Search

Maintenance treatment for patients with acute myeloid leukemia (AML) in remission has recently been controversially discussed and even abandoned by several groups. An analysis of 16 published multicenter trials, however, revealed the highest probabilities of relapse free survival (RFS) in the range of 35-42 % at 4-5 years only in patients assigned to maintenance treatment when adult age and intent-to-treat conditions were considered. After having demonstrated a superior RFS from 3 year maintenance following standard dose consolidation over that from consolidation alone (p

Intensive induction therapy-in acute myeloid leukemia (AML), as in some other systemic malignancies- is a strategy fundamentally different from post-remission strategies. Approaches like consolidation treatment, prolonged mainte¬nance, and autologous or allogeneic transplantation in the first remission are directed against minimal residual disease with a malignant cell population having survived the induction treatment. In contrast, induction therapy deals with naive tumor cells possibly different in their sensitivity from their counterparts in remission. Therefore, in AML it has been suggested to introduce intensification strategies into the induction part of treatment as a new step after the preceding intensification steps in the post-remission part. As expected from the dose effects observed in post-remission treatment using more AraC or longer treatment, similar dose effects have been found in the induction treatment both by the incorporation of high-dose AraC and by the double induction strategy administered in patients up to 60 years of age. For example, patients with poor risk AML due to an unfavorable karyotype, high LDH in serum, or delayed response, benefited from double induction containing high-dose AraC by a longer survival as compared to that from standard dose AraC. A corresponding dose effect in the induction treatment has been found in patients of 60 years and older receiving daunorubicin 60 vs 30 mg/m2 as part of the TAD regimen with higher dosage. This treatment significantly increased the response and survival rate in older patients who represented a poor risk group as a whole. Thus, we could demonstrate, both in younger and older patients, that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits a cumulative toxicity in that a repetition of courses containing high-dose AraC in the post-remission period is associated with considerable myelotoxicity leading to longlasting aplasias of about 6 weeks. However, after intensive induction treatment, high-dose chemotherapy in remission may become practicable using autologous stem cell rescue and may contribute to a further improvement of the outcome in poor risk as well as average patients with AML. These approaches are currently investigated by the German AMLCG. While there are clear limitations in the intensity of antineoplastic treatment for AML, as for other systemic malignancies, some further intensification may be possible and effective.

NPM1 mutations represent frequent genetic alterations in patients with acute myeloid leukemia (AML) associated with a favorable prognosis. Different types of NPM1 mutations have been described. The purpose of our study was to evaluate the relevance of different NPM1 mutation types with regard to clinical outcome. Our analyses were based on 349 NPM1-mutated AML patients treated in the AMLCG99 trial. Complete remission rates, overall survival and relapse-free survival were not significantly different between patients with NPM1 type A or rare type mutations. The NPM1 mutation type does not seem to play a role in risk stratification of cytogenetically normal AML.

The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany.500 patients (235 males, median age 64[IQR 54-73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29-41%] vs. 20.7%[95%CI 15-26%], p

Background Allogeneic hematopoietic cell transplantation is considered the preferred post-remission therapy in patients with acute myeloid leukemia cytogenetically defined as being at high risk. To substantiate evidence for allogeneic hematopoietic cell transplantation in first complete remission in these high-risk patients we performed a landmark analysis within a single prospective multicenter treatment trial.Design and Methods By the time of analysis, 2,347 patients had been accrued into the AMLCG 99 trial between 1999 – 2007. Out of this population, 243 patients under 60 years old fulfilled the criteria for high-risk cytogenetics. Landmark analyses were performed with a control cohort, who remained in first complete remission at least the median time from complete remission to transplantation in the intervention group.Results After standardized induction therapy, 111 patients under 60 years old achieved complete remission. A matched allogeneic donor was identified for 59 patients (30 sibling donors, 29 unrelated donors). Fifty-five patients received an allogeneic hematopoietic cell transplant after a median time of 88 days in first complete remission. Of the remaining 56 patients, 21 relapsed within 90 days after achieving first complete remission and for 7 patients with relevant comorbidities no donors search was initiated, leaving 28 patients given conventional post-remission therapy as the control cohort. The median follow-up of surviving patients was 60.4 months. Patients with an allogeneic donor had substantially better 5-year overall and relapse-free survival rates than the control group (48% versus 18%, P=0.004 and 39% versus 10%, P