Publications by authors named "Guido Gini"

35 Publications

Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi.

J Clin Oncol 2021 Feb 12:JCO2002465. Epub 2021 Feb 12.

Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano (PN), Italy.

Purpose: To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL).

Methods: We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050).

Results: We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases.

Conclusion: The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.
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http://dx.doi.org/10.1200/JCO.20.02465DOI Listing
February 2021

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial.

Cancer Med 2020 Dec 6;9(23):8735-8746. Epub 2020 Nov 6.

Ematologia, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

Background: The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance.

Methods: In 771 newly diagnosed advanced-stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL-HD0607 trial, all patients received two ABVD courses and if PET-2 negative received four additional ABVD cycles while if PET-2-positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review.

Results: Higher NLR and lower LMR were associated with a PET-2 positivity and failure to achieve long-term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET-2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET-2 status was added, only PET-2-positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET-2-negative patients, those with NLR > 6 had an inferior 3-year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P = .03).

Conclusion: In advanced-stage HL patients treated with a PET-2-driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response.
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http://dx.doi.org/10.1002/cam4.3396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724487PMC
December 2020

Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial.

J Clin Oncol 2020 Nov 18;38(33):3905-3913. Epub 2020 Sep 18.

Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

Purpose: To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy.

Patients And Methods: Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT).

Results: Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; = .53) in subgroup C (classic bulky).

Conclusion: cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.
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http://dx.doi.org/10.1200/JCO.20.00935DOI Listing
November 2020

Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study.

Leukemia 2020 Aug 11. Epub 2020 Aug 11.

Unit of Hematology, Humanitas Clinical and Research Center, Milan, Italy.

Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.
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http://dx.doi.org/10.1038/s41375-020-01013-3DOI Listing
August 2020

Nonpeghylated liposomal doxorubicin combination regimen (R-COMP) for the treatment of lymphoma patients with advanced age or cardiac comorbidity.

Hematol Oncol 2020 Oct 9;38(4):478-486. Epub 2020 Jul 9.

Ematologia e Trapianto Midollo Osseo, Ospedale Santa Maria della Misericordia, Azienda Ospedaliera Perugia, Perugia, Italy.

Doxorubicin is the most effective single agent in the treatment of non-Hodgkin's lymphoma (NHL). Its use is limited because of the cardiac toxicity primarily in elderly patients (pts) and in pts with history of cardiac disease. Liposomal doxorubicin has been proven to reduce cardiotoxicity. The aim of this retrospective study was the use of nonpeghylated liposomal doxorubicin (NPLD) in term of efficacy, response rate and incidence of cardiac events. We retrospectively collected the experience of 33 Hematological Italian Centers in using NPLD. Nine hundred and forty-six consecutive pts treated with R-COMP (doxorubicin was substituted with NPLD, Myocet) were collected. Median age was 74 years, the reasons for use of NPLD were: age (466 pts), cardiac disease (298 pts), uncontrolled hypertension (126 pts), other reasons (56 pts). According to clinicians' evaluation, 49.9% of pts would not have used standard doxorubicin for different situations (age, cardiomyopathy, previous use of doxorubicin, and uncontrolled hypertension). Overall 687 pts (72.6%) obtained a complete remission (CR). About 5% (n = 51) of subjects developed major cardiotoxic events including heart failure (N = 31), ischemic heart disease (N = 16), acute heart attack (N = 3), and acute pulmonary oedema (N = 1). After a median follow-up of 32 months, 651 pts were alive and the overall survival (OS) was 72%. After a median observation period of 23 months disease free survival (DFS) was 58%. Either in univariate or in multivariate analysis OS and DFS were not significantly affected by age or cardiac disease. Our findings strongly support that including R-COMP is effective and safe when the population is at high risk of cardiac events and negatively selected. Moreover, the use of this NPLD permitted that about half of our population had the opportunity to receive the best available treatment.
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http://dx.doi.org/10.1002/hon.2764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689940PMC
October 2020

Advanced Stage Hodgkin Lymphoma: Patient Management.

