Publications by authors named "Alessandro Broccoli"

92 Publications

Invited Review: Will Consolidation with ASCT Be a Thing of the Past for MCL and PTCL?

Curr Hematol Malig Rep 2021 Mar 1. Epub 2021 Mar 1.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.

Purpose Of Review: The treatment landscape of mantle cell (MCL) and peripheral T-cell lymphomas (PTCL) is rapidly changing; however, despite improvement in patients' survival, they still remain a largely incurable diseases. Treatment choice is dependent on patient factors, prior therapy, remission duration, and candidacy for stem cell transplantation (SCT). There are subsets of high-risk patients who do not benefit substantially from autologous SCT (ASCT) and for whom alternative targeted approaches are being examined. Here, we critically analyze the actual role of ASCT in PTCL and MCL.

Recent Findings: Research in areas of maintenance therapy and minimal residual disease is ongoing to identify MCL patients who may not require ASCT for durable response. Moreover, there are subsets of high-risk MCL patients who do not benefit substantially from ASCT and for whom alternative, targeted approaches are being examined. Much less clear evidence exists regarding the impact of consolidative ASCT in PTCL, mainly for the heterogeneity of these lymphomas: it is still controversial whether patients who achieved a complete response significantly take advantage of this procedure over active surveillance only. Several clinical and biologic markers are available to predict prognosis; however, despite improvements in outcomes, standard therapeutic approaches have not been able to overcome high-risk disease features for PTCL and MCL. Thus, the need of ASCT for these diseases is still matter of debate among hematologists.
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http://dx.doi.org/10.1007/s11899-021-00609-5DOI Listing
March 2021

Treatment and outcomes of primary mediastinal B cell lymphoma: a three-decade monocentric experience with 151 patients.

Ann Hematol 2020 Dec 10. Epub 2020 Dec 10.

IRCCS - Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1007/s00277-020-04364-0DOI Listing
December 2020

How do we sequence therapy for marginal zone lymphomas?

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):295-305

Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; and Istituto di Ematologia "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale. Università degli Studi, Bologna, Italy.

Marginal zone lymphomas are indolent diseases. Overall survival rates are very good, but patients tend to relapse and may do so several times. The concept of treatment sequencing is therefore important and necessary to preserve adequate organ function and to avoid excessive toxicity, with the final goal of achieving long survival times. Systemic treatments and chemotherapy are considered to be an option in multiply relapsing disease, in cases that are in an advanced stage at presentation or relapse, and in cases where initial local treatments lack efficacy. Targeted agents and new drugs can provide chemotherapy-free alternatives in heavily pretreated patients.
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http://dx.doi.org/10.1182/hematology.2020000157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727586PMC
December 2020

Controversies in the Treatment of Peripheral T-cell Lymphoma.

Hemasphere 2020 Oct 1;4(5):e461. Epub 2020 Sep 1.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

Peripheral T-cell lymphomas are a heterogeneous group of rare diseases with an aggressive behavior and dismal prognosis. Their classification is complex and still evolving, and several biomolecular markers now help refine the prognosis of specific disease entities, although still have limited impact in tailoring the treatment. First-line treatment strategies can cure only a minority of patients and relapsed-refractory disease still represents the major cause of failure. Frontline autologous transplantation may have an impact in the consolidation of response; however, its role is still questioned as far as complete responses obtained after induction chemotherapy are concerned. Newer drugs are now being evaluated in clinical trials, but effective salvage strategies for those who experience treatment failures are lacking. Here we review and discuss the most controversial aspects of diagnosis and treatment of peripheral T-cell lymphomas.
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http://dx.doi.org/10.1097/HS9.0000000000000461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469987PMC
October 2020

Potential survival benefit for patients receiving autologous hematopoietic stem cell transplantation after checkpoint inhibitors for relapsed/refractory Hodgkin lymphoma: A real-life experience.

Hematol Oncol 2020 Dec 30;38(5):737-741. Epub 2020 Sep 30.

Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.

