MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.

The International Prognostic Index (IPI) identifies poor-and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R ‫؍‬ 0.22, P < .0001) and bcl-2 (R ‫؍‬ 0.14, P ‫؍‬ .0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R ‫؍‬ ؊0.025, P ‫؍‬ .02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk.

We report the outcomes of reduced-intensity allogeneic stem cell transplantation using BEAM-alemtuzumab conditioning (carmustine, etoposide, cytosine arabinoside, melphalan, and alemtuzumab 10 mg/d on days ؊5 to ؊1) in 6 United Kingdom transplant centers. Sixty-five patients with lymphoproliferative diseases underwent sibling (n ‫؍‬ 57) or matched unrelated donor (n ‫؍‬ 8) transplantation. Sustained donor engraftment occurred in 60 (97%) of 62 patients. Of the 56 patients undergoing chimerism studies, 35 (63%) had full donor chimerism. Overall, 73% were in complete remission (CR) after transplantation. At a median follow-up of 1.4 years (range, 0.1-5.6 years), 37 remain alive and in CR. Acute graft-versus-host disease (GVHD) occurred in 11 (17%) of 64, grades I-II only. Estimated 1-year transplantation-related mortality (TRM) was 8% for patients undergoing first transplantation but was significantly worse for those who had previously undergone autologous transplantation. Six patients relapsed (estimated 2-year relapse risk, 20%). Histologic diagnosis (mantle cell lymphoma and high-grade non-Hodgkin lymphoma) and age at transplantation (> 46 years) were significantly associated with higher relapse risk and worse event-free survival. Relapse did not occur in any patient who developed acute or chronic GVHD. This study demonstrates that reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases using a BEAM-alemtuzumab preparative regimen is associated with sustained donor engraftment, a high response rate, minimal toxicity, and a low incidence of GVHD. (Blood. 2004;103: 428-434)

The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior Ctrough levels relative to IV rituximab 375 mg/m2 dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration.

Summary. Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of tumours, varying in clinical features, immunophenotype and cytogenetics. The aim of this study was to investigate the prognostic significance of BCL6 gene rearrangement at the 3q27 locus in patients with primary nodal disease, and to examine interrelationships with immunophenotype and International Prognostic Index (IPI). We have developed a fluorescent in situ hybridization (FISH)-based technique for the retrospective analysis of the effect of BCL6 gene rearrangements on survival, using nuclei extracted from paraffin-embedded tissue. FISH results were obtained in 111 presentation cases of nodal DLBCL. The IPI was calculated and each case was stained immunocytochemically for BCL6, BCL2 and CD10. 3q27 rearrangements were detected in 25% of cases. BCL2 protein and a germinal centre (GC) phenotype (defined as CD10 + , BCL6 + ) were expressed in 56% and 41% of cases respectively. In multivariate analysis, rearrangement of 3q27 and BCL2 expression and the absence of a GC phenotype were associated with a poor prognosis. These factors can be used in conjunction with the IPI to improve risk stratification in nodal DLBCL.

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Summary:We treated 17 patients with refractory (n ¼ 7) or relapsed lymphoid malignancy (n ¼ 10) following allogeneic HSCT with donor lymphocyte infusions (DLI). Patients with lowgrade disease received DLI alone (n ¼ 7) or following radiotherapy (n ¼ 1). Patients with aggressive disease (n ¼ 9) received prior chemotherapy. Nine out of 15 patients receiving DLI from sibling donors responded after one (n ¼ 6), two (n ¼ 2) and three (n ¼ 1) infusions. Both MUD recipients achieved CR after two and three DLI. In all, 10/17 patients achieved CR including 3/4 patients with chronic lymphatic leukaemia (CLL), 4/4 with mantle cell lymphoma (MCL), 3/4 with follicular NHL but 0/5 with aggressive NHL/Richters. The median CD3 cell dose to achieve CR for siblings was 2 Â 10 7 /kg. One patient with CLL had a second transplant following DLI-induced aplasia and is in CR at 14 months giving a final CR rate of 64%. Grade II-IV acute GVHD developed in 45% and chronic GVHD in 8/9 evaluable patients. Of the 11 patients finally achieving CR, one patient with MCL relapsed at 18 months post-DLI but all others remain in remission with a median follow-up of 40 months (range 12-64 months). Low-grade NHL and MCL have a high response rate and sustained remissions following DLI. Aggressive disease responds poorly however, despite pre-DLI chemotherapy.

We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM ( clinicaltrials.gov identifier: 01332968 ), and investigated the effect on early disease progression of the two randomization arms: obinutuzumab-based versus rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post randomization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601) versus rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95%CI: 25.0-61.1%; cumulative incidence rate 10.1% vs . 17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event [HR of time-varying progression status, 25.5 (95%CI: 16.2-40.3)]. Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression versus those without was 12.2 (95%CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progression did not seem to be influenced by treatment arm.