Novel Method for the Direct Measurement of the τ Lepton Dipole Moments.

A novel method for the direct measurement of the elusive magnetic and electric dipole moments of the τ lepton is presented. The experimental approach relies on the production of τ^{+} leptons from D_{s}^{+}→τ^{+}ν_{τ} decays, originating in fixed-target collisions at the LHC. A sample of polarized τ^{+} leptons is kinematically selected and subsequently channeled in a bent crystal. The magnetic and electric dipole moments of the τ^{+} lepton are measured by determining the rotation of the spin-polarization vector induced by the intense electromagnetic field between crystal atomic planes. The experimental technique is discussed along with the expected sensitivities.

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation.

BACKGROUND: A growing body of evidence is demonstrating that the nitrogen-containing bisphosphonate zoledronic acid (zol) improves clinical outcomes in various cancer settings, including multiple myeloma. Those findings provided the rationale for conducting an open-label randomized controlled phase iii trial to evaluate the effect of zol on overall survival (os) and progression-free survival (pfs) in patients with previously untreated high-risk multiple myeloma. METHODS: The trial randomly assigned 308 adult patients less than 65 years of age with previously untreated symptomatic multiple myeloma (1:1) to receive zol 4 mg intravenously once every 28 days for 24 months (n = 151) or no zol (n = 157). Before autologous stem-cell transplantation (asct), all patients received a high-dose noncytotoxic induction regimen of dexamethasone, all-trans-retinoic acid, and interferon alpha 2b. RESULTS: After a median follow-up of 69.8 months (range: 36.5-96 months), the 10-year pfs (66% vs. 52%, p < 0.001) and os (67% vs. 48%, p < 0.001) rates were significantly higher in treated patients than in control patients. Overall response (77% zol vs. 75% control), complete response (52% vs. 46%), and very good partial response (25% vs. 29%) rates were similar between the groups. Treatment was generally well tolerated, with no reports of renal impairment or osteonecrosis of the jaw. CONCLUSIONS: In symptomatic previously untreated multiple myeloma patients, zol combined with high-dose therapy followed by asct improved os and pfs without appreciable toxicity. These findings provide additional evidence of the meaningful anticancer activity of zol in this patient population.

A new therapeutic approach in very refractory diffuse large B-cell lymphoma.

PURPOSE: Patients with diagnosis of diffuse large B-cell lymphoma, who relapse after stem cell transplant (SCT) or are no candidates to SCT, have a poor prognosis and no current treatment is available. Thus, we conduct a rotatory chemotherapy schedule that employed low doses of chemotherapy agents to assess efficacy and toxicity in this setting of patients; the end point was the improved outcome. METHODS: Retrospectively we revised an analysis of 461 patients who were treated with a low-doses regimen of cytotoxic agents, who were treated in a single institution, all patients has been treated with at least two salvage regimens, including SCT, > 18 years, performance status < 3, and that were informed about the possibility of severe toxicities,, were considered candidates to the study. They received a weekly rotatory scheme including low doses of cytotoxic agents during 2 years. RESULTS: Overall response rate was achieved in 314 patients (68%, 95% Confidence interval (CI) 59-76%) and complete response was achieved in 151 cases (32%, 95% CI 25-38%); actuarial curves at 10 years show that progression-free survival was 58% (95% CI 51-66%) and OS was 50% (95% CI 43-57%). Dose reduction was not necessary; toxicity was minimal and well controlled. No death related to acute or late toxicities has been observed. CONCLUSION: Low doses of cytotoxic agents for continuous, prolonged periods, with minimal drug-free intervals, represent a novel, active, and easily tolerated approach to management of patients with DLBCL in a terminal phase and improved outcome.

Electromagnetic dipole moments of charged baryons with bent crystals at the LHC.

We propose a unique program of measurements of electric and magnetic dipole moments of charm, beauty and strange charged baryons at the LHC, based on the phenomenon of spin precession of channeled particles in bent crystals. Studies of crystal channeling and spin precession of positively- and negatively-charged particles are presented, along with feasibility studies and expected sensitivities for the proposed experiment using a layout based on the LHCb detector.

Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero.

