Francesco Angrilli - Academia.edu (original) (raw)

Papers by Francesco Angrilli

Clinical Nuclear Medicine, 2020

Blood

Background: Most patients (pts) with HL can be cured today. Nevertheless, 10 to 40% of pts fail t... more Background: Most patients (pts) with HL can be cured today. Nevertheless, 10 to 40% of pts fail to respond to front-line treatment or relapse both early and late. Pts who do not achieve complete remission with conventional treatment or who present early relapse have poor prognosis compared with pts who develop late relapse. The treatment of choice for refractory or early relapsed pts is high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT), while late relapsed pts may be treated with either conventional therapy or HDC plus ASCT. The purpose of this study is to evaluate the results of our experience in the treatment of refractory or relapsed HL pts. Methods: From January 1999 to December 2007, 179 untreated pts with HL have been admitted in our institution and 176 completed treatment today. Front-line treatment included 4–6 courses of ABVD polychemotherapy in combination with involved field radiotherapy (IFRT) (36 Gy) in clinical stage (CS) I–IIA, and 6...

Blood

Background: PMBCL accounts for nearly 2% of all non Hodgkin lymphoma. The most effective treatmen... more Background: PMBCL accounts for nearly 2% of all non Hodgkin lymphoma. The most effective treatment of this disease is unknown. In retrospective studies third generation chemotherapy regimens, namely MACOP-B or VACOP-B, plus radiotherapy achieved better results in comparison with conventional CHOP. Moreover, the value of the addition of rituximab (R) to CHOP or MACOP-B in PMBCL is not well-known today. The purpose of this study is to evaluate the results of our experience in the treatment of PMBCL. Methods: Between 1/2000 and 1/2008, 25 untreated patients (pts) with PMBCL have been admitted in our institution. Disease evaluation was performed with whole-body computed tomography at diagnosis, after 3–4 courses or after 2 months of chemotherapy and at the conclusion of treatment. At early restaging, pts who obtained at least a partial remission (PR) completed planned treatment, while unresponsive pts started high dose sequential chemotherapy (HDSC) (2 courses of APO, 2 courses of DHAP,...

Journal of Clinical Oncology

8006 Background: The optimal chemotherapy regimen for patients with advanced, active follicular l... more 8006 Background: The optimal chemotherapy regimen for patients with advanced, active follicular lymphoma (FL) has not been established yet. We conducted a randomized trial comparing R-CVP with R-CHOP and R-FM. Methods: Previously untreated patients with advanced FL were randomly assigned to receive 8 doses of rituximab associated to 8 cycles of CVP, or 6 cycles of CHOP or FM (fludarabine 25 mg/m2 day 1-3, mitoxantrone 10 mg/m2 day 1). No maintenance therapy was allowed. The principal study end point was Time to Treatment Failure (TTF). Events in TTF were failure of induction therapy, progressive or relapse disease and death from any causes. In order to show a hazard ratio between each experimental arms and standard arm of 0.53 we planned to accrue 534 patients (178 per arm) with 4 years of accrual and 1 year of follow-up. Statistical tests were two-sided with an alpha error of 0.05, adjusted by Bonferroni for multiple arm comparison, and power of 90%. Results: Between March 2006 and...

The International Journal of Artificial Organs

In this paper the impact of hemapheresis technology on 238 allogeneic bone marrow transplants per... more In this paper the impact of hemapheresis technology on 238 allogeneic bone marrow transplants performed in Pescara from 1982 through 1993 is described. Granulocyte transfusions were limited to patients with neutrophil level <0.2x109/L. An average of 4 units of packed red blood cells were required to maintain adequate hemoglobin levels. Patients with major ABO incompatibility showed an increased requirement of red blood cell support as compared to patients ABO-matched and ABO minor mismatched. For platelet support single-donor platelets collected on a blood-cell separator were given. A total of 1548 platelet transfusions were examined. The median number of platelet transfusions for each patient was 5. Platelet refractoriness occurred in 44% of patients. The hemorrhage related mortality was 0.9%. The advancement made in the field of hemapheresis technology, as well as the improved transplant technique, have contributed to increase the post-transplant survival from 17% in the early ...