In recent years, novel drugs are available for the patients with relapsed/refractory Hodgkin lymphoma (HL), like immune checkpoint inhibitors (CPi). These drugs have been able to rescue a cohort of patients who subsequently could receive an allogeneic stem-cell transplant (SCT). No data were reported for subsequent autologous SCT (ASCT) after CPi. Here, we report our real-life experience in heavily pretreated HL patients undergoing ASCT as consolidation approach after CPi treatment. A retrospective observational study was conducted. Patients had CPi therapy in the context of clinical trials (n = 6) or in the named patient program (n = 7) between July 2014 and November 2019: 9 out of 13 received pembrolizumab and the remaining four underwent nivolumab. A median of 12 cycles (range, 3-16) of CPi therapy were infused. Thirteen patients underwent ASCT after CPi: 11 (84.6%) patients obtained a complete response (CR) and 2 had progression of disease, with an overall response rate of 84.6%. With a median follow-up of 3.3 years (range, 1.1-5.5), only one CR patient had disease relapse after 3.9 months from ASCT, leading to an estimated disease-free survival of 87.5% at 56.9 months. The estimated 5-year progression-free survival was 73.4% and overall survival was 92.3% at 4.8 years, respectively. No unexpected or cumulative toxicity was observed. Our results indicated that ASCT may represent a further effective therapeutic option as consolidation in HL after CPi treatment that today represents the last conventionally recognized therapeutic line.
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http://dx.doi.org/10.1002/hon.2803DOI Listing
December 2020

Effectiveness of chemotherapy after anti-PD-1 blockade failure for relapsed and refractory Hodgkin lymphoma.

Cancer Med 2020 11 2;9(21):7830-7836. Epub 2020 Sep 2.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

Programmed death-1 (PD1) blockade is an efficient and safe therapeutic option in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, a substantial proportion of patients' progresses or loses the response to anti-PD1 treatment. We retrospectively investigated the effectiveness of salvage chemotherapies (CHT) for unsatisfactory response to anti-PD1, in 25 R/R cHL patients. Twenty-three patients (92%) were refractory to the last treatment before anti-PD1. After a median of 14 cycles (range 3-52), 68% (17/25) of patients had unsatisfactory responses to anti-PD1 therapy, whereas 6 had a partial response (PR) and 2 patients achieved complete response (CR), with an overall response rate (ORR) of 32%. After a median time of 1.5 months, 15 patients received a single agent treatment and 10 had a multi-agents regimen, due to the failure of PD1 blockade. The ORR was 60% (8 CR and 7 PR). Seven patients (3 in PR and 4 in CR) underwent a consolidation strategy with stem cell transplantation. Median progression-free survival (PFS) with salvage treatment was reached at 19.1 months, while median PFS after anti-PD1 has been reached at 8.2 months. After a median follow-up of 32.4 months, 6 patients died while 13 are still in CR. The median overall estimated from the start of CHT was not reached. The efficacy of treatment following anti-PD1 is not yet established, especially in lymphoma patients. To note, in our series, a subset of heavily pre-treated and chemo-refractory patients increased response rates to and survival with CHT given after exposure to immune-checkpoint inhibitors.
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http://dx.doi.org/10.1002/cam4.3262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643640PMC
November 2020

Cutaneous adverse-events in patients treated with Ibrutinib.

Dermatol Ther 2020 11 27;33(6):e14190. Epub 2020 Sep 27.

Division of Dermatology Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italia.

Ibrutinib is a Burton tyrosine kinase inhibitor (BTKi) approved for the treatment of several hematologic malignancies. Analyze skin adverse events (SAE). All the patients treated with Ibrutinib featuring cutaneous adverse events were selected. Twenty five patients were retrieved with a median interval between Ibrutinib start and SAE time of onset of 120 days. Most common SAE observed involved hairs and nails. Eczematous reaction and leucocytoclastic vasculitis were also detected. One patient had a long-history Ibrutinib treatment and experienced numerous cutaneous adverse events. Infective disease such as superficial mycosis and impetigo were rarely present in our series. Despite the development of cutaneous SAE, all the patients continued their concomitant drugs without the onset of any further SAE. Our data suggest Ibrutinib-associated rash should be distinguished in early and late events and a careful dermatologic management of patients should be scheduled.
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http://dx.doi.org/10.1111/dth.14190DOI Listing
November 2020

Bendamustine-rituximab regimen in untreated indolent marginal zone lymphoma: experience on 65 patients.

