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Background Autoimmune manifestations may occur in patients with hairy cell leukemia (HCL), and some rare cases of polyarteritis nodosa and leukocytoclastic vasculitis have been reported. However, data regarding the treatment of these cutaneous manifestations are lacking, given the rarity of the concomitance of HCL and vasculitic syndromes. Case presentation We present a 37-year-old man with paraneoplastic leukocytoclastic vasculitis complicating newly diagnosed HCL. The vasculitis completely resolved after the first 3 weekly administrations of cladribine, which is regarded as the gold-standard treatment for this disease. The underlying leukemia showed refractoriness to the same agent, thus requiring a second line of treatment. Conclusions The clinical picture we have observed is of interest for the following reasons: i) it confirms an existing pathogenetic relationship between this lymphoproliferative disorder and its cutaneous manifestations, as suggested by the prompt resolution of the purpuric lesions upon cladribine administration; ii) it indicates that cladribine is an effective treatment for HCL-related paraneoplastic syndromes, including leukocytoclastic vasculitis; iii) the evolution and the outcomes of the paraneoplastic manifestations may be independent of those of the underlying leukemia, which showed less than a partial response to its initial treatment.

Regarding primary mediastinal large B-cell lymphoma (PMLBCL), there are several controversial topics that warrant further investigation: the superiority of third-generation regimens, the impact of rituximab, the use of involved field radiotherapy (RT) and the assessment of clinical response by positron emission tomography (PET). We report our experience on 74 PMLBCL patients treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and rituximab: an observational retrospective single-centre study was conducted on patients diagnosed and treated between February 2002 and July 2011. All patients were evaluated by computed tomography scan and PET scan; after the final PET evaluation, PET-negative patients were observed, whereas PET-positive patients underwent mediastinal RT. Sixty-one (82.4%) patients achieved a complete response after the MACOP-B plus rituximab regimen; 68.9% presented a positive final PET and were treated with local RT, whereas 31.1% had a negative PET. Five patients relapsed within 12 months. At 10 years, overall survival was 82%, progression-free survival was 87.6% and disease-free survival (DFS) was 90.5% (median follow-up 4 years). No statistically significant differences were observed in DFS between the patients treated also with RT (PET positive) and patients only observed (PET negative): 90.7% vs 90% (p = 0.85), respectively. In our experience, adding rituximab does not change the final results in terms of complete response and DFS utilizing third-generation regimen. Furthermore, the introduction of the PET-guided RT approach leads to a patient-tailored treatment, which preserves the outcome and, at the same time, allows reducing the use of RT. Copyright © 2014 John Wiley & Sons, Ltd.

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

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

Current treatments for non-Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2-6) lymphoma patients in an off-label setting. Bortezomib therapy was scheduled for 4-6 cycles (1.3 mg/m(2) biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non-responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B-cell lymphoma patients obtained a response. Extra-hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3-4 thrombocytopenia in nine patients and grades 3-4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated.

Background A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkin’s lymphoma (NHL) patients. Patients and methods Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of 90Y-ibritumomab tiuxetan (90Y-IT), 8–14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). Results All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received 90Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. Conclusions This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with 90Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

No abstract available.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up to half of all patients relapse. Here we report the results from a phase 2, single-arm, single-center trial evaluating the safety and efficacy of lenalidomide plus rituximab in elderly patients with relapsed or refractory DLBCL. PATIENTS AND METHODS: Between March and June 2009, elderly patients (65 years of age or older) with relapsed/refractory DLBCL who had been heavily pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) was initiated for four cycles and rituximab (375 mg/m(2)) was administered on day 1 and day 21 of each 28-day cycle for four cycles. After this induction phase, patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were given lenalidomide maintenance therapy at the same schedule for another 8 months. RESULTS: A total of 23 patients with a median of three prior treatments (range, 2 to 8) were included. The overall response rate (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR, 1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of these patients achieved a CR. Adverse events were manageable and the most common included neutropenia and thrombocytopenia. CONCLUSION: Oral lenalidomide in combination with rituximab is active in elderly patients with relapsed/refractory DLBCL with a high percentage of patients achieving a continuous CR after lenalidomide maintenance.

Purpose: This study aimed to evaluate the efficacy and safety of the treatment with 90Y-ibritumomab tiuxetan following a short-course of rituximab with cyclophosphamide-adriamycin-vincristine-prednisone (R-CHOP) in high-risk elderly patients with previously untreated diffuse large B-cell lymphoma (DLBCL). Experimental Design: From December 2006 to October 2008, 55 high-risk elderly (age ≥60 years) untreated DLBCL patients were treated in seven Italian institutions with a short-course of chemotherapy consisting of four cycles of R-CHOP21 followed by 90Y-ibritumomab tiuxetan 6 to 10 weeks later. Results: Of the 55 patients, 48 underwent radioimmunotherapy. The overall response rate to the entire treatment regimen was 80%, including 73% complete remissions and 7% partial remissions. Eight (50%) of the 16 patients who achieved less than a complete response with CHOP improved their remission status after 90Y-ibritumomab tiuxetan administration. With a median follow-up of 18 months, the 2-year progression-free survival was estimated to be 85%, with a 2-year overall survival of 86%. 90Y-ibritumomab tiuxetan toxicity consisted of grade 3 to 4 hematologic toxicity in 28 of 48 patients, mainly neutropenia (23 patients) and thrombocytopenia (15 patients). Red cells and/or platelets transfusions were given to three patients. Conclusion: This study evaluated the feasibility, efficacy, and safety of a short-course R-CHOP21 regimen followed by 90Y-ibritumomab tiuxetan in high-risk elderly DLBCL patients. Clin Cancer Res; 16(15); 3998–4004. ©2010 AACR.

Background Peripheral T-cell lymphoma unspecified (PTCLU) and mycosis fungoides (MF) often show resistance to conventional chemotherapy. Gemcitabine should be considered a suitable option. We report the long-term update of 39 pretreated T-cell lymphoma patients treated with gemcitabine. Patients and methods From May 1997 to September 2007, 39 pretreated MF and PTCLU patients received gemcitabine. Inclusion criteria were as follows: histologic diagnosis of MF or PTCLU; relapsed/refractory disease; age ≥18 years; and World Health Organization performance status of two or less. Nineteen patients had MF and 20 PTCLU. All patients with MF had a T3–T4, N0, and M0 disease and patients with PTCLU had stage III–IV disease. Gemcitabine was given on days 1, 8, and 15 on a 28-day schedule (1200 mg/m2/day) for a total of three to six cycles. Results Overall response rate was 51% (20 of 39 patients); complete response (CR) and partial response (PR) rates were 23% (9 of 39 patients) and 28% (11 of 39 patients), respectively. Patients with MF had a CR rate of 16% and a PR rate of 32% compared with a CR rate of 30% and a PR rate of 25% of PTCLU patients. Among the CR patients, 7 of 9 are in continuous complete response with a variable disease-free interval (15–120 months). Conclusion In our experience, gemcitabine proved to be effective in pretreated MF and PTCLU patients, even in the long term.

BACKGROUND. Limited data exist about the role of second-line chemotherapy response assessed by positron emission tomography (PET) as a prognostic factor in patients with aggressive non-Hodgkin Lymphoma (NHL) who undergo autologous stem cell transplantation (ASCT). The objective of this analysis was to investigate the main determinants of prognosis in patients with aggressive B-cell NHL who undergo ASCT, focusing on the impact of pretransplantation PET, secondary age-adjusted International Prognostic Index (sAA-IPI) score, histology, and previous response to first-line chemotherapy. METHODS. Seventy-five patients with diffuse, large B-cell lymphoma or grade 3 follicular lymphoma who were treated at the author' institution with second-line chemotherapy (combined ifosfamide, etoposide, and epirubicin [IEV]) followed by ASCT between September 2002 and September 2006 were included. All patients were evaluated by PET after 1 to 3 courses of IEV chemotherapy before ASCT, and all patients received a conditioning regimen of combined carmustine, etoposide, cytosine arabinoside, and melphalan. The prognostic impact of pretransplantation PET, sAA-IPI score, histology, and previous response to first-line chemotherapy was evaluated by univariate and multivariate analyses. RESULTS. Seventy-two of 75 patients underwent ASCT. In a univariate analysis for progression-free survival (PFS) and overall survival (OS), a significant association was observed with pretransplantation PET (PFS, P < .00001; OS, P < .01) and previous first-line response (PFS, P = .02; OS, P = .04). In the multivariate framework, pretransplantation PET was identified as the only independent prognostic factor (PFS, P < .001; OS, P = .01). CONCLUSIONS. The current data indicated that pretransplantation PET is the main prognostic predictor in patients with aggressive B-cell NHL who are scheduled for ASCT. Cancer 2008. © 2008 American Cancer Society.

