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Aims The provision of high-quality education allows the European Society of Cardiology (ESC) to achieve its mission of better cardiovascular practice and provides an essential component of translating new evidence to improve outcomes. Methods and results The 4th ESC Education Conference, held in Sophia Antipolis (December 2016), brought together ESC education leaders, National Directors of Training of 43 ESC countries, and representatives of the ESC Young Community. Integrating national descriptions of education and cardiology training, we discussed innovative pathways to further improve knowledge and skills across different training programmes and health care systems. We developed an ESC roadmap supporting better cardiology training and continued medical education (CME), noting: (i) The ESC provides an excellent framework for unbiased and up-to-date cardiovascular education in close cooperation with its National Societies. (ii) The ESC should support the harmonization of cardiology training, curriculum development, and professional dialogue and mentorship. (iii) ESC congresses are an essential forum to learn and discuss the latest developments in cardiovascular medicine. (iv) The ESC should create a unified, interactive educational platform for cardiology training and continued cardiovascular education combining Webinars, eLearning Courses, Clinical Cases, and other educational programmes, along with ESC Congress content, Practice Guidelines and the next ESC Textbook of Cardiovascular Medicine. (v) ESC-delivered online education should be integrated into National and regional cardiology training and CME programmes. Conclusion These recommendations support the ESC to deliver excellent and comprehensive cardiovascular education for the next generation of specialists. Teamwork between international, national and local partners is essential to achieve this objective.

Aim To investigate sex differences in acute myocardial infarction (AMI) guideline-indicated care as defined by the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) quality indicators. Methods Nationwide cohort study comprising 691 290 AMI hospitalisations in England and Wales (n=233 hospitals) from the Myocardial Ischaemia National Audit Project between 1 January 2003 and 30 June 2013. Results There were 34.5% (n=238 489) women (median age 76.7 (IQR 66.3–84.0) years; 33.9% (n=80 884) ST-elevation myocardial infarction (STEMI)) and 65.5% (n=452 801) men (median age 67.1 (IQR 56.9–77.2) years; 42.5% (n=192 229) STEMI). Women less frequently received 13 of the 16 quality indicators compared with men, including timely reperfusion therapy for STEMI (76.8% vs 78.9%; p Conclusion According to the ESC ACCA AMI quality indicators, women in England and Wales less frequently received guideline-indicated care and had significantly higher mortality than men. Greater attention to the delivery of recommended AMI treatments for women has the potential to reduce the sex-AMI mortality gap.

Atrial fibrillation (AF) and stroke are important major health problems that share common risk factors and frequently coexist. Left atrial (LA) remodeling is an important underlying substrate for AF and stroke. LA dilation and dysfunction form a prothrombotic milieu characterized by blood stasis and endothelial dysfunction. In addition, alterations of the atrial cardiomyocytes, increase of noncollagen deposits in the interstitial space and fibrosis, favor the occurrence of re-entry that predisposes to AF. Eventually, AF further impairs LA function and promotes LA remodeling, closing a self-perpetuating vicious circle. Multimodality imaging provides a comprehensive evaluation of several aspects of LA remodeling and offers several parameters to identify patients at risk of AF and stroke. How multimodality imaging can be integrated in clinical management of patients at risk of AF and stroke is the focus of the present review paper.

Supplemental Digital Content is available in the text., Background: Lone atrial fibrillation (AF) may reflect a subclinical cardiomyopathy that persists after sinus rhythm (SR) restoration, providing a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics in patients with AF but no significant comorbidities. Methods: Fifty-three patients with symptomatic paroxysmal or persistent AF and without significant valvular disease, uncontrolled hypertension, coronary artery disease, uncontrolled thyroid disease, systemic inflammatory disease, diabetes mellitus, or obstructive sleep apnea (ie, lone AF) undergoing ablation and 25 matched control subjects in SR were investigated. Magnetic resonance imaging quantified LV ejection fraction (LVEF), peak systolic circumferential strain (PSCS), and left atrial volumes and function, whereas phosphorus-31 magnetic resonance spectroscopy evaluated ventricular energetics (ratio of phosphocreatine to ATP). AF burden was determined before and after ablation by 7-day Holter monitoring; intermittent ECG event monitoring was also undertaken after ablation to investigate for asymptomatic AF recurrence. Results: Before ablation, both LV function and energetics were significantly impaired in patients compared with control subjects (LVEF, 61% [interquartile range (IQR), 52%–65%] versus 71% [IQR, 69%–73%], P

Supplemental Digital Content is available in the text., Rationale: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. Objective: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase–derived O2−, whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2−. In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase–mediated translocation of Rac1 and p47phox from the cytosol to the membranes. Induction of O2− production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ in EpAT. Conclusions: We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress.

