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•R-COMP is a curative option for older patients with DLBCL and intermediate- to high-risk EPI, even in the presence of a baseline cardiopathy.•R-CHOP is confirmed as the standard therapy for patients at low risk based on the EPI.

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin's lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

This study reports on 382 COVID-19 patients having undergone allogeneic (n= 236) or autologous (n= 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p= 0.02), need for ICU (p< 0.0001) and moderate/high immunodeficiency index (p= 0.04) increased the risk while better performance status (p= 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19.

Background

In recent years the management of patients (pts) with chronic lymphocytic leukemia (CLL) has benefited from a deeper knowledge of the mechanisms underlying the disease and from the development of novel therapeutic approaches. That notwithstanding, local and national accessibility to drugs and tests may lead to distinct “real-world” practices in terms of management of pts that are worth of being recorded and compared to understand the degree of reproducibility and applicability of international guidelines. This could also be relevant for the design of future clinical trials, more tailored to the true patient's needs. To this end, within the GIMEMA cooperative study group the observational retrospective and prospective CLL2121 study (NCT04867915) has been designed with the objective of evaluating the diagnosis and management of CLL in all hematological centers in Italy through the assessment of: 1) the methods and the actual diagnostic/prognostic work-up capacity; 2) the algorithms applied to define disease progression and treatment requirements with respect to national and international guidelines; 3) the clinical and biological variables not strictly associated with CLL, but capable of influencing the clinical course and overall survival; 4) the true incidence of some rarer complications associated with CLL. The study consists of a collection of clinico-biological data from all pts with newly diagnosed CLL, small lymphocytic lymphoma (SLL) or CLL-like monoclonal B-cell lymphocytosis (MBL), according to the iwCLL 2018 criteria in Italy. The retrospective part aims at including all cases followed at the participating centers with a diagnosis between January 2010 and September 2021, while the prospective part will include all pts with a documented diagnosis of CLL, SLL or MBL between September 2021 and September 2025. In this pilot analysis of the study, we examined pts' demographics, diagnosis, treatment line and type. Data were collected using the REDCap electronic data capture platform, analyzed using the SAS software v.9.4 and reported as numbers and frequencies. Between 2 November 2021 and 28 June 2023, 3294 eligible pts were enrolled in 75 hematology centers (out of the total of 110 centers who will be activated during the study) across the entire Italian territory. At the time of the present report, 3033 pts had clinical data available for our preliminary analysis. The vast majority of pts registered (N=2599, 85.7%) belonged to the retrospective cohort while only a minority (N=434, 14.3%) to the prospective cohort. Pts had a median age of 68 years ranging from 29 to 97; 60% of pts were males. 2630 pts (86.8%) had a diagnosis of CLL, 187 (6.2%) of SLL and 214 (7.0%) of MBL (2 missing information). Among those with available results 112 pts (12.6%) were TP53mutated, 526 (45.6%) del(13q) positive, 174 (14.9%) del(11q) positive, 142 (11.9%) del(17p) positive and 226 (20.4%) presented a trisomy 12. The majority of pts (57.6%) were untreated, while 42.4% have been treated. Within the latter subset, 67.3% of pts have received one line of therapy, 21.4% 2 lines of therapy, 11.3% ≥3 lines of therapy. The most common therapeutic regimens were the combination of chemotherapy with an anti-CD20 antibody (39.3%), mainly rituximab, and those based on BTK inhibitors (33.3%), mainly ibrutinib. Chemotherapy alone was used in 12% of pts. Only 5% of pts was treated with the BCL2 inhibitor venetoclax. In the remaining 10% of pts, other approaches were used. This is the initial report of a nation-based real-world data collection aimed at describing the biological and clinical features of pts diagnosed with CLL in virtually all Italian hematology centers starting from 2010. The pattern of treatments highlighted in our preliminary analysis, with a wide use of the watch & wait policy and of chemoimmunotherapy, will help understand how the introduction of novel therapies impacted treatment habits also in light of the timing of the local reimbursement policy. The different time of drug access in Italy, typically delayed after the EU approval, may also have affected the limited use of venetoclax-based treatment. The continuous accrual of pts in this study will allow to obtain a close-to-registry vision of CLL management in Italy over time, in terms of coverage of the entire country but enriched with the granularity of the data and flexibility of the collection typical of a real-world study.