Blood

2837 Rai and Binet staging systems are not devoid of some limitations, including the lack of eval... more 2837 Rai and Binet staging systems are not devoid of some limitations, including the lack of evaluation of thoracic and abdominal lymphadenopathies. The widely-used IWCLL guidelines do not incorporate use of TB-CT scan in the diagnostic algorithm. In the present study, we investigated whether TB-CT scans could up-stage Binet stage A CLL patients included in the prospective multicenter O-CLL01 GISL study (clinicaltrial.gov ID: NCT00917549), and whether this subgroup presented differences in prognostic markers and in progression-free survival (PFS). To date, 454 patients have been enrolled and TB-CT scans were available in 238 patients. The median age was 60 years (range, 33–71) and 136 (57%) were male. According to Rai, 180 patients were at low risk (stage 0) and 58 at intermediate risk (stages I-II). b2-microglobulin was elevated in 35.5% of cases. Seventy-eight patients (32%) were IgVH unmutated, 108 patients (45%) had a high ZAP-70 expression, 45 patients (19%) were CD38 positive ...

Blood

BACKGROUND Secondary malignancies have been associated with Non Hodgkin Lymphoma (NHL) treatment.... more BACKGROUND Secondary malignancies have been associated with Non Hodgkin Lymphoma (NHL) treatment. Nevertheless few analyses have addressed this issue focusing on aggressive lymphoma. Aims of this study were to determine the incidence and the risk factors for developing secondary cancer during long term follow up of patients treated for aggressive lymphoma. METHODS For the purpose of this study we identified in the GISL database, 1259 naïve patients with histologically confirmed diagnosis of aggressive NHL. Observed cancer were classified by site. The incidence numbers of second neoplasia was compared to the incidence of malignancies in the Italian population. The standardized incidence ratio was calculated from the ratio between observed and expected number of cancers. Absolute excess risk was calculated by subtracting the expected from the observed cases and dividing by the person-years at risk. The Time Free 2nd Tumour (TF2T) was measured from the end of the first treatment to la...

Blood

Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associat... more Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associated with intrasinusoidal bone marrow infiltration. The encapsulation of doxorubicin into non-pegylated liposomes allows targeting of the drug to affected organs including spleen, lymphnodes and bone marrow. Methods: In 2005 the GISL started a phase II study for the treatment of patients with histologically confirmed SMZL, investigating safety and clinical profile of 6 courses of a modified R-CHOP regimen in which standard doxorubicin was substituted with non pegylated lyposomal doxorubicin (NPLD) used at the same doses (50mg/m2) (R-COMP). Main inclusion criteria were age > 18 yrs, normal cardiac function and active disease (at least one of the following; Hb <10g/dl; plt <100.000/mmc, symptomatic splenomegaly, elevated LDH, B symptoms, extrasplenic disease, LDT <12 months). Splenectomy was allowed prior to treatment start only in case of symptomatic spleen enlargement. The stud...

Blood

4208 Introduction: Patients with lymphoma are considered at high risk of thrombosis, due to the d... more 4208 Introduction: Patients with lymphoma are considered at high risk of thrombosis, due to the disease itself or to the use of chemotherapy. The global risk of thrombosis is around 5%, higher in Non Hodgkin Lymphoma compared to Hodgkin Lymphoma and in advanced stages compared to localized disease. So far few studies have addressed the risk of thrombosis in lymphomas with a prospective approach. In 2007 we started a prospective study on patients with malignant lymphoma (ML) to assess the risk of thromboembolism in such patients and to identify possible risk factors. Methods: from March 1st 2007 all patients enrolled in any of the active clinical trials conducted by the Gruppo Italiano Studio Linfomi for the initial treatment of ML were screened for the occurrence of thromboembolic events (TE) at 3 timepoints: at the time of diagnosis (D), during chemotherapy (C) and during follow-up (F). For each registered TE additional data were required with respect to presence of additional risk...