Acta Biomed 2020 05 25;91(S-5):5-12. Epub 2020 May 25.

Haematology and BMT Unit, Ospedale Monsignor R. Dimiccoli, Barletta, Italy.

Hodgkin lymphoma (HL) is a rare cancer of the lymphoid system. It clinically presents with swollen lymph nodes and/or systemic symptoms, such as fever, night sweats, or weight loss, as signs of a more advanced stage disease. For the purpose of treatment allocation, HL cases are classified as early-stage favorable, early-stage unfavorable, and advanced-stage disease. Here below we describe four different clinical cases from real life that address some key issues and medical needs that are present in the daily practice with patients affected by advanced stage HL. The four clinical cases are quite heterogeneous, but in each case there are strong inputs to manage a specific category of advanced phase HL patient that is going to be treated with first-line therapy.
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http://dx.doi.org/10.23750/abm.v91iS-5.9913DOI Listing
May 2020

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial.

Haematologica 2019 11 11;104(11):2241-2248. Epub 2019 Apr 11.

Onco-Hematology Division, IEO, European Institute of Oncology IRCCS, Milano

A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13-year estimates of 77.0% and 36.8% for complete remission no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (<0.001), along with younger age (=0.002) and female sex (=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma. (Registered at clinicaltrials.gov identifier: 00435955).
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http://dx.doi.org/10.3324/haematol.2018.209932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821615PMC
November 2019

Obinutuzumab and miniCHOP for unfit patients with diffuse large B-cell lymphoma. A phase II study by Fondazione Italiana Linfomi.

J Geriatr Oncol 2020 01 8;11(1):37-40. Epub 2019 Jul 8.

Hematology Unit, Arcispedale S.Maria Nuova, Azienda Unità Sanitaria Locale - IRCCS, Reggio Emilia, Italy; Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, University of Modena and Reggio Emilia, Reggio Emilia, Italy.

Objective: To evaluate activity and safety of obinutuzumab-miniCHOP (Ga101-miniCHOP) combination in older patients with Diffuse Large B-Cell Lymphoma (DLBCL) unfit to receive full dose immunochemotherapy.

Materials And Methods: We conducted a Simon's two-stage phase II multicenter trial to investigate response rate (primary endpoint) and safety of six courses of Ga101-miniCHOP in older patients with DLBCL (≥65 years), prospectively defined as unfit according to a simplified Comprehensive Geriatric Assessment (sCGA).

Results: Overall, 34 patients were enrolled (median age 82 years; range 68-89), with 27 out of the 33 eligible patients completing all six planned courses. Complete Remission (CR) rate was reported in fourteen patients (42%). After a median follow-up of sixteen months, the two-year Progression Free and Overall Survival (PFS and OS) were 49% (95% Confidence Interval (CI), 28 to 67) and 68% (95% CI, 49 to 81), respectively. The most frequent grade 3-4 adverse event was neutropenia in thirteen patients (26%).

Conclusions: Based on the observed CR rate, study accrual was interrupted due to the very low probability of demonstrating the initial study hypothesis that Ga101-miniCHOP could improve results of historical data obtained with R-miniCHOP in this group of patients. Nonetheless, results achieved with the 33 treated patients confirm activity and good tolerability of the Ga101-miniCHOP regimen for older unfit adult patients with DLBCL.
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http://dx.doi.org/10.1016/j.jgo.2019.06.020DOI Listing
January 2020

Gonadal Function Recovery and Fertility in Women Treated with Chemo- and/or Radiotherapy for Hodgkin's and Non-Hodgkin Lymphoma.

Chemotherapy 2019 22;64(1):36-41. Epub 2019 May 22.

Unit of Hematology, AUO Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.

Background: Fertility and gonadal function represent one of the most important aspects for long-term lymphoma survivors.

Aims: The aim of our study was to determine possible risk factors, such as age at treatment, chemotherapeutic regimen, protection with oral contraceptives (OCs), and gonadotropin-releasing hormone (GnRH) analogues in female patients treated for Hodgkin's lymphoma (HL) or non-Hodgkin lymphoma (NHL) at a reproductive age.

