

Incidental lymphomas (ILs) are rare and challenging lesions with poorly characterized clinical-epidemiological and histological features. The present study addressed the open issues concerning these tumors, by assessing the clinical-pathological features of 28 consecutive ILs, diagnosed over a 10-year period at a tertiary center for surgical pathology. ILs were more frequently documented in elderly males (mean age at surgery 70.8 years; M/F ratio 3.3), with sharp prevalence of gastrointestinal and urinary tract involvement (22/28 [78.6%] cases). Low-grade B-cell lymphomas outnumbered all other entities, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was the most common subtype (18/28 [64.3%] cases). Compared to other ILs, CLL/SLL occurred at older age and was the sole lymphoid neoplasm affecting the urinary tract. In conclusion, ILs are rare lesions, mostly affecting the gastrointestinal and urinary tract of elderly males. The diagnosis of IL is based on a high degree of suspicion and on careful morphological/phenotypic characterization., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m 2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505., Competing Interests: Gianluca Gaidano discloses roles in advisory boards or speakers' bureaus of AbbVie, Astra-Zeneca, Janssen, Roche, and Sunesys. Marco Ladetto declares in the last five years relationships in terms of consultancy, participation in advisory boards, invitation to scientific meetings, institutional research support and contracts with AbbVie, Acerta, Amgen, Archigen, ADC Therapeutics, BeiGene, Celgene, Gilead, J&J, Jazz, Roche, Sandoz, and Takeda. Luca Arcaini received advisory honoraria or speaker's bureau honoraria from Roche, Celgene, Janssen-Cilag, Verastem, EUSA Pharma, Incyte, and Sanofi and research support from Gilead. Ferreri Andres J. M. declares the following: speaker fee from Adienne; research grants from BMS, BeiGene, Pharmacyclics, Hutchison MediPharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, and Pfizer; advisory boards from Gilead, Novartis, Juno, and PletixaPharm; inventor of patents on NGR-hTNF/RCHOP in relapsed or refractory PCNSL and SNGR-hTNF in brain tumours. Maurizio Martelli declares the following: consultancy for Roche, Celgene, Janssen, Sandoz, Novartis, and Gilead; Membership on an Entity's Board or Advisory Committees for Roche, Celgene, Janssen, Sandoz, Novartis, Gilead, and Servier. No conflicts of interest are declared by the other authors regarding the publication of this article., (Copyright © 2022 Mario Petrini et al.)

The identification of prognostic factors for aggressive B-cell lymphomas still represents an unmet clinical need. We used forward phase protein arrays (FFPA) to identify proteins associated with overall survival (OS) from diagnostic formalin-fixed paraffin-embedded material of diffuse large B-cell lymphoma (DLBCL) patients ( n = 47). Univariate Cox regression analysis identified numerous proteins, including immune check-point molecules (PDCD1, PDCD2 and PD1L2) and BCL2 to be significantly associated with OS. However, only ETV6 and PIM2 proteins persisted following multivariate Cox analysis. Independent validation studies by immunohistochemistry and analysis of public gene expression profiles of DLBCL confirmed a prognostic role for high ETV6 and ETV6/PIM2 ratios in DLBCL. ETV6 is a recurrently mutated/deleted gene in DLBCL for which its function in this disease entity is currently unknown. We find that ETV6 is upregulated during oncogenic transformation of germinal center B-cells and that it regulates DLBCL survival, as its acute loss results in marked apoptosis. Fluctuations in survivin (BIRC5) expression levels were associated with this phenomenon. Furthermore, an inverse correlation between ETV6 and BIRC5 expression levels was found and correlated with a response to the BIRC5 inhibitor, YM155. In conclusion, we present evidence for an oncogenic function of ETV6 in DLBCL.