Blood

2471 Eighty-one previously untreated CLL patients, ≤60 years, with advanced/progressive disease w... more 2471 Eighty-one previously untreated CLL patients, ≤60 years, with advanced/progressive disease were included in the GIMEMA LLC0405 prospective multicenter study. Patients were stratified according to the biologic features. High risk (HR) patients were defined by the presence of: 1) 17p- (≥20% of analyzed cells), or 2) 11q- with ≥1 additional unfavorable factor (IGHV germline; Zap-70+ ≥10%; CD38+ ≥7%), or 3) germline IGHV or mutated VH3-21 and ≥2 unfavorable factors (Zap-70; CD38; 6q-; trisomy 12). Low risk (LR) patients were defined by the absence of the above features. HR patients received 4 monthly courses of fludarabine and campath-1H (FluCam; Flu 30 mg/m2 iv; Cam 30 mg iv, days 1–3). Responding patients underwent post-induction therapy: reduced intensity PBSC allogeneic transplant or, in the absence of a sibling donor, an autologous PBSC transplant or, in the absence of a sufficient harvest, Cam sc, 30 mg weekly for a maximum of 12 weeks. For LR patients, treatment included 6 m...

Blood

2341 Poster Board II-318 Background. The clinical heterogeneity of chronic lymphocytic leukemia (... more 2341 Poster Board II-318 Background. The clinical heterogeneity of chronic lymphocytic leukemia (CLL) requires parameters to stratify patients into prognostic subgroups to adapt treatment ranging from ‘watch and wait’ to allogeneic stem cell transplantation. To this end, several parameters such as lymphocyte doubling time, β-2 microglobulin, CD38 and ZAP-70 expression, immunoglobulin variable heavy chain (IgVH) mutation status and genetic abnormalities, as assessed by fluorescence in situ hybridization (FISH), have been integrated in clinical practice. Aims. In the present study, we investigated by FISH the incidence of the known major cytogenetic alterations (+12 and 13q14, 17p13, 11q23 deletions) in a series of Binet A B-CLL patients included in the prospective O-CLL1 GISL study started in April 2007. Methods. Molecular markers characterization and FISH analyses were performed as previously reported (Cutrona et al. Haematologica, 2008; Fabris et al. GCC, 2008). A cut-off value of ...

Haematologica, Jan 28, 2018

Leukemia, Jan 20, 2018

During the the last two decades several biological prognostic markers have been identified in chr... more During the the last two decades several biological prognostic markers have been identified in chronic lymphocytic leukemia (CLL) [1]. Some, like the IGHV mutational status and TP53 disruption, are also predictive of response to chemoimmunotherapy [2–6]. Rossi et al. reported an observational retrospective analysis on 404 CLL patients treated front-line with fludarabine-cyclophosphamide-rituximab (FCR) [6]. Based on the IGHV mutational status and FISH cytogenetics, patients were stratified into low risk (mutated IGHV and no adverse FISH cytogenetics [del(17p), del(11q)]), intermediate risk (unmutated IGHV and/or del11q in the absence of del17p), and high risk (del17p independent of co-occurring del11q or unmutated IGHV). This simple biologically based prognostic score based on the combination of three widely utilized biomarkers allowed to stratify patients with a significantly different progression-free survival (PFS) and overall survival (OS) after FCR treatment. In addition, they also demonstrated that low-risk patients had a durable remissions after FCR, with a life expectancy overlapping that observed in the age-matched general population [6]. Similarly, Laurenti et al. recently published a retrospective study on 102 patients with CLL treated front-line with chlorambucil-rituximab [7]. This analysis also showed that the above-mentioned biological score could distinguish patients with a different PFS. A trend toward a better OS was also observed. With the aim of investigating whether this biological score could also segregate CLL patients treated with bendamustine-rituximab (BR), we performed a retrospective study on previously untreated CLL patients who received BR as primary therapy. The cohort included 418 patients with progressive CLL from 34 different hematology centers (29 Italian, 3 Israeli, 1 German, and 1 American) who received at least one dose of BR as front-line treatment during the period 2008–2014; 279 of the 418 patients have been included in a previous multicenter study which reported on the front-line treatment of CLL patients with BR outside of clinical trials [8]. Relative survival, defined as the ratio between the actuarial survival observed in the CLL cohort and the expected survival of the general population matched by sex, age, nationality, and calendar year of starting BR was calculated using the Ederer II method. Expected survival estimates were calculated according to Italian, Israel, German, and American life expectancy tables (Human Mortality Database; http://www. mortality.org/, accessed 18 September 2017). Observed and expected survivals were compared using the Fisher test. Data analysis was carried out by STATA 13.1 (by StataCorp 4905 Lakeway Drive College Station, TX 77845, USA) (further details are in the Supplemental Appendix). The main clinical characteristics of the 418 patients are summarized in Table 1. After a median follow-up of 25 months, 86 patients progressed and 56 died, accounting for an estimated 2-year PFS of 73.2% and a 2-year OS of 88.9%. These results are similar to data of a multicenter prospective phase II trial enrolling 117 CLL patients who received BR as first-line therapy. Fisher et al. recorded a 2-year event-free survival of about 70% and a 2-year OS of 90% [3]. In 285 of the 418 cases complete molecular data were available (Table 1 * Massimo Gentile massim.gentile@tiscali.it

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and predni... more Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%...