To evaluate the risk of acute and late side effects in children whose mothers received chemotherapy during pregnancy for hematological malignancies, we performed an analysis of 84 children with a long-term follow-up. The 84 children in our study were born to mothers with hematological malignancies (29 acute leukemia, 26 Hodgkin's disease, and 29 malignant lymphoma) who received chemotherapy during pregnancy, including 38 during the first trimester. These children were examined for physical health; growth; development; and hematological, cytogenetic, neurological, psychological, and learning disorders. The occurrence of cancer or acute leukemia in these children was also considered. Some of these patients have become parents, and their children were also considered in this analysis. In all of the children studied, including the 12 second-generation children, the birth weight was normal; learning and educational performance were normal; and no congenital, neurological, or psychological abnormalities were observed. With a median follow-up of 18.7 years (range, 6-29 years), no cancer or acute leukemia has been observed. These results confirm our previous reports, suggesting that if a pregnant patient has an aggressive hematological malignancy, chemotherapy at full doses can be safely administered, even during the first trimester, if cure of the hematological malignancy is considered reasonable.

Second lethal events associated with treatment for Hodgkin's disease: a review of 2980 patients treated in a single Mexican institute.

Presence of second neoplasms and cardiac toxicity has been recognized as potential late lethal second events in patients treated for Hodgkin's disease. However, most reports analyze these association independently. We reviewed 2980 cases of patients treated during 1970-1995 with long-term follow-up (> 4 years) in an attempt to identify all late events in Hodgkin's disease secondary to the treatment or those which are unrelated. Three hundred and ten patients died, and of these 156 were secondary to relapse and tumor progression. Death associated second tumors and cardiac events were increased 37 fold and 29 fold respectively compared to the general population. The risk factors for this complications did not differ to previous reports and included alkylating agents and/or radiotherapy for second neoplasms and anthracycline therapy and radiotherapy for cardiac toxicity. Moreover, 61 patients died secondary to non-related events. Nevertheless, at 20-years overall survival was 90 % (95 % confidence interval (CI): 78 % to 97 %) and event free survival was 88 % (95 % CI: 76 % to 96 %) for these patients. Thus, second events, fatal in most cases, should be considered as an expected risk to the treatment in patients with Hodgkin's disease; the proposed modifications of therapy may indeed be useful to avoid or diminish these complications in the future.

In vitro hematopoiesis in patients with malignant lymphoma during active disease and at complete clinical remission after chemotherapy.

Malignant lymphomas are neoplastic diseases of lymphoid cells, which usually originate in the lymph nodes. During the last two decades, significant progress has been made in the characterization of chromosomal and molecular alterations in these malignancies. To date, however, the composition and function of the hematopoietic system in this group of hematological disorders is still not fully understood. In the present study, we have determined the progenitor cell content in 10 patients with diffuse large-cell lymphoma (DLCL) and characterized the proliferation of these cells in long-term marrow cultures. We have also addressed some issues regarding the composition and function of the hematopoietic microenvironment in this malignancy. All the patients included in this study showed normal hematological parameters in peripheral blood, both before and after chemotherapy, however, significant hematopoietic alterations were consistently observed. As compared to normal subjects, lymphoma patients showed a 35% reduction in progenitor cell numbers, including myeloid, erythroid and multipotent progenitors. The in vitro proliferation of these cells was also deficient, since their levels in long-term marrow cultures were significantly lower than those observed in normal bone marrow cultures. Fibroblastic progenitors were reduced by >50% and this correlated with a deficient adherent cell layer development in culture. A reduction was also seen in the levels in culture supernatant of the stimulatory cytokines Stem Cell Factor and Interleukin-6. Interestingly, all the hematopoietic alterations mentioned above were still present in patients at complete clinical remission after chemotherapy. Thus, in the present study we have demonstrated significant in vitro deficiencies in the composition and function of the hematopoietic system in patients with diffuse large-cell lymphoma, both during active disease and at the time of complete clinical remission.

Late lethal events in patients with diffuse large B cell lymphoma: a review of 714 patients treated in a single centre.

