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In HIV-associated B cell lymphomas (HIV+Ly), scanty data are available on the prevalence and prognostic impact of I MYC i rearrangements. DHL/THL were 10 (13 I MYC i + pts did not have data on I BCL2/BCL6 i ): compared to 26 SHL they had similar clinical characteristics, but worse outcome with 5y PFS (30% vs. 60%, I p i = 0.02) and 5y OS (50% vs. 67%, I p i = 0.07). B Introduction: b HIV negative patients (pts) with B cell lymphoma (Ly) carrying I MYC i rearrangements and I BCL2 i +/- I BCL6 i translocations [double hit (DHL) or triple hit Ly (THL)] have shown a dismal prognosis when treated with standard chemotherapy. [Extracted from the article]

Background: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABABR) and α-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. Methods: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABABR or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. Results: In 10 patients, we detected abs to GABABR. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABABR ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. Discussion: GABABR and AMPAR abs are well associated with LE. GABABR abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome. [ABSTRACT FROM AUTHOR]

Primary lymphoma of the female genital tract (PLFGT) is a rare type of extranodal lymphoma. In this retrospective study from the International Extranodal Lymphoma Study Group, we analyzed clinical data from 60 women diagnosed with PLFGT between 1982 and 2012. The median age was 52 years. Limited stage, as defined by the Ann Arbor and FIGO staging systems, was observed in 55% and 63% of cases, respectively. The uterus was the primary site of lymphoma in 25 cases, with the ovaries as the second most common site (n = 24). The most common histological subtype was diffuse large B-cell lymphoma (DLBCL, n = 44), followed by follicular lymphoma and marginal zone lymphoma (6 patients each). Two patients received surgery alone as first-line therapy, while 58 underwent systemic therapy, 16 following major surgery. Thirteen patients received consolidation radiotherapy and six were given central nervous system (CNS) prophylaxis. Twenty patients had disease progression or recurrence. Six patients with DLBCL (14%) experienced CNS relapse, which was the only site of recurrence in five of them. All but one patient with CNS relapse had primary ovarian involvement, and three had bulky disease; none of these patients had received CNS prophylaxis. With a median follow-up of 60 months, the median overall survival of the DLBCL cohort was approximately 13 years, with a 5-year survival rate of 77%. In multivariable analysis, advanced disease according to the FIGO system was the only parameter significantly associated with shorter overall, cause-specific, and progression-free survival in patients with DLBCL., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Abstract: Large B-cell lymphoma (LBCL) carrying MYC rearrangement, alone or together with BCL2 and/or BCL6 translocations, have shown a poor prognosis when treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the HIV population. Scanty data are available on the prevalence and prognostic impact of MYC rearrangements in HIV-associated LBCL. We conducted a retrospective study to evaluate the clinical effect of MYC rearrangement in HIV-associated LBCL. We evaluated clinical characteristics, treatment received, and outcome of LBCL in patients with HIV with MYC rearrangement (MYC+) and without MYC rearrangement (MYC-). A total of 155 patients with HIV who had received fluorescence in situ hybridization analysis for MYC were enrolled in 11 European centers: 43 with MYC+ and 112 MYC-. Among patients with MYC, 10 had double-/triple-hit lymphomas, and 33 had isolated MYC rearrangement (single-hit lymphoma). Patients with MYC+ had more frequently advanced stage, >2 extranodal site at presentation, and higher proliferative index. There were no significant differences in overall survival and progression-free survival (PFS) between the 2 groups. However, patients with MYC+ received more frequently intensive chemotherapy (iCT) (44%) than (R)CHOP alone (35%) or infusional treatment (DA-EPOCH-R and R-CDE) (19%). Among patients with MYC+, those who received iCT achieved a better outcome than patients who received nonintensive treatment (complete remission, 84% vs 52%; P = .028; 5-year PFS, 66% vs 36%; P = .021). Our retrospective results suggest that HIV-associated LBCL with MYC+ could be considered for an intensive therapeutic approach whenever possible, whereas (R)CHOP seems to give inferior results in this subset of patients in terms of complete remission and PFS., (© 2024 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.)

Purpose: 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 [Formula: see text], accuracy [Formula: see text], precision [Formula: see text], recall [Formula: see text] and F1-score [Formula: see text], 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., (© 2023. The Author(s).)

Primary 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 < 10-12). 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.

