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This narrative review aimed to identify young cancer survivors' behaviours, experiences, and perspectives concerning physical activity, and identify useful strategies for promoting a healthy lifestyle. A manual search on the following databases was conducted: PubMed, Scopus, and Web of Science. The search was conducted between June 1, 2023, and April 12, 2024. Articles published from database inception up to April 12, 2024, were retrieved. Articles published in any language were considered. Perspectives including ideas, perceived barriers, and facilitators have been identified. Young cancer survivors seem to engage in physical activity as a useful coping strategy to regain normality and keep healthy after the cancer diagnosis. Although emotional and social support seems fundamental to increase participation, several other factors, including physical limitations, fatigue, sex, cancer type, and socio-economic status can influence physical activity participation. For those engaged in physical activity, the preferred activities are walking, biking, going to the gym, and exercising at home, while the least preferred are exercising at the hospital or boot camp-based exercises. Yoga is more frequently chosen by those still under treatment. Young cancer survivors appear to have unique needs different from those of adult cancer survivors. Mode of treatment delivery, increased awareness concerning the effects of physical activity, including families and friends, connecting survivors, and providing social support together with increasing motivation are key strategies for the promotion of physical activity in young cancer survivors. Fitness and healthcare professionals should consider these aspects to increase young cancer survivors' involvement in physical activities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tripodo, Bertolazzi, Cancila, Morello and Iannitto.)

Purpose: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials., Patients and Methods: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT)., Results: About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HR ABVD vs BEACOPP  = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP., Conclusions: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective and Methods: In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed., Results: The median number of previous treatments was 2 (1-4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m 2 on days 1 and 2 of a 21-day cycle. The median number of BvB cycles was 4 (2-7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow-up of 19 months (5-47), median PFS was 18 months (95%CI: 23-29), and the 2-year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%)., Conclusion: Our real-world results suggest that BvB is an effective third-line rescue and bridge-to-transplant regimen for RR-cHL patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method. The primary endpoint was complete response rate. Fifty-six patients with SMZL diagnosis confirmed on central revision were treated with bendamustine (90 mg/m 2  days 1, 2) and rituximab (375 mg/m 2  day 1) every 28 days for six cycles (B-R). The overall response and CR rates were 91% and 73%, respectively. Duration of response, progression-free survival and overall survival at 3 years were 93% (95% confidence interval [CI] 81-98), 90% (95% CI 77-96) and 96% (95% CI 84-98), respectively. Toxicity was mostly haematological. Neutropenia grade ≥3 was recorded in 43% of patients; infections and febrile neutropenia in 5·4% and 3·6%. Overall, 14 patients (25%) experienced serious adverse events. Five patients (9%) went off-study because of toxicity and one patient died from infection. In conclusion, B-R resulted in a very effective first-line regimen for SMZL. Based on the results achieved in the BRISMA trial, B-R should be considered when a chemotherapy combination with rituximab is deemed necessary for symptomatic SMZL patients., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by hemolytic anemia, bone marrow failure and thrombosis, caused by a somatic mutation in PIG-A gene that results in the absence of CD55 and CD59, two important complement regulatory proteins. In this paper, a case of PNH is retrospectively examined looking for clinical and laboratory features, and the entire course of the disease from the onset of the symptoms is described, together with an adequate follow- up over a 7-years treatment period. In this case, the not specificity and the limited clinical relevance of the symptoms led to a delay in diagnosis. After thrombosis, Eculizumab therapy has been shown to be effective, and during seven years of followup no events have occurred that put the patient's life at risk. A multidisciplinary approach is crucial in cases like this, in order to allow early diagnosis and minimize the risks for the patients., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

Objective: To verify whether absolute monocyte count (AMC) and lymphocyte- monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL)., Patients and Methods: Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007., Results: The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm(3), and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; P<.001). The overall survival (OS) at 10 years for an AMC of more than 750 cells/mm(3) was 78% (70%-85%), and the OS at 10 years for an AMC of 750 cells/mm(3) or less was 88% (84%-90%; P=.01). In multivariate analysis, both AMC and LMR maintained prognostic significance for PFS (hazard ratio [HR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3)., Conclusion: This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

This current retrospective multicenter analysis represents, to our knowledge, the first Italian study evaluating the efficacy and toxicity profile of "lenalidomide plus dexamethasone" as salvage therapy in patients with recurrent-refractory MM in the real life contest. Our study included patients who are usually excluded from clinical trials because of unfavorable baseline characteristics. Median OS was significantly longer in patients receiving "lenalidomide plus dexamethasone" for more than 12 months compared with those who had received "lenalidomide plus dexamethasone" for a shorter interval (P<0.0001). Median OS was not affected by best response achieved (P 0.4) and age (P 0.3). Quality of response did not correlate with number of previous lines of therapy (P 0.77) and age. Higher ORRs were recorded in the patients group with relapsed MM compared to those with refractory disease, but this difference was not statistically significant (P 0.38)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Rituximab® provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP). Fifty-one patients were eligible for the analysis. The overall response rate was 84%. The 6-year progression-free survival and overall survival were 54% and 72%, respectively. Toxicity was substantial (grade≥3 neutropenia: 26%; grade≥3 infections: 8%). Of the 15 deaths, two occurred on treatment (one sepsis and one pneumonia). Six deaths were due to lymphoma progression, four to secondary neoplasia, one to sepsis, one to pneumonia and one to splenectomy complications. R-COMP should be restricted to patients with bulky disease associated with symptoms or to patients with possible histological transformation.

Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone genetics and the recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic relevance. We show that the quality of the BM stromal meshwork of SMZL infiltrates correlates with time to progression. In particular, we describe the unfavorable prognostic influence of dense CD40 expression by BM stromal cells, which involves the contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal cells and mast cells populating the SMZL microenvironment finds correlation in p53(-/-) mice developing SMZL and contributes to the engendering of detrimental proinflammatory conditions. Our study highlights a dynamic interaction, playing between nonneoplastic elements within the SMZL niche, toward disease progression.

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder accounting for about 2% of all leukemias. The clinical course is indolent, however HCL patients are particularly susceptible to infections. Here we report two cases of Q-fever as first manifestation of disease in two patients affected by HCL. Both patients described in this report showed an unusually sluggish clinical response to the antibiotic treatment with ciprofloxacin probably because of the marked immunodeficiency. However, treatment of HCL with cladribine administered soon after the resolution of QF pneumonitis was uneventful and led to a complete remission in both cases. Most probably the association of Coxiella burnetii (CB) infection and HCL that we observed in two patients is due to chance. However, a hairy cell resembling transformation of freshly isolated human peripheral blood lymphocytes upon CB has been showed. We think that the possibility of CB infection in febrile HCL patient should be always taken in mind, especially in endemic areas. In addition the potential for such infections to become chronic in HCL patients should not be overlooked and the reporting of further cases should be encouraged.

In chronic lymphocytic leukemia (CLL), the most prevalent lymphoid malignancy in western countries, patients have a median age at diagnosis of 72 years. In the last few years, there has been remarkable progress in understanding the biology of CLL, the detection of molecular prognostic factors and the development of more effective therapies. However, many of the milestone studies were conducted in populations that were considerably younger than the average age of the CLL population. Today, the challenge is to improve management of elderly patients. In this population, outcome of treatment with newer highly effective therapies is often compromised by comorbidities and poor performance status. Decision on how elderly patients should be treated is thus a complex issue. The management of these patients should rely on the development of risk-stratified treatment strategies based on the assessment of individual functional status and the biologic characteristics of CLL. New single agents with reduced toxic effects (i.e., inhibitors of BCR signalling) that have achieved promising results in Phase I/II studies when available should modify the paradigm of the treatment of elderly patients with CLL.

Total body computed tomography (TB-CT) scan is not mandatory in the diagnostic/staging algorithm of chronic lymphocytic leukemia (CLL). The aim of this study was to determine the value and prognostic significance of TB-CT scan in early stage CLL patients. Baseline TB-CT scan was performed in 240 Binet stage A CLL patients (179 Rai low- and 61 Rai intermediate-risk) included in a prospective multicenter observational study (clinicaltrial.gov ID:NCT00917549). The cohort included 69 clinical monoclonal B lymphocytosis (cMBLs). Patients were restaged considering only radiological data. Following TB-CT scans, 20% of cases reclassified as radiologic Binet (r-Binet) stage B. r-Binet B patients showed a higher incidence of unfavorable cytogenetic abnormalities (P = 0.027), as well as a shorter PFS (P = 0.001). At multivariate analysis, r-Binet stage [HR = 2.48; P = 0.004] and IGHV mutational status [HR = 3.01; P = 0.002] retained an independent predictive value for PFS. Among 179 Rai low-risk cases, 100 were redefined as r-Rai intermediate-risk based upon TB-CT scan data, showing a higher rate of cases with higher ZAP-70 (P = 0.033) and CD38 expression (P = 0.029) and β2-microglobulin levels (P < 0.0001), as well as a shorter PFS than those with r-Rai low-risk (P = 0.008). r-Rai stage [HR = 2.78; P = 0.046] and IGHV mutational status [HR = 4.25; P = 0.009] retained a significant predictive value for PFS at multivariate analysis. Forty-two percent of cMBL patients were reclassified as r-small lymphocytic lymphomas (r-SLLs) by TB-CT scan. TB-CT scan appears to provide relevant information in early stage CLL related to the potential and the timing of patients to progress towards the more advanced disease stages., (Copyright © 2013 Wiley Periodicals, Inc.)