The Lancet. Haematology, 2017

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomis... more The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of metho...

Hematological oncology, Jan 3, 2017

The incidence of non-Hodgkin lymphoma in patients 80 years of age or older is 50 times higher tha... more The incidence of non-Hodgkin lymphoma in patients 80 years of age or older is 50 times higher than in 20- to 24-year-olds. Very elderly patients are often not treated with standard immunochemotherapy because of poor performance status, comorbidities, and toxicity concerns. We retrospectively analyzed data for 29 patients diagnosed with diffuse large B-cell lymphoma or grade 3B follicular lymphoma and treated with rituximab in combination with nonpegylated liposomal doxorubicin between January 2010 and August 2015. The median age was 84 years. The overall 3-year survival, cause-specific survival, and progression-free survival rates were 46%, 55%, and 44%, respectively. Among prognostic factors, only the achievement of complete remission strongly correlated with overall survival, cause-specific survival, and progression-free survival rates. Treatment caused very mild toxicity, without treatment-related hospitalization or toxic deaths.

American Journal of Hematology, 2016

European journal of cancer (Oxford, England : 1990), Jun 26, 2016

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamusti... more Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10....

Biology of Blood and Marrow Transplantation, 2016

Clinical Nuclear Medicine, 2020

Blood

Background: Most patients (pts) with HL can be cured today. Nevertheless, 10 to 40% of pts fail t... more Background: Most patients (pts) with HL can be cured today. Nevertheless, 10 to 40% of pts fail to respond to front-line treatment or relapse both early and late. Pts who do not achieve complete remission with conventional treatment or who present early relapse have poor prognosis compared with pts who develop late relapse. The treatment of choice for refractory or early relapsed pts is high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT), while late relapsed pts may be treated with either conventional therapy or HDC plus ASCT. The purpose of this study is to evaluate the results of our experience in the treatment of refractory or relapsed HL pts. Methods: From January 1999 to December 2007, 179 untreated pts with HL have been admitted in our institution and 176 completed treatment today. Front-line treatment included 4–6 courses of ABVD polychemotherapy in combination with involved field radiotherapy (IFRT) (36 Gy) in clinical stage (CS) I–IIA, and 6...

Blood

Background: PMBCL accounts for nearly 2% of all non Hodgkin lymphoma. The most effective treatmen... more Background: PMBCL accounts for nearly 2% of all non Hodgkin lymphoma. The most effective treatment of this disease is unknown. In retrospective studies third generation chemotherapy regimens, namely MACOP-B or VACOP-B, plus radiotherapy achieved better results in comparison with conventional CHOP. Moreover, the value of the addition of rituximab (R) to CHOP or MACOP-B in PMBCL is not well-known today. The purpose of this study is to evaluate the results of our experience in the treatment of PMBCL. Methods: Between 1/2000 and 1/2008, 25 untreated patients (pts) with PMBCL have been admitted in our institution. Disease evaluation was performed with whole-body computed tomography at diagnosis, after 3–4 courses or after 2 months of chemotherapy and at the conclusion of treatment. At early restaging, pts who obtained at least a partial remission (PR) completed planned treatment, while unresponsive pts started high dose sequential chemotherapy (HDSC) (2 courses of APO, 2 courses of DHAP,...