Background: Consolidation therapy has improved the outcome of newly diagnosed PCNSL patients. Whole-brain radiotherapy (WBRT) was the first consolidation strategy used and represented the gold standard for many years, but at the expense of a high risk of neurotoxicity. Thus, alternative strategies are being investigated in order to improve disease outcomes and to spare the neurocognitive side effects due to WBRT., Methods: We reviewed published studies on PCNSL patients treated with HDC/ASCT, focusing on the efficacy and safety of the conditioning regimens. Prospective and retrospective studies, published in the English language from 1992 to 2022, in high-quality international journals were identified in PubMed., Results: Consolidation with HDC containing highly CNS-penetrating agents (thiotepa, busulfan or BCNU) followed by ASCT provided long-term disease control and survival in PCNSL patients. Two prospective randomized studies, comparing HDC/ASCT versus WBRT, reported similar progression-free survival (PFS) and similar results on the decline in neurocognitive functions in a substantial proportion of patients after WBRT but not after HDC-ASCT. A recent randomized study comparing HDC/ASCT versus non-myeloablative consolidation reported a longer PFS in transplanted patients., Conclusion: ASCT conditioned with regimens, including highly CNS-penetrating agents, represents, to date, the best choice among the available consolidation strategies for fit newly diagnosed PCNSL patients.

Patients with aggressive B-cell lymphoma and MYC rearrangement at fluorescence in situ hybridization exhibit poor outcome after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In the last decade, 68 patients with Burkitt lymphoma ([BL] n = 46) or high-grade B-cell lymphoma ([HGBCL] single, double, or triple hit; n = 22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen" at 5 Italian centers. Forty-six (68%) patients were HIV+. CARMEN included a 36-day induction with sequential, single weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine-based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM (carmustina, etoposide, cytarabine, melfalan)-conditioned autologous stem cell transplantation (ASCT) after consolidation. Sixty-one (90%) patients completed induction, and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade 4 hematological toxicity was common but did not cause treatment discontinuation; grade 4 nonhematological toxicity was recorded in 11 (16%) patients, with grade 4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in 4, COVID-19, acute respiratory distress syndrome). CR rate after the whole treatment was 73% (95% confidence interval [CI], 55% to 91%) for patients with HGBCL and 78% (95% CI, 66% to 90%) for patients with BL. At a median follow-up of 65 (interquartile range, 40-109) months, 48 patients remain event free, with a 5-year progression-free survival of 63% (95% CI, 58% to 68%) for HGBCL and 72% (95% CI, 71% to 73%) for BL, with a 5-year overall survival (OS) of 63% (95% CI, 58% to 68%) and 76% (95% CI, 75% to 77%), respectively. HIV seropositivity did not have a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas., (© 2022 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.)

To optimise management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection identifying high-risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we report on the presentation, management, and outcome of an international series of 91 patients with primary central nervous system lymphoma and SARS-CoV-2 infection. SARS-CoV-2 was diagnosed before/during first-line treatment in 64 patients, during follow-up in 21, and during salvage therapy in six. Among the 64 patients infected before/during first-line chemotherapy, 38 (59%) developed pneumonia and 26 (41%) did not clear the virus. Prolonged exposure to steroids before viral infection and/or treatment with high-dose cytarabine favoured pneumonia development and virus persistence and were associated with poorer survival; 81% of patients who did not clear virus died early from coronavirus disease 2019 (COVID-19). Vaccination was associated with lower pneumonia incidence and in-hospital mortality. Chemotherapy was initiated/resumed in 43 (67%) patients, more commonly among patients who did not develop pneumonia, cleared the virus, or did not receive steroids during infection. Chemotherapy resumption in patients with viral persistence should be indicated cautiously as it was associated with a poorer survival (6-month, 70% and 87%, p = 0.07). None of the 21 patients infected during follow-up died from COVID-19, requiring similar measures as infected subjects in the general population., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Chronic myeloid leukemia (CML) is a malignant clonal disorder of hematopoietic stem cells characterized by a translocation of genetic material between chromosomes 9 and 22 resulting in the BCR-ABL fusion oncogene expression. Nilotinib is a potent second-generation tyrosine kinase inhibitor available as first line treatment. Among side effects QTc interval prolongation, pancreatitis, metabolic disorders and skin reactions are the most commonly seen., Case Report: Here we describe a rare case of lichen planopilaris eruption that developed during therapy with nilotinib., Management & Outcome: Nilotinib dosage was reduced together with introduction of hydroxychloroquine with progressive improvement of alopecia., Discussion: Collaboration with dermatologist and nilotinib dose reduction allowed to continue the drug maintaining major molecular response and patient's quality of life.