Despite remarkable advances in antiarrhythmic drugs, ablation procedures, and stroke-prevention strategies, atrial fibrillation (AF) remains an important cause of death and disability in middle-aged and elderly individuals. Unstructured management of patients with AF sharply contrasts with our detailed, although incomplete, knowledge of the mechanisms that cause AF and its complications. Altered calcium homeostasis, atrial fibrosis and ageing, ion-channel dysfunction, autonomic imbalance, fat-cell infiltration, and oxidative stress, in addition to a susceptible genetic background, contribute to the promotion, maintenance, and progression of AF. However, clinical management of patients with AF is currently guided by stroke risk parameters, AF pattern, and symptoms. In response to this apparent disconnect between the known pathophysiology of AF and clinical management, we propose a roadmap to develop a set of clinical markers that reflect the major causes of AF in patients. Thereby, the insights into the mechanisms causing AF will be transformed into a format that can underpin future personalized strategies to prevent and treat AF, ultimately informing better patient care.

First line therapy of patients with marginal zone lymphomas (MZL) is not well established and various regimens with chemo-immunotherapy can be used. Rituximab plus bendamustine (BR) is an effective and manageable treatment option for patients affected by indolent non-Hodgkin lymphoma. The aim of this monocentric retrospective study was to analyze the effectiveness and safety of the use of BR regimen in MZL patients in first line in daily clinical practice. The treatment schedule was rituximab at the dose of 375 mg/m2 on day 1 of each cycle and bendamustine at the dose of 90 mg/m2 on day 2 and 3, every 28 days for a maximum of 6 cycles. We analyzed 65 MZL patients (28 extranodal [EMZL], 23 splenic [SMZL], and 14 nodal [NMZL]) who underwent BR regimen as first line treatment. The median time from diagnosis to therapy was 2.5 months. Final responses were: 38 complete response (CR, 58.5%), 20 partial response and 7 progressive disease, leading to an overall response rate (ORR) of 89.2%. With respect to the histology, the ORR was 89.3% for EMZL, 82.6% for SMZL and 100% for NMZL, respectively (difference not statistically significant). With a median follow-up time of 44.6 months (range, 3.3-175.0 months), 2 (one EMZL after 42 months and one SMZL after 10 months) of 38 (5.2%) CR patients had disease relapse, yielding an estimated disease free survival of 89.2% at 61.1 months. The estimated 6-year progression free survival was 71.8% with 15 relapsed/progressed patients showing lymphoma recurrence within 48 months from end of treatment. The most frequently reported adverse events (any grade) were neutropenia (N = 35, 53.8%), fatigue (N = 15, 23.0%), and nausea (N = 12, 18.4%). All toxicities quickly resolved and no treatment-related death occurred. The BR regimen is effective and feasible in MZL patients inducing prolonged disease control with manageable toxicities.

Immune checkpoint inhibitors (ICIs) show efficacy in the treatment of non-Hodgkin lymphomas (NHL). However, these agents are associated with a unique group of side effects called immune-related adverse events (irAEs). We conducted an observational retrospective/prospective study on patients with relapsed/refractory NHL treated with ICI to determine the incidence of irAEs assessing the type, severity, and timing of onset, outcome and relationship with study drugs of these events. Thirty-two patients underwent ICI as single agent (N = 20) or in combination (N = 12). Ten patients (31.3%) developed at least one irAE for a total of 17 irAEs. Median time to presentation of irAEs was 69 days (range 0–407) with a median resolution time of 16 days (range 0–98). Progression free survival at 24 months for patients who developed an irAE was 40% and 31.8% for who did not. Overall survival for the two groups did not differ (at 24 months 40.0% and 62.5% for patients without and with irAE, respectively), but the median for who developed an irAE was not reached. The incidence of irAEs was associated with better long-term survival in NHL treated with ICIs but patients’ disease conditions need to be carefully evaluated to decide the optimal management.