Journal of Clinical Oncology

8006 Background: The optimal chemotherapy regimen for patients with advanced, active follicular l... more 8006 Background: The optimal chemotherapy regimen for patients with advanced, active follicular lymphoma (FL) has not been established yet. We conducted a randomized trial comparing R-CVP with R-CHOP and R-FM. Methods: Previously untreated patients with advanced FL were randomly assigned to receive 8 doses of rituximab associated to 8 cycles of CVP, or 6 cycles of CHOP or FM (fludarabine 25 mg/m2 day 1-3, mitoxantrone 10 mg/m2 day 1). No maintenance therapy was allowed. The principal study end point was Time to Treatment Failure (TTF). Events in TTF were failure of induction therapy, progressive or relapse disease and death from any causes. In order to show a hazard ratio between each experimental arms and standard arm of 0.53 we planned to accrue 534 patients (178 per arm) with 4 years of accrual and 1 year of follow-up. Statistical tests were two-sided with an alpha error of 0.05, adjusted by Bonferroni for multiple arm comparison, and power of 90%. Results: Between March 2006 and...

The International Journal of Artificial Organs

In this paper the impact of hemapheresis technology on 238 allogeneic bone marrow transplants per... more In this paper the impact of hemapheresis technology on 238 allogeneic bone marrow transplants performed in Pescara from 1982 through 1993 is described. Granulocyte transfusions were limited to patients with neutrophil level <0.2x109/L. An average of 4 units of packed red blood cells were required to maintain adequate hemoglobin levels. Patients with major ABO incompatibility showed an increased requirement of red blood cell support as compared to patients ABO-matched and ABO minor mismatched. For platelet support single-donor platelets collected on a blood-cell separator were given. A total of 1548 platelet transfusions were examined. The median number of platelet transfusions for each patient was 5. Platelet refractoriness occurred in 44% of patients. The hemorrhage related mortality was 0.9%. The advancement made in the field of hemapheresis technology, as well as the improved transplant technique, have contributed to increase the post-transplant survival from 17% in the early ...

Blood

2837 Rai and Binet staging systems are not devoid of some limitations, including the lack of eval... more 2837 Rai and Binet staging systems are not devoid of some limitations, including the lack of evaluation of thoracic and abdominal lymphadenopathies. The widely-used IWCLL guidelines do not incorporate use of TB-CT scan in the diagnostic algorithm. In the present study, we investigated whether TB-CT scans could up-stage Binet stage A CLL patients included in the prospective multicenter O-CLL01 GISL study (clinicaltrial.gov ID: NCT00917549), and whether this subgroup presented differences in prognostic markers and in progression-free survival (PFS). To date, 454 patients have been enrolled and TB-CT scans were available in 238 patients. The median age was 60 years (range, 33–71) and 136 (57%) were male. According to Rai, 180 patients were at low risk (stage 0) and 58 at intermediate risk (stages I-II). b2-microglobulin was elevated in 35.5% of cases. Seventy-eight patients (32%) were IgVH unmutated, 108 patients (45%) had a high ZAP-70 expression, 45 patients (19%) were CD38 positive ...

Blood

BACKGROUND Secondary malignancies have been associated with Non Hodgkin Lymphoma (NHL) treatment.... more BACKGROUND Secondary malignancies have been associated with Non Hodgkin Lymphoma (NHL) treatment. Nevertheless few analyses have addressed this issue focusing on aggressive lymphoma. Aims of this study were to determine the incidence and the risk factors for developing secondary cancer during long term follow up of patients treated for aggressive lymphoma. METHODS For the purpose of this study we identified in the GISL database, 1259 naïve patients with histologically confirmed diagnosis of aggressive NHL. Observed cancer were classified by site. The incidence numbers of second neoplasia was compared to the incidence of malignancies in the Italian population. The standardized incidence ratio was calculated from the ratio between observed and expected number of cancers. Absolute excess risk was calculated by subtracting the expected from the observed cases and dividing by the person-years at risk. The Time Free 2nd Tumour (TF2T) was measured from the end of the first treatment to la...

Blood

Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associat... more Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associated with intrasinusoidal bone marrow infiltration. The encapsulation of doxorubicin into non-pegylated liposomes allows targeting of the drug to affected organs including spleen, lymphnodes and bone marrow. Methods: In 2005 the GISL started a phase II study for the treatment of patients with histologically confirmed SMZL, investigating safety and clinical profile of 6 courses of a modified R-CHOP regimen in which standard doxorubicin was substituted with non pegylated lyposomal doxorubicin (NPLD) used at the same doses (50mg/m2) (R-COMP). Main inclusion criteria were age > 18 yrs, normal cardiac function and active disease (at least one of the following; Hb <10g/dl; plt <100.000/mmc, symptomatic splenomegaly, elevated LDH, B symptoms, extrasplenic disease, LDT <12 months). Splenectomy was allowed prior to treatment start only in case of symptomatic spleen enlargement. The stud...