Background: Evidence for the choice of second line, standard vs high dose chemotherapy, (SDCT, HDCT) for patients with relapsed germ cell tumors (GCTs) comes mainly from retrospective studies., Material and Methods: relevant literature was reviewed, considering as endpoints both survival and long term quality of life (QoL). Patients with metastatic GCT progressing after first-line treatment at our Institution were retrospectively evaluated., Results: HDCT seems to achieve a higher rate of long-term remissions. QoL data for this group of patients are lacking. Our experience on 29 patients was in line with these results. Two-year OS for the 18 patients treated with one or two HDCT/PBSCT procedures was 47.5 %, while 2-year PFS was 44 %. For the 11 receiving SDCT 2-year OS was 36.4 %, and 2-year PFS was 32.7 %., Conclusions: HDCT/PBSCT confirmed to be effective in treating patients with relapsed GCT, but prospective studies are needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Robotic therapy (RT) has been internationally recognized for the motor rehabilitation of the upper limb. Although it seems that RT can stimulate and promote neuroplasticity, the effectiveness of robotics in restoring cognitive deficits has been considered only in a few recent studies., Objective: To verify whether, in the current state of the literature, cognitive measures are used as inclusion or exclusion criteria and/or outcomes measures in robotic upper limb rehabilitation in stroke patients., Methods: The systematic review was conducted according to PRISMA guidelines. Studies eligible were identified through PubMed/MEDLINE and Web of Science from inception to March 2021., Results: Eighty-one studies were considered in this systematic review. Seventy-three studies have at least a cognitive inclusion or exclusion criteria, while only seven studies assessed cognitive outcomes., Conclusion: Despite the high presence of cognitive instruments used for inclusion/exclusion criteria their heterogeneity did not allow the identification of a guideline for the evaluation of patients in different stroke stages. Therefore, although the heterogeneity and the low percentage of studies that included cognitive outcomes, seemed that the latter were positively influenced by RT in post-stroke rehabilitation. Future larger RCTs are needed to outline which cognitive scales are most suitable and their cut-off, as well as what cognitive outcome measures to use in the various stages of post-stroke rehabilitation.

Background: Robot-assisted arm therapy (RAT) has been used mainly in stroke rehabilitation in the last 20 years with rising expectations and growing evidence summarized in systematic reviews (SRs)., Objective: The aim of this study is to provide an overview of SRs about the effectiveness, within the ICF domains, and safety of RAT in the rehabilitation of adult with stroke compared to other treatments., Methods: The search strategy was conducted using search strings adapted explicitly for each database. A screening base on title and abstract was realized to find all the potentially relevant studies. The methodological quality of the included SRs was assessed using AMSTAR-2. A pre-determined standardized form was used to realize the data extraction., Results: 18 SRs were included in this overview. Generally, positive effects from the RAT were found for motor function and muscle strength, whereas there is no agreement for muscle tone effects. No effect was found for pain, and only a SR reported the positive impact of RAT in daily living activity., Conclusion: RAT can be considered a valuable option to increase motor function and muscle strength after stroke. However, the poor quality of most of the included SRs could limit the certainty around the results.

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The five-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results. Therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury.

Purpose: Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination., Patients and Methods: Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide-treated patients (L-MIND). Key eligibility criteria were aligned with L-MIND. Estimated propensity score-based Nearest Neighbor 1:1 Matching methodology balanced the cohorts for nine prespecified prognostic baseline covariates. The primary endpoint was investigator-assessed best overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and overall survival (OS)., Results: Data from 490 patients going through lenalidomide monotherapy were collected; 140 qualified for matching with the L-MIND cohort. The primary analysis included 76 patients from each cohort who received a lenalidomide starting dose of 25 mg/day. Cohort baseline covariates were comparable. A significantly better ORR of 67.1% (95% confidence interval, 55.4-77.5) was observed for the combination therapy versus 34.2% (23.7-46.0) for lenalidomide monotherapy [odds ratio, 3.89 (1.90-8.14); P < 0.0001]. Higher CR rates were achieved with combination therapy compared with lenalidomide monotherapy [39.5% (28.4-51.4) vs. 13.2% (6.5-22.9)]. Survival endpoints favored combination therapy. Lenalidomide monotherapy outcomes were similar to previously published data., Conclusions: RE-MIND enabled the estimation of the additional treatment effect achieved by combining tafasitamab with lenalidomide in patients with R/R DLBCL., (©2021 The Authors; Published by the American Association for Cancer Research.)