Hematol Oncol 2020 Oct 29;38(4):487-492. Epub 2020 Jul 29.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

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/m on day 1 of each cycle and bendamustine at the dose of 90 mg/m 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.
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http://dx.doi.org/10.1002/hon.2773DOI Listing
October 2020

Management of central nervous system relapse in a young patient affected by primary mediastinal large B-cell lymphoma: A case report.

Clin Case Rep 2020 Jun 8;8(6):933-937. Epub 2020 Apr 8.

Institute of Hematology "L. e A. Seràgnoli" University of Bologna Bologna Italy.

In primary mediastinal large B-cell lymphoma, central nervous system (CNS) relapse is an uncommon event with a dismal prognosis. We report about the successful management of CNS relapse with chemoimmunotherapy according to MATRix (methotrexate, cytarabine, thiotepa, and rituximab) protocol followed by autologous stem cell transplant.
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http://dx.doi.org/10.1002/ccr3.2706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303876PMC
June 2020

Diagnostic accuracy of positron emission tomography/computed tomography-driven biopsy for the diagnosis of lymphoma.

Eur J Nucl Med Mol Imaging 2020 12 15;47(13):3058-3065. Epub 2020 Jun 15.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, via Massarenti 9, 40138, Bologna, Italy.

Introduction: Biopsy of affected tissue is required for lymphoma diagnosis and to plan treatment. Open incisional biopsy is traditionally the method of choice. Nevertheless, it requires hospitalization, availability of an operating room, and sometimes general anesthesia, and it is associated with several drawbacks. Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) can be potentially used to drive biopsy to the most metabolically active area within a lymph node or extranodal masses.

Methods: A study of diagnostic accuracy was conducted to assess the performance of a PET-driven needle biopsy in patients with suspect active lymphoma.

Results: Overall, 99 procedures have been performed: three (3.0%) were interrupted because of pain but were successfully repeated in two cases. Median SUVmax of target lesions was 10.7. In 84/96 cases, the tissue was considered adequate to formulate a diagnosis (diagnostic yield of 87.5%) and to guide the following clinical decision. The target specimen was a lymph node in 60 cases and an extranodal site in 36. No serious adverse events occurred. The sensitivity of this procedure was 96%, with a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 75%.

Conclusion: Patients can benefit from a minimally invasive procedure which allows a timely and accurate diagnosis of lymphoma at onset or relapse.
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http://dx.doi.org/10.1007/s00259-020-04913-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680329PMC
December 2020

Elderly Non-GCB Diffuse Large B-Cell Lymphoma Patient Responding to Lenalidomide after Epicardial Relapse: A Case Report.

Acta Haematol 2020 11;143(6):594-597. Epub 2020 May 11.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy,

There is an unmet clinical need for elderly or unfit diffuse large B-cell lymphoma (DLBCL) patients ineligible for autologous stem cell transplantation. Lenalidomide is an immunomodulatory agent with antitumor activity in non-Hodgkin lymphoma, with an acceptable toxicity profile and manageable side effects. A 79-year-old Caucasian male with non-germinal center B-cell-like DLBCL achieved complete remission (CR) after first-line treatment with seven out of eight scheduled cycles of a polychemotherapy containing anthracycline, which had to be discontinued early due to the onset of atrial fibrillation. After 5 months, the patient had an early epicardial relapse. He underwent lenalidomide considering age, cardiological comorbidities, and chronic renal failure. After the third cycle, he achieved CR, confirmed at restaging after the sixth cycle of treatment. Lenalidomide was safe and well tolerated in a patient with atrial fibrillation developed after an anthracycline-based regimen and a relapse of the DLBCL. Moreover, this regimen was effective in a case with a rare extranodal involvement of the epicardium.
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http://dx.doi.org/10.1159/000505716DOI Listing
January 2021

Peripheral T cell lymphomas: from the bench to the clinic.