The past few decades have seen major advances in understanding the pathobiology and clinical management of Hodgkin lymphoma (HL), making it one of the most successfully treated cancers worldwide.[1][1] At present, more than 90% of patients with early-stage, and up to 80% with advanced-stage disease

Background Brentuximab vedotin (BV) has shown high overall response rate in refractory/relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) with reported long-term response duration in clinical trials, but few data are available regarding its role in long-term outcomes in real life. Patients and methods A single-center observational study was conducted on patients treated with BV in daily clinical practice to evaluate the long-term effectiveness of BV in HL and sALCL patients and to check whether clinical trial results are confirmed in a real-life context. Results The best response rate in the treated 53 patients (43 HL and 10 sALCL) was 69.8% (with 46.5% complete response [CR]) in HL and 100% (80% CR) for sALCL, respectively. With a median patient follow-up of 36.8 months, the estimated median duration of response was 31.5 months for HL and 17.8 for sALCL, respectively. At the latest available follow-up, 75% of patients were still in response, with 43% without any consolidation. Toxicity was primarily neurological and it was rarely so serious to require dose reduction or interruption. In addition, it always reversed completely after the end of treatment. Conclusion Our data showed that 51% of patients treated with BV can be regarded as "long-term responders." Among these cases, for all patients who underwent stem cell transplantation immediately after BV, the procedure was consolidative. For patients who have remained in continuous CR without any consolidation after therapy, BV can induce prolonged disease control. Implications for practice Brentuximab vedotin (BV) has shown a high overall response rate in refractory/relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma, with reported long-term response duration in clinical trials, whereas few data are available regarding its role in long-term outcomes in real life. The data reported in this study suggest that BV can induce the same results in daily clinical practice. The data showed that 51% of patients treated with BV can be regarded as "long-term responders." Among these cases, BV can induce prolonged disease control in patients who have remained in continuous complete response without any consolidation after the drug.

LETTER TO THE EDITOR

Langerhans cell histiocytosis (LCH) is a rare proliferative disease with a wide spectrum of clinical presentations and, as a consequence, the treatment choice is unclear. Recently, detection of the BRAF V600E mutation changed the perspective of this disease, suggesting a possible use for BRAF inhibitors in its treatment. Herein, a case is presented of a patient with LCH undergoing treatment with vemurafenib after several lines of therapy. After 4 months of vemurafenib treatment, skin lesions associated with cranial involvement were reduced in size at physical evaluation and nuclear imaging assessment showed a very good partial response, with the resolution of multiple lesions. Based on this very good partial response and because the patient tolerated treatment well, the patient was able to continue treatment with vemurafenib until disease progression nearly 10 months later. This approach should be considered for patients with severe and multiresistant LCH with a BRAF mutation. However, more studies are needed to evaluate the efficacy and duration of response in a larger patient population.

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

The definition of the role of positron emission tomography (PET) in peripheral T-cell lymphomas (PTCLs) is still under investigation. The purpose of the present observational retrospective study was to assess the early prognostic value of PET after the first three cycles of therapy (PET+3), evaluating visual data in de novo PTCL patients treated in first line with standard chemotherapy and followed by both PET and computed tomography scan. Of 27 PET+3-negative patients, 19 also had a negative PET at the end of treatment (PET+6), whereas 8 of 27 had a positive final one; 6 of 7 PET+3-positive patients had a positive PET+6, whereas only 1 patient had a negative PET+6. Estimated overall survival plotted according to PET+3 results showed 78.6% for negative patients and 21.4% for positive patients at 88.7 months with a significant difference. Patients with negative PET+3 had superior progression-free survival of 72.6% compared with 16.7% of PET+3-positive patients. At the time of this analysis, 17 of 19 (89.5%) patients with negative PET+3 are in continuous complete response (CCR) and only 1 of 7 (14.2%) patients with positive PET+3 is still in CCR. In conclusion, our results indicate that positive PET+3 is predictive of a worse outcome in PTCL, and this significant statistical difference between the two curves could be clinically informative. Larger and prospective studies and harmonization of PET reading criteria are needed.

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

Not available.

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

Importance: The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. Objective: To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). Design, Setting, and Participants: This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. Main Outcomes and Measures: Overall survival, disease-specific survival (DSS), and progression-free survival were the primary end points. Results: One hundred patients with OA-DLBCL were included in the study (median age, 70 years), of whom 54 (54.0%) were female. The following 3 groups of patients with lymphoma could be identified: primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57 patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4 (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43 of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments were external beam radiation therapy with or without surgery (31.0%) and rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam radiation therapy (21.0%). The 5-year overall survival among the entire cohort was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9% (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the Ann Arbor staging system was not. However, when taking all 100 patients into account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6-5.0; P = .03). Conclusions and Relevance: Most patients with primary OA-DLBCL were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years in this cohort. Increasing T category appears to be associated with decreased DSS among patients with primary OA-DLBCL. When taking all patients into account, sex and Ann Arbor stage also seem to be DSS predictors.

An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with 90Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration.

Current treatments for non-Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2-6) lymphoma patients in an off-label setting. Bortezomib therapy was scheduled for 4-6 cycles (1.3 mg/m(2) biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non-responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B-cell lymphoma patients obtained a response. Extra-hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3-4 thrombocytopenia in nine patients and grades 3-4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated.

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

BACKGROUND: The use of 18F-fluorodeoxyglucose positron-emission tomography (PET) scan has increased considerably in the clinical management of non-Hodgkin lymphoma patients, and its role as a prognostic factor during chemotherapy has been established recently. METHODS: Between May 2003 and May 2009, 91 newly diagnosed patients with primary mediastinal large B-cell lymphoma (PMLBCL) and diffuse large B-cell lymphoma (DLBCL) were treated with 12 weekly cycles of rituximab-MACOP-B (n = 12 patients with PMLBCL), 6 cycles of rituximab-CHOP21 (n = 65 patients with DLBCL, aged < 60 years and 1 patient with PMLBCL), or 8 weekly cycles of rituximab-VNCOP-B (n = 13 DLBCL patients, aged ≥ 60 years). All patients underwent a staging PET examination at baseline and a midtreatment (interim) PET examination after 6 weeks of rituximab-MACOP-B treatment, 3 cycles of rituximab-CHOP21 treatment, or 4 weeks of rituximab-VNCOP-B treatment and again at the end of the chemo-immunotherapy regimen. RESULTS: At midtreatment evaluation, 35 patients showed a persistently positive PET scan; only 6 (17%) of these patients achieved a continuous complete response (CCR). However, 56 patients presented with a negative interim PET, and 50 (89%) of these patients achieved and maintained a CCR. Comparison between the 2 PET groups indicated a statistically significant association between PET findings and event-free survival (P = .0001) and overall survival (P = .0001). CONCLUSIONS: The results of this study indicated that midtreatment PET may represent a significant step forward in helping physicians make crucial decisions on further treatment. Cancer 2011. © 2010 American Cancer Society.

Background We performed a retrospective investigation to assess the efficacy of chemotherapy and rituximab as front-line treatment for primary bone lymphoma (PBL). Patients and Methods Between 1999 and 2009, 21 previously untreated patients received a diagnosis of PBL. All the patients were treated with anthracycline-containing chemotherapeutic regimens, with the addition of rituximab; 11 patients received consolidative radiation therapy after induction treatment. Results Patients' median age was 34 years (range, 18-82 years); all presented with diffuse large B-cell lymphoma. Complete responses were seen in 95.2% of the patients treated. No relapses were observed at a median follow-up of 43.9 months. Eight-year overall survival and disease-free survival were 95.2% and 100.0%, respectively. Conclusion These data indicate that the combined chemotherapy plus rituximab treatment may represent a suitable front-line approach in PBL, with a high rate of responses and an excellent long-term survival.