Background. Treatment free remission (TFR) is one of the most important aims of CML treatment but, so far, the best treatment strategy to obtain a durable deep molecular response (DMR) and the overall rate of patients able to achieve a successful TKI discontinuation based on intention-to-treat principle from CML diagnosis are still debated. In November 2016 we launched an international, prospective, randomized, two arms study to evaluate both the depth of the molecular response and the rate of TFR in newly diagnosed CP-CML patients treated with a second generation TKI (Nilotinib, NIL) or with imatinib (IM) followed by switching to NIL in absence of optimal response (Clinical Trial number 02602314). Patients were randomized 1:1 between NIL and IM, stratifying on the Sokal score. All the patients achieving a MR4.0 or better by three years and maintaining this level of response up to the end of the fourth year of therapy were qualified for the discontinuation phase. We recently reported that patients enrolled in the NIL arm had a rate of MR4.5 at two years (primary co-endpoint of the study), significantly higher than those in the IM arm (32 vs 22%, p = 0.023 Pane F. et al, EHA 2022).

Introduction.The outcome of Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) has dramatically improved in the last decade, due with the introduction in the clinical practice of tyrosine kinase inhibitors (TKIs). A further improvement has been obtained with the use of blinatumomab as a consolidation strategy in newly diagnosed patients. We previously designed an induction/consolidation chemotherapy-free frontline trial with dasatinib followed by blinatumomab (GIMEMA LAL2116, D-ALBA); the preliminary results showed that after 2 cycles of blinatumomab (primary endpoint), molecular responses were achieved in 60% of cases and that, with a median follow-up of 18 months, overall survival (OS) and disease (DFS) were 95% and 88% (Foà et al, NEJM 2020). An updated follow-up at 53 months (Foà et al, under revision and ASH 2023) confirmed the favorable long-term outcomes with OS and DFS of 75.8% and 80.7%, respectively. A total of 9 relapses occurred. The median time to relapse was 4.4 months (1.9-25.8); 4 were at the central nervous system (CNS). To further improve the outcome of these patients, we designed a phase III trial (GIMEMA ALL2820) in which in the experimental arm dasatinib was substituted with ponatinib, followed - in the consolidation phase - by at least 2 cycles of blinatumomab. The trial is currently enrolling.

Rigolin: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Visentin:Janssen: Honoraria; Gilead: Honoraria; Abbvie: Honoraria. Coscia:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Gaidano:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Sunesys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Murru:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Varettoni:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Other: Travel/accommodations/expenses; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses. Sportoletti:Janssen: Honoraria; AbbVie: Honoraria. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Marasca:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Marchetti:Takeda: Other: Sponsored meetings; Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Mauro:Jannsen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Octopharma: Consultancy; Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Molica:Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pane:Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gozzetti:Janssen: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Galieni:Celgene: Honoraria; Takeda: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Montillo:AbbVie: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding; Janssen: Honoraria, Speakers Bureau; Verastem: Honoraria; Gilead: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria. Foà:Incyte: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees. Cuneo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background.The PI3Kδ inhibitor idelalisib given in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia (R/R CLL) has been associated with an objective response in 81% of cases with a median PFS of 20.3 months in a phase-3 clinical trial (Sharman et al, JCO 2019). Because the efficacy of new drugs reported in clinical trials may not translate into similar results in the day-to-day practice, we performed an observational retrospective-prospective study on the efficacy and safety of idelalisib and rituximab (IR) in R/R CLL patients treated outside of clinical trials in Italian centers belonging to the GIMEMA group.

COVID-19 is a severe infectious complication in patients with underlying medical conditions such as having undergone hematopoietic stem cell transplantation (HCT). This prospective survey reports outcome on 272 COVID-19 patients from 19 countries having undergone allogeneic (n = 175) or autologous (n = 97) HCT reported to the EBMT registry or to the GETH. All patients had the diagnosis of SARS-CoV-2 documented by PCR. Patients were included in this analysis if COVID-19 diagnosis was before April 10, 2020. The overall survival was estimate by using the Kaplan Meier methods, considering the death due to any cause as an event and the time from COVID-19 infection to the latest follow-up as survival time; difference between groups were tested by the log-rank test. Univariate and multivariate risk factor analysis for overall survival were performed with the Cox regression model.