Methods: Patients between the age of 16 and 50 years at the time of HL or NHL diagnosis were selected. Eligible patients were requested to respond to a questionnaire by phone interview about fertility, menstrual status, sexual aspects, and treatment with OCs or GnRH analogues during chemotherapy.

Results: The resumption of menstrual activity was associated with the use of the OCs and GnRH analogues during chemotherapy (p = 0.008 and 0.034, respectively). At univariate analysis, the use of OCs during chemotherapy was associated with a lower risk of amenorrhea (prevalence ratio [PR] = 0.37; 95% CI 0.17-0.82). A higher age at the time of treatment correlated positively with therapy-induced amenorrhea, with a difference of 12.8 years between the mean age at diagnosis of the women with therapy-induced amenorrhea and those who resumed their menses. Amenorrhea was significantly higher in women receiving R-CHOP than in women treated with ABVD (PR = 6.00; 95% CI 2.32-15.54). Moreover, NHL had an infertility PR of 1.51 (95% CI 0.86-2.45) at multivariate analysis compared to HL.

Conclusions: This study suggests a possible role of pharmacological prophylaxis with OCs and GnRH analogues.
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http://dx.doi.org/10.1159/000499535DOI Listing
July 2019

Efficacy of bendamustine and rituximab in splenic marginal zone lymphoma: results from the phase II BRISMA/IELSG36 study.

Br J Haematol 2018 12 8;183(5):755-765. Epub 2018 Nov 8.

APHP, Saint-Louis Hospital, Haemato-oncology- Paris Diderot University, Paris, France.

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method. The primary endpoint was complete response rate. Fifty-six patients with SMZL diagnosis confirmed on central revision were treated with bendamustine (90 mg/m  days 1, 2) and rituximab (375 mg/m  day 1) every 28 days for six cycles (B-R). The overall response and CR rates were 91% and 73%, respectively. Duration of response, progression-free survival and overall survival at 3 years were 93% (95% confidence interval [CI] 81-98), 90% (95% CI 77-96) and 96% (95% CI 84-98), respectively. Toxicity was mostly haematological. Neutropenia grade ≥3 was recorded in 43% of patients; infections and febrile neutropenia in 5·4% and 3·6%. Overall, 14 patients (25%) experienced serious adverse events. Five patients (9%) went off-study because of toxicity and one patient died from infection. In conclusion, B-R resulted in a very effective first-line regimen for SMZL. Based on the results achieved in the BRISMA trial, B-R should be considered when a chemotherapy combination with rituximab is deemed necessary for symptomatic SMZL patients.
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http://dx.doi.org/10.1111/bjh.15641DOI Listing
December 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

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial.

J Clin Oncol 2018 02 23;36(5):454-462. Epub 2018 Jan 23.

Andrea Gallamini, Centre Antoine Lacassagne, Nice, France; Corrado Tarella, Istituto Europeo di Oncologia; Daniela Gottardi, Ospedale Mauriziano Umberto I di Torino; Paolo Gavarotti, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin; Simonetta Viviani and Paolo Corradini, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori; Paolo Corradini, Alessandro Massimo Gianni, and Alessandro Rambaldi, Università degli Studi di Milano; Andrés J.M. Ferreri and Federico Fallanca, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele; Giuseppe Prosperini, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan; Andrea Rossi, Chiara Pavoni, and Alessandro Rambaldi, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo; Caterina Patti and Antonino Mulé, Azienda Villa Sofia-Cervello; Umberto Ficola, La Maddalena, Palermo; Marco Picardi, Università Federico II, Naples; Alessandra Romano, Ospedale Ferrarotto, Catania; Maria Cantonetti, Policlinico Tor Vergata; Roberta Battistini, Ospedale San Camillo; Agostino Chiaravalloti, Università Tor Vergata, Rome; Giorgio La Nasa, Ospedale Roberto Binaghi di Cagliari, Cagliari; Livio Trentin, Università di Padova, Padua; Silvia Bolis, Ospedale San Gerardo, Monza; Davide Rapezzi, Alberto Biggi, Fabrizio Bergesio, and Stephane Chauvie, Azienda Ospedaliera Santa Croce e Carle, Cuneo; Michele Cimminiello, Ospedale San Carlo, Potenza; Corrado Schiavotto, Presidio Ospedaliero San Bortolo, Vicenza; Guido Parvis, Azienda Ospedaliera San Luigi, Orbassano; Roberta Zanotti, Azienda Ospedaliera Universitaria Integrata, Verona; Guido Gini, Nuovo Ospedale Torrette, Ancona; Piera Viero, Ospedale dell'Angelo, Mestre; Maurizio Miglino, Azienda Ospedaliera Universitaria San Martino, Genoa; Atto Billio, Ospedale Centrale di Bolzano, Bolzano; Michele Gregianin, Ospedale San Giacomo, Castelfranco Veneto, Italy; and Abraham Avigdor, Chaim Sheba Medical Center, Tel HaShomer, Israel.