To complement the existing treatment guidelines for all tumour types, ESMO organizes consensus conferences to focus on specific issues in each type of tumour. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, next to the 11th International Conference on Malignant Lymphoma. The conference convened ∼30 experts from all around Europe, and selected six lymphoma entities to be addressed; for each of them, three to five open questions were to be addressed by the experts. For each question, a recommendation should be given by the panel, referring to the strength of the recommendation based on the level of evidence. This consensus report focuses on the three less common lymphoproliferative malignancies: marginal zone lymphoma, mantle cell lymphoma, and peripheral T-cell lymphomas. A first report had focused on diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukaemia.

The management of patients with Hodgkin lymphoma (HL) recurring after stem cell transplantation (SCT) and multiply relapsed disease remains challenging. We report on 41 such patients who received bendamustine hydrochloride, a bifunctional mechlorethamine derivative mechanistically unrelated to traditional alkylators, after a median of four prior chemotherapy lines, including SCT in 85% of cases. Bendamustine was given at doses of 90-120 mg/m(2) every 21 or 28 d. At first assessment (2-4 cycles), the overall response rate (ORR) was 78% with 12 (29%) complete (CR) and 20 (49%) partial responses (PR). Upon treatment prolongation to 6-8 courses, 40% of PRs progressed, yielding a final ORR of 58% with 31% of CRs. Eight patients (two CRs, six PRs) were subsequently allotransplanted. Median progression-free and overall survival exceeded 11 and 21 months respectively; complete responders displayed a median disease-free survival above 9 months with a relapse rate of only 30%. Outcomes were independent of disease chemosensitivity, previous transplant and bendamustine dose-intensity. No life-threatening or unexpected adverse events occurred. Within the limits of a retrospective analysis and schedule heterogeneity, these results appear very encouraging and prompt prospective trials to confirm bendamustine as a valuable option in the palliative setting and in cytoreductive strategies before allotransplantation., (© 2012 Blackwell Publishing Ltd.)

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the lesions except bone marrow involvement, which was quantified by calculation. The relationship with early resistance was analysed with logistic regressions. The rTB demonstrated to be the best predictor of early failure in both patient subsets, being superior to the multiparameter International Prognostic Score. The rTB showed a significant exponential relationship with the relative risk of early failure, and with inclusion of the extranodal involvement into the model, a single equation became adequate to predict resistance in both early unfavourable and advanced stage patients. The conclusions are that the rTB is the best pretreatment factor related to the risk of resistance to combined ABVD + radiotherapy and that this relationship can be mathematically expressed in an easy way. A simplified assessment of rTB is highly desirable., (Copyright © 2012 John Wiley & Sons, Ltd.)

This international retrospective study of 593 Splenic Marginal Zone Lymphoma (SMZL) patients aimed to identify factors that determine treatment initiation and influence lymphoma-specific survival (LSS). Logistic regression was used to identify the factors associated with treatment. A Cox regression was used to analyse LSS in a derivation cohort of 366 patients. This produced a prognostic index (PI) and enabled the identification of three risk groups. The resulting stratification was validated in another cohort of 227 patients and compared with the Interguppo Italiano Linfomi (IIL) score in the group of 450 patients for whom all the required data were available using an extension of the net reclassification improvement. Haemoglobin concentration (Hb), extrahilar lymphadenopathy and hepatitis C virus status were associated with the initiation of treatment. Hb, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy were independently associated with LSS. Three risk groups with significantly different five-year LSS (94%, 78% and 69%, respectively) were identified. This stratification (named HPLL on the basis of determinant factors) had a better discriminative power than the IIL score. This system is useful for stratifying SMZL patients into risk groups and may help in the selection of risk-tailored treatment approaches., (© 2012 Blackwell Publishing Ltd.)

The relative tumor burden (rTB), the tumor burden normalized to body surface area, is of prime clinical and prognostic value in Hodgkin's lymphoma. However, its measurement is rather complicated and a bedside computation cannot be proposed. We investigated the possibility of estimating, instead of measuring, rTB from elementary parameters of the initial staging. The rTB of 507 patients, treated with therapeutic protocols of the Gruppo Italiano Studio Linfomi according to their staging characteristics, was measured through their pre-therapy computed tomographies. The relationships between rTB and staging characteristics were analyzed with simple and multiple regressions both in a training sample (254 patients) for a selection of predictive parameters, and in a test sample (253 patients) for validation of the results. The number of involved sites, bulky mass and the IPI score were the variables best related to rTB. The resulting final equation {estimated rTB=-4.3+8.3xIPI2+22.7x[no. of involved sites (+3 if a bulky mass is present)]} provided the maximal approximation to the measured rTB (R2=0.671). The validity of the equation was confirmed on the test sample and the predictive superiority of the estimated rTB over IPI was still evident in terms of failure-free survival in both groups of patients. The estimated rTB is accurate enough to retain most of the prognostic advantage of the measured rTB over the IPI score. It can be easily calculated, allows a valid approximation of the measured rTB, and can be proposed as a useful tool for clinical research and practice.

