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This international prospective study showed that maintenance therapy with rituximab was more effective than interferon alfa in prolonging the duration of remission and extending survival in older patients with mantle-cell lymphoma. Patients with mantle-cell lymphoma typically present with extensive disease and involvement of multiple lymph nodes as well as the spleen, bone marrow, blood, and gastrointestinal tract. The median age at diagnosis is about 65 years. 1 , 2 Standard therapy for these patients consists of chemotherapy (e.g., the CHOP regimen, consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone) combined with the anti-CD20 monoclonal antibody rituximab (e.g., R-CHOP). 2 – 4 Only a minority of patients have a complete remission, and relapse or progression usually occurs within 2 to 3 years, resulting in an overall survival of less than 5 years. To improve this grim prognosis, . . .

Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.

This trial compared a combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with CHOP plus rituximab, a monoclonal antibody against a surface protein (CD20) on lymphoma cells, in elderly patients with diffuse large-B-cell lymphoma. As compared with CHOP alone, CHOP plus rituximab had superior results without an increase in toxicity. CHOP plus rituximab had superior results without an increase in toxicity. The results are likely to change the management of diffuse large-B-cell lymphoma. The most frequent type of non-Hodgkin's lymphoma, diffuse large-B-cell lymphoma, accounts for approximately 40 percent of new cases of lymphoma. 1 More than half of patients with diffuse large-B-cell lymphoma are over 60 years of age, 2 – 4 and the treatment of these elderly patients is a difficult challenge. The CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is the standard of care for younger and elderly patients with diffuse large-B-cell lymphoma, 5 but it induces complete responses in only 40 to 50 percent of elderly patients, with three-year event-free and overall survival rates of 30 percent and 35 to 40 percent, respectively. 6 Attempts . . .

This investigation of the treatment of multiple myeloma compared one cycle of high-dose chemotherapy plus a single autologous stem-cell transplantation with two cycles of high-dose chemotherapy, each followed by stem-cell transplantation. The double-transplantation regimen had a substantial survival benefit. Survival benefits, especially for younger patients. The failure of conventional chemotherapy to improve the outlook in multiple myeloma 1 has led to the treatment of this disease with high-dose chemotherapy plus autologous stem-cell transplantation. Promising results have been obtained in pilot studies, 2 , 3 and randomized trials comparing autologous stem-cell transplantation with conventional chemotherapy in patients with newly diagnosed myeloma have been reported. 4 – 8 These studies demonstrated the superiority of autologous stem-cell transplantation over conventional treatment in terms of the response rate and event-free survival, but the effects on overall survival were unclear. A survival benefit was observed in French and British trials, 4 , 5 but not in others, . . .

Allo-SCT is regularly performed in advanced lymphoma. Haploidentical family donors are a valuable source of hematopoietic stem cells and transplants from these donors, using T-repleted grafts, has recently been successfully reported. We report on 49 patients with refractory lymphoma who received T-repleted haploidentical SCT with a non-myeloablative regimen and post-transplant CY. The median time to recover ANC >0.5 × 10e9/L and transfusion independent plt count >20 × 10e9/L was 20 days (range 14–38) and 26 days (range 14–395). The probability to reach ANC >0.5 × 10e9/L at 30 days was 87% and transfusion independent plt count >20 × 10e9/L at 100 days was 87%. The cumulative incidence of grade 2–4 acute GVHD (aGVHD) was 25.6% (95% confidence interval (CI): 12.9–38.3%) and the cumulative incidence of chronic GVHD (cGVHD) was 5.2% (95% CI: 0–12.4%). The median follow-up is 20.6 months (range 12–54), and the projected 2-year OS and PFS were 71 and 63%. The relapse rate was 18.7% (95% CI: 7.6–29.8%) and the median time to relapse was 4.4 months (range 1.1–8.3). At 2 years, cumulative incidence of NRM was 16.3% (95% CI: 5.9–26.8%). T-repleted Haploidentical transplantation with post-infusion CY is a feasible and effective therapy in the poor prognosis of advanced lymphoma patients.

We investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. At 100 days, the cumulative incidence of grades 2–3 and grades 3–4 acute GVHD was 23% and 4%, respectively. The chronic GVHD (cGVHD) cumulative incidence was 16%, with one patient experiencing severe cGVHD. The 3-year OS, PFS, relapse rates and 1-year non-relapse mortality (NRM) were 63%, 59%, 21% and 20%, respectively. Uncontrolled disease status and high hematopoietic cell transplantation comorbidity index (HCT-CI) were associated with lower OS, whereas PBSC was an independent protective factor. Uncontrolled disease and HCT-CI >2 was predictive for NRM. Finally, disease status other than CR was predictive of relapse. In conclusion, haplo-HSCT is a valid treatment in advanced HL, offering excellent rates of survival and acceptable toxicities.

Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.

Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II–IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II–IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Of 497 patients (median age 55 years [IQR 49–60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6·1 years (95% CI 5·4–6·4), time to treatment failure was significantly longer in the cytarabine group (median 9·1 years [95% CI 6·3–not reached], 5 year rate 65% [95% CI 57–71]) than in the control group (3·9 years [3·2–4·4], 40% [33–46]; hazard ratio 0·56; p=0·038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3·4%]) in both groups. Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma. European Commission, Lymphoma Research Foundation, and Roche.