Nat Rev Cancer 2020 06 6;20(6):323-342. Epub 2020 Apr 6.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of orphan neoplasms. Despite the introduction of anthracycline-based chemotherapy protocols, with or without autologous haematopoietic transplantation and a plethora of new agents, the progression-free survival of patients with PTCLs needs to be improved. The rarity of these neoplasms, the limited knowledge of their driving defects and the lack of experimental models have impaired clinical successes. This scenario is now rapidly changing with the discovery of a spectrum of genomic defects that hijack essential signalling pathways and foster T cell transformation. This knowledge has led to new genomic-based stratifications, which are being used to establish objective diagnostic criteria, more effective risk assessment and target-based interventions. The integration of genomic and functional data has provided the basis for targeted therapies and immunological approaches that underlie individual tumour vulnerabilities. Fortunately, novel therapeutic strategies can now be rapidly tested in preclinical models and effectively translated to the clinic by means of well-designed clinical trials. We believe that by combining new targeted agents with immune regulators and chimeric antigen receptor-expressing natural killer and T cells, the overall survival of patients with PTCLs will dramatically increase.
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http://dx.doi.org/10.1038/s41568-020-0247-0DOI Listing
June 2020

Chronic lymphocytic leukemia focus in the context of a cardiac mass in a pretreated patient: an exceptional incidental finding.

Tumori 2020 Dec 12;106(6):NP29-NP32. Epub 2020 Mar 12.

Institute of Haematology "L. e A. Seràgnoli," University of Bologna, Bologna, Italy.

Background: B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder consisting of clonal proliferation and accumulation of small, mature, CD5-positive B-lymphocytes in the blood, bone marrow, and lymphoid tissues. Among extranodal localizations, cardiac involvement is extremely rare: to our knowledge, there are no findings reported in the literature of concomitant B-CLL diagnosis in the context of atrial myxoma (so-called collision tumours) and the best strategy to treat these malignancies is unclear.

Case Report: We report the case of a 67-year-old woman diagnosed with B-CLL and atrial myxoma. Our patient was cardiologically symptomless and the cardiac mass was an incidental finding. The cardiac tumor appeared several years after B-CLL diagnosis. Histologic examination of the cardiac mass, removed in the suspicion of an atrial myxoma, revealed a lymphoid focus of B-CLL. The patient underwent surgery and subsequent systemic therapy for B-CLL.

Conclusions: The concomitant presence of B-CLL in the context of an atrial myxoma is extremely rare. The best strategy to treat these cardiac hematologic malignancies is unclear.
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http://dx.doi.org/10.1177/0300891620909421DOI Listing
December 2020

Clinical characteristics of interim-PET negative patients with a positive end PET from the prospective HD08-01 FIL study.

Ann Hematol 2020 Feb 23;99(2):283-291. Epub 2019 Dec 23.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18-4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.
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http://dx.doi.org/10.1007/s00277-019-03889-3DOI Listing
February 2020

Idelalisib as a Bridge to Allogeneic Transplantation in Relapsed/Refractory Lymphoma With Renal Cancer: A Case Report.

Clin Lymphoma Myeloma Leuk 2020 01 21;20(1):e15-e17. Epub 2019 Oct 21.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.clml.2019.10.008DOI Listing
January 2020

V600E-positive monomorphic epitheliotropic intestinal T-cell lymphoma complicating the course of hairy cell leukemia.

Onco Targets Ther 2019 20;12:4807-4812. Epub 2019 Jun 20.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

Hairy cell leukemia (HCL) is an uncommon B-cell chronic lymphoproliferative disorder whose pathogenesis and recurrence are strictly dependent on the presence of the BRAF V600E mutant. A 65-year-old male presented a monomorphic epitheliotropic intestinal T-cell lymphoma (formerly enteropathy-associated T-cell lymphoma, type II) with HCL not responding to first-line induction with cladribine. The intestinal lymphoma bears the BRAF V600E mutant, which is the molecular hallmark of HCL, being implicated in its pathogenesis. The case is of interest, as it provides the first description of a V600E-positive intestinal T-cell lymphoma, along with immunohistochemical and molecular demonstration, occurring in concomitance with HCL. A novel digital PCR-base method for HCL disease assessment is also suggested.
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http://dx.doi.org/10.2147/OTT.S202061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590676PMC
June 2019

Role of 18F-FLT PET/CT in suspected recurrent or residual lymphoma: final results of a pilot prospective trial.