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.
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http://dx.doi.org/10.1200/JCO.2017.75.2543DOI Listing
February 2018

Italian real life experience with brentuximab vedotin: results of a large observational study on 234 relapsed/refractory Hodgkin's lymphoma.

Oncotarget 2017 Oct 23;8(53):91703-91710. Epub 2017 May 23.

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

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity. Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients.
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http://dx.doi.org/10.18632/oncotarget.18114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710959PMC
October 2017

Italian real-life experience with brentuximab vedotin: results of a large observational study of 40 cases of relapsed/refractory systemic anaplastic large cell lymphoma.

Haematologica 2017 11 3;102(11):1931-1935. Epub 2017 Aug 3.

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

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.
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http://dx.doi.org/10.3324/haematol.2017.171355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664397PMC
November 2017

[Primary cardiac lymphoma in an immunocompetent young adult: outcome with chemotherapy].

G Ital Cardiol (Rome) 2017 Jan;18(1):7-10

Divisione di Cardiologia, Dipartimento Cardiovascolare, Ospedali Riuniti di Ancona, Ancona.

Primitive cardiac lymphoma (PCL) is a rare disease accounting for only 1-2% of primary cardiac tumors. Diffuse large B cell lymphoma is the most common type and shows a rapid progression with poor prognosis. The clinical presentation of PCL is nonspecific, and echocardiographic study is essential to the initial work-up. Magnetic resonance imaging and computed tomography scan are the methods of choice for the assessment of tumor extension. The definitive diagnosis is histopathology examination. Chemotherapy and radiotherapy represent the best treatment and should be started promptly after PCL diagnosis. We here report a case of PCL in a 59-year-old man complicated by pulmonary microembolism, atrial fibrillation and signs of right outflow tract obstruction.
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http://dx.doi.org/10.1714/2628.27021DOI Listing
January 2017

Modern Management of Anthracycline-Induced Cardiotoxicity in Lymphoma Patients: Low Occurrence of Cardiotoxicity with Comprehensive Assessment and Tailored Substitution by Nonpegylated Liposomal Doxorubicin.

Oncologist 2017 04 8;22(4):422-431. Epub 2017 Mar 8.

Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy.

Background: Anthracyclines (AC) are still undeniable drugs in lymphoma treatment, despite occasionally causing cardiotoxicity. Liposomal AC may reduce cardiotoxicity while retaining clinical efficacy; also, biomarker monitoring during chemotherapy allows early detection of cardiac damage, enabling strategies to prevent left ventricular ejection fraction (LVEF) deterioration.

Materials And Methods: We conducted a prospective observational trial in a real-life population of lymphoma patients, combining advanced echocardiography and biomarkers (Troponin I [TnI]) for early detection of cardiotoxicity; we applied a prespecified policy to minimize cardiotoxicity, selecting patients with higher baseline risk to replace doxorubicin with nonpegylated liposomal doxorubicin (NPLD) and starting cardioprotective treatment when subclinical cardiotoxicity was detected.

