BioOncology Watch Timely Information for Practicing Physicians
august 2002 Non-Hodgkin's Lymphoma (NHL) Ibritumomab tiuxetan radioimmunotherapy. Gregory Wiseman et al. conducted a multicenter phase II study in which 30 mildly thrombocytopenic (100-149 x 10^9/L) patients with relapsed or refractory low-grade NHL were treated with a reduced dose of ^90Y ibritumomab tiuxetan (0.3 instead of 0.4 mCi/kg). Grade 4 hematologic toxicity was observed, but it was transient and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. The overall response rate was 83% with an estimated median time to progression of 9.4 months (range, 1.7-24.6 months). These results demonstrate that a reduced dose of ^90Y ibritumomab tiuxetan is well tolerated and has significant clinical activity in thrombocytopenic patients with relapsed or refractory low-grade NHL. (Wiseman GA, et al. Blood 2002;99:4336-4342) Molecular profiling. Andreas Rosenwald and colleagues retrospectively reviewed tumor biopsy specimens and clinical data from 240 patients with previously untreated diffuse large B-cell lymphoma (DLBCL). All patients had received prior anthracycline-based chemotherapy. Lymphochip DNA microarrays were used to quantitate the expression of messenger RNA in the lymphomas. Hierarchical clustering grouped the DLBCLs into 3 large subgroups: germinal-center B-cell-like; activated B-cell-like; and type 3 DLBCL. Bcl-2 translocation and c-rel amplification were detected in only the germinal-center B-cell-like subgroup and patients in this subgroup had the greatest 5-year survival rate (60% vs. 35% vs. 39%; p<0.001). Four gene-expression signatures (comprising 16 genes; 3 germinal center B-cell genes, 4 MHC class II genes, 6 lymph-node genes, and 3 proliferation genes) were found to predict survival. BMP6 was the only individual gene found to increase the predictive value for survival of the 4 gene-expression signatures. Thus, these 17 genes were used to construct a predictor of overall survival after chemotherapy, and this gene-based tool and the standard international prognostic index were found to be independent prognostic indicators. This study shows that DNA microarrays can be used to formulate molecular predictors of survival. (Rosenwald A, et al. N Eng J Med 2002;346:1937-1947) Epstein-Bar Virus-Lymphoproliferative Disease (EBV-LPD) Preemptive rituximab. Joost van Esser and colleagues recently monitored 49 recipients of TCD allogeneic SCT for EBV reactivation and treated 15 of these patients who showed EBV reactivation to ³1000 geq/mL with a single infusion of rituximab (375 mg/m^2). Fourteen patients had a complete clearance of EBV-DNA from plasma in a median of 8 days (range, 1-46 days). One patient developed EBV-LPD but achieved a complete remission after further rituximab and donor lymphocyte infusions. Comparison with historical controls (n=26) demonstrated a decrease in EBV-LPD-related mortality at 6 months with preemptive rituximab therapy (0% vs. 26% ±10%; p=0.04). These preliminary findings show that rituximab is an effective treatment for the prevention of EBV-LPD-related mortality in high-risk patients. (van Esser JWJ, et al. Blood 2002;99:4364-4369) Relapsed Chronic Myelogenous Leukemia (CML) Donor lymphocyte infusion (DLI). Cesare Guglielmi and investigators with the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation retrospectively analyzed data from 298 relapsed CML patients treated at 51 centers with DLI and found a lower ICD to be associated with improved outcomes. Patients who received £0.2 x 10^8 mononuclear cells/kg, compared to those who received either >0.2 to 2.0 or >2.0 x 10^8 mononuclear cells/kg, had less myelosuppression (p=0.01) and less graft versus host disease (p<0.001) while achieving a similar response rate. These results translated to a greater 3-year survival rate (84% vs. 63% vs. 58%) and a lower DLI-related mortality rate (5% vs. 20% vs. 22%) for patients receiving the lower ICD. The data suggest that the first DLI cell dose should not exceed 0.2 x 10^8 mononuclear cells/kg. (Gugliemi C, et al. Blood 2002;100:397-405) Idiopathic Thrombocytopenia (ITP) Effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Shosaku Nomura and coworkers report the treatment of 4 patients with ITP refractory to standard therapy (platelet count <30 x 10^9/L) with PEG-rHuMGDF 0.5 ug/kg/day intravenously for up to 7 days. Platelet counts were increased in 3 patients. In addition, reticulated (indicating newly produced) platelets were observed resulting in decreased bleeding episodes even in patients for whom platelet counts remained low. Two patients developed thrombocytosis (platelet count >700 x 10^9/L) a week after the last administration of PEG-rHuMGDF. Platelet counts returned to baseline levels within 4-6 weeks in all cases. These very early results suggest that PEG-rHuMGDF may be an effective therapy for patients with ITP. Further clinical studies are needed. (Nomura S, et al. Blood 2002;100:728-730) Cytomegalovirus (CMV) Infection Role of Campath-1H. Suparno Chakrabarti and colleagues used PCR-based assays in a multicenter study to monitor the incidence and pattern of CMV infection in 101 patients undergoing nonmyeloablative conditioning containing Campath-1H. CMV infection occurred in 51 patients (50%) at a median of 27 days after SCT. The median time to CD4+ T-cell count >200/uL was 9 months in the 48 patients tested and a low CD4+ T-cell count at 3 months was found to be a risk factor for late recurrence of CMV infection. The results demonstrate an association of Campath-1H treatment with prolonged immune deficiency and a high incidence of CMV infection. (Chakrabarti S, et al. Blood 2002;99:4357-4363)
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