Letters to the Editor

Background Based on historical data on the role of radioimmunotherapy (RIT) in pretreated non-Hodgkin lymphoma, we reviewed our hospital's clinical database. Patients and Methods Between 2005 and 2008, 57 patients previously treated with at least 1 rituximab-containing chemotherapy were treated with Yttrium-90–labeled ibritumomab tiuxetan ( 90 Y-IT). The median number of pretreatments was 3 (range, 1-9 pretreatments). A total of 46 patients had stage III/IV disease (31 with bone marrow involvement); 6 had bulky disease. According to histology, 53 were follicular lymphoma (FL), 2 were marginal zone lymphoma, and 2 were small lymphocytic lymphoma. Results Overall response rate was 93% (53 of 57); complete response (CR) rate was 70% (40 of 57). Twenty-six of 40 patients (65%) who obtained a CR are in continuous CR (CCR) with a median follow-up of 20 months (range, 10-42 months); 4 of them still maintain their CCR after 36 months. All patients achieving a CCR had FL, and 21 of them with stage III/IV disease; 12 of 26 had been heavily pretreated (≥ 3 previous treatments), and 2 had had autologous stem cell transplantation. Toxicity was primarily hematologic and mostly transient; no grade 4 extrahematologic toxicity was observed. Conclusion This study confirms the safety and high efficacy of 90 Y-IT RIT in heavily pretreated FL patients, with the possibility of having a subset of long-term responders.

BACKGROUND: Historically, the first treatment choices for hairy cell leukemia (HCL) were splenectomy and alpha-interferon. Recently, purine analogues (pentostatin and cladribine) changed radically the treatment modality, inducing complete and durable responses in the majority of patients. METHODS: The authors analyzed the outcome of different lines of therapy in 121 HCL patients followed in their institute from 1986 to 2008, with a median follow-up of 105 months. Patients were divided into subgroups according to the number of treatments; Group A included 121 patients who underwent a front-line therapy, Group B patients (n =53) were treated with 2 lines, Group C patients (n = 34) with 3 lines, Group D patients (n = 17) with 4 lines, and Group E patients (n = 8) with 5 lines. RESULTS: In Group A, 92 (77%) patients obtained a complete response (CR), 23 (18%) a partial response, and the remaining 6 (5%) a minor or no response; median duration of response was 2.7 years. In Group B, 53 relapsed patients achieved a second CR rate of 73.5%; median duration of response was 2.5 years. Group C contained 34 patients in a second relapse, with a CR rate after the third line of treatment of 70.5% (median duration of response, 2.2 years). In Group D, 11 (64.7%) patients obtained a CR (median duration of response, 1.6 years), and in Group E 4 (50%) of 8 patients achieved a CR (median duration of response, 1.3 years). CONCLUSIONS: This study confirms the high risk (>40% of all patients) of retreatment of HCL patients and the need to maximize primary response. Cancer 2010. © 2010 American Cancer Society.

Young patients (aged 18-60 years) with good-prognosis diffuse large B-cell lymphoma (DLBCL) [0 and 1 risk factor according to age-adjusted international prognostic index (aa-IPI)] are distinguished from patients with poor-prognosis. Six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) in combination with rituximab achieved best results in young patients with low-risk DLBCL. We retrospectively analyzed the data of 82 patients (18-60 years) with untreated aa-IPI 0-1 DLBCL, from six Italian institutions, who underwent, between January 2002 and January 2007, rituximab-cyclophosphamide, doxorubicin, vincristine, methotrexate, bleomicin and prednisone (R-MACOP-B) therapy followed, in patients with bulky presentation, by 30-36 Gy involved-field radiation therapy (34 patients). An overall response rate was noted in 77 out of 82 (94%) patients (75 patients had a complete response (91%), 2 patients had a partial response). With a median follow-up of 46 months, 7-year progression-free and overall survival were estimated to be 91% and 94%, respectively. R-MACOP-B regimen followed by involved-field radiation on bulky presentation is safe and very effective in the treatment of young patients with low-risk DLBCL.

Introduction. A monocentric prospective study was designed to evaluate the role of F-18-fluoro-3-deoxy-3-L-fluorothymidine (FLT) PET/CT in lymphoma patients presenting with positive or equivocal F-18-deoxyglucose (FDG) PET/CT at end-treatment or follow-up evaluation. Methods. From May 2010 to March 2015, 40 patients were enrolled in the study, all undergoing FLT PET/CT within 3 weeks from a previous positive FDG scan and, when possible, biopsy confirmation as standard of reference to define PET results (true positive-TP; true negative-TN; false positive-FP; false negative-FN). The highest lesion standardized uptake value (SUVmax) was measured with both tracers. Median age was 55 (range 20-76); 24 patients were male and 16 female. Thirty patients had non-Hodgkin lymphoma and 10 Hodgkin lymphoma (HL). At diagnosis, 8 patients had stage II, 8 stage III and 24 stage IV. Six patients were evaluated at the end of their treatment and 34 during follow-up. Results. FDG-PET was judged positive in 36 out of 40 cases (SUVmax range 3-31; mean 10.1); 28/36 resulted also FLT positive (SUVmax range 3-16.8; mean 7.8) and 16/28 patients had the most active lesion biopsied, demonstrating 15 TP but 1 FP (cervical node, patient with a history of HL, SUVmax 6.9 and 6.8 for FDG and FLT respectively: reactive follicular hyperplasia). The remaining 12 patients could not be biopsied: however, clinical judgment and subsequent follow-up data confirmed 11 TP cases and 1 FP (reactive node). Eight FLT scans resulted inconclusive because of the low SUVmax values (range: 1.7-11.7; mean 4.8); 5 were judged as TP at biopsy (2 patients) or clinical evaluation (3 patients), whereas 3 represented reactive-inflammatory tissue. Among the 4 FDG-PET considered inconclusive (SUVmax range 4.9-8.8; mean 7.2), 3 out of 4 also resulted FLT inconclusive (SUVmax range 2.6-4.9; mean 4), but the final clinical evaluation excluded lymphoma (1 reactive cervical node, 1 nodal sarcoid-like disease, 1 aspecific pericecal finding). The remaining 1/4 resulted FLT positive (SUVmax 6.9 and 6.5 for FDG and FLT, respectively) and was clinically confirmed to be a TP case. Conclusions. In the particular setting of residual/recurrent lymphoma, our preliminary data suggest that FLT can be complementary to FDG, although the elimination of inconclusive PET findings remains a controversial step. Further lesion-based, semi-quantitative analyses (i.e. target to background/mediastinal blood pool/liver ratio) and correlation with Ki67 proliferation index are ongoing. Disclosures Cavo: Janssen: Honoraria; Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria. Zinzani:Pfizer: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Introduction. Relapsed and primary refractory peripheral T-cell lymphomas (PTCL) show a dismal outcome, with a 5-year overall survival of only 30%. There is no standard salvage chemotherapy for these patients. Gemcitabine was proved to be an effective monotherapy, yelding 60-70% overall response rates in patients with advanced heavily pre-treated disease. Romidepsin, a histone deacetylase inhibitor recently approved by Food and Drug Administration, has demonstrate an overall response rate (ORR) of 30% and a complete response (CR) rate of 16%. We have recently designed a multicentric trial to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed or refractory PTCL, looking for a potential synergistic effect of the two drugs. Methods. Twenty relapsed/refractory PTCL patients were included in a multicentric, prospective phase II trial which contemplated an induction with romidepsin 12 mg/m2 intravenously (i.v.) on days 1, 8, 15, and gemcitabine, 800 mg/m2 i.v. on day 1 and 15, for 6 cycles, each cycle to be repeated every 28 days. After the induction phase, patient who obtained at least a partial remission (PR) proceeded onto romidepsin maintenance at the dose of 14 mg/m2 i.v. until disease progression. The primary endpoint was to evaluate the efficacy of GEMRO regimen after the induction phase, as assessed by complete response (CR) rate; safety assessment was regarded as a secondary objective. The trial was registered under EudraCT (2012-001404-38). Results. Twenty patients have been recruited for this study. At present time, all patients underwent the induction phase and are evaluable for response and toxicity. The median age of patients was 55 years (range, 24-77). According to histology, 10 patients had PTCL not otherwise specified, 9 had an angioimmunoblastic T-cell lymphoma, 1 had a kinase negative anaplastic large cell lymphoma. The median number of prior therapies was 2 (range, 1-4); 7/20 (35%) patients had failed a prior stem cell transplant. Nineteen out of 20 (95%) patients presented with advanced stage. At the end of induction phase, the ORR was 31% including 2 CRs and 3 PRs. One of the 2 CR patients discontinued the treatment after 4 cycles due to cardiac toxicity, however maintaining a continuous CR with a follow up of 2 years. The other CR patient is still on treatment in maintenance phase. Grade ≥3 adverse events were represented by thrombocytopenia (60%), neutropenia (50%), and anemia (20%). Conclusions. To date, data failed to show a superiority of the GEMRO combination regimen over single agent romidepsin as salvage therapy for refractory or relapsed PTCL patients. More mature data and an adequate follow-up will be required to better understand the role of this combination regimen. Disclosures Zinzani: Takeda: 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; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; J&J: 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.

