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)
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