Eur J Nucl Med Mol Imaging 2019 Jul 17;46(8):1661-1671. Epub 2019 May 17.

Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Albertoni 15, 40138, Bologna (BO), Italy.

Purpose: To evaluate the role of F-18-Fluorothymidine (FLT) PET/CT in lymphoma patients with suspected recurrent or residual disease.

Methods: Adult lymphoma patients presenting with positive or equivocal F-18-FDG PET/CT at end-treatment or follow-up were prospectively addressed to an additional F-18-FLT-PET/CT. SUV max and tumour-to-background ratios (TBRs) were recorded for the most avid lesion. Biopsy or, when not available, clinical or imaging assessment were employed as standard of reference.

Results: Overall 52 patients were recruited. Histology was available in 20/52 patients (38%), proliferation-index (Ki-67) in 14/20. Disease was excluded in 13/52 patients (25%) (one reactive follicular hyperplasia, five reactive-inflammatory tissues, four reactive nodes, two nodal sarcoid-like and one non-specific peri-caecal finding). FDG and FLT scans were concordant in disease restaging in 34/52 patients (65%), whereas in 18/52 cases (35%) relevant discrepancies were recorded. SUV max and TBR were significantly higher in the disease versus the disease-free group, with both tracers (p = 0.0231 and 0.0219 for FDG; p = 0.0008 and 0.0016 for FLT). FLT-SUVmax demonstrated slightly better performance in discriminating benign from malignant lesions (ROC-AUC: 0.8116 and 0.7949 for FLT-SUV max and TBR; 0.7120 and 0.7140 for FDG). Optimal FLT-SUV max cut-offs were searched: three would lead to 95% sensitivity, 81% accuracy, and 39% specificity, whereas seven led to 100%, 41%, and 56% respectively. No statistically significant correlation was observed between the two FLT indices and Ki-67.

Conclusions: According to our results in a clinical setting of recurrent or residual lymphoma, FLT is not significantly superior to FDG and it is unlikely that it will be employed independently. FLT may be restricted to a few specific cases, as complementary to standard FDG imaging, to confirm a diagnosis or to define a better target to biopsy. However, due to FLT suboptimal performance, many findings would remain inconclusive, requiring further diagnostic procedures and reducing the effectiveness of performing an additional FLT scan.
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http://dx.doi.org/10.1007/s00259-019-04323-6DOI Listing
July 2019

Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified.

Mod Pathol 2020 02 25;33(2):179-187. Epub 2019 Apr 25.

Division of Haematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy.

Peripheral T-cell lymphoma not otherwise specified represents a diagnostic category comprising clinically, histologically, and molecularly heterogeneous neoplasms that are poorly understood. The genetic landscape of peripheral T-cell lymphoma not otherwise specified remains largely undefined, only a few sequencing studies having been conducted so far. In order to improve our understanding of the genetics of this neoplasm, we performed whole exome sequencing along with RNA-sequencing in a discovery set of 21 cases. According to whole exome sequencing results and mutations previously reported in other peripheral T-cell lymphomas, 137 genes were sequenced by a targeted deep approach in 71 tumor samples. In addition to epigenetic modifiers implicated in all subtypes of T-cell neoplasm (TET2, DNMT3A, KMT2D, KMT2C, SETD2), recurrent mutations of the FAT1 tumor suppressor gene were for the first time recorded in 39% of cases. Mutations of the tumor suppressor genes LATS1, STK3, ATM, TP53, and TP63 were also observed, although at a lower frequency. Patients with FAT1 mutations showed inferior overall survival compared to those with wild-type FAT1. Although peripheral T-cell lymphoma not otherwise specified remains a broad category also on molecular grounds, the present study highlights that FAT1 mutations occur in a significant proportion of cases, being provided with both pathogenetic and prognostic impact.
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http://dx.doi.org/10.1038/s41379-019-0279-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994417PMC
February 2020

Lenalidomide in Pretreated Patients with Diffuse Large B-Cell Lymphoma: An Italian Observational Multicenter Retrospective Study in Daily Clinical Practice.