Brentuximab vedotin (BV) is an antibody drug-conjugate targeting CD30 linked to monomethyl auristatin E. Several studies have shown the efficacy of BV in patients with refractory or relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). We reviewed our clinical database to evaluate the long-term efficacy of this treatment. From July 2009 to February 2015, 57 patients were treated with BV in our Institute: 43 with a diagnosis of HL and 14 with sALCL. Thirty-six were males and 21 were females, with a median age of 33 years (range 16-77). All of them had been heavily pretreated before BV with a median number of previous therapies of 3 (range 2-10). Thirty-nine had refractory disease and 18 were relapsed. Autologous stem cells transplantation had failed in 30 patients. BV was administered at a dosage of 1.8 mg/mq, every 21 days, for a maximum of 16 cycles. The median number of cycles was 8 (range 2-16); 13 patients completed the entire schedule. The best overall response rate was globally 57,8% (33 of 57 patients), including 25 (43.8%) complete responses (CR): 18 with HL and 7 with sALCL. At present, 20/25 (80%) patients are still in continuous CR (CCR) with a median follow up of 9 months (range 3-41): 10 of them have consolidated the response with a stem cell transplantation (SCT) (4 auto-SCT and 6 allo-SCT) and 10 patients have remained in CR without any other therapy after BV. Among these long-term responders without any consolidation (7 patients with HL and 3 with sALCL), the median follow-up is 12 months (range 3-37); in particular there are 3 patients in CCR after at least 24 months. The global overall survival rate at 68 months is 71% (no patients with sALCL dead) and the median overall survival has not been reached yet. The global progression-free survival rate at 48 months is 30%, the median is achieved at 11,7 months. Toxicity was primarily neurological with peripheral sensory symptoms (30%) and motor neuropathy (5%); the majority was grade 3 in severity (8 patients). This study confirms the safety and the high efficacy of BV that can be considered an effective treatment in patients with relapsed or refractory HL or sALCL. This drug can induce a durable complete response representing a "bridge" to auto-SCT or allo-SCT. However our data show a subset of patients that can be considered "long-term responders", who have remained in CCR without any consolidation after BV. Disclosures Zinzani: Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Honoraria; Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria.

The first line treatment for primary mediastinal large B-cell lymphoma (PMLBCL) still remains a matter of debate even if the literature confirms that an anthracycline-containing regimen should be the main choice. The European experience shows the superiority of “third-generation” dose-dense regimen like MACOP-B (methotrexate, doxurubicin, cyclophosphamide, vincristine, bleomycin, prednisone) or VACOP-B (same as MACOP-B, with etoposide instead of methotrexate) over CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) or CHOP-like regimen. The addition of rituximab to third-generation regimen does not seem to cause any advantages in terms of overall survival (OS) and progression free-survival (PFS), while external radiotherapy (RT) has shown a good efficacy as a consolidation strategy at the end of induction chemotherapy, especially in converting partial responses (PR) into complete responses (CR). Between October 1989 and April 2010, 98 (58 females and 40 males) previously untreated PMLBCL patients were diagnosed and subsequently treated at our Institution. All patients were treated with MACOP-B regimen, concurrent rituximab was administered in 57 patients (58.2%) and 67 patients (68.4%) received mediastinal RT. Among 57 patients who received rituximab, 37 (64.9%) underwent RT whereas, among 41 who did not receive rituximab, RT was delivered in 30 (group 4, 73.2%) patients. 11 patients (group 1, 11.2%) received chemotherapy alone and 37 (group 3, 37.8%) received besides immunotherapy and RT (Table 1). All patients were assessed at the diagnosis and after the treatment with computed tomography and positron emission tomography (after 2001) scan. Main aims of our study were the effectiveness of the regimen measured as overall response rate (ORR) and patients survival. Sixty-one (62.2%) out of 98 patients achieved a CR and 27 (27.6%) were in PR after 12 cycles of MACOP-B regimen (with or without rituximab). Twenty-one patients in PR after (immuno)chemotherapy converted the response into CR with mediastinal RT. At the end of the scheduled treatment, 82 patients (83.7%) achieved a CR and 6 a PR (6.1%), yielding an ORR of 89.8%. At a median follow-up of 5.6 years, 9 patients relapsed within the first 2 years of treatment. During the follow-up 15 patients died, of whom 13 as a consequence of disease relapse or progression . The projected OS at 17 years is 72% with a PFS and a disease free survival (DSF) of 86.8% and 88.4% respectively ([Figure 1][1] A-C). The subgroup analysis shows a statistically significant difference in term of OS (p=0.0003) but not in term of PSF and DFS among the four groups of treatment ([Figure 1][1] D-F). All the patients receiving consolidation RT obtained a CR without differences between subgroup 3 and 4. RT seems to have a small consolidative potential in patients who obtained CR after chemo-immunotherapy alone: there are no differences in term of DFS between subgroup 2 and 3. No statistically significant differences in terms of OS, PFS and DSF occurred among patients received rituximab or not, regardless of a subsequent RT. Our monocentric experience spans a period of 20 years and indicates that a third-generation regimen like MACOP-B is feasible and could be a standard of first line treatment for PMLBCL. In agreement with the literature, adding rituximab doesn’t improve the outcome. Mediastinal RT, delivered as a consolidative strategy, impacts on global survival and on CR rates. In particular, RT after third-generation regimen remains a good strategy to convert PR into CR, but it may be avoided in patients obtaining CR after (immuno)chemotherapy. | Group | MACOP-B | Rituximab | Radiotherapy | N (%) | | ----------- | --------- | ---------- | ------------ | ---------- | | 1 | Yes | No | No | 11 (11.2%) | | 2 | Yes | Yes | No | 20 (20.4%) | | 3 | Yes | Yes | Yes | 37 (37.8%) | | 4 | Yes | No | Yes | 30 (30.6%) | | TOTAL N (%) | 98 (100%) | 57 (58.2%) | 67 (68.4%) | 98 (100%) | Table 1 ![Figure 1][2] Figure 1 Disclosures No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes

Langerhans cell histiocytosis (LCH), is a rare disorder which has a substantially unknown etiology, pathophysiology, and may manifest through a variety of clinical presentations ranging from solitary eosinophilic granuloma to severe multisystem disease. LCH is more common in children, although it can affect any age; the most common sites of involvement are bone, skin, and lung. From a histological point of view LCH derives from accumulation of proliferating cells with surface markers and ultrastructural features similar to cutaneous Langerhans cells, intermixed with inflammatory cells, particularly eosinophils. Below, a retrospective analysis of LCH patients treated at our institution. Between 1997 and 2013 we have treated 11 LCH patients, including 6 females and 5 males with a median age at time of diagnosis of 42.9 years (range 22.2-62.3). All diagnoses were reviewed by our pathologist. With regard to the site at onset, 9 patients had bone involvment, among these, four patients had only bone involvment, the other five patients also lung, oral cavity and lymph nodes. At time of onset 4 patients showed no symptoms, while the remaining 7 showed a variety of symptoms ranging from B symptoms to tinnitus, dizziness, and other neurological symptoms such as diplopia. Among the study group 6 patients had multisystemic involvement. All patients except one had CT scan performed before, during, and at follow-up, the remaining patient was studied and followed through follow-up with PET scan. As first-line therapy 8 patients underwent chemotherapy, 2 patients radiation therapy, 1 patient required only steroid therapy. The most frequently used chemotherapy regimen for these 8 patients was MACOP-B, a third generation, CHOP-like regimen. Responses to first-line therapy were as follows: 7 complete remissions (CR), resulting with chemotherapy (5), radiation therapy and steroid therapy, two partial remissions (both obtained with chemotherapy) and two stable diseases (1 with chemotherapy and 1 with radiation therapy). Two patients relapsed, of whom one has ran several lines of chemotherapy, including autologous stem cell transplantation. Both are alive at the time of the last follow-up. To date all patients are alive but one, who died of pulmonary embolism while he was in stable disease. Six patients are in CR (60%), two in SD (20%) and two in PD (20%). In conclusion, our monocentric experience of 11 LCH patients confirms what reported in the literature in terms of heterogeneity of presentation, age, sites of involvement, symptomatology and treatment demanded. Coming to the the results our retrospective analisys shows that ten of the eleven study population patients (90.9%) are to date still alive after a significant median time of follow-up; six out of these ten patients (60%) are in CR. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION. Chemotherapy (CHT)-induced anemia is a consequence of the myelosuppressive effect of CHT, delivered for solid or hematologic malignancies, and tends to worsen over the course of repeated cycles of therapy. Erythropoietic agents have shown their efficacy in correcting CHT-induced anemia in cancer patients, in reducing the need of blood transfusion and in improving patients’ quality of life. Epoetin (EPO) biosimilars have emerged as an alternative to originator products, sharing an equivalent mechanism of action, efficacy and safety, as a result of a rigorously conducted comparability exercise. PATIENTS AND METHODS. This study was aimed at evaluating the response to EPO alpha biosimilar (Binocrit®, Sandoz, 40,000 IU/week subcutaneously) after a 4-weeks (and 8-weeks, when applicable) treatment period, as well as the rate of CHT cycles delays or interruptions due to anemia, in 49 consecutive adult patients, affected by chronic lymphoproliferative disorders, undergoing CHT, either as a first-line induction (35 patients) or second-line or salvage treatment (14 patients), and presenting with CHT-induced anemia. The median age was 69 (range 21-90) years, with 49% of the patients older than 70. Fourteen had diffuse large B-cell lymphoma, 14 an indolent non-Hodgkin’s lymphoma, 6 had chronic lymphocytic leukemia, 5 mantle cell lymphoma, 4 T-cell lymphoma, 2 hairy cell leukemia and 1 had histiocytosis. Response to EPO was defined as an increase in hemoglobin (Hb) levels after 4 (ΔHb4) and 8 weeks (ΔHb8) of treatment of at least +1 g/dL, or as the achievement of Hb > 11 g/dL independently of ΔHb, with a complete transfusion-independence. Hb stability was regarded as a ΔHb comprised between -1 and +1 g/dL. A ΔHb < -1 g/dL or an acquired transfusion dependence was judged as a lack of response. Treatment with EPO was started at the first occurrence of Hb < 10 g/dL during chemotherapy, when anemia was not due to any different concomitant cause (e.g. hemolysis, iron deficiency, malabsorption, etc). Treatment duration was established by the treating physician; however, treatment was stopped when Hb reached at least 11 g/dL, in patients whose chemotherapy programme had reached its completion and in those who became transfusion dependent. RESULTS. Mean Hb (± standard deviation) at presentation was 11.0 ± 1.6 g/dL, with 49% of patients being anemic mostly as a consequence of their disease. Nine patients had grade 2 anemia, while one presented with grade 3 anemia. Twenty-one were treated with a cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) every 21 days or with a weekly CHOP-like regimen; 10 received a fludarabine-based regimen; 6 underwent a bendamustine-based second-line treatment. The remaining 12 patients were treated with various regimens (lenalidomide, rituximab, cladribine, temsirolimus, gemcitabine). Mean Hb level at EPO treatment start was 9.3 ± 0.5 g/dL. After 4 weeks of treatment, the reached mean Hb level was 10.8 ± 1.4 g/dL for patients receiving a first-line CHT, and 11.4 ± 1.6 g/dL for those on a second or later CHT line, with a mean ΔHb4 of 1.4 ± 1.4 g/dL and 2.1 ± 1.6 g/dL for each group of patients, respectively. Sixteen patients had their Hb level measured after 8 weeks of treatment, achieving a mean Hb level of 11.0 ± 1.7 g/dL and 9.8 ± 1.4 g/dL for each treatment subgroup, with a ΔHb8 of 1.7 ± 1.6 g/dL and 0.5 ± 1.3 g/dL, respectively. Overall, 36 patients responded to the treatment, yielding to a 73.4% hematological improvement rate. Eleven patients (22.5%) showed a stable Hb level throughout their treatment course, and 2 (4.1%) were considered non-responders (figure). Among responders, 2 patients required a new biosimilar EPO alpha treatment, again with response; 2 patients showed a late recurrence of anemia, and were managed with blood transfusions. Overall, 22 patients (44.9%; 61.1% of responders) had an Hb increase of at least 2 g/dL. CHT cycles were delayed in 9 cases (18.4%) because of anemia; interruptions of the planned CHT programme occurred in 6 cases (12.2%). No adverse events were documented; in particular, no thromboembolic or pure red-cell aplasia episodes have been demonstrated. CONCLUSION. The treatment of CHT-induced anemia with biosimilar EPO alpha in patient with chronic lymphoproliferative disorders is correlated with a high rate of responses and allows a safe completion of the planned CHT programme in most of the cases, both in induction and salvage treatment settings. Figure 1 Figure 1. Disclosures Broccoli: Sandoz: Membership on an entity's Board of Directors or advisory committees. Zinzani:Sandoz: Membership on an entity's Board of Directors or advisory committees.

Introduction Autologous stem cell transplantation (ASCT) is a potentially curative treatment option for relapsed Follicular Lymphoma (FL) patients, but to date available data do not support the use of ASCT as first line consolidation, given the lack of overall survival (OS) advantage compared to standard therapy. R-CHOP (Rituximab-Cyclophosphamide, Vincristine, Doxorubicin, Prednisone) and R-FM (Rituximab, Fludarabine, Mitoxantrone), have comparable efficacy and are widely used as first and second line combinations. The best way to sequence the available therapies in FL is still undefined. Here we show the long term results of a phase II trial of sequential chemotherapy alternating CHOP and FM plus Rituximab followed by ASCT in patients with stage III-IV and/or bulky FL either at disease onset or first relapse, conducted in our Institution from 2002 to 2008. Methods Patients at diagnosis or first relapse were treated in sequence with R-CHOP for 4 cycles, Endoxan 7g/m2 followed by hematopoietic stem cell harvest, R-FM for 4 cycles and ASCT. The ASCT conditioning schedule was BEAM (BCNU, ARA-C, Etoposide, Melphalan) in all cases. Results 24 patients were enrolled, 12 pts were male. Median age was 44 years. One patient did not undergo ASCT for insufficient left ventricular ejection fraction and was excluded from the analysis. 13 patients were treated upfront whereas 10 patients at first relapse. After a median follow-up of 10 years, progression free survival (PFS) and OS in the whole study cohort were respectively 65% and 87%, with a complete response (CR) rate after the completion of sequential treatment of 100%. PFS and OS for patients treated at disease relapse were 60 and 70% (4 relapses, 3 deaths). Remarkably PFS and OS for the 13 patients treated upfront was 70% and 100% (4 relapses). To date no secondary malignancies were observed. Conclusions Sequential treatment alternating standard R-CHOP and R-FM followed by ASCT results in impressive long term PFS and OS rates, both in first line and at relapse. These data represent the proof of principle of a sequential therapy containing alternating alkylating agents and purine analogs followed by ASCT in FL. Disclosures: No relevant conflicts of interest to declare.