Results: Ninety-nine patients received ≥1 cycle of chemotherapy (39 with NPLD): 38 (NPLD = 34) were older than 65 years. At baseline, the NPLD subgroup had more cardiovascular risk factors and comorbidities than the doxorubicin subgroup. After treatment, echocardiographic parameters did not worsen in the NPLD subgroup; significant LVEF reduction occurred in two patients treated with doxorubicin. Over treatment course, TnI rises increased linearly in the doxorubicin subgroup but modestly in the NPLD subgroup. At doxorubicin doses >200 mg/m the difference was statistically significant, with more TnI rises in the doxorubicin subgroup. NPLD-treated patients did not experience higher rates of grade 3-4 adverse events. Within the diffuse large B-cell lymphomas category, we observed similar rates of complete and overall responses between doxorubicin- and NPLD-treated patients.

Conclusion: A comprehensive strategy to prevent, detect, and treat cardiotoxicity allows an optimal management of the lymphoma with low incidence of cardiac complications. 2017;22:422-431 IMPLICATIONS FOR PRACTICE: Despite the recent advances of targeted therapy in cancer, old cytotoxic drugs such as anthracyclines (AC) still play a fundamental role in the treatment of many lymphoma patients. We tested and validated in a real-life setting a personalized approach to prevent, detect, and treat AC-induced cardiotoxicity; biomarker monitoring was accomplished by Troponin I measurements before and after chemotherapy infusions, allowing detection of early subclinical cardiotoxicity, which was preemptively treated with cardio-protectants (beta blockers and angiotensin-converting-enzyme inhibitors). A telemedicine system allowed interdisciplinary management of the patients with an expert cardiologist. Furthermore, tailored use of liposomal AC following a prespecified policy appeared to prevent the excess cardiotoxicity expected in high-risk patients.
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http://dx.doi.org/10.1634/theoncologist.2016-0289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388379PMC
April 2017

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

J Clin Oncol 2016 11 31;34(33):4015-4022. Epub 2016 Oct 31.

Sergio Cortelazzo, Atto Billio, Andrea Piccin, and Giovanni Negri, Ospedale Centrale di Bolzano, Bolzano; Corrado Tarella and Riccardo Bruna, Azienda Ospedaliera Ordine Mauriziano and University of Turin; Marco Ladetto and Manuela Zanni, Azienda Ospedaliera Universitaria (AOU) Città della Salute e della Scienza, Turin; Alessandro Massimo Gianni, Paolo Corradini, and Massimo Di Nicola, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, University of Milano; Andrés J.M. Ferreri, IRCCS San Raffaele Scientific Institute; Valentina Tabanelli and Stefano Pileri, Istituto Europeo di Oncologia; Alessandro Rambaldi, University of Milano, Milan; Anna Maria Barbui, Andrea Rossi, Giuseppe Gritti, Arianna Masciulli, Federica Delaini, Cristina Boschini, and Alessandro Rambaldi, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo; Caterina Patti and Antonino Mulé, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo; Valerio Zoli, Ospedale San Camillo Forlanini, Rome; Claudia Castellino, Ospedale S. Croce e Carle, Cuneo; Francesco Di Raimondo, AOU Policlinico Vittorio Emanuele University of Catania, Catania; Fabio Benedetti, University of Verona; Marco Chilosi, Azienda Ospedaliera Universitaria Integrata Verona, Verona; Giorgio La Nasa, Ospedale Binaghi, Cagliari; Guido Gini, Ospedali Riuniti, Ancona; Livio Trentin, Azienda Ospedaliera-Università di Padova, Padua; Maurizio Frezzato, Ospedale San Bortolo, Vicenza; Leonardo Flenghi, Azienda Ospedaliera di Perugia, Perugia; and Simona Falorio, Ospedale Civile Spirito Santo, Pescara, Italy.

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.
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http://dx.doi.org/10.1200/JCO.2016.67.2980DOI Listing
November 2016

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study.

Int J Radiat Oncol Biol Phys 2016 Mar 17;94(4):783-91. Epub 2015 Dec 17.

Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano, Italy.

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported.

Methods And Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m(2), days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients.

Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis.

Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.
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http://dx.doi.org/10.1016/j.ijrobp.2015.12.019DOI Listing
March 2016

Evaluation of the prognostic role of tumour-associated macrophages in newly diagnosed classical Hodgkin lymphoma and correlation with early FDG-PET assessment.

Hematol Oncol 2017 Mar 7;35(1):69-78. Epub 2015 Aug 7.

Unit of Hematology, Azienda Ospedaliera Universitaria Senese, Italy.

In Hodgkin Lymphoma (HL), about 20% of patients still have relapsed/refractory disease and late toxic effects rate continue to rise with time. 'Early FDG-PET' and tissue macrophage infiltration (TAM) emerged as powerful prognostic predictors. The primary endpoint was to investigate the prognostic role of both early FDG-PET and TAM; the secondary endpoint was to test if early FDG-PET positivity could correlate with high TAM score. A cohort of 200 HL patients was analysed. Induction treatment plan consisted of two to six courses of ABVD and, if indicated, involved field radiation therapy. All patients repeated CT scan and FDG-PET after two cycles and after the completion of therapy. TAM in diagnostic specimens was determined by immunohistochemistry with a monoclonal antibody (anti-CD68 KP1). Overall, early FDG-PET was negative in 163 patients (81.5%) and positive in 37 patients (18.5%), showing a significant correlation with the achievement of CR (p < 0.0001). After a median follow-up of 40 months, progression free survival (PFS) was significantly better for PET negative patients (p < 0.0001). CD68 expression was low, intermediate or high in 26 (13%), 100 (50%) and 74 (37%) cases, without difference in the distribution between responders and non-responders. PFS analysis showed no significant difference in any score group. TAM score did not show any correlation with early FDG-PET result. This study confirms that early FDG-PET has a high prognostic power, while TAM score does not seem to influence the outcome; in contrast to our original hypothesis, it does not correlate with FDG-PET assessment. Copyright © 2015 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/hon.2249DOI Listing
March 2017

Bendamustine and rituximab combination is safe and effective as salvage regimen in Waldenström macroglobulinemia.

Leuk Lymphoma 2015 14;56(9):2637-42. Epub 2015 Mar 14.

a Department of Hematology , Niguarda Ca' Granda Hospital , Milano , Italy.

According to the European Society for Medical Oncology and National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia, bendamustine (B) may be considered a suitable therapeutic option. To address the role of B in combination with rituximab (BR), we analyzed the outcome of 71 patients with relapsed/refractory disease, median age 72 years, treated with R 375 mg/m(2) day 1 and B days 1 and 2 (dosage ranging from 50 to 90 mg/m(2)). Patients had previously received a median number of 2 lines of treatment (range 1-5). Overall and major response rates were 80.2% and 74.6%. Major toxicity was grade 3/4 neutropenia occurring in 13% of courses. There was no significant association between baseline features or patients' characteristics and response achievement. Median progression-free survival was not reached after a median follow-up of 19 months (range 3-54). None of the patients developed aggressive lymphoma or secondary myelodysplastic syndrome/acute myeloid leukemia. BR was found to be an active and well-tolerated salvage regimen leading to rapid disease control.
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http://dx.doi.org/10.3109/10428194.2015.1012714DOI Listing
August 2016

Primary B-cell lymphoblastic lymphoma of the testis.

Arch Ital Urol Androl 2014 Dec 30;86(4):400-1. Epub 2014 Dec 30.

Institute of Urology, AOU United Hospitals, Polytechnic University of Marche Region, Ancona.

