2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography in primary extranodal lymphomas: treatment response evaluation and prognosis.

BACKGROUND: We evaluated the role of [18F]FDG PET/CT in tumor response assessment and prognosis of primary extranodal lymphoma (PEL) patients. METHODS: We examined retrospectively, 56 PEL patients: 31 with aggressive diffuse large B cell lymphoma (DLBCL) and 25 with indolent lymphoma (20 mucosa-associated lymphoid tissue lymphoma and five follicular lymphoma). All patients had undergone [18F]FDG PET/CT at diagnosis (PET-I) and 50 of them also after therapy (PET-II). Moreover, 52 patients were subjected to a mean follow-up period of 76 months. RESULTS: PET-I was positive in 50 (89%) patients (mean SUVmax 10.3±6.7). In the assessment of tumor response, according to Lugano classification, 45 patients showed complete metabolic response (CMR), four patients had partial metabolic response (PMR) and one had progressive metabolic disease (PMD). Based on 66% ΔSUVmax cut-off, among CMR patients, 41 showed a ΔSUVmax>66% whereas among non-responders, four patients showed a ΔSUVmax<66%. At follow-up, univariate analysis showed that age, performance status, prognostic index, ΔSUVmax and Lugano classification predicted progression-free survival (PFS) (P<0.05), while, performance status, prognostic index, ΔSUVmax and Lugano classification predicted overall survival (OS) (P<0.05). At multivariate analysis only Lugano classification was retained in the model for prediction of both PFS (P<0.05) and OS (P<0.05). By Kaplan-Meier analysis and log-rank testing both PFS and OS were significantly better in patients in CMR as compared to patients in PMR or PMD according to Lugano classification (P<0.01). CONCLUSIONS: [18F]FDG PET/CT represents a useful tool in the detection of disease response and in the evaluation of outcome in PEL patients.

Efficacy and safety of new direct antiviral agents in hepatitis C virus-infected patients with diffuse large B-cell non-Hodgkin's lymphoma.

The association of hepatitis C virus (HCV) with non-Hodgkin's lymphoma (NHL) has been demonstrated throughout the world. The new interferon-free direct antiviral agents (DAAs) showed high efficacy and safety, and preliminary data seem to confirm their activity on low-grade NHL. The question arises as whether or not-and how-to treat the HCV-positive patients suffering from diffuse large B-cell lymphomas (DLBCLs). The aim of this observational study was to evaluate whether DAA antiviral treatment of DLBCL/HCV-infected patients in concomitance with chemotherapy is a safe and effective option. Twenty (13 males and 7 females) HCV genotype 1b-positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all patients underwent antiviral therapy (AVT) with sofosbuvir/ledipasvir and chemotherapy (14 rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and 6 cyclophosphamide, doxorubicin, vincristine, and prednisone) for DLBCL. Complete hematological (Revised European-American Lymphoma classification, Ann Arbor, and International Prognostic Index [IPI] scores) and hepatological (viral markers, liver stiffness, and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV-positive patients not undergoing AVT was enrolled for comparison. DAA-treated and untreated patients were similar for sex distribution, IPI score, and NHL stage, and differed for age (older in treated), chemotherapy and use of AVT. Overall survival (OS) and disease-free survival (DFS) were evaluated among a 52-week of follow-up. No statistical difference was found in OS after 52 weeks (P = 0.122), whereas a statistically significant higher DFS was achieved in treated patients (P = 0.036). At the multivariate analysis, only IPI score and AVT were independently correlated with a better DFS. No differences in adverse events were reported. CONCLUSION: DAA treatment in concomitance with chemotherapy was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients. (Hepatology 2018;67:48-55).

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

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

Pegfilgrastim in primary prophylaxis of febrile neutropenia following frontline bendamustine plus rituximab treatment in patients with indolent non-Hodgkin lymphoma: a single center, real-life experience.

