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The Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research (HOVON-SAKK) collaborative study group evaluated outcome of patients (pts) with acute myeloid leukemia (AML) in first remission (CR1) entered in 3 consecutive studies according to a donor versus no-donor comparison. Between 1987 and 2004, 2287 pts were entered in these studies of whom 1032 pts (45%) without FAB M3 or t(15;17) were in CR1 after 2 cycles of chemotherapy, received consolidation treatment, and were younger than 55 years of age and therefore eligible for allogeneic hematopoietic stem cell transplantation (allo-SCT). An HLA-identical sibling donor was available for 326 pts (32%), whereas 599 pts (58%) lacked such a donor, and information was not available in 107 pts. Compliance with allo-SCT was 82% (268 of 326). Cumulative incidences of relapse were, respectively, 32% versus 59% for pts with versus those without a donor (P < .001). Despite more treatmentrelated mortality (TRM) in the donor group (21% versus 4%, P < .001), disease-free survival (DFS) appeared significantly better in the donor group (48% ؎ 3% versus 37% ؎ 2% in the no-donor group, P < .001). Following risk-group analysis, DFS was significantly better for pts with a donor and an intermediate-(P ‫؍‬ .01) or poor-risk profile (P ‫؍‬ .003) and also better in pts younger than 40 years of age (P < .001). We evaluated our results and those of the previous MRC, BGMT, and EORTC studies in a meta-analysis, which revealed a significant benefit of 12% in overall survival (OS) by donor availability for all patients with AML in CR1 without a favorable cytogenetic profile. (Blood.

Inactivation of the tumour suppressor p53 is the most common defect in cancer cells. p53 is a sequence specific transcription factor that is activated in response to various forms of genotoxic stress to induce cell cycle arrest and apoptosis. Induction of p53 is subjected to complex and strict control through several pathways, as it will often determine cellular fate. The p73 protein shares strong structural and functional similarities with p53 such as the potential to activate p53 responsive genes and the ability to induce apoptosis. In addition to alternative splicing at the carboxyl terminus which yields several p73 isoforms, a p73 variant lacking the Nterminal transactivation domain (DNp73) was described in mice. In this study, we report the cloning and characterisation of the human DNp73 isoforms, their regulation by p53 and their possible role in carcinogenesis. As in mice, human DNp73 lacks the transactivation domain and starts with an alternative exon (exon 3'). Its expression is driven by a second promoter located in a genomic region upstream of this exon, supporting the idea of two independently regulated proteins, derived from the same gene. As anticipated, DNp73 is capable of regulating TAp73 and p53 function since it is able to block their transactivation activity and their ability to induce apoptosis. Interestingly, expression of the DNp73 is strongly upregulated by the TA isoforms and by p53, thus creating a feedback loop that tightly regulates the function of TAp73 and more importantly of p53. The regulation of DNp73 is exerted through a p53 responsive element located on the DN promoter. Expression of DNp73 not only regulates the function of p53 and TAp73 but also shuts off its own expression, once again finely regulating the whole system. Our data also suggest that increased expression of DNp73, functionally inactivating p53, could be involved in tumorogenesis. An extensive analysis of the expression pattern of DNp73 in primary tumours would clarify this issue. Cell Death and Differentiation (2001) 8, 1213 ± 1223.

The potential benefits of extended rituximab treatment have been investigated in a randomized trial comparing the standard schedule with prolonged treatment in 202 patients with newly diagnosed or refractory/relapsed follicular lymphoma (FL). All patients received standard treatment (rituximab 375 mg/m 2 weekly ؋ 4). In 185 evaluable patients, the overall response rate was 67% in chemotherapynaive patients and 46% in pretreated cases (P < .01). Patients responding or with stable disease at week 12 (n ‫؍‬ 151) were randomized to no further treatment

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Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

Purpose: The recognition of a number of leukemiaspecific cytogenetic abnormalities and their role as independent prognostic factors have provided considerable insights into leukemia pathogenesis and have paved the way to adopt risk-adapted treatment. However, f 50% of newly diagnosed acute myeloid leukemia (AML) have a normal karyotype. There has therefore been much interest in identifying molecular markers that could help to improve the prognostic stratification of patients with normal-karyotype AML.Experimental Design: Consecutive untreated AML patients (n = 67) from a single institution all with normal karyotype were analyzed for the presence of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/ enhancer binding protein-A), for internal tandem duplications (ITD) of the tyrosine kinase receptor gene FLT3 (for fms-like tyrosine kinase 3), and for expression of the BAALC gene (for brain and acute leukemia, cytoplasmic).Results: 17.9% of normal-karyotype AML had mutations in the CEBPA gene, and 28.4% had FLT3-ITD; 65.7% (44 of 67) had high BAALC expression and 34.3% (23 of 67) had low BAALC expression. Patients with CEBPA mutations had a very favorable course of their disease. Median diseasefree survival (DFS) and overall survival (OS) were 33.5 and 45.5 months, respectively, compared with 10 (e.g., 12 months in patients without CEBPA mutations; P = 0.0017; P = 0.0007). AML patients with FLT3-ITD had significantly shorter median DFS (P = 0.0328) and OS (P = 0.0148) than patients without FLT3-ITD. High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations. We found that high BAALC expression in normalkaryotype AML with neither FLT3-ITD nor CEBPA mutations (18 of 67) indicates adverse prognosis for both DFS and OS (P = 0.0001; e.g., P = 0.0001) compared with the group with low BAALC expression and absent FLT3-ITD and CEBPA mutations (18 of 67). Thus, BAALC expression represents a novel prognostic marker particularly for normal-karyotype AML patients with neither FLT3-ITD nor CEBPA mutations.Conclusions: Assessment of CEBPA mutations, FLT3-ITD, and BAALC expression permits to split normalkaryotype AML into clinically distinct subgroups.