We present a rare case of primary lymphoblastic B-cell lymphoma of the testis focusing on ultrasonographic and pathological features and clinical implications. Pathological examination revealed primary testicular lymphoblastic B-cell lymphoma which was treated with adjuvant chemotherapy, including rachicentesis with administration of chemotherapy and with radiotherapy of contralateral testis. Primary testicular lymphoblastic B cell lymphoma is an aggressive disease and it is necessary a multimodal therapy (surgery, chemotherapy and radiotherapy) to prevent metastasis.
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http://dx.doi.org/10.4081/aiua.2014.4.400DOI Listing
December 2014

Fatal necrotizing angiotropic Epstein-Barr virus-negative large B-cell lymphoma: a case report with unusual clinicopathological features in-between lymphomatoid granulomatosis and T-cell/histiocyte-rich large B-cell lymphoma.

Medicine (Baltimore) 2014 Dec;93(29):e353

From the Haematology Clinic, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona (AO, ST, FS, G. Gini, PL, JO); Haematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna (ES, SAP); Pathologic Anatomy Unit, Marche Polytechnic University, Ancona (G. Goteri); and Internal Medicine Unit, Senigallia Hospital, Senigallia (AS), Italy.

In the spectrum of diffuse large B-cell lymphomas (DLBCL), both T-cell/histiocyte-rich large B-cell lymphoma (TCHRBCL) and most lymphomatoid granulomatosis (LG) cases are characterized by the relative rarity of the neoplastic B-cell population, with respect to the overwhelming non-neoplastic counterpart of T cells or histiocytes. Here we report a case of aggressive B-cell lymphoma with unusual clinicopathological features partially overlapping these two entities. The patient was a previously healthy 55-year-old male, presenting with a computed tomography finding of a pelvic mass, inguinal lymphadenopathies, and pulmonary nodules. Two excisional lymph node biopsies resulted inconclusive for lymphoproliferative disease. Because of a colonic perforation, the patient underwent an urgent laparotomy, which disclosed a large pelvic abscess. The pathological examination of the surgical specimen could not discriminate between a primary aggressive B-cell lymphoproliferative disorder and an abnormal inflammatory hyper-reaction. The patient developed a septic state, not resolving until death, which occurred because of an abdominal hemorrhage. A second perimortem surgical specimen consisting of a nodal mass revealed a diagnosis of an Epstein-Barr virus-negative high-grade large B-cell lymphoma with massive necrosis, angiocentric pattern of growth, and prominent T-cell infiltrate. The unique clinicopathological features did not allow to classify this tumor within any of the recognized WHO entities, potentially representing a new clinicopathological variant of DLBCL in-between TCHRBCL and LG.
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http://dx.doi.org/10.1097/MD.0000000000000353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602609PMC
December 2014

Mobilization-driven postconsolidation therapy in elderly patients with acute myeloid leukemia: feasibility and efficacy of autologous stem cell transplantation versus low-dose gemtuzumab ozogamicin.

Biol Blood Marrow Transplant 2014 Sep 28;20(9):1399-406. Epub 2014 May 28.

Hematology Department, University of Ancona, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Torrette di Ancona, Italy. Electronic address:

We prospectively evaluated 2 postconsolidation strategies, administered according to the mobilization outcome, in 72 acute myeloid leukemia (AML) fit elderly patients, achieving complete remission after the first high-dose cytarabine-based induction. Autologous stem cell transplantation (ASCT) was performed in patients collecting ≥3 × 10(6) CD34(+)/kg and low-dose gemtuzumab ozogamicin (GO) was performed in poor mobilizers (collecting <3 × 10(6) CD34(+)/kg). Fifty-five patients (76.3%) underwent peripheral blood stem cell (PBSC) mobilization, after first consolidation, and 24 of 55 (44%) collected >3 × 10(6) CD34(+) cells/kg. Among the 55 patients eligible for PBSC mobilization, 7 did not receive the planned treatment, 23 were allocated for ASCT, and 25 were allocated for GO on an intention-to-treat basis. With a median follow-up of 70 months (range, 24 to 124), 20 of 55 patients are alive, 18 of them in continuous complete remission. The 8-year overall survival (OS) and disease-free survival (DFS) are, respectively, 35.9% (95% confidence interval [CI] 24% to 49.8%) and 31.2% (95% CI, 21% to 43.8%), median OS and DFS were 22 and 16 months, respectively. In multivariate analysis, postconsolidation treatment and hyperleukocytosis (WBC > 50,000/μL) significantly predicted OS and DFS, whereas secondary AML was significantly associated with a higher relapse rate (83.4% versus 54% of de novo AML). Patients with hyperleukocytosis had 0% 3-year OS versus the 46% (at 8 years) in patients without hyperleukocytosis (P = .01); 57% of patients in the GO arm are alive at 8 years, compared with 25.4% of patients in the ASCT arm, who had an overall relative risk (RR) of death of 2.6 (95% CI, 1.2 to 5.8; P = .02). DFS at 8 years was 45.3% in patients receiving GO, compared with 26% in ASCT arm (RR, 2.1; 95% CI, 1 to 4.3; P = .05). Our study outlines low feasibility and efficacy of ASCT in elderly AML patients, whereas postconsolidation with GO appears safe and effective in this unfavorable setting. The study was registered at Umin Clinical Trial Registry (www.umin.ac.jp/ctr), number R000014052.
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http://dx.doi.org/10.1016/j.bbmt.2014.05.019DOI Listing
September 2014