18F-FDG-PET/MR images, including DWI, of a 46-year-old male admitted to the Emergency Room of our tertiary center, who was suffering from diplopia, left orbital pain, and a headache for two weeks, demonstrated multiple hepatic nodules, a pancreatic mass, and skeletal metastases, in addition to thrombosis of the left cavernous sinus, thickening of the small intestine, and a large hepatic lesion identified at head and neck MR and whole-body CT, respectively. Hepatic and bone marrow biopsies revealed the diagnosis of Burkitt lymphoma. After four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, and high dose cytarabine (R- CODOX-M/IVAC), a complete metabolic response occurred.

Background: Robot-assisted Arm Therapy (RAT) has been increasingly applied in the last years for promoting functional recovery in patients with disabilities related to neurological health conditions. Evidence of a knowledge-to-action gap for applying robot-assisted technologies in the rehabilitation of patients with neurological health conditions and the difficulty to apply and tailor the knowledge to the local contexts solicited the need for a national consensus conference on these interventions., Aim: The aim of this paper was to explain the methodology used by the working group dedicated to synthesizing evidence on the effectiveness of RAT in neurological health conditions in the context of the CICERONE Italian Consensus Conference., Design: The methodological approach of the working group., Setting: All rehabilitation settings., Population: Patients with disability following a neurological health condition., Methods: Following the indications proposed by the Methodological Manual published by the Italian National Institute of Health, a Promoting Committee and a Technical Scientific Committee have been set up. Six working groups (WGs) have been composed to collect evidence on different questions, among which WG2.2 was focused on the effectiveness of RAT in neurological health conditions., Results: WG2.2 started its work defining the specific research questions. It was decided to adopt the ICF as the reference framework for the reporting of all outcomes. Literature search, data extraction and qualitative assessment, evidence analysis and synthesis have been performed., Conclusions: This paper summarized the methodological approaches used by the WG2.2 of the CICERONE Italian Consensus Conference to define the effectiveness of RAT in the management of patients with neurological health conditions., Clinical Rehabilitation Impact: WG2.2 synthesis might help clinicians, researchers, and all rehabilitation stakeholders to address the use of RAT in the Individualized Rehabilitation Plan, to guide the allocation of resources and define clinical protocols and indications for the management of patients with different neurological health conditions.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30 + lymphoproliferative disorder characterized by the development of lesions ranging from papules to large tumors. Most cases present as localized disease, however multifocal and generalized involvement of the skin can occur. Several treatments have been proposed for PCALCL; however a highly effective standard approach to multifocal disease has not yet been elucidated. The disease expression of CD30 antigen in at least 75% of the tumor makes it an optimal target for immunotherapy. The current study presents a case of a 62-year-old male referred to the University of Padua Dermatology Clinic complaining about nodular and ulcerated lesions involving the frontal area and scalp that were 8 cm in diameter. Doses of 180 mg brentuximab vedotin (BV), which is an antibody drug conjugate binding CD30 antigen, were administered every 21 days. A 75% decrease in dimensions after the first infusion and a complete remission after the second was observed. Disease response appeared to be dose-related and adverse reactions, in particular peripheral neuropathy, may be an effect of cumulative toxicity, meaning that treatment cycle reduction should be considered. Based on the present results, A high dose, short course of BV is recommended as a cost-effective approach for PCALCL. However, further studies are required to assess the efficacy and other potential advantages of this therapeutic regimen., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

