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Background: Thalidomide is an immunomodulatory drug with strong antimyeloma activity. It is an effective treatment for multiple myeloma at disease recurrence and at diagnosis, both as a single agent and in combination with steroids or chemotherapy. No data are available on the association of thalidomide with oral melphalan and prednisone, still considered the standard treatment for elderly patients., Methods: The feasibility and efficacy of the combination of melphalan, prednisone, and thalidomide (MPT) have been valuated in 49 newly diagnosed patients with multiple myeloma., Results: According to European Bone Marrow Transplantation/ International Bone Marrow Transplantation Registry (EBMT/IBMTR) criteria, 18% of patients achieved immunofixation-negative complete disease remission (CR), 6% achieved immunofixation-positive near CR, 4% achieved a very good partial response, and 45% achieved a partial response, with a 50-89% reduction in monoclonal paraprotein. Six percent did not respond and 10% showed progressive disease. The median time to maximum response was 4 months. The Kaplan-Meier estimates of event-free survival and overall survival at 2 years were 64% and 91%, respectively. The major acute adverse events (National Cancer Institute Common Toxicity Criteria Grade III-IV) included thrombosis (20%), infections (12%), constipation (6%), and hematologic (22%) and neurologic (8%) toxicities. One patient died of pulmonary thromboembolism., Conclusions: These data suggested that MPT induced rapid and durable tumor responses with CR rates similar to those observed after autologous transplantation. Administration of prophylactic anticoagulant was required to prevent thromboembolism. MPT merits further investigation in randomized clinical trials.

Background: The authors investigated the clinical role of tumor burden (TB) in patients with Hodgkin lymphoma, relating this parameter to most of the current clinical and prognostic factors and to the best predictive multifactorial models., Methods: The volume of TB at diagnosis was measured directly from the initial staging computed tomography scans in 351 patients who were treated on standard protocols. The mean patient age was 34.0 years +/- 16.4 years. Forty-six patients had clinical Stage I disease, 201 patients had Stage II disease, 64 patients had Stage III disease, and 40 patients had Stage IV disease. There were 146 symptomatic patients. Overall survival (OS), disease-free survival (DFS), and time to treatment failure (TTF) were the time parameters evaluated in the multivariate analysis. Logistic regression was applied according to those who achieved or failed complete remission., Results: The mean TB normalized to body surface area (rTB) was 137.8 cm(3)/m(2) +/- 124.7 cm(3)/m(2) (range, 1.9-694.5 cm(3)/m(2)). In multivariate analysis, rTB was the best predictor of TTF, DFS, and complete remission; the second best predictor of OS after patient age; and largely superior to all prognostic models analyzed. For the same stage and treatment, patients who were destined to clinical failure had an initial rTB 60-108% higher compared with the initial rTB in patients who achieved a cure, whereas differences in drug dose intensity were not significant., Conclusions: In the current study, it was found that the rTB, as a prognostic factor, was more effective than and was independent of hitherto used factors and scores. The rTB may be a tool for evaluating the curative potential of treatment combinations, allowing physicians and patients to make better therapeutic choices earlier.

Background: To assess the impact of T-cell/B-cell phenotype on clinical outcome, the authors retrospectively compared patients who had peripheral T-cell lymphoma, unspecified (PTCL-U), with patients who had diffuse large B-cell lymphoma (DLBCL)., Methods: Two hundred ninety-seven cases of PTCL-U and 496 cases of DLBCL that had been transferred from the files of the Intergruppo Italiano Linfomi or the Gruppo Italiano Linfomi were integrated into a unique working file and reviewed by the authors., Results: The PTCL-U group and the DLBCL group had significantly different distribution patterns with respect to patient age, gender, disease stage, performance status (PS), the presence or absence of systemic "B" symptoms, the presence or absence of bulky disease, lactic acid dehydrogenase (LDH) levels, and number of extranodal sites (ENS). A significantly greater number of patients in the DLBCL group experienced complete remission (P < 0.0001). Multinomial logistic regression analysis confirmed that immunophenotype, PS, LDH concentration, and number of ENS were independent predictors of response. At a median follow-up duration of 43 months, there was no observable difference in disease-free survival (DFS) between patients with DLBCL and patients with PTCL-U; however, multivariate analysis did reveal that poorer PS and bone marrow involvement were significantly associated with shorter DFS. Furthermore, although the overall survival (OS) curves associated with the T-cell and B-cell immunophenotypes were significantly different from each other at a median follow-up duration of 37 months (P = 0.0012), Cox multivariate analysis excluded immunophenotype from the final OS model., Conclusions: The findings made in the current study indicate that the natural history of PTCL-U may differ from that of DLBCL. Patients with PTCL-U tended to have less favorable clinical outcomes, although the observed difference in outcome was only partially attributable to immunophenotype, which was independently associated with response, but not with survival. Differences in prognostic factor distributions between patients with PTCL-U and patients with DLBCL may account for some portion of the expected phenotype-associated risk., ((c) 2004 American Cancer Society.)

This study evaluates residual disease in 28 B-cell chronic lymphocytic leukemia (B-CLL) patients who obtained a clinicohematologic remission after intensive chemotherapy. Sixteen of 28 patients (57%) showed a normal number of circulating B-lymphocytes, as demonstrated by the low percentage of mouse rosette-forming cells (M-RFC), surface immunoglobulins (SIg), and CD24-positive cells. Clinically, a lower number of relapses occurred in this group of patients compared to those with a persistent expansion of peripheral B-cells (P less than 0.05). In order to assess monoclonality of the residual peripheral B-cell population, the distribution of SIg light chains was investigated on the B-cell-enriched fraction of 15 of these 16 cases. Only six of them had a kappa/lambda ratio which ranged between 1.7:1 and 3:1, whereas the remaining patients still displayed a clearly imbalanced kappa/lambda Ig light chain distribution. On the other hand, the analysis of the configuration of the Ig heavy chain gene region, performed in nine cases (including five of the above six cases), showed the persistence of a rearranged pattern in all cases tested but one. Therefore, residual monoclonal B-cells were found also in the majority of cases which displayed the lowest kappa/lambda ratio, a normal bone marrow lymphocytosis and a long-lasting clinical remission. Studies at the DNA level confirm that a remission is rarely achieved in this disease in spite of intensive and prolonged chemotherapy. Nonetheless, the follow-up of B-CLL patients by conventional immunologic markers may be helpful to better define response to therapy and to predict the occurrence of clinical relapse.