Due to limited prospective studies, the optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still a matter of debate. Third-generation MACOP-B (adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone) regimen in combination with mediastinal radiotherapy (RT) seems to improve disease free survival of patients. In addition, the impact of additional treatment with rituximab and the role of PET are still under investigation due to controversial reported results. As per institutional guidelines, MACOP-B plus RT was recommended in all PMLBCL patients until 2002. Aim of this report was evaluate the outcome of PMBCL patients diagnosed and treated with MACOP-B plus rituximab and consolidative mediastinal RT (30-36 Gy) after 2002. PET role was also investigated. Seventy-four patients were deemed eligible for this study (follow up of at least 2 years). Fifty patients had stage II and 24 stage IIE-IV, bulky disease was documented in 93% of patients. Median age was 34 years (range, 17-62) and 59.5% were females. All patients were evaluated by both CT and PET scan. After the final PET evaluation, PET-negative patients were observed while PET-positive patients underwent mediastinal RT. At the end of treatment, 61 (82.4%) patients achieved a complete response (CR); 51 (68.9%) presented a positive final PET and were treated with local RT, while the other 23 (31.1%) had a negative PET. Five patients relapsed within 12 months. At 10 years, estimated overall survival was 82%, progression-free survival was 87.6% and disease-free survival (DFS) for the 61 CR patients was 90.5% (median follow-up 4 years). Regarding the DFS curve (figure 1), no statistically significant differences were observed between patients who underwent also RT (PET-positive, group 1) and patients who remained under observation (PET-negative, group 2): 90.7% (4/51 relapses) vs 90% (1/23 relapse) (p= 0.85), respectively. Comparing these results with our institutional historical series when the front-line for PMLBCL patients included only MACOP-B plus RT without any decision related to PET results (before 2002), the 10-year DFS resulted lower, i.e. 82.8%. Although with the limitations of an observational retrospective study, the present report underlines that the additional treatment with rituximab does not change the final results in terms of CRs and DFS utilizing third-generation regimens. Moreover, the introduction of the PET-guided RT approach after MACOP-B plus rituximab allows a patient tailored strategy which reduces the use of RT and preserves clinical outcomes. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

Abstract 3019 Background: Radioimmunotherapy (RIT) is an effective and manageable treatment option for those patients (pts) affected by follicular B-cell lymphoma (FL) who experience disease relapse. The results of RIT in the setting of first line consolidation are also very promising in terms of progression free and overall survival. On the other hand autologous stem cell transplantation (ASCT) is a suitable treatment option for relapsed FL patients. Although major concerns about the widespread use of RIT early in the disease course are the long term hematologic toxicity and the theoretical possible irreparable damage to bone marrow function with impairment of peripheral stem cell harvest, very few data are available about mobilization rates after Zevalin exposure. Methods: The aim of this monocentric study was to analyze the impact of prior Zevalin administration on peripheral blood stem cells (PBSC) mobilization and on the outcome of subsequent ASCT. Moreover the impact of different prior treatment regimens [Cyclophosphamide, Doxorubicin, Vincristine, Prednisone plus Rituximab (R-CHOP) or CHOP-like regimens vs Fludarabine, Mitoxantrone plus Rituximab (FM-R) vs Zevalin] and number of previous lines of therapy given earlier in the disease course, was prospectively evaluated in all FL patients (n=100) who underwent stem cell mobilization from January 2005 to March 2012. Results: At the time of mobilization, 68 pts had received R-CHOP or CHOP-like regimens, 20 pts FM-R, 12 pts RIT with Zevalin earlier in the disease course. Characteristics of pts such as age, weight and number of prior therapies, were well balanced in the 3 groups. Sixty one pts had received one prior therapy, 31 pts 2 therapies, 8 pts ≥ 3 lines of therapy. All pts received chemotherapy plus granulocyte colony stimulating factor (G-CSF) 5 μg/kg (n=94) or G-CSF alone (10 μg/kg) (n=6) as mobilization regimen. Mean CD34+ cells yield was 8.9 × 106/kg in the CHOP group, vs 5.8 × 106 CD34 + cells/kg in the FM-R group, vs 2.7 × 106 CD34 + cells/kg in the Zevalin group (p=0.05 CHOP vs FM-R; p 1000/μL) and platelets recovery (>20000/μL) was 10 and 11 days in all groups respectively. Only one pt in the CHOP group and one in the FM-R group did not undergo ASCT because of insufficient CD34+ harvest. Considering the Zevalin group (n=12), median age was 51 years (range 36–66). Seven pts received Zevalin as first line consolidation, 5 patients at disease relapse. Median number of prior therapies was 2 (range 1–4). Ten pts received chemotherapy plus G-CSF as initial mobilization regimen, 2 pts received G-CSF alone. Median time from RIT to mobilization was 13 months (4–60 months). Five pts (42%) reached the collection yield of > 2.0 × 106 CD34 + cells/kg with the first mobilization attempt. Considering the remaining 7 pts who failed (CD34+ cells below 10/mL before apheresis, or cell harvest below 2.0 × 106 CD34 + cells/kg), a surgical procedure was attempted in 4 pts, G-CSF + Plerixafor (240 μg/kg) in 3 pts. Remarkably the second harvest allowed 5 additional pts (3 pts after surgery, 2 pts after G-CSF + Plerixafor) to undergo ASCT. Finally ASCT was succesfully performed in 9 pts (75%). Median number of reinfused CD34+ cells was 2.3 × 106 CD34 + cells/kg (0.4–4.2). Three pts did not undergo ASCT, one because of disease progression, 2 pts because of insufficient CD34+ harvest. Conclusions: The type of previous therapy may significantly influence the mobilization rate in FL pts. Although mobilization was significantly impaired in pts previously treated with Zevalin compared to other chemotherapy regimens, stem cell harvest after RIT was feasible and the vast majority of patients retained the possibility to undergo ASCT with a second stem cell harvest, with no significant impact on engraftment. The use of Plerixafor seems to be particularly promising for those patients previously exposed to RIT who failed the first mobilization. Disclosures: No relevant conflicts of interest to declare.

Abstract 2736 In this retrospective single-center study we aimed at evaluating the efficacy and safety of fludarabine, mitoxantrone and rituximab (FMR) regimen as first line therapy in untreated patients with follicular non-Hodgkin lymphoma (NHL) and indolent non-follicular NHL considering also the role of positron emission tomography (PET) after this chemo-immunotherapy induction as predictor of survival. Between January 2000 and May 2011, 285 patients with stage II-IV untreated indolent follicular (excluding grade IIIb) NHL (n=142) and indolent non-follicular (including marginal zone lymphoma, MZL [n=111] and small lymphocytic lymphoma, SLL [n=31]) NHL (n=143) were diagnosed and treated at our institution in the outpatient clinic. Median age was 63 years (range, 25–83 years) and the median time from diagnosis to study entry was 3 months (range, 1–5 months). 20 patients had stage II, 75 patients had stage III, and 190 had stage IV disease (155 patients had bone marrow involvement). Standard fludarabine (25 mg/m2 iv on days 2, 3 and 4), mitoxantrone (10 mg/m2 iv on day 2) and rituximab (375 mg/m2 iv on day 1) were given every 28 days for six cycles. Globally, after FMR regimen, the overall response rate (ORR) was 83.2%, including a 71.6% complete remission (CR) rate (204 patients) and a 11.6% partial remission (PR) rate (33 patients). According to the histology, in the follicular subset, the ORR was 81.1% with a CR rate of 69.2% while in the indolent non-follicular subset the ORR was 85.2% with a CR rate of 73.9%. In particular, in the indolent non-follicular NHL subgroup the CR rate was 80.2% in MZLs and 51.6% in SLLs, respectively. Toxicities were generally mild and mainly hematologic. Overall 88 (30.8%) patients had grade ≥3 hematologic toxicity, and 26 (9.1%) patients had non-hematologic toxicity with 3 cases of grade ≥3 (1 neurologic toxicity and 2 hepatic toxicity). In terms of secondary malignancies, only 3 (1.0%) hematologic neoplasms were reported (1 myelodisplastic syndrome after 9 months from the end of the treatment and 2 acute lymphoblastic leukemia after 8 and 11 months from the end of the treatment, respectively). Globally with a median follow up of 40 months (range, 12–144 months), at 11 years the overall survival (OS) was 78.8%, the disease-free survival (DFS) was 73.4% (with only 29 relapses), and the progression-free survival (PFS) was 71.9%. Regarding the comparison between the two subsets, follicular vs indolent non-follicular, no statistically significant differences were observed in OS, DFS and PFS curves. Furthermore, a sub-sample of 132 patients (75 follicular NHLs and 57 indolent non-follicular NHLs) had a PET evaluation before the treatment (staging) and 4 to 6 weeks after completion of the sixth cycle of chemo-immunotherapy (restaging, final PET [f-PET]). Post-induction PET-positive patients had a significantly inferior OS at 6 years: 71.4% compared with 98.4% for f-PET-negative patients (p Figure 1a. Figure 1a. Figure 1b. Figure 1b. In conclusion, this study suggests and confirms that FMR is a very active, well tolerated (in terms of acute and long-term side effects) chemo-immunotherapy front-line treatment for follicular NHL and indolent non-follicular NHL. PET status at the end of this chemo-immunotherapy induction is quite controversial as a predictor of survival. Disclosures: No relevant conflicts of interest to declare.