BACKGROUND: In this prospective study, the impact of granulocyte colony-stimulating factors (G-2 CSF) administered during induction treatment with bendamustine plus rituximab for indolent non- Hodgkin Llymphoma (NHL) was evaluated by comparing patients who received secondary prophylaxis with filgrastim (control group) versus. patients who received pegfilgrastim as primary prophylaxis (peg-group). The primary endpoint was the incidence rate of febrile neutropenia (FN)- related chemotherapy disruptions (regarding dose-dense and/or dose-intensity of schedule). The Ssecondary endpoint included days of hospitalization due to FN, and G-CSF-related side effects (grade ≥3 WHO toxicity criteria) in each group. METHODS: One hundred twenty-two: 122 consecutive patients, with untreated indolent NHL, were referred to our outpatient unit for remission induction immuno-chemotherapy with bendamustine-rituximab. During the first period, 61 patients received secondary prophylaxis with filgrastim, given "on demand" if ANC was <1000/mm3. During the second period, 61 patients received primary prophylaxis with pegfilgrastim in a single administration. RESULTS: Pegfilgrastim was significantly associated with fewer incidence rate of FN-related chemotherapy disruptions (11.4% in the control group vs. 1.6% in the peg-group, p = 0.04) and fewer days of hospitalization due to FN (median number 18 days in the control group vs. 6 in the peg-group, p = 0.04). In terms of G-CSF-related extra-hematological grade III side effects, no significant difference has been found in the two groups (9.8% in the control group vs. 11.5% in the peg-group, p = 0.77). Only one patient stopped the treatment in the peg-group due to intolerance. CONCLUSIONS: In patients with indolent NHL, in front-line treatment with bendamustine plus rituximab, primary prophylaxis with pegfilgrastim seems to reduce the incidence of chemotherapy disruptions due to FN, and the days of hospitalization. Moreover, it is well- tolerated and may increase the opportunity to maintain the planned schedule of treatment. These results make pegfilgrastim an advantageous option in most cases both in terms of cost-effectiveness and quality of life. These preliminary observations need to be validated by controlled clinical trials.

Intravenous versus subcutaneous immunoglobulin replacement in secondary hypogammaglobulinemia.

In this study, we compared intravenous immunoglobulins (IVIG) and subcutaneous immunoglobulins (SCIG) in terms of serum IgG concentration and incidence of infections in patients with hypogammaglobulinemia secondary to chemo-immunotherapy regimens including the anti-CD20 monoclonal antibody rituximab. Fourteen patients with a B-cell lymphoproliferative disease treated for at least six months with a rituximab-including chemo-immunotherapy regimen were recruited. Mean serum levels of IgG were higher during replacement therapy than at the end of rituximab treatment (p<0.001). Moreover, serum IgG level was higher during replacement therapy with SCIG than with IVIG (p<0.001). No differences in the incidence of infections were observed. Although the non-randomized design and the small number of patients do not allow definitive conclusions to be drawn, study results suggest that higher mean serum IgG levels are reached when using the subcutaneous route after a switch from the intravenous regimen, and that IVIG and SCIG offer comparable protection against infections.

Successful and Safe Long-Term Standard Antiviral Therapy in a Patient with "Explosive" Immune Response in Course of HCV-Related Liver Cirrhosis.

Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin's lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen.

Management of the HBV reactivation in isolated HBcAb positive patients affected with Non Hodgkin Lymphoma.

BACKGROUND: Occult HBV infection (OBI) is defined by the persistence of HBV in the liver without serum HBsAg and HBVDNA. It represents a life-threatening event during immunosuppressive chemotherapies. An OBI occurs in approximately 18% of HBcAb + patients. International guidelines suggest surveillance for HBV markers in immunosuppressed patients. In Non-Hodgkin Lymphoma (NHL), the prevalence of OBI reactivation remains to be established. METHODS: In order to determine the prevalence of occult HBV reactivation in a large cohort of patients during chemotherapy for NHL, we analysed 498 NHL patients in a centre of Southern Italy. We evaluated HBV markers, NHL type, treatment type and occurrence of HBV reactivation. RESULTS: Forty % of patients were treated with monoclonal antibodies and 60.3% without. Ninety-six patients were HBcAb+, HBsAg-. HBV reactivation occurred in ten subjects of this subgroup. All of them were successfully treated with Lamivudine. None of the patients experienced liver-related death. The prevalence of OBI reactivation was of 10.42% in HBcAb + HBsAb- patients. This event occurred in 50% of patients treated with mild immunosuppressive therapies. Each reactivation was treated with Lamivudine. DISCUSSION: This report suggests that a strict surveillance is important and cost-effective in HBcAb + HBsAg- NHL patients treated with mild immunosuppressive therapies, in order to detect an occult HBV reactivation.