Blood

4208 Introduction: Patients with lymphoma are considered at high risk of thrombosis, due to the d... more 4208 Introduction: Patients with lymphoma are considered at high risk of thrombosis, due to the disease itself or to the use of chemotherapy. The global risk of thrombosis is around 5%, higher in Non Hodgkin Lymphoma compared to Hodgkin Lymphoma and in advanced stages compared to localized disease. So far few studies have addressed the risk of thrombosis in lymphomas with a prospective approach. In 2007 we started a prospective study on patients with malignant lymphoma (ML) to assess the risk of thromboembolism in such patients and to identify possible risk factors. Methods: from March 1st 2007 all patients enrolled in any of the active clinical trials conducted by the Gruppo Italiano Studio Linfomi for the initial treatment of ML were screened for the occurrence of thromboembolic events (TE) at 3 timepoints: at the time of diagnosis (D), during chemotherapy (C) and during follow-up (F). For each registered TE additional data were required with respect to presence of additional risk...

Blood

2471 Eighty-one previously untreated CLL patients, ≤60 years, with advanced/progressive disease w... more 2471 Eighty-one previously untreated CLL patients, ≤60 years, with advanced/progressive disease were included in the GIMEMA LLC0405 prospective multicenter study. Patients were stratified according to the biologic features. High risk (HR) patients were defined by the presence of: 1) 17p- (≥20% of analyzed cells), or 2) 11q- with ≥1 additional unfavorable factor (IGHV germline; Zap-70+ ≥10%; CD38+ ≥7%), or 3) germline IGHV or mutated VH3-21 and ≥2 unfavorable factors (Zap-70; CD38; 6q-; trisomy 12). Low risk (LR) patients were defined by the absence of the above features. HR patients received 4 monthly courses of fludarabine and campath-1H (FluCam; Flu 30 mg/m2 iv; Cam 30 mg iv, days 1–3). Responding patients underwent post-induction therapy: reduced intensity PBSC allogeneic transplant or, in the absence of a sibling donor, an autologous PBSC transplant or, in the absence of a sufficient harvest, Cam sc, 30 mg weekly for a maximum of 12 weeks. For LR patients, treatment included 6 m...

Blood

2341 Poster Board II-318 Background. The clinical heterogeneity of chronic lymphocytic leukemia (... more 2341 Poster Board II-318 Background. The clinical heterogeneity of chronic lymphocytic leukemia (CLL) requires parameters to stratify patients into prognostic subgroups to adapt treatment ranging from ‘watch and wait’ to allogeneic stem cell transplantation. To this end, several parameters such as lymphocyte doubling time, β-2 microglobulin, CD38 and ZAP-70 expression, immunoglobulin variable heavy chain (IgVH) mutation status and genetic abnormalities, as assessed by fluorescence in situ hybridization (FISH), have been integrated in clinical practice. Aims. In the present study, we investigated by FISH the incidence of the known major cytogenetic alterations (+12 and 13q14, 17p13, 11q23 deletions) in a series of Binet A B-CLL patients included in the prospective O-CLL1 GISL study started in April 2007. Methods. Molecular markers characterization and FISH analyses were performed as previously reported (Cutrona et al. Haematologica, 2008; Fabris et al. GCC, 2008). A cut-off value of ...