Chimeric antigen receptor (CAR) T-cell therapy is an emerging highly effective treatment for refractory haematological malignancies. Unfortunately, its therapeutic benefit may be hampered by treatment-related toxicities, including neurotoxicity. Early aggressive treatment is paramount to prevent neurological sequelae, yet it potentially interferes with the anti-cancer action of CAR T-cells. We describe four CAR T-cells infused patients who presented with reiterative writing behaviours, namely paligraphia, as an early manifestation of neurotoxicity, and eventually developed frontal predominant encephalopathy (one mild, three severe). Paligraphia may represent an early, specific, and easily detectable clinical finding of CAR T-cell therapy-related neurotoxicity, potentially informing its management.

Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24–88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04–28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p

BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of themutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long-term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR.

International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.

The treatment of hairy cell leukemia (HCL) has considerably changed over years. Purine analogues, namely cladribine, now represent the treatment of choice. One hundred and eighty-four patients were followed between 1986 and 2018 and treated according to era-specific guidelines. Responses were classified by combining Consensus Resolution criteria and marrow immunohistochemistry. Patients were grouped according to the number of treatment lines they received. Patients treated first line responded in 86% of cases, with complete response (CR) in 44% of cases. Response rates remained high throughout the first four lines (84%, 81%, 79% for the second line onward, with CR in 38%, 37%, 15% of cases respectively). One hundred and twenty-two patients received cladribine as first line treatment, with a response rate of 86% and a CR rate of 54%. Among the 66 CR patients, 45 (68%) have never received further therapy: 11 patients are in continuous CR between 5 and 10 years after treatment, 14 between 10 and 20 years and three patients at more than 20 years. Median time-to-next treatment (TTNT) for frontline cladribine-treated patients was 8.2 years: partial responders had a significantly shorter median TTNT than CR patients (5.3 years vs median not reached at 25.8 years, p< 0.001). Patients with HCL require subsequent lines of therapy in more than 50% of cases. Purine analogues allow significant response rates when applied first line and upon retreatment. Some patients may enjoy long lasting treatment-free intervals after one course of cladribine.

Primary mediastinal B cell lymphoma is a rare entity and often should be promptly treated as a hematological emergency: The initial treatment decision is crucial for the management of this disease. An observational retrospective study was conducted with the aim to improve information on treatment and outcomes of primary mediastinal B cell lymphoma in real practice. After 12 cycles of MACOP-B regimen (methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone) with or without rituximab, 120 patients out of 151 (79.5%) achieved a complete response and 12 (7.9%) a partial response leading to a global response of 87.4%. The 21-year overall survival is 82.6%; progression-free and disease-free survivals are 69.3% and 86.4%, respectively. Regarding the role of radiotherapy (RT), patients with a negative PET scan after MACOP-B did not undergo RT: One out of these 48 (2.1%) showed a relapse at 11 months. All relapsed/refractory patients who achieved a response with checkpoint inhibitors are still in continuous complete response with a median follow-up of 14 months. Data that we have gathered over a 30-year experience in the treatment of primary mediastinal B cell lymphoma patients clearly indicate that a third-generation chemotherapy regimen such as MACOP-B is feasible and easily deliverable on an outpatient basis. Regarding the unmet medical need of relapsed/refractory patients, new encouraging results occurred with the advent of the checkpoint inhibitors.