Assessment of metabolic response to radioimmunotherapy with 90Y-ibritumomab tiuxetan in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

PURPOSE: To prospectively compare the assessment of metabolic response to yttrium 90 ((90)Y)-ibritumomab tiuxetan radioimmunotherapy (RIT) by using fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomographic-computed tomographic (PET/CT) imaging at 2 and 6 months to determine the most appropriate time to detect therapeutic response in refractory non-Hodgkin lymphoma (NHL) patients treated with RIT. MATERIALS AND METHODS: The ethical committee of the university approved the protocol and all patients signed informed consent. Twenty-three consecutive patients (10 women, 13 men; mean age, 51.8 years +/-7.3 [standard deviation]) treated by using RIT for relapsed or refractory follicular NHL were enrolled. For all patients, (18)F FDG PET/CT scanning was performed at baseline and at 2 and 6 months after RIT. Response was assessed by using the International Workshop Criteria (IWC) and revised criteria (IWC + PET) as well as the criteria of the European Organization for Research and Treatment of Cancer. One-way analysis of variance for repeated measures, receiver operator curve analysis, and Kaplan-Meier curves were used for statistical analysis. RESULTS: PET/CT performed at 2 months revealed complete (n = 12) or partial (n = 4) metabolic response in 16 of 23 patients with complete or partial clinical response. These findings were all confirmed at 6-month scanning. PET/CT indicated refractory or persistent disease at 2 and 6 months in the remaining seven patients. Better overall survival was observed for patients with a reduction in the maximum standard uptake value of 49% or higher (both at 2 and 6 months after RIT) when compared with those with a decrease of less than 49% (P < .05). CONCLUSION: Early assessment of response to RIT by using PET/CT might be useful in the identification of patients needing additional therapeutic strategies.

Immune signatures in human PBMCs of idiotypic vaccine for HCV-related lymphoproliferative disorders.

Hepatitis C virus (HCV) is one of the major risk factors for chronic hepatitis, which may progress to cirrhosis and hepatocellular carcinoma, as well as for type II mixed cryoglobulinemia (MC), which may further evolve into an overt B-cell non-Hodgkin's lymphoma (NHL). It has been previously shown that B-cell receptor (BCR) repertoire, expressed by clonal B-cells involved in type II MC as well as in HCV-associated NHL, is constrained to a limited number of variable heavy (VH)- and light (VL)-chain genes. Among these, the VK3-20 light chain idiotype has been selected as a possible target for passive as well as active immunization strategy. In the present study, we describe the results of a multiparametric analysis of the innate and early adaptive immune response after ex vivo stimulation of human immune cells with the VK3-20 protein. This objective has been pursued by implementing high-throughput technologies such as multiparameter flow cytometry and multiplex analysis of cytokines and chemokines.

Cutaneous needle track seeding of mesothelioma diagnosed by fine needle aspiration cytology: a case report.

BACKGROUND: Diagnostic and therapeutic procedures for mesothelioma require surgical biopsy or the usage of different-sized needles. Thoracic wall involvement along the surgical or needle tracks has been reported. CASE: A 57-year-old woman who had suffered from non-Hodgkin's lymphoma complained of dyspnea and left pleural effusion. The patient had been treated with chemotherapy and radiotherapy and was in remission since then. Thoracentesis was performed using a 22-gauge needle; the cytologic diagnosis was malignant pleural mesothelioma. Within 2 weeks from thoracentesis, the patient complained of an erythematous swelling in her left chest wall, in the area of the needle track. Fine needle aspiration cytology (FNAC) of the swelling was performed using a 23-gauge needle; 2 smears and a cell block were prepared. Smears showed neoplastic cells in sheets and papillary configuration with the features of mesothelial lineage. Immunocytochemistry showed positivity for calretinin and vimentin. Cytologic slides of the former effusion showed an overlapping of the cytologic and immunocytochemical features. A diagnosis of chest wall involvement from mesothelioma was established and histologically confirmed. CONCLUSION: Chest wall infiltration is a definite risk in the management of pleural mesothelioma, and FNAC is a useful procedure for a timely diagnosis of this ominous complication.