Duarte: Incyte Corporation: Other: Has received speaker and advisor fees. Kwon:Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Mielke:Novartis: Honoraria, Other: received via my institution, Speakers Bureau; Celgene/BMS: Honoraria, Other: received via my institution , Speakers Bureau; Bellicum: Honoraria, Other: received via my institution, Speakers Bureau; Kite/Gilead: Honoraria, Other: received via my institution , Speakers Bureau; Miltenyi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: received via my institution , Speakers Bureau; KIADIS Pharma: Honoraria, Other: received via my institution , Speakers Bureau; DNA Prime: Honoraria, Other: received via my institution , Speakers Bureau. López Jiménez:MSD: Speakers Bureau; Roche: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Abbvie: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau.

In the pre—positron emission tomography era, the Gruppo Italiano Studio Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients.

Introduction:All the available CLL therapies differ for relevant aspects as duration of response, mode of administration, treatment duration and adverse events: the CHOICE study was designed to investigate CLL patients' Quality of Life (QoL) and preferences towards different treatment attributes through a Discrete Choice Experiment (DCE) in Italy. Due to the timeline of the study, started in Feb2020, the collected data offer an insight of patients' perception and attitude during the 1 stwave of the COVID-19 pandemic, as opposed to other DCE results available in CLL (1-2).

Background: Inotuzumab-ozogamicin (IO) is one of the drugs of choice for relapse/refractory (R/R) acute lymphoblastic leukemia (ALL). Patients who received IO in a clinical trial had a CR rate of approximately 81% and a median overall survival of approximately 8 months, superior to best available therapy and numerically comparable with blinatumomab. Toxicities were generally manageable, veno-occlusive disease/ sinusoidal obstruction syndrome (VOD/SOS) was reported as a rare adverse event possibly linked to the drug that require attention, especially during hematopoietic stem cell transplant after IO. Data on IO effectiveness in the real-life setting are generally lacking, for the low incidence of the disease and the high number of possible therapies that are emerging.

Introduction:We recently demonstrated in a large multicentre study that sGA can identify fit older patients with aggressive lymphoma able to tolerate first-line intensive treatment with curative intent and to obtain similar results than younger people (Merli at al JCO 2021). Regardless of age, about 40% of patients with aggressive lymphoma are either refractory or will eventually relapse after treatment with curative intent. Salvage platinum-based regimens followed by ASCT in responsive disease is a standard of care to obtain longer second remission. However, in many case series, patients over 65 years are excluded from the transplant approach because of potential severe toxicities of high-dose therapy in older patients. This study was designed to evaluate the feasibility and activity of high-dose treatment followed by ASCT in older FIT patients with R/R aggressive lymphoma selected with a sGA.

Tucci: Takeda: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees. Musuraca: janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavallo: ROCHE: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Gilead: Speakers Bureau. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau; Takeda: Other: travel expenses, accommodation. Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Marcheselli: sandoz: Membership on an entity's Board of Directors or advisory committees. Rossi: Abbvie: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees.

Papayannidis: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Astellas: Honoraria; Janssen: Honoraria. Fracchiolla: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Di Raimondo: Amgen: Honoraria; AbbVie: Honoraria; Pfizer: Honoraria; Jazz Pharmaceutical: Honoraria; Janssen Pharmaceuticals: Honoraria; Bristol Myers Squibb: Honoraria. Lanza: Pfizer: Research Funding; Abbvie: Consultancy; Jazz: Consultancy; Sanofi: Consultancy. Borlenghi: Amgen, Janssen: Consultancy. Sica: Pfizer: Honoraria. Corradini: AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy; KiowaKirin; Incyte; Daiichi Sankyo; Janssen; F. Hoffman-La Roche; Kite; Servier: Consultancy; Amgen; Takeda; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations; Novartis; Gilead; Celgene: Consultancy, Other: Travel and accommodations; BMS: Other: Travel and accommodation; Sanofi: Consultancy, Honoraria; Incyte: Consultancy; Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Pane: Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy. Passamonti: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martinelli: Stemline Therapeutics: Consultancy; Astellas: Consultancy, Speakers Bureau; Roche: Consultancy; Incyte: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Abbvie: Consultancy; Pfizer: Consultancy, Speakers Bureau; Daichii Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy.