Mechanisms associated with reactivation of hepatitis B virus (HBV) in patients with occult HBV infection (OBI) remain unclear. In some cases immunosuppression is an enhancer of viral replication. However, not all patients with OBI who undergo immunosuppression experience reactivation. This study explores the role of viral heterogeneity as a determinant of occult HBV reactivation. HBV genotype, mutation patterns and quasispecies were assessed by sequencing the PreS/S region of 16 patients with OBI undergoing chemotherapy, 3 of whom experienced a OBI reactivation. The latter were also assessed at the time of reactivation. Phylogenetic analysis identified low nucleotide and amino acid diversity rates. There were no differences in the viral quasispecies, or common mutation patterns, detected between patients who underwent reactivation of OBI, and those who did not. Furthermore, upon reactivation, the quasispecies evolved towards a loss of most of the variants present during the initial OBI stage, probably representing the fittest version of the virus. The genetic variability of HBV alone did not account for the transition from occult to overt infection, which appears to be governed principally by the host immune response.

Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody. One hundred seventy-five relapsed or refractory lymphoma patients were enrolled. The median age was 69 years (range 26-87). Seventy-nine patients were relapsed, 35 were refractory and 61 presented a progressive disease after partial response. The diagnoses were 60 indolent non-follicular lymphomas, 34 diffuse large B-cell lymphomas, 48 follicular lymphomas, 30 mantle cell lymphomas and three peripheral T-cell lymphomas. All patients were evaluable for response: 52 (29%) with complete remission, 72 (43%) with partial response with an overall response rate of 71%, and 51 non-responders. With a median observation period of 10 months (1-43), 70% of patients are alive. In summary, this retrospective study shows that treatment with bendamustine alone or in combination with rituximab is a safe and effective regimen in a subset of multi-resistant patients.

We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele (*)04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2(*)04 peaked at 31%. The IGHV1-2(*)04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7%) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95%) IGHV1-2(*)04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6%) carried few mutations (97-99.9% germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super)antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2(*)04 allele.

Polymorphisms of the Glutathione-S Transferase (GST) family may influence the prognosis in lymphoma patients. We aimed to validate the impact of GSTT1 and GSTM1 deletions and of the GSTP1Ile105Val polymorphism on outcome and toxicity in 140 patients with advanced Hodgkin's lymphoma enrolled in the prospective multicenter HD2000-GISL trial, comparing ABVD, BEACOPP and CEC regimens. Carriers of the GSTP1Ile105Val polymorphism had a higher rate of grade 3-4 anemia following treatment. Overall, our study failed to validate GST genotyping as prognostic factor for progression-free survival (PFS). Only the small cohort of patients with an international prognostic score (IPS) >3 and undeleted GSTT1 and/or GSTM1, treated with ABVD had worse progression-free survival (PFS) (GSTT1 + vs GSTT1-: HR 5.02, 95% C.I., 1.16-21.8, p = 0.031, GSTM1 + /GSTT1 + vs GSTM1-and/or GSTT1-: HR 4.61, 95% C.I. 1.28- 16.6, p = 0.019, respectively). No differences were observed for patients treated with intensified regimens, as BEACOPP and CEC. In conclusion, the prognostic role of GST polymorphism, if at all, is limited to a small subgroup of patients treated with standard ABVD regimen.

A prospective, multicenter, randomized trial comparing pamidronate administration (60-90 mg once a month for 1 year) versus simple observation in 177 patients with asymptomatic myeloma was performed to explore whether the administration of this drug reduces the rate of and/or the time to progression to overt, symptomatic disease. No relevant side effects were recorded in pamidronate-treated patients. With a minimum follow-up of 5 years for live patients, there were 56/89 (62.9%) progressions in the pamidronate-treated group and 55/88 (62.5%) within the controls (p = NS). Median time to progression was 46 and 48 months, respectively (p = NS). Overall survival was also similar between the two groups. Skeletal-related events at the time of progression were observed in 40/55 (72.7%) controls, but only in 22/56 (39.2%) pamidronate-treated patients (p = 0.009). In conclusion, the administration of pamidronate in asymptomatic myeloma, while reducing bone involvement at progression, did not decrease the risk of transformation and the time to progression into overt myeloma.

To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8). Twenty-two patients received bendamustine alone and 87 patients received R-B (median B dosage: 100 mg/m(2) per day, range 90-130 mg/m(2) per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R-B (P = 0·014) and in those responsive to the previous treatment (P=0·04). After a median follow-up of 7·9 months (range 1-148), the median progression-free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response (P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4-7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R-B was an effective and well-tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity., (© 2011 Blackwell Publishing Ltd.)