Objective: Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous T-cell malignancies representing 5%–10% of aggressive lymphomas. The prognosis is poor for patients with relapsed/refractory (R/R) disease, with a median overall survival of less than 6 months and no standardized treatments. We discuss the role of the phosphatidylinositol 3-kinase (PI3K) γδ inhibitor duvelisib as bridge to allotransplantation in a patient with R/R PTCL. Methods: Case report. Results: A 55-year-old woman diagnosed with relapsed nodal PTCL with T-follicular helper phenotype received PI3K γδ inhibitor duvelisib in the context of the phase II PRIMO clinical trial. After two cycles at a dose of 75 mg twice daily, the patient achieved complete response (CR), which was subsequently consolidated with human leukocyte antigen fully matched unrelated donor allotransplantation. No major toxicities were recorded during the duvelisib treatment period or during hospitalization for allotransplantation. At the latest follow-up, the patient was alive and still in CR 10 months posttransplant. Conclusions: Duvelisib should be further explored as a bridge to allotransplantation in patients with R/R PTCL, given the success and low toxicity in our patient.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder caused by the clonal proliferation and accumulation of small, mature-appearing CD5+ B-lymphocytes in the blood, bone marrow and ...

Cold agglutinin mediated autoimmune hemolytic anemia is an uncommon disorder characterized by the presence of cold agglutinins and it is associated with clinical symptoms caused by anemia and agglu...

[Figure][1] ![Figure][1] Together, our 2 societies, the European Society of Cardiology (ESC) and the European Society of Medical Oncology (ESMO), have clocked up more than a century advancing their respective fields. Although ESMO is half the age of the ESC, it draws a similar

While pralatrexate (PDX) has been successfully developed for the treatment of T‐cell lymphoma, the mechanistic basis for its T‐cell selectivity and acquired resistance remains elusive. In an effort to potentially identify synergistic combinations that might circumnavigate or delay acquired PDX resistance, we generated resistant cells lines over a broad concentration range. PDX‐resistant cell lines H9‐12 and H9‐200 were developed, each exhibiting an IC50 of 35 and over 1000 nM, respectively. These lines were established in vitro from parental H9 cells. Expression analysis of the proteins known to be important determinants of antifolate pharmacology revealed increase expression of dihydrofolate reductase (DHFR) due to gene amplification, and reduced folate carrier1 downregulation, as the putative mechanisms of resistance in H9‐12 and H9‐200 cells. Cross resistance was only seen with methotrexate but not with romidepsin, azacitidine (AZA), decitabine, gemcitabine, doxorubicin, or bortezomib. Resistance to PDX was reversed by pretreatment with hypomethylating agents in a concentration‐dependent fashion. Comparison of gene expression profiles of parental and resistant cell lines confirmed markedly different patterns of gene expression, and identified the dual specificity phosphatase four (DUSP4) as one of the molecular target of PDX activity. Reduced STAT5 phosphorylation following exposure to PDX was observed in the H9 but not in the H9‐12 and H9‐200 cells. These data suggest that combination with hypomethylating agents could be potent, and that DUSP4 and STAT5 could represent putative biomarkers of PDX activity.

Indolent non-follicular lymphomas (inFLs) are generally regarded as incurable, apart from extranodal mucosa-associated lymphatic tissue lymphomas, which can be partially cured by surgery, local radiotherapy, or antibiotic treatment. The aim of the present study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab (FMR) in inFL patients considering all the different entities belonging to this group. An observational retrospective study was conducted on 143 inFL patients providing that their first chemoimmunotherapy performed was FMR regimen and diagnosis from September 2000 to March 2011. There were 32 small lymphocytic lymphomas and 111 marginal zone lymphomas. At the end of treatment, overall response rate was 96.5% with 88% of complete responses (CR) and 8.5% of partial responses. With a median follow-up of 48 months, 10 out of 125 (8%) CR patients had disease relapse, yielding an estimated 9-year disease-free survival (DFS) of 74.9% and an estimated 10-year overall survival of 92.8%. The estimated 9-year progression free survival was 70.5%. The 10 relapsed patients showed lymphoma recurrence within 52 months: after this time, the DFS curve presented a plateau configuration. Only two (1.4%) patients developed a secondary hematological neoplasia. This study showed promising findings for the use of a fludarabine-based regimen in combination with rituximab in the front-line treatment of symptomatic inFL with a noteworthy high percentage of CR associated to an interesting long-term DFS and favorable acute and long-term safety profile. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical Practice Points Relapsed and refractory T-cell lymphomas represent a great challenge for clinicians because of their scarce tendency to show a response to further conventional treatments: in particular, for systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) treatment outcomes remain unknown and their potential benefits are still difficult assess. The conventional therapy in relapsed/refractory ALCL is poorly defined and no standard of care exists in this setting. It is difficult to obtain complete remissions using single-agent therapy. The wide expression of the CD30 antigen in ALCL cells makes this molecule a suitable target for monoclonal antibodies. In a phase II trial, the anti-CD30 monoclonal immunoconjugated brentuximab vedotin has shown an impressive effect in patients with relapsed ALKnegative ALCL, with high overall and complete response rates. Brentuximab vedotin is now approved by the Food and Drug Administration for the treatment of patients with relapsed ALCL, and now represents a valid treatment strategy for heavily pretreated patients.