Molica: Astrazeneca: Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Laurenti: AbbVie: Consultancy, Honoraria, Research Funding; Gilead: Honoraria; Roche: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; BeiGene: Honoraria. Ghia: Gilead: Consultancy, Research Funding; Celgene/Juno/BMS: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; ArQule/MSD: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding. Coscia: Gilead: Honoraria; Janssen: Honoraria, Other, Research Funding; AstraZeneca: Honoraria; AbbVie: Honoraria, Other. Cuneo: AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Gaidano: Beigene: Honoraria; Janssen: Honoraria, Speakers Bureau; AstraZeneca: Honoraria; AbbVie: Honoraria, Speakers Bureau; Incyte: Honoraria. Mauro: Takeda: Consultancy, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy. Gualberti: AbbVie: Current Employment. Iannella: AbbVie: Current Employment. Finsinger: AbbVie: Current Employment. Caira: AbbVie: Current Employment. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P< .001), albumin levels below 3.5 g/dL (P= .001), International Prognostic Index (IPI) scores of 2 to 3 (P< .001), lactate dehydrogenase (LDH) levels above normal (P< .001), age older than 60 years (P= .01), platelet counts below 100 000/μL (P= .04), HbsAg-positivity (P= .01), and no splenectomy at diagnosis (P= .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (× 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100 000/μL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (× 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

Background Venous thromboembolism (VTE) is a quite common complication in acute leukemia, although its real incidence is unknown. The best treatment of this complication is still a matter of debate due to the very high risk of hemorrhage in this group of patients.Patients and methods From December 2000 to December 2002 four Caucasian patients with acute leukemia developed VTE complications. The patients were three men and one woman, mean age 55.7 years (range, 27-77). Two patients with acute lymphoid leukemia (L1 and L2 according to the FAB classification) developed deep venous thrombosis during the administration of chemotherapy; one patient with acute myeloid leukemia (AML, M2 according to the FAB classification) had pulmonary thromboembolism at diagnosis, while another AML patient (M4 according to FAB) showed deep venous thrombosis as the first symptom of leukemia. The clinical diagnosis of symptomatic VTE was confirmed by objective imaging procedures including lower limb venous color Doppler imaging in all cases and a ventilation-perfusion lung scan in one case. All patients were treated with enoxaparin 100 IU/kg subcutaneously twice daily for one month, followed by 150 IU/kg once daily for at least five months. When the platelet count was below 20,000 × 109/L, the dose was reduced by 50%.Results During antithrombotic treatment neither VTE recurrences nor hemorrhagic complications or heparin-induced thrombocytopenia occurred. The platelet count at the beginning of enoxaparin treatment was very low (mean, 55,750 × 109/L; range, 12,000-121,000 × 109/L) and treatment did not affect platelet recovery.Conclusions Enoxaparin proved to be efficacious and safe in the management of deep venous thrombosis with or without pulmonary embolism in patients affected by acute leukemia. Enoxaparin cured acute venous thrombosis, prevented recurrences and did not cause any hemorrhagic complications despite prolonged severe thrombocytopenia.

