Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia—a phase 3 study

Abstract

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = “dose-dense”) and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = “standard”). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184). The primary endpoint overall response rate (ORR) consisting of complete remission (CR) and incomplete remission (CRi) was not significantly different (P = 0.202) between S-HAM (77%) and double induction (72%). The median overall survival was 35 months after S-HAM and 25 months after double induction (P = 0.323). Duration of critical leukopenia was significantly reduced after S-HAM (median 29 days) versus double induction (median 44 days)—P < 0.001. This translated into a significantly shortened duration of hospitalization after S-HAM (median 37 days) as compared to standard induction (median 49 days)—P < 0.001. In conclusion, dose-dense induction therapy with the S-HAM regimen shows favorable trends but no significant differences in ORR and OS compared to standard double induction. S-HAM significantly shortens critical leukopenia and the duration of hospitalization by 2 weeks.

Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia

“…Our study included a total of 1116 previously untreated adult AML patients who had been enrolled on two subsequent multicenter phase III trials of the German AML Cooperative Group (AMLCG-1999, clinicaltrials.gov identifier NCT00266136, n = 857; and AMLCG-2008, NCT01382147, n = 259) [7][8][9]. Treatment regimens are summarized in the Supplementary Methods and Supplementary Fig.…”

Clinical and molecular relevance of genetic variants in the non-coding transcriptome of patients with cytogenetically normal acute myeloid leukemia

“…To examine whether our findings were reproducible in an independent cohort of CN-AML patients, we examined patients treated on AMLCG protocols, 38,39 who had available clinical outcome data, and were analyzed with poly-A selected RNAseq (n=135). As was the case with the TCGA dataset, 8 the use of an alternative RNA sequencing technique limited the number of lncRNA variants that could be detected and analyzed.…”

“…Confirmatory analyses were conducted in a set of 135 CN-AML patients (75 of whom were younger than 60 years and 60 were older) enrolled on clinical trials of the German AML Cooperative Group (AMLCG). 38,39 All patients provided written informed consent regarding the research use of their specimens. All study protocols were in accordance with the Declaration of Helsinki and approved by Institutional Review Boards at each center.…”

“…31, [41][42][43] Molecular and cytogenetic profiling of the AMLCG cohort were obtained as described previously. 38,39 Transcriptome analyses RNA samples of the patients treated on CALGB/Alliance protocols were analyzed with total RNA Seq after depletion of ribosomal and mitochondrial RNA using the Illumina HiSeq 2500 platform. The results of the RNA Seq analysis have been deposited in the functional genomics data repository GEO and are publicly available under the accession number GSE137851.…”

Response assessment in acute myeloid leukemia by flow cytometry supersedes cytomorphology at time of aplasia, amends cases without molecular residual disease marker and serves as an independent prognostic marker at time of aplasia and post-induction

“…4 Remission status is routinely assessed at time of post-induction; however, study groups and the current National Comprehensive Cancer Network guidelines have incorporated even earlier evaluation of treatment response by morphology (most commonly defined as day 14-21 after start of induction therapy) into treatment protocols. [5][6][7] However, the relevance of response assessment by flow cytometry at this time point requires further exploration, since previous reports have given conflicting results. 3,5 We have demonstrated significant correlation of persistent disease with survival using a 3-color panel.…”