Can early switch to rituximab-bendamustine in a patient with follicular non-Hodgkin lymphoma progressing during R-CHOP be considered frontline treatment?: A case report.

RATIONALE: Follicular non-Hodgkin lymphoma (fNHL) is a neoplasm characterized by an indolent course and chemosensitivity, but also by disease recurrence. Bendamustine is often used as frontline treatment or second line. HEADING DIAGNOSIS:: fNHL. PATIENT CONCERNS: A 63-year-old Caucasian male with diagnosis of fNHL lymphoma underwent to cyclophosphamide, doxorubicin, vincristine, and prednisone associated with rituximab chemoimmunotherapy, during which interim reevaluation showed progressive disease and severe toxicity. INTERVENTIONS: Early switch to rituximab-bendamustine. OUTCOMES: This regimen was well tolerated, patient compliance was optimal, there were no delays in administration and no infectious episodes. An interim reevaluation after 3 courses revealed that the patient was fit, the blood cell count was normal, and lymphadenopathies and nocturnal sweating had completely regressed. Of note, the PET/CT scan did not show fluorodeoxyglucose pathological uptake, clearly confirming disease regression. LESSONS: Early switching to a bendamustine-rituximab-based scheme, even during conventional chemotherapy, decreases toxicity and reduces the risk of treatment interruption or delay, with favorable effects on overall response and prognosis.

Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ).

BACKGROUND: Follicular lymphoma is the most common form of lymphoma in Europe and the USA. In this prospective, single-arm, open-labelled, multicentre non-randomised phase II trial (FLUMIZ [FLUdarabine, MItoxantrone, Zevalin] trial) we aimed to assess the efficacy and safety of fludarabine and mitoxantrone plus radioimmunotherapy in untreated patients with follicular non-Hodgkin lymphoma (NHL). METHODS: Patients with stage III or IV untreated indolent follicular NHL were enrolled between June 1, 2004, and April 15, 2006, at 13 Italian institutions, and were treated with oral fludarabine (40 mg/m2 on days 1 to 3) and intravenous mitoxantrone (10 mg/m2 on day 1) every 28 days for six cycles. Patients who had at least a partial response (PR) with normal platelet counts (>100x10(9)/L) and granulocyte counts (1.5x10(9)/L), and bone-marrow infiltration less than 25% 4-6 weeks after completion of the sixth cycle of chemotherapy were deemed eligible for consolidation treatment 6-10 weeks after the sixth cycle with one course of yttrium-90 ((90)Y)-labelled ibritumomab tiuxetan (Zevalin), which consisted of an initial infusion of intravenous rituximab (250 mg/m2) on day 1 followed by a second 250 mg/m2 infusion on day 7, 8, or 9. The second infusion was followed by a weight-based dose of 90Y-ibritumomab tiuxetan, administered as a slow intravenous push over 10 min. Primary endpoints were complete response (CR) and haematological toxic effects and secondary endpoints were overall survival and progression-free survival. Responses were classified according to the International Workshop for Response Criteria for non-Hodgkin's lymphomas. Analysis was per protocol. This trial is registered as a European Standard Controlled Trial on the EudraCT website http://oss-sper-clin.agenziafarmaco.it, number 2004-002211-92. FINDINGS: 61 patients were enrolled in the trial and received six cycles of fludarabine and mitoxantrone, after which an overall response was noted in 98% (60 of 61) of patients (43 of 61 patients had CR and 17 of 61 patients had PR). 57 patients (43 with CR and 14 with PR) were deemed eligible for subsequent (90)Y-ibritumomab tiuxetan. Of the 14 patients who had PR after the initial treatment, 12 obtained CR after (90)Y-ibritumomab tiuxetan. By the end of the entire treatment regimen 55 of 57 patients achieved CR. With a median follow-up of 30 months (range 21-48), 3-year progression-free survival was estimated to be 76% (95% CI 72.3-82.4) and 3-year overall survival 100%. 36 of 57 patients had grade 3 or 4 haematological toxic effects, and blood transfusions were given to 21 of 57 patients. INTERPRETATION: This trial has provided evidence for the feasibility, tolerability, and efficacy of fludarabine and mitoxantrone plus (90)Y-ibritumomab tiuxetan in untreated patients with follicular NHL.