Presence of late lethal events has been recognized as a complication in patients with malignant lymphoma. We reviewed 714 cases of patients treated during 1975-1995 with a long term follow-up (>4 years) in an attempt to identify all late events secondary to malignant lymphoma, either to the treatment or those which are unrelated. Forty-three patients died, and of these 21 (2.8%) were secondary to relapse and tumor progression; deaths associated with second neoplasm and cardiac events were increased 9.6 fold and 26.4 fold respectively compared to the general population. The risk factors for these complications did not differ from those in previous reports and included alkylating agents and/or radiotherapy for second neoplasms and anthracycline therapy and radiotherapy for cardiac toxicity. Moreover, 10 patients died secondary to non-related events. Nevertheless, at 10 years overall survival was 94% (95% confidence interval (CI): 82% to 98%) and event free survival was 97.1% (95% CI: 81% to 98%), for these patients. Thus, second events, fatal in most cases, will be considered as an expected risk in the treatment of patients with malignant lymphoma. The proposed modifications of therapy many indeed be useful to avoid or diminish these complications in the future.

Evaluation on a six-dose treatment of anti CD 20 monoclonal antibody in patients with refractory follicular lymphoma.

Treatment of refractory follicular lymphoma with monoclonal antibody CD 20 has been proven to be a good therapeutic option. However, most studies used four weekly doses and time to treatment failure (TTF) and overall survival (OS) could be considered very short: 11.0 and 13.6 months respectively. We started a pilot study to evaluate if six infusions at the same doses and schedule could improve the outcome in these patients. Seventeen patients with refractory follicular lymphoma heavily treated with chemotherapy (> 2 regimens), radiotherapy and biological modifiers were enrolled in a pilot study. They received 6 weekly doses, at 375 mg/m2, of monoclonal anti CD 20. In an intent to treat analysis, overall response was 76%, of which 47% (8 patients) were complete response and 5 patients were partial response. With a median follow-up of 28.6 months, 7 complete responders remain alive, free of disease, and 2 partial responses remain stable without additional treatment. Median to TTF has not been reached; yet, actuarial curves showed that at 3 years, 53% of patients are alive. The four patients who were failure died secondary to tumor progression. Overall survival (OS) at 3-year was 76%. Toxicity was mild, all patients completed the schedule on time and doses. The addition of two doses of anti CD 20 clearly improved OS and TTF in a group of patients with refractory follicular lymphoma heavily treated and with poor prognostic factors. However, the number is too short to draw definitive conclusions; more clinical trials are necessary to determine if 4 or 6 doses of anti CD 20 therapy are better in this setting of patients.

Treatment of refractory Hodgkin's disease with modified Stanford V program.

This study analyzes the results using an Stanford V modified program in the treatment of refractory Hodgkin's disease (RHD). We used cyclophosphamide instead of mechloretamine, and epirubicin instead of doxorubicin to avoid the risk of acute and late side effects associated with this drugs. Seventy-one patients with RHD were treated. All were at an advanced stage at therapy and had associated adverse prognostic factors. The complete response (CR) rate was 84% (60 patients; 95% confidence interval [CI]: 72-91%). At 5 yr, actuarial overall survival (CS) is 71% (95% Cl: 59-78%) and event-free survival (EFS) is 70% (95% CI: 59-79%). Only the duration of the initial complete response (> 12 mo) influenced the duration of EFS and OS. Toxicity was mild. Granulocyte colony-stimulating factor to ameliorate the presence of severe myelosuppression was used only in a few patients. Cardiac function was not affected and, until now, late side effects has not been observed. Thus, the use of this modified Stanford program retains the usefulness of the original scheme both with less frequent and less severe acute and late side effects. A controlled clinical trial in untreated patients comparing the Stanford program with standard chemotherapy is warranted to define the role of this therapeutic option in patients with Hodgkin's disease.

Long-term evaluation of cardiac function in children who received anthracyclines during pregnancy.