The incidental finding of an isolated splenomegaly during clinical assessment of patients evaluated for unrelated causes has become increasingly frequent because of the widespread use of imaging. Therefore, the challenging approach to the differential diagnosis of spleen disorders has emerged as a rather common issue of clinical practice. A true diagnostic dilemma hides in distinguishing pathologic conditions primarily involving the spleen from those in which splenomegaly presents as an epiphenomenon of hepatic or systemic diseases. Among the causes of isolated splenomegaly, lymphoid malignancies account for a relevant, yet probably underestimated, number of cases. Splenic lymphomas constitute a wide and heterogeneous array of diseases, whose clinical behavior spans from indolent to highly aggressive. Such a clinical heterogeneity is paralleled by the high degree of biologic variation in the lymphoid populations from which they originate. Nevertheless, the presenting clinical, laboratory, and pathologic features of these diseases often display significant overlaps. In this manuscript, we present our approach to the diagnosis and treatment of these rare lymphomas, whose complexity has been so far determined by the lack of prospectively validated prognostic systems, treatment strategies, and response criteria., (© 2011 by The American Society of Hematology)

Splenic lymphangiomatosis is a very rare condition that, from 1990 to date, has been described only nine times. In the present report, we describe the first case of splenic lymphangiomatosis with rapid growth during lactation in a 35-year-old woman. We also underline the difficultly in making an accurate preoperative diagnosis, despite more modern imaging techniques. Total splenectomy was considered to be the treatment needed, both to make a definitive diagnosis and to exclude the presence of malignancy.

Peripheral T-cell lymphomas (TCLs) are uncommon neoplasms, accounting for about 12% of all lymphoid tumors worldwide. TCLs in which gammadelta T-cell receptors are expressed (gammadelta TCLs) are extremely aggressive and rare (<1% of lymphoid neoplasms). gammadelta TCLs originate from gammadelta T cells, a small subset of peripheral T cells with direct antigen recognition capability acting at the interface between innate and adaptive immunity. Two distinct gammadelta TCL entities are recognized: hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous gammadelta T-cell lymphoma (PCGD-TCL). HSTL is a well-characterized extranodal lymphoma that has a disguised onset, secondary to intrasinusoidal infiltration of the spleen, liver and bone marrow, has a rapidly progressive course that is poorly responsive to chemotherapy, and often ensues in the setting of immune system suppression. PCGD-TCL can present with prominent epidermal involvement or with a panniculitis-like clinical picture that can be complicated by a concurrent hemophagocytic syndrome; the disease shows biological and phenotypic overlap with other extranodal gammadelta TCLs that involve the respiratory or gastrointestinal tract mucosa. The regular application of phenotypic and molecular techniques is crucial for the diagnosis of gammadelta TCLs. In this Review, we discuss the clinical and biological features, the diagnostic challenges and the therapeutic perspectives of HSTL and PCGD-TCL.

Purpose: To determine the efficacy and safety of the combination of gemcitabine plus oxaliplatin, with and without rituximab, in patients with relapsed/refractory B-cell lymphoma unsuitable for high dose therapy., Methods: Patients were prospectively enrolled in two subsequent trials, GEMOX [gemcitabine (1200 mg/m(2), days 1 and 8) and oxaliplatin (120 mg/m(2), day 2), three-weekly] and R-GEMOX [rituximab (375 mg/m(2), day 1), gemcitabine (1200 mg/m(2), day 1) and oxaliplatin (120 mg/m(2), day 2), bi-weekly], up to six courses., Results: Sixty-two patients were enrolled: GEMOX [n = 30; median age, 66 years (range, 46-85); previous chemotherapy > or =2, 70%; PS ECOG > or = 2, 57%]; R-GEMOX [n = 32; median age, 65 years (range 32-79); previous chemotherapy > or =2, 75%; PS ECOG > or = 2, 47%]. Overall and complete response rates were 57 and 30% (95% CI, 15-49) for GEMOX and 78 and 50% (95% CI, 32-68) in R-GEMOX, respectively. Grade 3/4 neutropenia occurred in 57 and 47% of cycles and grade 3/4 thrombocytopenia in 26 and 17% of courses for GEMOX and R-GEMOX, respectively. At 42 months, the failure-free survival (FFS) was 7% (95% CI, 0-16) for GEMOX and 28% (95% CI, 9-47) for R-GEMOX (P = 0.014), with overall survivals of 7 (95% CI, 0-16) and 37% (95% CI, 20-55), respectively (P = 0.016)., Conclusions: Both regimes showed good tolerability and appealing response rates. FFS was more prolonged in R-GEMOX, but patients continuously relapsed without a clear plateau on survival curves.