Oncologist 2019 09 2;24(9):1246-1252. Epub 2019 Apr 2.

Institute of Hematology, University of Bologna, Bologna, Italy

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.
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http://dx.doi.org/10.1634/theoncologist.2018-0603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738312PMC
September 2019

Histological findings in patients with suspected mediastinal lymphoma relapse according to positive positron emission tomography scan during follow-up: a large retrospective analysis in 96 patients.

Leuk Lymphoma 2019 09 1;60(9):2247-2254. Epub 2019 Mar 1.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna , Bologna , Italy.

Residual masses in patients with mediastinal lymphoma may be positron emission tomography (PET) positive during follow-up also in cases of complete response. The aim of this retrospective study is to verify the reliability of mediastinal PET-positive findings in suggesting disease relapse or progression during follow-up by histological verification. From January 2002 to March 2016, 96 patients with mediastinal lymphoma underwent PET follow-up after front-line treatment. A surgical biopsy was performed to confirm the suspected relapse (for a total of 113 procedures). A lymphoma relapse was diagnosed in 66/102 successful procedures (64.7%). Diagnosis at relapse was concordant with the initial diagnosis in all but 3 cases. Standardized uptake value was significantly higher among patients with relapse than among those who remained in remission (10 versus 5,  < .05). PET scan helps individuate patients with a high suspect of lymphoma relapse and may guide the surgeon to the most suitable target.
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http://dx.doi.org/10.1080/10428194.2019.1581931DOI Listing
September 2019

A case report of the long treatment experience of a Sézary syndrome responder patient: 16 years through all the systemic and innovative therapies.

Hematol Oncol 2019 Apr 30;37(2):202-204. Epub 2019 Jan 30.

Institute of Hematology "L. e A. Seràgnoli,", University of Bologna, Bologna, Italy.

Existing therapies for Sézary syndrome (SS) are limited in efficacy and in disease control, and patients have very poor prognosis. Here, we report a case report of a patient who has a 16-year history of SS and related treatments (both standard and experimental). In particular, two drugs, one conventional (gemcitabine) and one experimental (mogamulizumab), were able to induce long lasting response. Patient refused to undergo allogeneic stem cell transplantation. After eleven lines of therapeutic approaches, the patient is in very good partial response and free of therapy at the latest available follow-up.
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http://dx.doi.org/10.1002/hon.2573DOI Listing
April 2019

The role of transplantation in Hodgkin lymphoma.

Br J Haematol 2019 01 8;184(1):93-104. Epub 2018 Nov 8.

Institute of Haematology, "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

Autologous stem cell transplantation is the standard salvage strategy for young and fit patients with Hodgkin lymphoma failing induction therapy, and is effective in nearly 50% of cases. The quality of response at transplantation is the most relevant prognostic aspect, as patients in complete response can obtain better outcomes. Therefore, first-line salvage treatments applied before transplantation need to produce high quality responses without excessive myelotoxicity and without affecting peripheral blood stem cell mobilisation. In this sense, the incorporation of new agents active in Hodgkin lymphoma, such as brentuximab vedotin and anti-programmed death 1 antibodies, in conventional regimens, may help to enhance complete remission rates. Working on conditioning regimen and applying a post-autologous consolidation treatment (for example with brentuximab vedotin) are two ways for improving transplant outcomes, particularly in patients displaying high-risk features for early relapse or progression. Allogeneic transplantation maintains its curative potential also in the era of new drugs, although its most correct timing and the most suitable sequence of post-autologous salvage treatments still remain to be determined.
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http://dx.doi.org/10.1111/bjh.15639DOI Listing
January 2019

The unique biology and treatment of primary mediastinal B-cell lymphoma.

Best Pract Res Clin Haematol 2018 09 3;31(3):241-250. Epub 2018 Jul 3.