BACKGROUND: The use of anthracyclines in patients with cancer has been associated with the presence, even when standard doses were employed, of cardiac toxicity, most frequently after 5 years of therapy. Treatment of cancer during pregnancy remains a dilemma because cytotoxic therapy has been associated with the presence of severe side-effects. The outcome of children that received antracyclines during pregnancy, including during the first trimester, remain unknown because long-term follow-up is not available. PATIENTS AND METHODS: Eighty-one children whose mothers (29 acute leukemia, 33 malignant lymphoma and 19 Hodgkin's disease) were treated with cytotoxic drugs, including anthracyclines, during pregnancy were evaluated to detect cardiac toxicity, including clinical evaluation and echocardiogram [all parameters were evaluated, but fraction shortening (FS) was taking as the best parameter to evaluate cardiac toxicity in children] every 5 years after birth until 29 years of age. RESULTS: Children with actual age of 9.3-29.5 years (mean 17.1) did not show any clinical date of cardiac disfunction, in all cases echocardiogram was normal and FS did not showed any abnormality during the follow-up. CONCLUSIONS: The use of anthracyclines did not show any clinical or echocardiogram evidence of late cardiac toxicity. We hope that the present report increases the number of reports of the long-term follow-up of children who received cytotoxic drugs, in order to define the best treatment in this special patient setting.

Biological modifiers as cytoreductive therapy before stem cell transplant in previously untreated patients with multiple myeloma.

BACKGROUND: High dose chemotherapy with supporting autologous stem cell transplantation is now considered the treatment of choice in patients with multiple myeloma <65 years old. The best regimen appears to be VAD (vincristine, doxorubicin and dexamethasone), but acute and late toxicity can limit the use of this combination. The use of biological modifiers has not been considered in this situation. We developed a new cytoreductive regimen, in an attempt to retain clinical efficacy but reduce toxicity. PATIENTS AND METHODS: Thirty-six patients, previously untreated with diagnosis of multiple myeloma were enrolled to received the DAI regimen (dexamethasone 30 mg/m(2), i.v., days 1-4, all-trans-retinoic acid 45 mg/m(2), p.o., days 5-14 and interferon alpha 2a, 4.5 MU s.c., days 5-14) administered every 28 days for six cycles before high-dose chemotherapy (melphalan 200 g/m(2)) and autologous stem cell transplantation. RESULTS: Overall response was observed in 29 cases (80%), complete response in 19 and partial response in 10 patients. Five patients were >65 years old and were treated with dexamethasone/thalidomide. Twenty-four patients underwent transplants. At a median follow-up of 31.6 months, no relapse or disease progression was observed, thus actuarial curves at 3-years showed that event-free survival was 86% and overall survival was 94%. Toxicity was mild. CONCLUSIONS: This regimen appears to be an excellent alternative as cytoreductive treatment before high-dose chemotherapy and autologous stem cell transplantation with excellent overall response and minimal toxicity. Controlled clinical trials are warranted to define the role of this new therapeutic approach.

Interferon as maintenance therapy in refractory malignant lymphoma.

Patients with refractory malignant lymphoma (RML) have a poor prognosis when treated with conventional chemotherapy, as less than 20% remain alive and free of disease after 5 years. The use of myeloablative chemotherapy followed by BMT has improved the complete remission (CR) rate. Nevertheless, relapse rates remain unchanged, and only a few patients remain alive and free of disease for more than 3 years. For this reason, we began a prospective randomized clinical trial to determine if IFN-alpha2B (5.0 MU three times a week for 1 year) can improve the prognosis in RML. Ninety-six patients with high or high-intermediate clinical risk RML and in CR after intensive chemotherapy were randomly assigned to receive or not to receive IFN as maintenance therapy. A median follow-up of 48.1 months, the time to treatment failure and survival were similar in both groups. Toxicity secondary to IFN administration was mild, and all patients received the planned doses of IFN. We conclude that IFN is not recommended at this dose and schedule as maintenance therapy in patients with RML who achieve CR. Different therapeutic approaches may be developed to improve outcomes for these patients.

Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP-BLEO regimens.