Introduction: The modern treatment of patients with primary central nervous system lymphoma (PCNSL) consists of two phases: induction, currently represented by a high-dose-methotrexate-based polychemotherapy, and consolidation. The optimal consolidation therapy has not been defined yet, but several strategies, such as whole-brain radiotherapy (WBRT), high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT) or nonmyeloablative chemotherapy, have been addressed in important randomized trials., Areas Covered: This review provides an overview of the current role of consolidation strategies in young and fit patients with newly diagnosed PCNSL. Publications in English language, peer-reviewed, from high-quality international journals, edited from 2003 to 2021 were identified on PubMed., Expert Opinion: Consolidation treatment significantly improved outcomes of PCNSL. Radiotherapy had represented for years the only choice in the consolidation therapy, but large randomized trials have demonstrated that HDC/ASCT is equally effective and associated with lower neurotoxicity risk in patients younger than 65-70 years. Encouraging results have been obtained using reduced-dose WBRT, while a recent randomized trial failed to demonstrate that consolidation with nonmyeloablative chemotherapy is more effective than HDC/ASCT in PCNSL patients. A personalized consolidation treatment, driven also by a response prediction model based on radiological and molecular details, may improve the management of PCNSL patients.

Purpose of Review: We review the preclinical and clinical experience with first and subsequent generation Bruton's tyrosine kinase inhibitors in B-cell lymphoproliferative diseases, highlighting the rationale for their clinical use in primary central nervous system diffuse large B-cell lymphoma (PCNSL)., Recent Findings: Growing knowledge on the molecular and genetic profile of PCNSL has provided the basis for new drug development targeting aberrantly activated oncogenic signal transduction pathways. PCNSL exhibits frequent genetic alterations of components of the B-cell and Toll-like receptor signalling pathways. On the basis of these discoveries and the limited efficacy obtained with chemotherapy in refractory and relapsed PCNSL, activity of new targeted agents, such as Bruton's tyrosine kinase inhibitors, has been explored with promising results., Summary: Innovative therapeutic strategies, applied in first line, have contributed to improved outcomes in patients with PCNSL, making this disease potentially curable in young and fit patients. However, response to induction therapies remains suboptimal and the best consolidative therapy has yet to be defined. In this regard, given the activity of Bruton's tyrosine kinase inhibitors in the refractory and relapsed PCNSL setting, these agents are currently being explored as part of combination regimens for induction therapy of newly diagnosed PCNSL., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) represents a relevant challenge in onco-hematology. PCNSL has specific molecular profile and biological characteristics that distinguish it from systemic DLBCL. Several translational studies have allowed for significant improvement in the knowledge about its genomic and molecular profile. High-dose-methotrexate-based chemotherapy followed whole-brain irradiation or autologous stem cell transplantation is the most commonly used therapeutic approach in PCNSL patients. Areas covered: This work provides an overview of the new biomarkers of PCNSL, focusing on their potential diagnostic, predictive and prognostic role. Publications in English language, peer-reviewed, high-quality international journals, were identified on PubMed. Expert opinion: Early diagnosis, a better antitumor response definition and recognition of new effective treatments are important research fields aiming to improve PCNSL outcome and management. The acquisition of new molecular and genomic knowledge in PCNSL has allowed for the attainment of promising diagnostic and prognostic tools as well as the development of clinical trials with new therapeutic approaches beyond chemotherapy agents, which have demonstrated activity in refractory/relapsed PCNSL and deserve to be investigated in first-line therapy.

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR-human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF/R-CHOP would be declared active if ≥12 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11., (© 2020 by The American Society of Hematology.)

We report final results of a phase II trial addressing efficacy and feasibility of lenalidomide maintenance in patients with chemosensitive relapse of diffuse large B-cell lymphoma (DLBCL) not eligible for or failed after autologous stem cell transplantation (ASCT). Patients with relapsed DLBCL who achieved at least a partial response to salvage chemoimmunotherapy were enrolled and treated with lenalidomide 25 mg/day for 21 of 28 days for 2 years or until progression or unacceptable toxicity. Primary endpoint was 1-year PFS. Forty-six of 48 enrolled patients were assessable. Most patients had IPI ≥2, advanced stage and extranodal disease before the salvage treatment that led to trial registration; 28 (61%) patients were older than 70 years. Lenalidomide was well tolerated. With the exception of neutropenia, grade-4 toxicities occurred in <1% of courses. Three patients died of complications during maintenance and three died due to second cancers at 32 to 64 months. There were 13 SAEs recorded in 12 patients; all these patients but two recovered. Lenalidomide was interrupted due to toxicity in other 6 patients, and 25 patients required dose reduction (transient in 21). At 1 year from registration, 31 patients were progression free. After a median follow-up of 65 (range 39-124) months, 22 patients remain progression free, with a 5-year PFS of 48% ± 7%. The duration of response to lenalidomide was longer than response to prior treatment in 30 (65%) patients. Benefit was observed both in de novo and transformed DLBCL, germinal-center-B-cell and nongerminal-center-B-cell subtypes. Twenty-six patients are alive (5-year OS 62% ± 7%). With the limitations of a nonrandomized design, these long-term results suggest that lenalidomide maintenance might bring benefit to patients with chemosensitive relapse of DLBCL not eligible for or failed after ASCT. Lenalidomide was associated with durable disease control and was well tolerated in this elderly population. Further investigations on immunomodulatory drugs as maintenance in these high-risk patients are warranted., (© 2020 John Wiley & Sons Ltd.)

