The prognostic score we developed may be useful in designing clinical trials for the treatment of advanced Hodgkin's disease and in making individual therapeutic decisions, but a distinct group of patients at very high risk could not be identified on the basis of routinely documented demographic and clinical characteristics.

Recently, many new drugs have been developed for the treatment of Waldenströ m macroglobulinemia (WM). To optimize the treatment according to the prognosis and to facilitate the comparison of trials, we developed an International Prognostic Scoring System for WM in a series of 587 patients with clearly defined criteria for diagnosis and for initiation of treatment. The median survival after treatment initiation was 87 months. Five adverse covariates were identified: advanced age (>65 years), hemoglobin less than or equal to 11.5 g/dL, platelet count less than or equal to 100 ؋ 10 9 /L, ␤2-microglobulin more than 3 mg/L, and serum monoclonal protein concentration more than 7.0 g/dL. Low-risk patients (27%) presented with no or 1 of the adverse characteristics and advanced age, intermediate-risk patients (38%) with 2 adverse characteristics or only advanced age, and high-risk patients (35%) with more than 2 adverse characteristics. Five-year survival rates were 87%, 68%, and 36%, respectively (P < .001). The ISSWM retained its prognostic significance in subgroups defined by age, treatment with alkylating agent, and purine analog. Thus, the ISSWM may provide a means to design risk-adapted studies. However, independent validation and new biologic markers may enhance its significance. (Blood. 2009;113:4163-4170)

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.

Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.

When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation.

Enteropathy-associated T-cell lymphoma (EATL) is a complication of celiac disease (CD). This tumor derives from the neoplastic transformation of aberrant intraepithelial T lymphocytes emerging in celiac patients unresponsive to a gluten-free diet. Poor adherence to a gluten-free diet, HLA-DQ2 homozygosity, and late diagnosis of CD are recognized as risk factors for malignant evolution of CD. Recurrence of diarrhea, unexplained weight loss, abdominal pain, fever, and night sweating should alert physicians to this complication. The suspicion of EATL should lead to an extensive diagnostic workup in which magnetic resonance enteroclysis, positron emission tomography scan, and histologic identification of lesions represent the best options. Treatment includes high-dose chemotherapy preceded by surgical resection and followed by autologous stem cell transplantation, although biologic therapies seem to be promising. Strict adherence to a gluten-free diet remains the only way to prevent EATL. (Blood. 2012;119(11): 2458-2468) IntroductionCeliac disease (CD) is a chronic gluten-sensitive enteropathy characterized by a high prevalence in the general population and an increased mortality. 1,2 It is well known that the increased mortality is mainly the result of the complications of CD itself, represented by refractory CD (RCD) and enteropathy-associated T-cell lymphoma (EATL). 2 RCD is a form of CD that does not respond histologically to at least 12 months of a strict gluten-free diet (GFD). 3 RCD can also evolve in patients who initially responded normally to a GFD and who are still maintaining a strict GFD. On the basis of the intraepithelial lymphocyte (IEL) population, RCD is further classified into type 1 and type 2. RCD type 1 (RCD1) is characterized by persisting villous atrophy despite a strict GFD associated with increased but still phenotypically normal IELs. Conversely, a clonal expansion of abnormal IELs lacking surface CD3, CD8, and T-cell receptor (TCR) markers but expressing intracellular CD3 indicates RCD type 2 (RCD2), a condition that frequently evolves into EATL, the most serious complication of CD. 4 In the past, up to 20% of celiac patients were considered to be affected by a nonresponsive form of CD. This was obviously because of the lack of consensus on the definition of nonresponsiveness. 4 In the last few years, some evidence has suggested that the prevalence of RCD is low, ranging from 0.6% to 1.5%. 3,5,6 Although the presence of RCD in CD is probably to be approximately 1%, the prevalence of RCD2 among patients with RCD is far from being ascertained. Probably because of not only the great differences in the diagnostic criteria, 4 but also referral bias, different papers report very different results, which vary from 15% to 75%. 7-9 Finally, although the incidence of EATL was reported to be rare in the general population (1 per million person-years), 10,11 it was shown that it occurs in 60% to 80% of patients with RCD2 within 5 years. [7][8][9]12 The description of EATL arising in patients with RCD...

Hodgkin lymphoma (HL) is a curable malignancy which shows a bimodal curve in incidence in economically developed countries; there is a putative association with Epstein-Barr virus. The WHO 2008 classification schema recognises two histological types of HL: the nodular lymphocyte predominant and the "classic" HL. The latter encompasses four entities: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich. Most patients with HL present with asymptomatic superficial lymphadenopathy. The commonest sites of disease are the cervical, supraclavicular and mediastinal lymph nodes, while sub-diaphragmatic presentations and bone marrow and hepatic involvement are less common. Splenic involvement is usually concomitant with hepatic disease and systemic symptoms; extranodal presentations are quite rare. Systemic symptoms are present in ∼35% of cases. The stage of disease is defined according to the Ann Arbor staging system or its Cotswolds variant, and staging work-up includes physical examination, chest X-rays, chest and abdominal CT scan, and bone marrow biopsy. (18)FDG-PET ((18)fluordeoxyglucose positron emission tomography) plays a central role in staging, response assessment and prognosis definition. Classic HL usually spreads by contiguity within the lymphatic tissue network, with a late extension to adjacent and distant viscera. Mortality from HL has been progressively decreasing, as confirmed by the most recent 5-year survival figure of 81%. The list of putative prognostic factors in HL has been increasing, but most factors still require prospective validation. Some of these variables are used to stratify early-stage disease into "favourable" and "unfavourable" categories, with "unfavourable early-stage" being intermediate between "favourable early-stage" and "advanced-stage". ABVD (adriamycin(doxorubicin), bleomycin, vinblastine, dacarbazine) combination chemotherapy followed by involved-field irradiation is the standard treatment for patients with early-stage HL, with a 5-year OS >95%. Several trials assessing less intensive approaches for patients with favourable early-stage HL are ongoing. More intensified combinations, such as the BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone) regimen, are being investigated, usually in patients with unfavourable early-stage HL and interim PET+. ABVD is the standard chemotherapy treatment also for patients with advanced disease. Although some evidence suggests that more intensive combinations provide better disease control, the inevitable increased risk of relevant late toxicity worries investigators. Consequently, there has been a shift towards investigating the innovative strategy of a more aggressive schedule for patients with (18)FDG-PET positive results after the first 2 courses of ABVD. High-dose chemotherapy supported by ASCT (autologous stem cell transplantation) is considered the standard of care in patients with HL which has relapsed after, or is refractory to conventional chemoradio...

PCD is not a rare form of CD. Having found no difference at all in age at diagnosis and clinical features between PCD and active CD could suggest that PCD is not a prodrome of CD but is a separate entity that can only subsequently evolve into active CD.