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 Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050)., Results: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases., Conclusion: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL., Competing Interests: Francesco MerliConsulting or Advisory Role: Janssen, Gilead Sciences, MSD, Takeda, RocheTravel, Accommodations, Expenses: Janssen, Gilead Sciences, EUSA Pharma, Celgene, Roche, Takeda Stefano LuminariConsulting or Advisory Role: Roche, Gilead Sciences, CelgeneTravel, Accommodations, Expenses: Janssen, Celgene Alessandra TucciConsulting or Advisory Role: Janssen, TakedaTravel, Accommodations, Expenses: Sandoz Annalisa ArcariConsulting or Advisory Role: Janssen-CilagTravel, Accommodations, Expenses: Janssen-Cilag, Takeda Luigi RigacciConsulting or Advisory Role: Roche, Gilead Sciences, Takeda, Janssen-Cilag, AbbVie, Celgene/Bristol-Myers Squibb, Merck, MenariniSpeakers' Bureau: Roche, Gilead Sciences, CelgeneTravel, Accommodations, Expenses: Takeda Eliza HawkesConsulting or Advisory Role: Merck Sharpe & Dohme, Roche/Genentech, AstraZeneca, Gilead SciencesSpeakers' Bureau: Roche/GenentechResearch Funding: AstraZeneca, Celgene, Merck KGaA, Janssen-Cilag, Gilead Sciences, Mundipharma, Bristol-Myers SquibbTravel, Accommodations, Expenses: Roche/Genentech Carlos S. ChiattoneConsulting or Advisory Role: Roche, Takeda, Janssen Federica CavalloHonoraria: Takeda, Janssen-Cilag, Gilead SciencesConsulting or Advisory Role: Janssen-Cilag, Gilead SciencesTravel, Accommodations, Expenses: Celgene Alberto FabbriHonoraria: Takeda, Servier/PfizerTravel, Accommodations, Expenses: Takeda Allison BarracloughTravel, Accommodations, Expenses: Roche Simone FerreroConsulting or Advisory Role: Janssen-Cilag, EUSA Pharma, Clinigen GroupSpeakers' Bureau: Janssen-Cilag, Servier, EUSA Pharma, Gilead SciencesTravel, Accommodations, Expenses: Roche, Servier, Sanofi, Janssen-Cilag, EUSA Pharma, Gentili Alice Di RoccoSpeakers' Bureau: Roche/GenentechTravel, Accommodations, Expenses: Roche, Novartis Stefan HohausConsulting or Advisory Role: MSD, EusaPharma, Servier, GentiliniTravel, Accommodations, Expenses: Roche Luca NassiEmployment: SanofiStock and Other Ownership Interests: Sanofi, MolMedConsulting or Advisory Role: Takeda Gerardo MusuracaConsulting or Advisory Role: Janssen Oncology, Servier Leonardo FlenghiTravel, Accommodations, Expenses: Roche, Janssen Michele SpinaEmployment: Bristol-Myers Squibb/Medarex, SanofiConsulting or Advisory Role: Gilead Sciences, IncyteNo other potential conflicts of interest were reported.

Introduction: Upper limb motor impairment is one of the most frequent stroke consequences. Robot therapy may represent a valid option for upper limb stroke rehabilitation, but there are still gaps between research evidence and their use in clinical practice. The aim of this study was to determine the quality, scope, and consistency of guidelines clinical practice recommendations for upper limb robotic rehabilitation in stroke populations., Evidence Acquisition: We searched for guideline recommendations on stroke published between January 1st, 2010 and January 1st, 2020. Only the most recent guidelines for writing group were selected. Electronic databases (N.=4), guideline repertories and professional rehabilitation networks (N.=12) were searched. We systematically reviewed and assessed guidelines containing recommendation statements about upper limb robotic rehabilitation for adults with stroke (PROSPERO registration number: CRD42020173386)., Evidence Synthesis: Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and textual syntheses were used to appraise and compare recommendations. From 1324 papers that were screened, eight eligible guidelines were identified from six different regions/countries. Half of the included guidelines focused on stroke management, the other half on stroke rehabilitation. Rehabilitation assisted by robotic devices is generally recommended to improve upper limb motor function and strength. The exact characteristics of patients who could benefit from this treatment as well as the correct timing to use it are not known., Conclusions: This systematic review has identified many opportunities to modernize and otherwise improve stroke patients' upper limb robotic therapy. Rehabilitation assisted by robot or electromechanical devices for stroke needs to be improved in clinical practice guidelines in particular in terms of applicability.

Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK- ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK- ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674., (© 2021 by The American Society of Hematology.)

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection., (© AlphaMed Press 2020.)