LETTER TO THE EDITOR

Hairy cell leukemia (HCL) patients could have an excellent prognosis with adequate treatment. Treatments are not generally curative but are extremely effective in inducing long-lasting clinical remissions. An observational retrospective study was conducted on a single-center registry of 144 patients with a median follow-up of 11.5 years, focusing on long-lasting continuous first complete remissions (CR) wondering if patients can be cured only with front-line approach. CR for more than 5 years after first-line therapy were found in 22.2 \% cases. The median duration of response was 9.8 years, while for relapsed patients, the first response had a median duration of 2.4 years. Three different subsets of long-lasting first CR were identified: 15 patients are between 5 and 10 years with a median duration of CR of 6.5 years; 7 patients are between 10 and 15 years with a median duration of CR of 12.3 years; and 10 patients present a follow-up superior to 15 years with a median duration of CR of 20.0 years. There is a need for continuous study in this field to better define the optimal therapeutic regimen and, in particular, the biological issues since at least 20-25 \% of HCL patients can be cured with only one treatment.

Not available.

Bronchial-associated lymphoid tissue (BALT) lymphoma is an extranodal primary pulmonary lymphoma. The optimal therapy for this rare disease is still debated, and few heterogeneous data are available in literature. The aim of our study was to critically review data of patients with BALT lymphoma treated in first-line therapy with fludarabine and mitoxantrone-containing regimens (with or without rituximab) to investigate the effectiveness and the safety of this approach and patients' survival. An observational retrospective study was performed on homogenous clinical data from 17 patients with biopsy-proven diagnosis of BALT. All the patients were treated with fludarabine and mitoxantrone-containing regimen therapy. Radiological findings were also reviewed to assess the role of (18) fluoro-deoxyglucose positron emission tomography in the initial assessment and in the monitoring of this extranodal lymphoma. A high percentage of response was observed: 82.3% of patients achieved a complete response, 11.8% a partial response. Furthermore, a very remarkable progression-free survival (71%) and overall survival (100%) were estimated at 14 years. No relevant toxicities were registered. Our results support the use of fludarabine and mitoxantrone-containing regimens as first-line therapy in the treatment of BALT lymphoma even if further data are necessary to consolidate our findings. Positron emission tomography scanning may provide additional valuable information in the assessment of BALT lymphoma. Copyright © 2012 John Wiley & Sons, Ltd.

There is no international consensus on front-line optimal chemotherapy regimen for advanced stage follicular lymphoma (FL) patients, or a clear definition of cure for this disease. Aim of this study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab in a subset of poor prognosis FL patients with particular focus on the long-term disease-free survival. A retrospective study was conducted on 142 intermediate/high-risk FL patients treated in first-line with fludarabine, mitoxantrone, and rituximab regimen. Responses, safety, and survival were evaluated. The prognostic value of positron emission tomography (PET) was also investigated in a 56-patients subset. Overall response rate was 95.5% including 88% of complete responses. With a median follow-up of 48 months, 18% of patients had disease relapse, yielding an estimated 12-year disease-free survival (DFS) of 72%. All cases showed the lymphoma recurrence within 40 months: after this timing the DFS curve presented a plateau. Overall survival was 73% at 12 years. Post-treatment PET positivity remains a highly significant predictor of disease progression. The observed high rate of complete responses following the use of fludarabine, mitoxantrone-based regimen in combination with rituximab seems to be the first step to improve DFS. Our study could be the starting point to consider DFS as a potential alternative endpoint of future clinical trials on FL patients. Am. J. Heamtol. 88:E273–E276, 2013. © 2013 Wiley Periodicals, Inc.