Background/aim: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases., Methods: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy., Results: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (anti-HBc and/or anti-HBs positive). Baseline serum HBV DNA was positive in nine out of 33 HBV-seronegative patients and in nine out of 42 HBV-seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs. 14%, P=0.9), and in five out of 18 HBV DNA-positive vs. six out of 57 HBV DNA-negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found in 18 patients (24.3%), although with no correlation to HBV serological status, presence of serum HBV DNA or frequency of HBsAg seroconversion., Conclusions: In oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV DNA testing at baseline has a 28% predictive ability to forecast HBsAg seroconversion in HBV DNA-positive patients, and a 90% ability to forecast persistent HBsAg negativity in HBV DNA-negative patients, a better performance than serological tests.

The aim of this study was to evaluate the apoptotic damage to bone marrow cells caused by three chemotherapy regimens for advanced Hodgkin's lymphoma, ABVD, COPPEBVCAD and BEACOPP, which were randomly administered in the HD 2000 GISL trial. Bone marrow mononuclear cells (BMMCs) stained with anti-CD34 antibody and Annexin V, were evaluated by flow cytometry before starting chemotherapy, 30 days after completing chemotherapy and after 6 months. Results are expressed as the percentages of BMMCs positive to anti-CD34, to Annexin V or to both. Fourteen patients treated with ABVD, 11 with COPPEBVCAD and 13 with BEACOPP were evaluated before and 30 days after treatment. Late assessments were made in 6, 7 and 8 of them, respectively. No differences were found among the pretherapeutic flow cytometry findings in relation to the staging characteristics (marrow involvement included). All the regimens increased the apoptotic fraction of the whole mononuclear bone marrow cells (COPPEBVCAD did so significantly) and increased the CD34+ compartment (with significant early differences after ABVD and BEACOPP, tending to late persistence for ABVD, only). All the regimens increased the apoptotic CD34+ cells within the whole BMMC population (significantly after BEACOPP), although with a general trend to decrease in their percentage within the CD34+ compartment over time, even after the most dose-dense regimens. Based on the variations induced in the apoptotic fraction of all mononuclear and CD34+ cells, ABVD was the least toxic regimen and COPPEBVCAD the most toxic one.

Aims: Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as "key-cells". The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders., Methods: Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax, Bad) and anti-apoptotic (Bcl-2, Bcl-XL, hTERT (human telomerase reverse transcriptase)) molecules and the "executioner" molecule caspase-3. The fraction of MKCs undergoing apoptosis was assessed by deoxynucleotidyl transferase-mediated dUTP nick-end labelling., Results: Only the mitochondrial pathway seemed to be involved in MKC apoptosis. The anti-apoptotic molecule Bcl-XL was predominantly found in ET MKCs (50.5% of ET MKCs versus 35% of PMF MKCs; p = 0.036), while pro-apoptotic molecules Bax and Bad showed a prevalent expression in PMF MKCs (30.5% of ET MKCs versus 55% of PMF MKCs; 41% of ET MKCs versus 52% of PMF MKCs; p = 0.001 and p = 0.068, respectively). A significant fraction of PMF MKCs were committed to apoptosis according to caspase-3 expression and TUNEL, while only few ET cells were committed to apoptosis. hTERT was significantly more expressed in PMF (32% of ET MKCs versus 46% of PMF MKCs; p = 0.022), in agreement with the proliferative nature of this disease., Conclusions: It was found that ET and PMF MKCs, which barely differ in terms of morphology and aggregation, are characterised by markedly different apoptotic profiles. The rather high apoptotic fraction of PMF was able to support the fibrotic nature of this process, while the anti-apoptotic profile of ET cells fits well with their "steady" maturative state.

Purpose: In the pre-positron emission tomography era, the Gruppo Italiano Studio Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients., Patients and Methods: Patients with stage I/II showing at least one adverse prognostic factor and stage IIIA without adverse prognostic factors were recruited. Treatment included a first step of 3 ABVD courses, followed by an early-restaging. Patients in CR/CRu received 1 additional ABVD cycle, patients in PR received 3 more ABVD, and nonresponder patients went off study. Involved-field radiation therapy (RT) was recommended on chemotherapy completion., Results: The median age was 30 years (range, 15-68 years) and 131 patients (61%) were female. Seven percent of patients were in stage I, 78% in stage II, and 15% in stage III; B-symptoms, bulky tumor and erythrocyte sedimentation rate > 30 were recorded in 20%, 26%, and 43% of cases, respectively. The CR/CRu rate was 62% at early restaging, 72% at the end of chemotherapy, and 95% following RT. With a median follow-up of 74 months (range, 6-193 months), 7-year overall survival, relapse-free survival, and freedom from treatment failure were 91.8% (95% CI, 86%-95.5%), 89.2% (95% CI, 82.8%-93.3%), and 81.8% (95% CI, 75.2%-86.7%), respectively. Patients in CR/CRu on early restaging, receiving 4 ABVD, had an excellent outcome with 7-year RFS and cause-specific survival similar to those of the late responders treated with 6 ABVD (RFS, 87.5% vs. 90.5% and CSS, 96.6% vs. 92.7%, respectively)., Conclusion: The response-guided ABVD program we report, based on standard clinical staging procedures, proved to be feasible and safe in patients with intermediate-stage Hodgkin lymphoma.