Fludarabine, cyclophosphamide, and rituximab in salvage therapy of Waldenström's macroglobulinemia.

Clin Lymphoma Myeloma Leuk 2013 Apr 13;13(2):231-4. Epub 2013 Mar 13.

Division of Hematology, Ospedale Niguarda Ca' Granda Milano, Milano, Italy.

The combination FCR (fludarabine, cyclophosphamide, and rituximab) proved to be active in Waldenström's macroglobulinemia in a mixed population of untreated and previously treated patients. Prolonged myelosuppression and concerns about purine analogue treatment led to the conclusion that this regimen should be avoided in younger patients in first-line treatment. In this retrospective study on 40 patients we observed a response rate of 80% (32) after FCR salvage treatment with 32.5% (13) of patients reaching at least a very good partial remission. None of the prognostic variables had a significant effect on response or good quality of response achievement. Median event-free survival was reached at 77 months; median progression-free survival was not reached after a median follow-up of 51 months with any difference when categorizing patients according to quality of response. The results of this study suggest that the FCR regimen might overcome poor prognostic features and should be taken into account as salvage treatment. Tardive immunosuppression and myelosuppression warrant accurate patient follow-up.
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http://dx.doi.org/10.1016/j.clml.2013.02.011DOI Listing
April 2013

Tailored therapy in an unselected population of 91 elderly patients with DLBCL prospectively evaluated using a simplified CGA.

Oncologist 2012 24;17(5):663-72. Epub 2012 Apr 24.

Clinica di Ematologia e Clinica Medica, Università Politecnica delle Marche, Ancona, Italy.

Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) are a heterogeneous population; clinical trials have evaluated a minority of these patients.

Patients And Methods: Ninety-one elderly patients with DLBCL received tailored treatment based on a comprehensive geriatric assessment (CGA). Three groups were identified: I, fit patients; II, patients with comorbidities; III, frail patients. Group I received 21-day cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21), group II received R-CHOP-21 with liposomal doxorubicin, and group III received 21-day cycles of reduced-dose CHOP. Fifty-four patients (59%) were allocated to group I, 22 (25%) were allocated to group II, and 15 (16%) were allocated to group III.

Results: The complete response (CR) rates were 81.5% in group I, 64% in group II, and 60% in group III. With a median follow-up of 57 months, 42 patients are alive, with 41 in continuous CR: 31 patients (57%) in group I, seven patients (32%) in group II, and four patients (20%) in group III. The 5-year overall survival, event-free survival, and disease-free survival rates in all patients were 46%, 31%, and 41%, respectively. Multivariate analysis selected group I assignment as the main significant prognostic factor for outcome.

Conclusions: This approach in an unselected population of elderly DLBCL patients shows that treatment tailored according to a CGA allows the evaluation of elderly patients who are currently excluded from clinical trials.
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http://dx.doi.org/10.1634/theoncologist.2011-0355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360906PMC
January 2013