Institute of Haematology "L. e A. Seràgnoli", Via Massarenti, 9, 40138, University of Bologna, Bologna, Italy. Electronic address:

The unique biological features of primary mediastinal large B-cell lymphoma are offering suggestions for the development and application of innovative drugs in patients who do not respond to first-line regimens or relapse. This lymphoma, in fact, is characterised by high rates of curability with standard anthracycline-containing chemoimmunotherapy regimens, but still displays a severe prognosis if adequate responses are not rapidly achieved or if the disease recurs. Radiotherapy has proved to be effective to consolidate responses after induction, but it may be safely avoided in certain cases, especially when a metabolic complete response is obtained, as to reduce the incidence of radiation-induced long-term sequelae. The current management of this lymphoma, both at diagnosis and at relapse, is reviewed in this paper, along with the description of its peculiar biological panorama.
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http://dx.doi.org/10.1016/j.beha.2018.07.001DOI Listing
September 2018

A patient with plasmablastic lymphoma achieving long-term complete remission after thalidomide-dexamethasone induction and double autologous stem cell transplantation: a case report.

BMC Cancer 2018 Jun 8;18(1):645. Epub 2018 Jun 8.

Institute of Haematology "L. e A. Seràgnoli", University of Bologna, Via Massarenti, 9 -40138, Bologna, Italy.

Background: No standard of care is established for plasmablastic lymphoma (PBL) and prognosis remains extremely poor, given that patients relapse early after chemotherapy and display resistance to commonly applied cytostatic drugs.

Case Presentation: We report a case of nodal, HIV-unrelated PBL in a patient who achieved and maintained a very long lasting complete remission after an intensive therapy consisting consisting of thalidomide plus dexamethasone followed by a consolidation with double autologous stem cell transplantation. Our approach was based on the full application of a standard multiple myeloma treatment and, to the best of our knowledge, it represents the only reported experience so far. This treatment was overall well tolerated.

Conclusions: Multiple myeloma-like treatment may represent a possible alternative to intensive lymphoma-directed therapies.
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http://dx.doi.org/10.1186/s12885-018-4561-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992724PMC
June 2018

Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma.

Oncotarget 2018 May 4;9(34):23443-23450. Epub 2018 May 4.

Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy.

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventy-seven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world.
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http://dx.doi.org/10.18632/oncotarget.25215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955107PMC
May 2018

Lenalidomide in Pretreated Mantle Cell Lymphoma Patients: An Italian Observational Multicenter Retrospective Study in Daily Clinical Practice (the Lenamant Study).

Oncologist 2018 09 19;23(9):1033-1038. Epub 2018 Apr 19.

Institute of Hematology, University of Bologna, Bologna, Italy

Background: Mantle cell lymphoma (MCL) has the worst prognosis of B-cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo-immunotherapy. Options for relapsed MCL are limited, although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL 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 in real practice.

Results: Seventy patients received lenalidomide for 21/28 days with a median of eight cycles. At the end of therapy, there were 22 complete responses (31.4%), 11 partial responses, 6 stable diseases, and 31 progressions, with an overall response rate of 47.1%. Eighteen patients (22.9%) received lenalidomide in combination with either dexamethasone ( = 13) or rituximab ( = 5). Median overall survival (OS) was reached at 33 months and median disease-free survival (DFS) at 20 months: 14/22 patients are in continuous complete response with a median of 26 months. Patients who received lenalidomide alone were compared with patients who received lenalidomide in combination: OS and DFS did not differ. Progression-free survivals are significantly different: at 56 months, 36% in the combination group versus 13% in patients who received lenalidomide alone. Toxicities were manageable, even if 17 of them led to an early drug discontinuation.

Conclusion: Lenalidomide therapy for relapsed MCL patients is effective and tolerable even in a real-life context.

Implication For Practice: Several factors influence treatment choice in relapsed/refractory mantle cell lymphoma (rrMCL), and the therapeutic scenario is continuously evolving. In fact, rrMCL became the first lymphoma for which four novel agents have been approved: temsirolimus, lenalidomide, ibrutinib, and bortezomib. The rrMCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for rrMCL patients is effective and tolerable even in a real-life context.
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http://dx.doi.org/10.1634/theoncologist.2017-0597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192660PMC
September 2018