Haematologica, Jan 28, 2018

Leukemia, Jan 20, 2018

During the the last two decades several biological prognostic markers have been identified in chr... more During the the last two decades several biological prognostic markers have been identified in chronic lymphocytic leukemia (CLL) [1]. Some, like the IGHV mutational status and TP53 disruption, are also predictive of response to chemoimmunotherapy [2–6]. Rossi et al. reported an observational retrospective analysis on 404 CLL patients treated front-line with fludarabine-cyclophosphamide-rituximab (FCR) [6]. Based on the IGHV mutational status and FISH cytogenetics, patients were stratified into low risk (mutated IGHV and no adverse FISH cytogenetics [del(17p), del(11q)]), intermediate risk (unmutated IGHV and/or del11q in the absence of del17p), and high risk (del17p independent of co-occurring del11q or unmutated IGHV). This simple biologically based prognostic score based on the combination of three widely utilized biomarkers allowed to stratify patients with a significantly different progression-free survival (PFS) and overall survival (OS) after FCR treatment. In addition, they also demonstrated that low-risk patients had a durable remissions after FCR, with a life expectancy overlapping that observed in the age-matched general population [6]. Similarly, Laurenti et al. recently published a retrospective study on 102 patients with CLL treated front-line with chlorambucil-rituximab [7]. This analysis also showed that the above-mentioned biological score could distinguish patients with a different PFS. A trend toward a better OS was also observed. With the aim of investigating whether this biological score could also segregate CLL patients treated with bendamustine-rituximab (BR), we performed a retrospective study on previously untreated CLL patients who received BR as primary therapy. The cohort included 418 patients with progressive CLL from 34 different hematology centers (29 Italian, 3 Israeli, 1 German, and 1 American) who received at least one dose of BR as front-line treatment during the period 2008–2014; 279 of the 418 patients have been included in a previous multicenter study which reported on the front-line treatment of CLL patients with BR outside of clinical trials [8]. Relative survival, defined as the ratio between the actuarial survival observed in the CLL cohort and the expected survival of the general population matched by sex, age, nationality, and calendar year of starting BR was calculated using the Ederer II method. Expected survival estimates were calculated according to Italian, Israel, German, and American life expectancy tables (Human Mortality Database; http://www. mortality.org/, accessed 18 September 2017). Observed and expected survivals were compared using the Fisher test. Data analysis was carried out by STATA 13.1 (by StataCorp 4905 Lakeway Drive College Station, TX 77845, USA) (further details are in the Supplemental Appendix). The main clinical characteristics of the 418 patients are summarized in Table 1. After a median follow-up of 25 months, 86 patients progressed and 56 died, accounting for an estimated 2-year PFS of 73.2% and a 2-year OS of 88.9%. These results are similar to data of a multicenter prospective phase II trial enrolling 117 CLL patients who received BR as first-line therapy. Fisher et al. recorded a 2-year event-free survival of about 70% and a 2-year OS of 90% [3]. In 285 of the 418 cases complete molecular data were available (Table 1 * Massimo Gentile massim.gentile@tiscali.it

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and predni... more Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%...

The Lancet. Haematology, 2017

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomis... more The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned to receive four courses of metho...

Hematological oncology, Jan 3, 2017

The incidence of non-Hodgkin lymphoma in patients 80 years of age or older is 50 times higher tha... more The incidence of non-Hodgkin lymphoma in patients 80 years of age or older is 50 times higher than in 20- to 24-year-olds. Very elderly patients are often not treated with standard immunochemotherapy because of poor performance status, comorbidities, and toxicity concerns. We retrospectively analyzed data for 29 patients diagnosed with diffuse large B-cell lymphoma or grade 3B follicular lymphoma and treated with rituximab in combination with nonpegylated liposomal doxorubicin between January 2010 and August 2015. The median age was 84 years. The overall 3-year survival, cause-specific survival, and progression-free survival rates were 46%, 55%, and 44%, respectively. Among prognostic factors, only the achievement of complete remission strongly correlated with overall survival, cause-specific survival, and progression-free survival rates. Treatment caused very mild toxicity, without treatment-related hospitalization or toxic deaths.

American Journal of Hematology, 2016

European journal of cancer (Oxford, England : 1990), Jun 26, 2016

Recently, encouraging results in terms of safety and efficacy have been obtained using bendamusti... more Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR as front-line therapy. The cohort included 279 patients with progressive CLL from 33 centers (29 Italian, 3 Israeli and 1 German) who received at least 1 cycle of BR as first-line treatment during the 2008-2014 period. The primary objective of this study was to evaluate the efficacy and safety of BR administered as front-line therapy, outside of controlled clinical trials. Median age was 70 years (range, 43-86 years); 62.4% were males and 35.8% had Binet stage C. Forty-two patients (15.2%) were unfit (cumulative illness rating scale [CIRS] score ≥7), and 140 (50.2%) had creatinine clearance ≤70 ml/min. Fluorescent in situ hybridisation analysis, available for 192 cases, showed that 21 (10....

Biology of Blood and Marrow Transplantation, 2016