Purpose: To compare doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, and bleomycin (COPPEBVCAD; CEC) for advanced Hodgkin's lymphoma (HL)., Patients and Methods: Three hundred seven patients with advanced HL (stage IIB, III, and IV) were randomly assigned to receive six courses of ABVD, four escalated plus two standard courses of BEACOPP, or six courses of CEC, plus a limited radiation therapy program., Results: After a median follow-up of 41 months, BEACOPP resulted in a superior progression-free survival (PFS), with a significant reduction in risk of progression (hazard ratio [HR] = 0.50) compared with ABVD. No differences between BEACOPP and CEC, or CEC and ABVD were observed. The 5-year PFS was 68% (95% CI, 56% to 78%), 81% (95% CI, 70% to 89%), and 78% (95% CI, 68% to 86%), for ABVD, BEACOPP, and CEC, respectively (BEACOPP v ABVD, P = .038; CEC v ABVD and BEACOPP v CEC, P = not significant [NS]). The 5-year overall survival was 84% (95% CI, 69% to 92%), 92% (95% CI, 84% to 96%), and 91% (95% CI, 81% to 96%) for ABVD, BEACOPP, and CEC, respectively (P = NS). BEACOPP and CEC resulted in higher rates of grade 3-4 neutropenia than ABVD (P = .016); BEACOPP was associated with higher rates of severe infections than ABVD and CEC (P = .003)., Conclusion: As adopted in this study BEACOPP is associated with a significantly improved PFS compared with ABVD, with a predictable higher acute toxicity.

CD146(+) bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. In this study we used immunohistochemical analysis to investigate the contribution of CD146(+) bone marrow osteoprogenitors to the stromal remodeling occurring in the different stages of primary myelofibrosis. We found that CD146(+) cells sited at the abluminal side of the bone marrow vessels and branching among hematopoietic cells significantly increased in the advanced stages of primary myelofibrosis (p<0.001), paralleling the extent of fibrosis (rho=0.916, p<0.0001) and the microvascular density (r=0.883, p<0.0001). Coherently with a mural cell function, such cells also displayed smooth-muscle actin expression. Our data providing evidence of CD146(+) cell involvement in bone marrow stromal changes occurring in primary myelofibrosis are consistent with the capability of these cells to participate in fiber deposition, angiogenesis, and bone formation. They could also represent rationale for new therapies targeting the bone marrow stroma in primary myelofibrosis.

The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive neoplasm clinically characterized by sudden onset of constitutional symptoms, lymphadenopathy, hepatosplenomegaly, frequent autoimmune phenomena, particularly hemolytic anemia and thrombocytopenia, and polyclonal hypergammaglobulinemia. The lymph node histological picture is also distinctive, constituted by a polymorphic infiltrate, a marked proliferation of high endothelial venules, and a dense meshwork of dentritic cells. The neoplastic CD4+ T-cells represent a minority of the lymph node cell population; its detection is facilitated by the aberrant expression of CD10. Almost all cases arbor an EBV infected B-cell population. Patients with AITL have a poor prognosis with conventional treatment, with a median overall survival of less than 3 years. Patients achieving a good clinical response seem beneficiate from a consolidation with high-dose therapy and autologous stem cell transplantation. Constitutional symptoms and autoimmune phenomena, and some times also the neoplastic masses may respond to immunosuppressive or immunomodulatory agents such as thalidomide.

Background: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program., Patients and Methods: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas)., Results: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms., Conclusions: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL.

Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992, an increasing number of publications have dealt with multiple aspects of SMZL diagnosis, molecular pathogenesis and treatment. This process has identified multiple inconsistencies in the diagnostic criteria and lack of clear guidelines for the staging and treatment. The authors of this review have held several meetings and exchanged series of cases with the objective of agreeing on the main diagnostic, staging and therapeutic guidelines for patients with this condition. Specific working groups were created for diagnostic criteria, immunophenotype, staging and treatment. As results of this work, guidelines are proposed for diagnosis, differential diagnosis, staging, prognostic factors, treatment and response criteria. The guidelines proposed here are intended to contribute to the standardization of the diagnosis and treatment of these patients, and should facilitate the future development of clinical trials that could define more precisely predictive markers for histological progression or lack of response, and evaluate new drugs or treatments.

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day -1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follow-up of 16 months (range, 5-42 months), 14 patients were alive, 9 had died from progressive disease, and 1 had died from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effects were grade 4 neutropenia and cytomegalovirus (CMV) reactivation. Major infections were Jacob-Creutzfeldt (J-C) virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis, and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement; and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID no. 141202.