Splenic and nodal marginal zone lymphomas (MZL) are subtypes of marginal zone-derived neoplasms. Due to their rarity, little is known concerning their relation, pattern of dissemination, and treatment outcome. The authors analyzed the clinicopathologic features and outcome of 43 patients (34 patients with splenic MZL and 9 patients with nodal MZL). All lesional tissues obtained at diagnosis were reviewed histologically. Among the patients with splenic MZL, 30 patients had Stage IV disease (based on the Ann Arbor staging system). Twenty-six patients presented with splenomegaly with or without limited involvement of abdominal lymph nodes, whereas 7 patients showed disease extension to superficial lymph nodes. Hepatitis C virus (HCV) serology was positive in 35% of patients. Seventeen patients underwent splenectomy, 8 patients received chemotherapy, and 7 patients were followed without initial treatment. Interferon produced a lymphoma response in three of four HCV positive patients. Of 27 treated patients, 13 patients achieved a complete response, and 12 patients achieved a partial response. The median event-free survival (EFS) was 3.3 years (5.1 years for patients with disease confined to the abdomen and 2.1 years for patients with disease extension to superficial lymph nodes). Among nine patients with nodal MZL, four patients had Stage IV disease. HCV serology was positive in two patients. Five patients responded to chemotherapy. The median EFS was 2.8 years. The median overall survival was not reached for patients with both types of MZL. The results of the current study demonstrated that splenic and nodal MZL are indolent lymphomas with different presenting features but common morphologic and biologic characteristics, including high HCV seroprevalence. Studies will be required to identify specific biologic markers and to define the best treatment. Cancer 2004;100:107–15. © 2003 American Cancer Society.

Human immunodeficiency virus (HIV) is likely to play a role in the onset of plasma cell tumors (PCT). In fact, HIV could be involved in plasmacytomagenesis in several ways: it has the ability to lessen the immunosurveillance to such a degree as to impair the immune response against tumor cell growth. This decreased immunosurveillance could further facilitate the transforming malignant role of possible Epstein-Barr virus (EBV) infection occurring in this setting. Lastly, a murine retrovirus has been shown to be able to accelerate plasmacytomagenesis in mice, thus indicating that these viruses may be directly involved in the onset of PCT. According to cases previously reported in the literature, the clinical features of this case of HIV-associated PCT were more aggressive and the survival was shorter than expected for PCT cases in the general population. Further, the pattern of alteration of gam-maglobulinemia differed in this setting. These alterations strongly suggest a direct role of HIV in PCT. Further in-depth investigations are therefore warranted to elucidate this issue.

Summary:

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m2 of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure.Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11). We observed an eventual total of 120 treatment failures, 64 (61%) in the group treated with P-C and 56 (54%) among those treated with M-B (P = 0.29). Patients alive without disease at four years were estimated to be 42% in the P-C arm and 49% in the M-B arm (P = 0.27). The estimated 4-year overall survival was 54% for P-C and 61 % for M-B, and the differences were also not significant (P = 0.29). Patients treated with M-B experienced more and more severe side effects, including mucositis, infections, neurologic, pulmonary and cardiac abnormalities. Patients treated with P-C had a 1.3 g mean decrease of hemoglobin over the induction therapy, while patients treated with M-B experienced a 2.2 g mean decrease (P = 0.01).In conclusion, both P-C and M-B resulted in effective treatment for patients with aggressive NHL, and provided similar activity. However P-C was more manageable in an outpatient setting and produced less acute toxic effects.

We report two cases of brain glioma that developed in the scar of an old brain trauma. The first is that of a 40-year-old man who presented with severe headaches; CT and MRI showed a large mass in the right parietal region. The tumor was unresectable and surgical biopsy showed a glioblastoma multiforme. The patient had suffered a cranial trauma in a road accident 20 years previously with an intrathecal hematoma in the right parietal region. The second case concerns a 60-year-old man who, 15 years after severe head injury in a road accident, developed a glioblastoma multiforme which was localized in the scar of the brain contusion. These cases fulfill the established criteria for a traumatic origin of brain tumors and add further support to the relationship between cranial trauma and the onset of glioma. As stated by other authors, an association between head trauma and brain tumor risk cannot be ruled out and should be studied further.

Lymphoproliferative disorders affecting the lung are infrequent. Therefore the diagnosis is often not easy, specially when the lung is primary affected. Moreover, new clinical-pathological entities are responsible of primary lung lymphoma that require specific treatment. It is important to keep in mind the chance that lung may be involved by lymphoproliferative disorders so to avoid the mistake of the misdiagnosis of this curable diseases since sometimes they have a good prognosis and a very different management from epithelial neoplasia of the lung.