While classical nodal mantle cell lymphoma (cMCL) is often associated with involvement of multiple extranodal sites, isolated extranodal disease (ED) at the time of diagnosis is a rare event; data on the outcome of these forms are lacking. On behalf of the European MCL Network, we conducted a retrospective analysis on the clinical characteristics and outcomes of MCL presenting with isolated or predominant ED (MALT MCL). We collected data on 127 patients with MALT MCL diagnosed from 1998 to 2015: 78 patients (61%) were male with a median age of 65 years. The involved sites include: upper airways + Waldeyer ring (40; 32%), gastrointestinal tract (32; 25%), ocular adnexa (17; 13%), oral cavity and salivary glands (17; 13%) and others (13; 1%); 7 patients showed multiple extranodal sites. The median follow-up was 80 months (range: 6-182), 5-year progression-free survival (PFS) was 45% (95% CI: 35-54) and 5-year overall survival (OS) was 71% (95% CI: 62-79). In an explorative setting, we compared MALT MCL with a group of 128 cMCL patients: MALT MCL patients showed a significantly longer PFS and OS compared with nodal cMCL; with a median PFS of 4.5 years vs 2.8 years (p = 0.001) and median OS of 9.8 years vs 6.9 years (p = 0.018), respectively. Patients with MALT MCL at diagnosis showed a more favorable prognosis and indolent course than classical nodal type. This clinical variant of MCL should be acknowledged to avoid possible over-treatment., (Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. It is highly aggressive and represents the second most common cause of skin cancer-related death. Ruxolitinib is an orally administered selective inhibitor of Janus associated kinases1 and 2, which is used in the management of patients with symptomatic myelofibrosis and polycythemia vera who are non-responders or intolerant to hydroxyurea. Herein, we report the case of a 47-year-old woman with a 14-year history of chronic myeloproliferative syndrome initially treated with hydroxyurea for 4 years. She was then enrolled in the Response trial and treated for 7 years with ruxolitinib subsequently developing an MCC. This report shows the possibility of development of MCC in patients treated with ruxolitinib. Periodic skin examination is indicated in patients who undergo ruxolitinib therapy, especially if they have a history of skin cancer; dermatologists and oncohematologists should be aware of this possibility in order to introduce appropriate preventive strategies., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype, and approximately 50% of the patients are >60 years of age. Patients with relapsed/refractory (rr) disease have a poor prognosis with currently available treatments. Lenalidomide is available in Italy for patients with rrDLBCL based on a local disposition of the Italian Drug Agency., Subjects, Materials, and Methods: An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use for rrDLBCL in real practice., Results: One hundred fifty-three patients received lenalidomide for 21/28 days with a median of four cycles. At the end of therapy, there were 36 complete responses (23.5%) and 9 partial responses with an overall response rate (ORR) of 29.4%. In the elderly (>65 years) subset, the ORR was 33.6%. With a median follow-up of 36 months, median overall survival was reached at 12 months and median disease-free survival was not reached at 62 months. At the latest available follow-up, 29 patients are still in response out of therapy. Median progression-free survivals differ significantly according to age (2.5 months vs. 9.5 in the younger vs. elderly group, respectively) and to disease status at the latest previous therapy (15 months for relapsed patients vs. 3.5 for refractory subjects). Toxicities were manageable, even if 30 of them led to an early drug discontinuation., Conclusion: Lenalidomide therapy for patients with rrDLBCL is effective and tolerable even in a real-life context, especially for elderly patients., Implications for Practice: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and approximately 50% of the patients are >60 years of age. Patients with relapsed/refractory (rr) disease have a poor prognosis, reflected by the remarkably short life expectancy of 12 months with currently available treatments. The rrDLBCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for patients with rrDLBCL is effective and tolerable even in a real-life context, especially for elderly patients., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported., Subjects, Materials, and Methods: We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ ConC ]: n = 9) or subsequently (sequential cohort [ SeqC ]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like)., Results: Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens ( n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC . DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC . At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%)., Conclusion: Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity., Implications for Practice: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76 years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF <50% (12%). Based on the intent to treat analysis, overall response rate was 72%, including 28 patients in complete remission (complete remission rate, 56%), and 8 in partial remission (16%). At the end of treatment, grades 3 to 4 cardiac events were observed in 6 patients. No significant modifications from baseline values of LVEF were observed during treatment and follow-up. Nonpegylated liposomal doxorubicin instead of doxorubicin in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is a feasible option for patients with diffuse large B-cell lymphoma presenting with concomitant cardiac disorders., (Copyright © 2017 John Wiley & Sons, Ltd.)

