A TaqMan low-density array to predict outcome in advanced Hodgkin's lymphoma using paraffin-embedded samples.

PURPOSE: Despite major advances in the treatment of classic Hodgkin's lymphoma (cHL), approximately 30% of patients in advanced stages may eventually die as result of the disease, and current methods to predict prognosis are rather unreliable. Thus, the application of robust techniques for the identification of biomarkers associated with treatment response is essential if new predictive tools are to be developed. EXPERIMENTAL DESIGN: We used gene expression data from advanced cHL patients to identify transcriptional patterns from the tumoral cells and their nonneoplastic microenvironment, associated with lack of maintained treatment response. Gene-Set Enrichment Analysis was used to identify functional pathways associated with unfavorable outcome that were significantly enriched in either the Hodgkin's and Reed-Sternberg cells (regulation of the G2-M checkpoint, chaperones, histone modification, and signaling pathways) or the reactive cell microenvironment (mainly represented by specific T-cell populations and macrophage activation markers). RESULTS: To explore the pathways identified previously, we used a series of 52 formalin-fixed paraffin-embedded advanced cHL samples and designed a real-time PCR-based low-density array that included the most relevant genes. A large majority of the samples (82.7%) and all selected genes were analyzed successfully with this approach. CONCLUSIONS: The results of this assay can be combined in a single risk score integrating these biological pathways associated with treatment response and eventually used in a larger series to develop a new molecular outcome predictor for advanced cHL.

Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 Trial.

PURPOSE: The optimal postremission therapy for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is not well established. This randomized trial compared three options of postremission therapy: chemotherapy and allogeneic or autologous stem-cell transplantation (SCT). PATIENTS AND METHODS: All 106 VHR-ALL patients received induction with five drugs followed by intensification with three cycles of chemotherapy. Patients in complete remission (CR) with an HLA-identical family donor were assigned to allogeneic SCT (n = 24) and the remaining were randomly assigned to autologous SCT (n = 38) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n = 38). RESULTS: Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5-year disease-free survival (DFS) and overall survival (OS) probabilities were 45% (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups were comparable in the main pretreatment ALL characteristics. Intention-to-treat analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27% to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI, 43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS: 44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v 57%; 95% CI, 43% to 73%). No differences were found within the different subgroups of ALL and neither were differences observed when the analysis was made by treatment actually performed. CONCLUSION: This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in children with VHR-ALL.