OBJECTIVES: We conducted a randomized clinical trial to evaluate the role of interferon alfa 2b (IFN) as maintenance therapy in patients with diffuse large B-cell lymphoma with high or high-intermediate clinical risk on complete remission (CR) after CHOP-BLEO regimens. METHODS: Patients were initially treated with CHOP-BLEO regimens (which include increased doses of cyclophosphamide and epirubicine, instead of doxorubicin). If the patients achieved CR they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU, three times at week by 1 yr, or no treatment (control group). RESULTS: Two hundred and twenty-three patients were considered as candidates for the study. They were of high (80%) or high-intermediate (20%) clinical risk; additionaly most patients had poor prognostic factors such as high levels of beta 2 microglobulin, lactic dehydrogenase levels, bulky disease (defined as a tumor mass >10 cm) or multiple extranodal involvement. In an intent-to-treat analysis all patients were evaluable to efficacy and toxicity. Median follow-up was 45 months, the estimated 5-yr overall survival and event-free survival (EFS) for patients who received IFN were 71% (95% confidence interval (CI): 61-83%) and 57% (95% CI: 39-69%), respectively, values which were not statistically different from the control group: 69% (95% CI: 63-79%) and 54% (95% CI: 37-63%), respectively (p=0.2). Toxicity was mild. CONCLUSIONS: These results suggest that IFN used as maintenance therapy at these doses and schedules is not useful in aggressive malignant lymphoma when more intensive chemotherapy has been employed during induction treatment. Nevertheless, follow-up is too short, and long-term follow-up would be necessary in order to draw definitive conclusions. Probably, an multicenter study is necessary to define the role of IFN as maintenance therapy in this patient setting.

Angiocentric nasal T/natural killer cell lymphoma: a single centre study of prognostic factors in 108 patients.

Angiocentric T cell/natural killer (NK) nasal lymphoma remains a rare clinical presentation in North America and Europe but is more common in Asia and Latin America. We have reviewed 108 cases of angiocentric T/NK cell lymphoma of the nasal cavity with a view to establishing prognostic factors. Most patients were high or high intermediate clinical risk and had additional poor prognostic factors such as bulky disease, high levels of beta 2 microglobulin, advanced stage and multiple extranodal involvement. At 8 years, overall survival was 82%, 90% and 84% for low-intermediate, high-intermediate and high clinical, respectively. Disease free survival was very similar: 79%, 83% and 80%, respectively. Multivariate analysis did not identify any factor influencing overall survival and disease-free survival. There was no evidence that the international prognostic index (IPI) was applicable in these patients and it appears that angiocentric T/NK cell lymphoma is an independent prognostic factor itself.

Results in the treatment of recurrent dislocation of the patella after 30 years' follow-up.

The authors compare the clinical and radiographic outcome in patients with comparable bilateral recurrent patellar dislocation treated surgically on only one side, to clarify the appropriateness of the surgical indication. Sixteen patients were evaluated at an average follow-up of 30 years (20-45); all had been treated by the Roux technique. The results on both the operated and the unoperated knee were evaluated; the Crosby and Insall schedule was used for the clinical evaluation. Anteroposterior, lateral, and Merchant's view X-rays were examined for osteoarthritis and to measure the height of the patella. The congruence angle and the distance between anterior tibial tuberosity and trochlear groove (ATT-TG) were measured by computed tomography. The results in the operated knees were: 3 excellent, 9 good, 1 fair, and 3 worse; results in the nonoperated knees were 6 excellent, 8 good, 1 fair, and 1 worse. In the operated knees arthritis was grossly marked in 8, marked in 3, moderate in 1, and light in 4; in the nonoperated ones it was grossly marked in 8, moderate in 3, and light in 5. The congruence angle was normal in 10, medially displaced in 3, and laterally displaced in 3 cases on the operated side; on the nonoperated side it was normal in 7 cases and lateralized in the remaining 9. The ATT-TG in the operated knees was negative in 9 cases, normal in 1, and positive in 6; on the non-operated side it was positive or normal. In 7 operated cases a low patella was documented. The Roux technique yields positive results in the correction of recurrent dislocation. No clinical or radiographic differences were found between surgically and conservatively treated knees. The clinical results are generally not comparable with the radiographic features or with severity of degenerative modifications presented at long-term follow-up. The absence of a difference is due basically to the complete lack of adaptation of the surgical procedure to the variable pathogenesis of this disorder.

Results of a Controlled Clinical Trial Radiotherapy versus Combined Therapy in the Management of Stage IE Orbital Marginal Zone B-cell Lymphoma.

