No abstract

No abstract

The incidence of CNS relapse in 1693 patients treated for aggressive lymphomas on DSHNHL protocols from 1990 to 2000 was low (2.2%), although CNS prophylaxis was administered to <5% of patients. Thus, a general prophylaxis for all patients is not warranted, the less so since the effectiveness of i.th. prophylaxis itself is judged controversially. Increased LDH and involvement of more than one extranodal site were confirmed as independent risk factors. A cumulative 20% incidence of CNS disease in certain prognostic subgroups of elderly patients may render these candidates for i.th. prophylaxis; however, this approach would imply a potential overtreatment of approximately 80% of these patients deemed at high risk.

No abstract

In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.

Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis, however the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adult AML patients recruited into Study Alliance Leukemia trials to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%), 131 CEBPAbi and 109 CEBPAsm (60 affecting the amino-terminal transactivation domains (CEBPAsmTAD) and 49 the carboxy-terminal DNA-binding or basic leucine zipper region (CEBPAsmbZIP)). Interestingly, CEBPAbi and CEBPAsmbZIP patients shared several clinical factors, i.e. were significantly younger (median 46 years and 50 years) and had higher WBC counts at diagnosis (median 23.7 and 35.7 109/l) compared to CEBPAsmTAD patients (median age 63 yrs., median WBC 13.1 109/l; p&lt;.001). Co-mutations were also similar in both groups, e.g. GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs. 6.7% CEBPAsmTAD; p&lt;.001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs. 38.3% CEBPAsmTAD; p&lt;.001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (median OS: 103 and 63 vs. 13 months) and event-free survival (median EFS: 20.7 and 17.1 vs. 5.7 months), in univariate and multivariable analyses. More detailed analysis revealed that the clinical and molecular features as well as the favorable survival were confined to patients showing in-frame mutations in bZIP (CEBPAbZIP-inf). When grouping patients into CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and other non-CEBPAbZIP-inf patients), only CEBPAbZIP-inf patients showed superior CR rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutations.

In fit patients with newly diagnosed acute myeloid leukemia (AML), immediate treatment start is recommended due to the poor prognosis of untreated acute leukemia. We explored the relationship between the time from diagnosis to treatment start (TDT) and prognosis in a large set of real-world data from the German SAL-AML registry. All registered non-APL patients from the registry with intensive induction treatment and a minimum follow-up time of 12 months were selected (n=2,263). We analyzed the influence of TDT on remission, early death and overall survival (OS) in univariable analyses for each day of treatment delay, in groups of 0-5, 6-10, 11-15 and &gt;15 days of TDT, and adjusted for the influence of established prognostic variables on the outcomes. The median TDT was 3 days (IQR 2-7). The unadjusted 2-y OS rates stratified by TDT of 0-5, 6-10, 11-15, &gt;15 days were 51, 48, 44, and 50% (p=0.211). In multivariable Cox regression analysis accounting for established prognostic variables, the HR for TDT as continuous variable was 1.00 (p=0.617). When OS was analyzed separately stratified for age ≤60 and &gt;60 ys and for high versus lower initial WBC, no significant differences between TDT groups were observed. Our study suggests that TDT is not related to survival. As treatment stratification in intensive first-line treatment of AML evolves, the TDT data suggests that it may be a feasible approach to wait for genetic and other laboratory test results in order to assign clinically stable patients to the best available treatment option.

Female gender is a significant independent favorable prognostic factor in lung cancer. To study the possible role of sex hormones in lung cancer, the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry, ligand-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation, NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in 13 and androgen receptor in I2 out of 17 cases examined; sex-steroidreceptor expression was virtually absent in SCLC cell lines. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochernistry. Among patients with primary lung-cancer sex-steroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of I6 cases, vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. lmmunohistology is a feasible method of studying steroid-receptor expression in lung cancer.o 1996 Wiley-Lhs, Inc.Analyses of large clinical trials have shown that female gender is a significant independent favorable prognostic factor in small-cell lung cancer (Albain et al., 1990;Johnson et al., 1988). Further multivariate analysis of a German multicenter study comprising 766 patients revealed significance only for women under the age of 60 years (Wolf et al., 1991). Two studies of patients with unresectable non-small-cell lung cancer who were treated with chemotherapy also showed a longer survival rate for women (O'Connell et al., 1986;Finkelstein et al., 1986).To determine the influence and possible therapeutical value of sex hormones in lung cancer, we decided to study the expression of their receptors in lung-cancer cell lines and tumor biopsies, since these are a prerequisite for steroid action. There are basically 3 methods for the detection of steroid-hormone receptors: gene expression, binding assays and immunohistochemistry. The gene expression of receptors has not been investigated in lung cancer so far. Binding assays which use radioactive ligands in whole-cell or cytosolic assays are the standard method for studying receptor expression. Immunohistochemistry uses monoclonal antibodies and has been well established for the detection of estrogen receptors and progesterone receptors in breast cancer. Numerous studies have shown a close correlation between immunocytochemical methods and binding assays in mammary carcinoma (Charpin et UL, 1986).The diagnosis of lung cancer is made predominantly on small bronchoscopic biopsies or cytological specimens. Therefore binding assays for which large amounts of fresh tissue have to be provided cannot readily be performed. Immunohistochemistry may overcome this problem, since this method ...