This report describes 2 patients who developed acute myelocytic leukemie (AML) type M2 and chronic myelomonocytic leukemia (CMML) of the FAB classification, respectively 2 months and 2 weeks after diagnosis of operable breast cancer. The patient with AML showed pancytopenia 2 months before the diagnosis of AML, had a normal karyotype, and showed a good response to chemotherapy. The patient with CMML had a normal karyotype, and she was treated with hydroxyurea and supportive therapy. The 2 patients had no previous exposure to irradiation or cytotoxic therapy. These cases show that breast cancer and either leukemia or myelodysplastic syndrome may be associated even without previous irradiation or combination chemotherapy.

Efficace: Bristol Meyers Squibb: Consultancy; Seattle Genetics: Consultancy; Orsenix: Consultancy; Incyte: Consultancy; TEVA: Research Funding; TEVA: Consultancy; Lundbeck: Research Funding; Amgen: Consultancy; AMGEN: Research Funding. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Platzbecker:Celgene: Research Funding. Stauder:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia:Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Voso:Celgene: Research Funding, Speakers Bureau. Santini:AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Novartis: Honoraria. Lubbert:Teva: Other: Study drug; Celgene: Other: Travel Grant; Janssen: Honoraria, Research Funding. Cuneo:Gilead: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; Roche: Other: advisory board, Speakers Bureau; janssen: Other: advisory board, Speakers Bureau.

Background and aims

Background:

Gaidano: Amgen: Consultancy, Honoraria; Morphosys: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Ladetto:Celgene: Honoraria; Sandoz: Honoraria; Jannsen: Honoraria; Roche: Honoraria; Abbvie: Honoraria; Acerta: Honoraria.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative option for patients with relapsed or refractory Hodgkin's lymphoma (RR HL).

Background:

Rusconi: Janssen: Consultancy, Other: Congress attendance; Teva: Consultancy, Other: Congress attendance; Takeda: Consultancy. Spina:Teva Pharmaceuticals Industries: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees.

From November 2012 to July 2014, brentuximab vedotin (BV) was available in Italy for patients with relapsed Hodgkin’s lymphoma (HL) outside a clinical trial context based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96: "medicinal products that are provided free of charge on the national health service"). A large Italian observational retrospective study was conducted on the use of BV in the everyday clinical practice to check if clinical trial results are confirmed even in a real life context. Primary endpoint was the best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and the safety profile. BV was infused intravenously at the dose of 1.8 mg/kg every 3 weeks. A total of 234 HL patients were treated in 40. All patients had histologically documented CD30+ HL; 49% had relapsed and 51% had refractory disease. Patients were heavily pretreated with a median of 3 previous therapies (including autologous stem cell transplant [SCT] in the 69% of cases). 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 (>60 years): 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 29 months and progression free survival 31.9% at 55 months. We identified 30 long term responders (patients with a response ≥ 12 months) of whom 18 are still in CR, 7 with a consolidative SCT and 11 without any consolidative procedure. Duration of response did not differ who achieved at least PR and then either did or did not undergo consolidative SCT. All patients were included in the safety profile for the analysis; in general, the treatment was well tolerated in everyday clinical practice and the toxicity profile was closely similar to the previously published data; no death has been linked to BV-induced toxicity. This preliminary analysis could indicate that BV displays a number of features favoring its use as a bridge to transplant in patients with active disease who achieve a suboptimal response to salvage treatment. Even in a real life context, BV induces clinical responses quite rapidly, i.e. within the first 4 cycles in most responders, thus permitting the timely application of the transplantation phase. BV displays a favorable toxicity profile, without overlapping toxicities with most of the agents employed in high-dose conditioning regimens. Furthermore, for HL patients ineligible for transplant or for who transplant failed, may represent a feasible effective therapeutic option.

Patriarca: Janssen-Cilag, Celgene, Merck Sharp & Dohme: Honoraria. Zinzani:Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Background:The most important drawback of clinical trials of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) in lymphomas is the high heterogeneity of histological entities. Therefore, the statistical power is reduced, and data are not conclusive. We previously demonstrated the safety of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (BeEAM) prior to ASCT in resistant/relapsed lymphoma patients. This combination of drugs was able to induce a high CR rate in a population that did not have an opportunity of being cured with other therapies. However, that study enrolled both Hodgkin and non-Hodgkin lymphoma patients.