Purpose: Starting from November 2001, 260 newly diagnosed patients with Hodgkin's lymphoma (HL) were consecutively enrolled in parallel Italian and Danish prospective trials to evaluate the prognostic role of an early interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan and the International Prognostic Score (IPS) in advanced HL, treated with conventional ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy., Patients and Methods: Most patients (n = 190) presented with advanced disease (stages IIB through IVB), whereas 70 presented in stage IIA with adverse prognostic factors. All but 11 patients were treated with standard ABVD therapy followed by consolidation radiotherapy in case of bulky presentation or residual tumor mass. Conventional radiologic staging was performed at baseline. FDG-PET scan was performed at baseline and after two courses of ABVD (PET-2). No treatment change was allowed on the basis of the PET-2 results., Results: After a median follow-up of 2.19 years (range, 0.32 to 5.18 years), 205 patients were in continued complete remission and two patients were in partial remission. Forty-three patients progressed during therapy or immediately after, whereas 10 patients relapsed. The 2-year progression-free survival for patients with positive PET-2 results was 12.8% and for patients with negative PET-2 results was 95.0% (P < .0001). In univariate analysis, the treatment outcome was significantly associated with PET-2 (P < .0001), stage IV (P < .0001), WBC more than 15,000 (P < .0001), lymphopenia (P < .001), IPS as a continuous variable (P < .0001), extranodal involvement (P < .0001), and bulky disease (P = .012). In multivariate analyses, only PET-2 turned out to be significant (P < .0001)., Conclusion: PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL.

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.

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

Objective: To evaluate the clinical characteristics and outcome of NK/T-cell lymphoma 'nasal type' developed in Italian patients., Patients: Between 1997 and 2004, 26 new cases of NK/T-cell lymphoma 'nasal type' were diagnosed in 10 Italian Hematology institutions., Results: All patients were Caucasian, male/female ratio was 19/7, with a median age of 50 years (range 20-80). In 23 cases presentation at the onset was in the nasal cavity or adjacent structures, in two cases the lymphoma onset with skin lesions was followed successively by rhynopharyngeal dissemination, while the remaining case had bone marrow and lymph node involvement followed by oro-pharyngeal involvement. Regarding the stage of disease: 12 patients were in stage I; six in stage II; eight in stage IV. Diagnosis was based on the finding of a NK/T-cell phenotype at the histological and immunophenotypic examination of oropharyngeal or cutaneous lesions. All patients but one were treated with chemotherapy, alone in nine cases or associated to radiotherapy in 14 cases; two patients had chemotherapy, radiotherapy and surgery, while one patient underwent only surgery. Chemotherapy was anthracycline-based in 17 out of 25 cases. In those patients in whom radiotherapy was performed, radiation dosages ranged between 36 Gy and 47.5 Gy, with a median dosage of 40 Gy. Nine patients (34%) were responsive to the treatments: six patients obtained a complete remission and other three a partial remission. The remaining 17 patients resulted refractory or presented a limited response to therapy. The median disease-free survival was 14 months and the median overall survival time was 9 months., Conclusion: The results of this retrospective survey confirmed that NK/T-cell lymphoma 'nasal type' is a very rare lymphoma in the Italian population, and it is characterized by a very bad prognosis. Due to the rarity of this disease, a standardized therapeutic approach is lacking. More data are needed to know the epidemiology of this kind of lymphoma in Europe.

Background and Objectives: We explored the predictive value on therapy outcome of an early evaluation of treatment response by 18F-fluorodeoxyglucose position emission tomography (18F-FDG-PET) scan performed after two courses of conventional standard-dose chemotherapy in advanced-stage Hodgkin's disease., Design and Methods: One hundred and eight patients with newly-diagnosed Hodgkin's disease in stage IIA with adverse prognostic factors, or in stage IIB through IVB, were re-staged with FDG-PET after two cycles of ABVD (PET-2). The end-point of the study was the predictive value of PET-2 on 2-year progression-free survival and 2-year failure-free survival. No treatment variation based only on PET-2 results was allowed., Results: Eighty-eight patients attained complete remission (CR) while 20 showed disease progression during therapy or within 6 months after having reached CR; one patient relapsed. PET-2 was positive in 20 patients: 17 progressed during therapy, one relapsed and two remained in CR. By contrast, 85/88 (97%) patients with a negative PET-2 remained in CR; three progressed or relapsed early after the end of the chemotherapy. Thus, the positive predictive value of a PET-2 was 90% and the negative predictive value was 97%. The sensitivity, specificity and overall accuracy of PET-2 were 86%, 98% and 95%, respectively. The 2-year probability of failure-free survival for PET-2 negative and for PET-2 positive patients was 96% and 6%, respectively (log rank test = 116.7, p < 0.01)., Interpretation and Conclusions: 18F-FDG-PET scan performed after two courses of conventional standard-dose chemotherapy in advanced-stage Hodgkin's disease was able to predict treatment outcome in 103/108 (95%) of the patients.

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.