The addition of rituximab to anthracycline-based chemotherapy significantly improves outcome in 'Western' patients with intravascular large B-cell lymphoma.

Some case reports and a Japanese series suggest benefit from the use of rituximab in patients with intravascular large B-cell lymphoma (IVL). Rituximab efficacy was evaluated in Western patients with IVL, comparing outcome of 10 patients treated with rituximab + chemotherapy (R-CT) and of 20 patients treated with chemotherapy alone (CT). There were no significant differences in patients' characteristics between the two subgroups. The addition of rituximab was associated with improved complete remission rate (90% vs. 50%; P = 0.04), event-free survival (3-year: 89% vs. 35%; P = 0.003) and overall survival (3-year: 89% vs. 38%; P = 0.01). In conclusion, rituximab may substantially change the dismal prognosis of IVL.

Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin's lymphoma.

BACKGROUND: Primary Hepatic (PHL) and Primary Splenic (PSL) non-Hodgkin's Lymphoma are rare entities. Small series of PHL and PSL have been reported, suggesting a non-fortuitous association with Hepatitis C Virus (HCV) infection. The prognosis is believed to be dismal, with early recurrence and short survival. PATIENTS: We retrospectively reviewed all PHL and PSL patients diagnosed at our institution between 1990 and 2005. RESULTS: Twenty-five adult patients were identified, six with PHL and 19 with PSL. Twenty-four patients had a B-cell lymphoma, defined as Diffuse Large B-cell lymphoma in 18. The prevalence of HCV infection was 68% among PSL and 66% among PHL. Combination chemotherapy was the mainstay of treatment for PHL and PSL; all but one patient with PSL underwent splenectomy before chemotherapy. Complete remission was achieved in all the cases after frontline therapy; only four patients relapsed but responded to additional chemotherapy courses. Most patients presented with aggressive histological subtypes; 92% were alive at a median follow up of 79 months. HCV infection did not appear to influence the results of therapy. CONCLUSION: Our study confirms the rarity of PHL and PSL, shows a high prevalence of HCV infection, and demonstrates that the outcome of patients with PHL and PSL may be favourable.

Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans.

This study aimed at evaluating the role of consolidation radiation in a setting of Hodgkin's lymphoma (HL) patients, using event-free survival (EFS) as end point. Among 260 patients treated with induction chemotherapy for bulky HL, 160 patients achieved negative residual masses at 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) scans. They were randomly divided into two well-matched groups to receive either 32 Gy radiotherapy to bulky area or no further therapy. At a median follow-up of 40 months, histology showed a malignancy in 14% of patients in the chemotherapy-only group (HL, 11 patients) and in 4% of patients in the chemotherapy + radiotherapy group (HL, 2 patients; carcinoma in previously irradiated area, 1 patient) (P = 0.03). All the relapses in the chemotherapy-only group involved the bulky site and the contiguous nodal regions. Thus, the overall diagnostic accuracy of FDG-PET to exclude future relapses in the patients nonprotected by radiotherapy was 86% with a false-negative rate of 14%. Our study suggests that the addition of irradiation helps improve EFS in HL patients with post-chemotherapy FDG-PET-negative residual masses.

Rare HVR1-HCV genotype 1b variants in patients with B non Hodgkin's lymphoma. Comparison with viral sequences detected in cases of lymphoproliferative disorders and B cell compartmentalisation.

We compared the E2-HVR1 region in HCV-1b positive B-NHL cases from a multicenter study with sequences from studies related to lymphoproliferative disorders and B cell compartmentalisation. We found rare and unique mutations both in B-NHL isolates and in cases with lymphoproliferative disorders and lymphocyte infection. These rare mutations could have an important effect on HVR1 region and, as a consequence, on the binding of E2 on CD81, with a possible implication for both antigenic stimulation and HCV entry. In conclusion, the HCV predominants circulating in B-NHL cases seem to be associated with clonal selection of rare variants.

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

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