Rationale: Koebner phenomenon is occasionally reported in patients affected by classic Kaposi sarcoma (KS)., Patient Concerns: Here, we report 2 cases of KS associated with Koebner phenomenon and the correlation of human herpesvirus 8 molecular analysis with the clinical outcome., Interventions: In the first case, a patient with a history of sporadic cutaneous KS developed a recurrent lesion at the laryngeal tract, the site of a previous nodulectomy. In our second case, immunodeficiency induced by chemotherapy triggered the development of KS and Koebner phenomenon was limited to the skin at the site of safenectomy., Lessons: Our observations suggest that careful planning of surgical treatment is required in immunocompetent and immunocompromised patients with a medical history of KS. Moreover, mucosal sites (both respiratory and in the gastrointestinal tract) should be considered as potential sites for KS development., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R-B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12-71 months). Toxicity was moderate, mainly grades 1 and 2. R-B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs.

Transposition of great arteries (TGA) is one of the most common and severe congenital heart diseases (CHD). It is also one of the most mysterious CHD because it has no precedent in phylogenetic and ontogenetic development, it does not represent an alternative physiological model of blood circulation and its etiology and morphogenesis are still largely unknown. However, recent epidemiologic, experimental, and genetic data suggest new insights into the pathogenesis. TGA is very rarely associated with the most frequent genetic syndromes, such as Turner, Noonan, Williams or Marfan syndromes, and in Down syndrome, it is virtually absent. The only genetic syndrome with a strong relation with TGA is Heterotaxy. In lateralization defects TGA is frequently associated with asplenia syndrome. Moreover, TGA is rather frequent in cases of isolated dextrocardia with situs solitus, showing link with defect of visceral situs. Nowadays, the most reliable method to induce TGA consists in treating pregnant mice with retinoic acid or with retinoic acid inhibitors. Following such treatment not only cases of TGA with d-ventricular loop have been registered, but also some cases of congenitally corrected transposition of great arteries (CCTGA). In another experiment, the embryos of mice treated with retinoic acid in day 6.5 presented Heterotaxy, suggesting a relationship among these morphologically different CHD. In humans, some families, beside TGA cases, present first-degree relatives with CCTGA. This data suggest that monogenic inheritance with a variable phenotypic expression could explain the familial aggregation of TGA and CCTGA. In some of these families we previously found multiple mutations in laterality genes including Nodal and ZIC3, confirming a pathogenetic relation between TGA and Heterotaxy. These overall data suggest to include TGA in the pathogenetic group of laterality defects instead of conotruncal abnormalities due to ectomesenchymal tissue migration.

Are there gender differences in prevalence, surgical results and long-term survival of patients with congenital heart disease? Available literature data allow us to state what follows. At birth there is a mild but significant prevalence of congenital heart disease in females. The most severe congenital heart diseases are less frequent in girls, but when they are present in females, they are linked to a higher surgical mortality rate, due perhaps to lower weight at birth and to the prevalence of extracardiac malformations and/or of associated genetic syndromes. On the other hand, in adults, surgery for congenital heart disease is at higher risk in males, and so the long-term survival rate is higher in females. Particular psychological attitudes, a higher incidence of pulmonary hypertension, as well as specific problems linked to the reproductive function characterize congenital heart disease in adult women. The knowledge and analysis of these data are essential for a correct management of congenital heart disease in neonates, children and adults.

A 63-year-old man was admitted to our Oncology department for management of a follicular non-Hodgkin lymphoma, stage IV A FLIPI 5. The patient entered chemotherapy following the R-CHOP schedule, and a PET scan after three cycles showed partial remission. One week later he was admitted to our hospital after developing serious pain in his left arm resulting in an impaired function, right facial hemiplegia, and ophthalmoplegia. Neuroimaging studies and laboratory features were negative. Given his symptoms, we suspected Miller Fisher syndrome and the patient was administered high dose immunoglobulin, but showed no improvement. Finally, chemotherapy with methotrexate 3 g/mq was initiated, but his condition progressively worsened and the patient died 2 months later. We suggest that any patient with neurological symptoms who has received rituximab should undergo PCR analysis for all neurotropic viruses together with neurophysiological and neuroimaging studies.