The aim of the present study was to compare the usefulness of radiotherapy (34-40 Gy, median 3.8 Gy) versus radiotherapy following by adjuvant chemotherapy in the management of 73 patients with stage I marginal zone B cell lymphoma (MZBCL) of the orbit. Complete response was similar in both arms: 95% (95% confidence interval (CI): 89-99%) in the radiotherapy group and 100% (95% CI: 92-104%) in the combined therapy arm. At a median follow-up of 8 years no median has been reached in event free survival (EFS) and overall survival (OS). At 8-years EFS shown that 87% (95%CI: 82-93%) and 82%, (95%CI: 78-87%), respectively remain in first complete response (p=0.6). OS was very similar 87% (95% CI: 84-89%) and 90%, (95% CI: 84-95%), respectively (p=0.5). Because we use low-radiation therapy (<50Gy) acute and late toxicities were mild. We concluded that combined therapy it is not useful in the treatment of MZBCL primary of the orbit and confirm that radiotherapy is the treatment of choice in this setting of patients.

Rituximab in the treatment of refractory follicular lymphoma -- six doses are better than four.

Seventeen patients with refractory follicular lymphoma heavily treated with chemotherapy (>2 regimens), radiotherapy, and biological modifiers were enrolled in a pilot study to receive six weekly doses, instead of the more frequent four doses, of monoclonal anti CD20, at a standard dose of 375 mg/m(2). In an intent-to-treat analysis, overall response was 76%, of which 47% (8 patients) were a complete response. With a median follow-up of 33.6 months, 7 complete responders remained alive and free of disease, and 2 partial-response patients remained stable without additional treatment. Actuarial curves showed that at 3 years, 53% of patients should be alive and free of disease. The 4 patients who were failures died secondary to tumor progression. Overall survival at 3 years was 76%. Toxicity was mild; all patients completed the schedule on time and doses. The addition of two doses of anti-CD 20 clearly improved the outcome in a group of patients with refractory follicular lymphoma heavily treated and poor prognostic factors. However, the number is too small to drawn definitive conclusions, and more clinical trials are necessary to determine if four of six doses of anti-CD20 therapy are better in this setting of patients.

Combined therapy in the treatment of primary mediastinal B-cell lymphoma: conventional versus escalated chemotherapy.

Treatment of patients with primary mediastinal B-cell lymphoma (PMBCL) remains controversial. We started a controlled clinical trial to evaluate the efficacy and toxicity of a conventional versus more intensive regimen of combined chemotherapy followed by radiotherapy to the mediastinum with the mantle technique. From 1989 to 1997, 68 patients diagnosed with previously untreated PMBCL, aged 18-65 years and negative for immunodeficiency virus test, were considered candidates to receive either conventional chemotherapy with CEOP-Bleo (cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2), prednisone 40 mg/m(2), epirubicin 70 mg/m(2), and bleomycin 10 mg/m(2)) or mega CEOP-Bleo (cyclophosphamide 1000 mg/m(2), epirubicin 120 mg/m(2), vincristine, prednisone, and bleomycin at the same doses) every 21 days for six cycles, followed by radiotherapy to the mediastinum with the mantle technique (35-45 Gy, mean 38 Gy). Complete response (CR) rates were not statistically different: 64% [95 percent confidence interval (CI): 58 percent to 70 percent] for conventional arm vs 81 percent (95 CI: 77-86 percent) in the intensive group (p=0.2). However, failure-free survival (FFS) and overall survival (OS) had statistical differences. At 5 years, actuarial FFS for patients treated with conventional chemotherapy was 51 percent (95 percent CI: 44-59 percent) compared to 70 percent (95 percent CI: 65-76 percent) in the intensive arm (p>0.01). OS rates were also different: 54 percent (95 percent CI: 48-57 percent) vs 70 percent (95 percent CI: 65-76 percent), respectively (p<0.01). Toxicity was mild and no therapy-related deaths were observed. At a median follow-up of 7.3 years, no second neoplasia or acute leukemia has been observed. The international prognostic index was not useful to define clinical risk in this selected group of patients. Multivariate analysis identified pleural and pericardial effusion and chemotherapy regimen as prognostic factors influencing FFS and OS. We feel that patients with PMBCL should be treated with more intensive, but not myeloablative chemotherapy, followed by adjuvant radiotherapy to achieve an improvement in outcome in this setting of patients. Patients with pleural or pericardial effusion are considered at high risk for failure with the actual programs of treatment and probably will be considered for experimental therapeutic approaches.