Background Lymphomas with involvement of soft tissues as a primary event are very rare. The published studies have a small sample size, most of them being reported as case reports. Patients and Methods In this article we describe our experience with soft tissue non-Hodgkin lymphomas (NHL) diagnosed and treated in our institution over a 15-year period. Moreover, we systematically review the available data from the literature in the past 2 decades, considering all the published series and case reports available from 1990 to 2011 using a PubMed access. Results In the monocentric analysis, 16 consecutive patients treated at our Institution from 1996 to 2011 were considered. In the literature search, we selected 16 case reports (18 patients) and 5 case series (49 patients), including a total of 67 patients. Eighty-three patients were finally considered in the combined analysis. The most common histologic subtype was diffuse large B cell lymphoma (DLBCL) (>50% of cases in both groups). In both analyses we observed an inferior outcome for DLBCL compared with indolent B-cell NHL (5-year progression free survival: 34% vs. 64%, respectively, in the combined analysis; P = .01). Furthermore, the prognosis in the DLBCL group appears to be worse compared with the historical data of DLBCL patients treated with chemoimmunotherapy. Conclusions Though indolent soft tissue B-cell NHLs appear to have a good outcome, soft tissue DLBCLs represent an anatomic-clinical entity with aggressive features, and dismal prognosis. Strategies of first-line therapy intensification could be considered. Studies aiming to a better biologic characterization of this peculiar entity are warranted.

Introduction Over the past 30 years, we have obtained remarkable progress in the treatment of patients with hairy cell leukemia (HCL). Despite his, the disease-free survival after effective therapy (purine nucleoide analogues) has not reached a plateau, suggesting control rather han cure of the disease. Combined chemoimmunotherapy may be onsidered the most promising treatment for disease eradication, but he optimal strategy for using this approach is still under active nvestigation. We report the case of a patient with HCL who was treated with everal therapeutic approaches including pentostatin, cladribine, inerferon-alpha (IFN), and rituximab during the 11 years of his isease history. After disease progression, the patient was successfully reated with allogeneic stem cell transplantation (allo-SCT), achievng a clinical remission.

The radiosensitivity of lymphomas as well as the local targeted delivery of high doses of radiation make radioimmunotherapy (RIT) an attractive therapeutic option. RIT is indeed an underestimated tool. In follicular lymphoma (FL), RIT represents one of the most effective single agents. The two most commonly used radioimmunoconjugates are 90Y-ibritumomab tiuxetan (Zevalin®) and 131I-tositumomab, both based on murine anti-Cd20 antibodies. RIT has demonstrated efficacy in relapsed/refractory FL and was approved for this indication [1]. Subsequently, many trials have evaluated the role of RIT consolidation after initial tumor debulking with chemotherapy or immunochemotherapy [2] and several phase II studies supported these results [3–5]. We now report updated long-term efficacy and toxicity results of a multicenter nonrandomized phase II trial of fludarabine and mitoxantrone plus RIT (fludarabine, mitoxantrone, zevalin trial), demonstrating that this combination was safe and very effective in untreated FL patients.

We report 13 multiple myeloma (MM) or lymphoma patients who were failing PBSC mobilization after disease-specific chemotherapy and granulocyte-CSF (G-CSF), and received plerixafor to successfully collect PBSCs. Patients were considered poor mobilizers when the concentration of PB CD34(+) cells was always lower than 10 cells/μL, during the recovery phase after chemotherapy and/or were predicted to have inadequate PBSC collection to proceed to autologous transplantation. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to three consecutive days, while continuing G-CSF, 10-11 h before the planned leukapheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a 4.7 median fold-increase in the number of circulating CD34(+) cells after plerixafor as compared with baseline CD34(+) cell concentration (from a median of 6.2 (range 1-12) to 21.5 (range 9-88) cells/μL). All patients collected >2 × 10(6) CD34(+) cells/kg in 1-3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization.