Search

Summary: This study compared decitabine exposure when administered IV (DEC‐IV) at a dose of 20 mg/m2 for 5‐days with orally administered decitabine with cedazuridine (DEC‐C), as well as the clinical efficacy and safety of DEC‐C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC‐IV or oral DEC‐C (days 1–5 in a 28‐day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC‐C for subsequent treatment cycles until treatment discontinuation. Equivalent systemic decitabine exposures were demonstrated (5‐day area under the curve ratio between the two decitabine formulations of 99.64 [90% confidence interval 91.23%, 108.80%]). Demethylation rates also were similar (≤1.1% difference). Median overall survival (OS), clinical response and safety profile with oral DEC‐C were consistent with those previously observed with DEC‐IV. Next‐generation sequencing was performed to identify molecular abnormalities that impact OS and TP53 mutations were associated with a poor outcome. These findings support the use of oral DEC‐C in patients with AML. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss their retrospective analysis of the effects of centralised care of younger patients with acute myeloid leukaemia (AML) in the U.S. and Czech Republic. Other topics include the data on early mortality following allogeneic transplantation of haematopoietic stem cells (HSCT), and the complete remission (CR) rate following induction chemotherapy.

Loss of heterozygosity is considered to be the most common type of tumour‐specific somatic mutation of the human leucocyte antigens (HLA) genes in patients with haematological malignancies. Nevertheless, subtle DNA sequence changes, namely short insertions/deletions, may also abolish the expression of HLA molecules and interfere with routine HLA typing. Two male patients with acute myelogenous leukaemia (AML) were indicated for the search of a suitable donor for allogeneic haematopoietic stem cell transplantation (aHSCT). The patients and their relatives were initially HLA typed by serological and DNA techniques at a low‐resolution level. The HLA high‐resolution (HR) type was obtained by means of sequencing‐based typing (SBT). In both cases, anomalous frameshifts in the sequence were observed in the HLA‐B gene, namely in exon 3 (Case 1, heterozygous deletion of two bases) and exon 4 (Case 2, heterozygous insertion of two bases). In the second case, the insertion variant was associated with a loss of HLA‐B8 expression. To reveal whether these sequence patterns may be caused by somatic mutations in the malignant cells, blood sample in remission (Case 1) and buccal swab sample (Case 2) were collected from the patients. In an important manner, the SBT in these germline samples revealed common HLA‐B*07:02,*15:01 (Case 1) and HLA‐B*08:01,*35:02 (Case 2) types with no evidence for the sequence alteration observed in the initial samples. In conclusion, the insertion/deletion sequence variants of the HLA‐B gene in two patients were limited to the initial blood samples with a substantial proportion of AML cells and thus may be attributed to the somatic mutation in the malignant cells. HLA somatic mutations should be taken into account in patients with haematological malignancies to prevent HLA mistyping and inappropriate selection of an aHSCT donor. [ABSTRACT FROM AUTHOR]