Abstract 2721 Role of interim- and final-PET in peripheral T-cell lymphoma (PTCL) is quite unknown. To determine predictive value of PET on overall survival (OS), we evaluated interim-PET (i-PET) and final-PET (f-PET) in PTCL patients treated in first-line with 6 CHOP-21 courses. From September 2003 to July 2010 we diagnosed and treated in our institution 34 advanced stage PTCL patients (15 females and 19 males). The median age at diagnosis was 46 years (range, 21–81 years); 9 patients were in stage III, and 25 in stage IV. According to the histologic subtype there were 11 PTCL-nos, 6 AILT, 9 ALCL Alk+, 6 ALCL Alk-, and 2 NK/T nasal type patients. Four patients had bulky disease; eight patients had bone marrow involvement, 15 patients had 1 extranodal involvement and 10 had more than 2 extranodal sites. All patients underwent initial staging PET/CT; i-PET was performed after 3 cycles of CHOP-21 and the median time from the end of third course to i-PET was 14 days (range, 7– 18 days). f-PET scans were performed 35 days (range, 30– 45 days) after the end of therapy. The table summarizes the correspondence between i-PET and f-PET results: N=34 f-PET negative, n (%) f-PET positive, n (%) i-PET negative 27 19 (70.4) 8 (29.6) i-PET positive 7 1 (14.2) 6 (85.8) With a median follow-up of 71 months (range, 5.8–120.9 months), 17/19 (89.5%) patients with i-PET negative are in continuous CR (CCR) and only 1/7 (14.2%) patient with i-PET positive is still in CCR. Figures show the overall survival (OS) according to response at i-PET and f-PET. In figure 1a we observe OS plotted according to i-PET results: 78.6% for negative patients (solid line) and 21.4% for positive patients (dashed line) at 88.7 months (p=0.02); in figure 1b we observe OS plotted according to f-PET results: 93.7% for negative patients (solid line) and 21.4% for positive patients (dashed line) (p In conclusion, our results demonstrate that positive i-PET is not predictive of a worse outcome in PTCL. On the contrary, the f-PET seems to represent a significant step forward in the prediction of survival for these patients. Larger and prospective studies and harmonization of PET reading criteria are needed. Disclosures: No relevant conflicts of interest to declare.

Abstract 1604 We previously reported the results of a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus radioimmunotherapy (RIT) [FLUMIZ (Fludarabine, Mitoxantrone, Zevalin) trial], demonstrating that this combination was safe and very effective in untreated patients with follicular non-Hodgkin lymphoma. We are now providing long term efficacy and toxicity results of this combination strategy. Sixty-one patients with stage III and IV untreated follicular lymphoma were enrolled between June 2004 and April 2006, at 13 Italian institutions. Briefly, treatment schedule was the following: oral fludarabine 40 mg/m2 on days 1–3, intravenous mitoxantrone 10 mg/m2 on day 1 every 28 days for six cycles, followed by one course of yttrium-90 (90Y)-labelled ibritumumab tiuxetan (Zevalin), which consisted in two weekly infusions of Rituximab 250 mg/m2 followed by a weight based dose of 90Y-ibritumumab tiuxetan. Primary endpoints at the time of the first analysis were complete response and hematological toxic effects, secondary endpoints were overall survival (OS) and progression free survival (PFS). Fifty-seven patients were treated with RIT after the completion of six courses of fludarabine and mitoxantrone (FN) regimen. Four patients were excluded because of disease progression (n=1) and bone marrow infiltration > 25% (n=3) at the end of the FN regimen. Median follow up at the time of the last analysis was 52 months (range 24–75). Five-year PFS was estimated to be 68%, 5-year OS was estimated to be 93.0%. Noteworthy, late hematological side effects such as myelodisplastic syndromes or acute myeloid leukemias have not been observed so far. All patients had a complete hematological recovery after the completion of the sequential treatment. 16 patients relapsed during the follow-up period and 4 patients died due to disease progression. 22 patients (38%) are in first complete remission after more than 4 years of follow-up. All relapsed patients underwent second line chemotherapy and high dose chemotherapy with stem cell rescue was performed in 4 patients. These results confirm the long term efficacy and safety of 6 cycles of fludarabine and mitoxantrone followed by consolidation with 90Y-ibritumumab tiuxetan: the 5-year PFS and OS compare favourably with the results of chemoimmunotherapy alone in untreated follicular lymphoma, with no increased incidence of secondary hematologic malignancie Disclosures: No relevant conflicts of interest to declare.

Abstract 3879 Purpose. The use of early (interim) positron emission tomography (PET) restaging during front-line therapy in Hodgkin's lymphoma (HL) has considerably increased in clinical practice as an early recognition of treatment failure allows patients to be addressed to more intensive treatment regimens. Patients and Methods. Between June 1997 and June 2009, 304 newly-diagnosed Hodgkin's lymphoma patients (147 early-stage and 157 advanced-stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent to a PET staging and restaging at baseline, after 2 cycles of therapy and at the end of the treatment. Results. 53 patients showed a positive interim PET and only 13/53 (24.5%) achieved a complete response (CR), whereas 251 patients showed a negative PET and 231/251 (92%) remained in CR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival (p=0.0000) and 9-year overall survival (p=0.0000), with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET and only 4 (21%) achieved a CR; among the 128 negative interim PET patients, 122 (97.6%) obtained a CR. In the advanced-stage subset, 34 patients showed a persistently positive PET (with only 9/34, 26.4% in CR), whereas 123 showed a negative interim PET, with 109 (88.6%) remaining in CR. Conclusions. Our results confirm the role of early PET as a significant step forward for the management of both early and advanced-stage HL patients, offering the potential for an immediate switch to high-dose treatments, if required. Disclosures: No relevant conflicts of interest to declare.