Purpose: Less invasive left ventricular assist device implantation became feasible with the development of smaller devices. This study evaluated a sutureless aortic anastomosis device to facilitate the implant procedure., Description: The novel anastomotic device deploys and anchors an acute-angled stent in the aortic wall to create a sutureless outflow graft anastomosis in the ascending aorta. Four aortic anastomoses were performed on the beating hearts of two pigs without cross-clamping or cardiopulmonary bypass., Evaluation: The procedure was fast and simple. The time of anastomosis averaged 8.1 minutes, with merely oral instructions to the operating surgeon. The design of the stent allowed the outflow graft to be implanted with the intended angulation of 45 degrees., Conclusions: This proof-of-concept study demonstrates the feasibility and short-term success of the proposed sutureless anastomotic device. Further preclinical studies are necessary to evaluate long-term durability of the anastomosis., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow-up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa-associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty-five per cent of the patients were female. The median age at diagnosis was 62 (range 28-88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression-free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long-term disease-free survival for patients with localized disease. Systemic treatment, including alkylating-containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can't be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of "naked" or "conjugated" anti-CD20 monoclonal antibodies as a single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role in the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs, and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.

The outcome of patients with follicular lymphoma has substantially improved in recent years, mainly due to the widespread use of the monoclonal antibody rituximab and partially due to autologous and allogeneic transplantation, and the introduction of new drugs and to the improvement in diagnostic accuracy. The choice of therapy is still based on patient characteristics, extension of disease and clinical prognostic factors. The majority of patients in need of treatment are still treated with cytotoxic agents in combination with rituximab; nevertheless a number of new agents, which are active in this disease, have recently been developed. It has yet to be determined, whether they will partly or completely replace chemotherapy in the near future. This review focuses on the role and the choice of chemotherapy in different clinical situations of follicular lymphoma, in a time when chemotherapy-free treatment becomes more and more of a topic of discussion.

Pegfilgrastim has equivalent efficacy to daily G-CSF in enhancing neutrophil recovery after chemotherapy, but conclusive data concerning its use for peripheral blood stem cell (PBSC) mobilization are lacking. From 2003 to 2008 we used high-dose chemotherapy in 64 lymphoma patients. At mobilization chemotherapy (ESHAP) the first 26 patients used unconjugated G-CSF, while the remaining 38 patients received Pegfilgrastim. At the time of harvest 25 patients collected stem cells after the use of G-CSF and 36 in the Peg group. No statistical by significant differences were observed in median peripheral CD34+ cells mobilized (77 μL versus 71 μL) and in collected PBSC (12.3 × 10(6)/kg versus 9.4 × 10(6)/kg p = 0.76). In the PEG group all patients collected the target PBSC with a single apheresis with a greater proportion of "optimal" mobilizers (83% versus 64%; p = 0.05). In conclusion a single dose of Pegfilgrastim could be a valid alternative to unconjugated G-CSF to mobilize PBSC in lymphoma patients., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

There is growing interest in defining biomarkers that could predict response to different chemotherapeutic agents. Excision repair cross complement 1 (ERCC1) enzyme has been shown to predict benefit of cisplatin in different types of cancer. As cisplatin-based regimens are frequently used in the salvage treatment of diffuse large B-cell lymphomas (DLBCL), a small pilot study was conducted to determine whether ERCC1 is expressed in this disease or not. Out of seven patients examined, only one had a 25% ERCC1 expression, which could represent a tumour truly expressing this marker. However, expression was not able to predict response to treatment. It remains unclear whether ERCC1 could serve as a predictive marker for cisplatin in this disease requiring further studies. Key Words : ERCC1 -Large B-cell lymphoma -Cisplatin resistance.