Abstract 2720 Poster Board II-696 Introduction: In 2008 we published a phase II trial abuot the combination of 6 cycles of CHOP plus 90Y-IT for previously untreated elderly patients with DLBCL. The CCR was 95% with OS at 2 years of 95% and PFS at 2 years of 75%. The results of this study support a further evaluation of 90Y-IT in combination of chemotherapy. We conducted a prospective, single-arm, non-randomized, phase II trial with CHOP plus Rituximab followed by 90Y-IT reducing the number of CHOP cycles from 6 to 4 but introducing Rituximab. The rational is to utilize all the therapeutic approaches (chemotherapy, immunotherapy and radioimunotherapy) reducing conventional chemotherapy and probably related toxicity. Patients and Methods: Patient elegibility was represented by: patients older than 60 years with biopsy proven, untreated, bidimensionally mesurable stage II, III or IV DLBCL. Expression the CD-20 antigen; WHO performance status of 0 to 2. patients were treated with standard CHOP chemotherapy plus Rituximab every 21 days for 4 cycles. Patients were restaged 4 to 6 weeks after completion of 4 cycles of R-CHOP chemotherapy. Patients achieving CR, PR or SD after chemotherapy were eligible for consolidation with 90Y-IT provided the granulocyte count was greater than 1500/microl, the platelet count exceded 100.000/microl and the bone marrow examination at the completion of chemotherapy demostrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y-IT 14.8 MBq/kg (0.4 mCi/kg). Fifty-five patients have been enrolled: 26 were male and 29 female; the median age was 70 years (range 60–83); 17 were stage II, 38 were stage III-IV. Results: Fifty-one patients had completed the R-CHOP treatment and the overall response rate was 94.1% including 30 (58.8%) of patients in CR and 17 (35.3%) in PR. Treatment was well tolerated; grade 3–4 AEs are comparable with previous experience and the most common grade 3–4 AEs was neutropenia. At this time 47 patients had just received 90Y-IT and 45 are evaluable. In particular, 9/17 (52.9%) patients converted from PR to CR after treatment with 90Y-IT. Conclusions: These preliminary data indicate that radioimmunotherapy appears highly effective and feasible as “consolidation” after 4 cycles of immunochemotherapy in elderly DLBCL patients, improving quality of response without any cumulative toxicity. Disclosures: Off Label Use: The drug Yttrium 90 (90Y) Ibritumomab Tiuxetan (90Y-IT) (Zevalin) is off-label for Diffuse Large B-Cell Lymphoma (DLBCL).

Abstract 1659 Poster Board I-685 Background Hodgkin lymphoma (HL) is a curable malignancy with a long-term survival of around 80%. FDG-PET is a noninvasive imaging modality widely used in lymphoma patients. Early PET assessment of response to therapy is a routine part of management in HL patients, and an independent, strong predictor of progression-free survival. Patients and Methods 178 patients, with a diagnosis of HL, underwent to an early PET evaluation during their course of chemotherapy and were considered eligible for the study. 85 patients (48%) were male and 93 (52%) female; the median age at diagnosis was 33 (13-78) years. 6 patients (3%) had stage I disease; 106 patients (60%) stage II; 34 (19%) stage III and 32 (18%) stage IV (bone marrow involvement in 5 cases). B-symptoms were detected in 81 patients (46%). A mediastinal bulk was detected in 54 cases (30%). The majority of patients (173, 97%) underwent to ABVD as first line therapy; 5 received BEACOPP chemotherapy (3%). Early PET evaluation was performed after the second course of therapy. Results were classified into complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) according to International Workshop standardized response criteria. PET scan was performed again at the end of the first-line treatment. 44 patients have been addressed to a second-line therapy, in presence of PR, PD or relapsing disease; in particular, 39 patients received an autologous stem-cells transplantation (ASCT), and 3 an allogeneic bone marrow transplantation (ABMT). Results At a median follow up of 41,85 (5,23-141,77) months, 152 patients are alive and in CR; 7 in PR; 3 alive with SD and 7 present a PD. 9 patients have died. 150 patients presented with a negative PET after 2 cycles, and 28 with a positive one (26 in PR, 1 with SD and 1 with PD). More specifically, of the 178 initial patients, 150 (84%) had a negative early PET and 28 (16%) a positive early PET. Of those with a negative PET, 135 (90%) experienced a continuous CR, while among those with a positive early PET, none obtained at least a stable CR. Of this unfavourable group of patients, 9 (32%) reached, and still maintain, a CR after ASCT. Conclusions Our experience indeed confirms the highly predictive value of a negative early PET during the therapy for HL. Moreover we may suggest the potential role of ASCT in inducing a CR in around one-third of those unfavorable patients with a positive early interim PET. Disclosures No relevant conflicts of interest to declare.

Abstract 3743 Poster Board III-679 Introduction In 2008 we published a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus 90Y-IT in untreated patients with FL. By the end of the entire treatment regimen 95% of the patients achieved complete remission (CR). With a median follow-up of 30 months, 3-year PFS was estimated to be 76% and 3-year OS 100%. On the basis of these results we are currently conducting a prospective, multicenter, non-randomized, phase II study of R-FM followed by 90Y-IT in untreated patients with FL in which the number of fludarabine and mitoxantrone cycles has been decreased to four and in which rituximab is administered before each cycle. The rationale of the trial is to use different forms of treatment and to reduce the use of conventional chemotherapy and its related toxic effects. Patients and Methods Patients eligibility is represented by: age more than 18, stage II-IV, FL grade I-II, WHO performance status 0-2. Patients are treated with standard FM chemotherapy plus rituximab every 28 days for 4 cycles. Patients are restaged 4 to 8 weeks after completion of immunochemotherapy and those achieving at least a partial response are eligible for 90Y-IT. All patients receive a single dose of 90Y-IT 14,8 MBq/kg. At the time of the analysis we enrolled 55 patients. 25 patients were male and 30 female; the median age was 56 years (range 26-84); 12 patients were stage II, 13 stage III and 30 stage IV; 11 patients had a bulky disease. 52 patients completed the induction chemotherapy, all except 5 were eligible for the consolidation treatment with 90Y-IT and 44 patients were restaged after the entire treatment regimen. Results After the R-FM chemotherapy, the overall response rate was 92.3% (48/52) including 39 (75%) CR and 9 (17.3%) partial remissions (PR). Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated grade 3-4 haematologic AEs (mostly neutropenia) were seen in 50% of the patients. Among the 44 patients (9 PR and 35 CR) subsequentially treated with 90Y-IT and reassessed for the response, 8/9 (88.9%) PR patients improved their remission status from PR to CR. 90Y-IT toxicity included mostly grade 3-4 neutropenia and thrombocytopenia and was comparable to the literature data. Conclusions These preliminary data indicate that radioimmunotherapy appears highly effective and feasible as “consolidation” after short (4 cycles) immunochemotherapy in FL patients, improving quality of response without any cumulative toxicity. Disclosures: No relevant conflicts of interest to declare.

In the last 20 years, the major improvement over the use of CHOP has been the addition of anti-CD20 immunotherapy (Rituximab). This advancement was first demonstrated in a randomized trial in elderly patients with diffuse large B-cell lymphoma (DLBCL). Single-agent radioimmunotherapy activity, in particular Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®), has been demonstrated in heavily pretreated DLBCL patients. Recently, the preliminary data of a phase II trial have showed that 90Y Ibritumomab Tiuxetan have useful activity in the treatment of relapsed/refractory elderly DLBCL (Morschhauser et al, Blood 2004, 104: 41a), with no unexpected toxicities observed. The results of this study support a further evaluation of 90Y Ibritumomab Tiuxetan in combination with chemotherapy earlier in the time course of elderly DLBCL. We conducted a prospective, single-arm, open-label, non-randomized, phase II to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with CHOP followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated elderly DLBCL. Patient eligibility was represented by: patients older than 60 years with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV DLBCL expressing the CD20 antigen; WHO performance status of 0 to 2. All patients signed a written informed consent approved in accordance with institutional guidelines. The study was approved by the institutional review board. Patients were treated with standard CHOP chemotherapy every 21 days for 6 cycles. Patients were restaged 4 to 6 weeks after completion of the sixth cycle of CHOP chemotherapy. Patients achieving at least a partial response after 6 cycles of CHOP chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of CHOP chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). A total of 20 patients have been enrolled: 12 were male and 8 female; the median age was 68 years (range 61–84); 6 were stage II, 14 stage III-IV. After the CHOP treatment the overall response rate was 100%, including 15 (75%) CR and 5 (25%) PR. Treatment was well tolerated; grade ≥ 3 AEs were seen in 13 patients; the most common grade ≥ 3 AEs was neutropenia. After the treatment of all 20 patients with 90Y Ibritumomab Tiuxetan, 4/5 (80%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 11/20 patients; the most common grade ≥ 3 AEs were neutropenia (11 patients) and thrombocytopenia (7 patients). Transfusions of red cells and/or platelets were given to 2 patients. Time to event analyses, including TTP and duration of response are pending further follow-up. These preliminary data indicate the feasibility, tolerability, and efficacy of the CHOP plus 90Y Ibritumomab Tiuxetan regimen for patients with untreated elderly DLBCL.