Therapy of older persons with acute myeloid leukaemia. (September 2017)

• Record Type: Journal Article
• Authors: Krug, Utz; Gale, Robert Peter; Berdel, Wolfgang E.; Müller-Tidow, Carsten; Stelljes, Matthias; Metzeler, Klaus; Sauerland, M. Cristina; Hiddemann, Wolfgang; Büchner, Thomas
• Is Part Of: Leukemia research. Volume 60(2017:Sep.)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-09
• Subjects: ASXL1 additional sex combs like 1 -- BCOR BCL6 corepressor -- BRAF v-Raf murine sarcoma viral oncogene homolog B -- CEBPA CCAAT/enhancer binding protein alpha -- DNMT3A DNA methyltransferase 3A -- FLT3 fms-like tyrosine kinase -- IDH1/2 isocitrate dehydrogenase 1/2 -- ITD internal tandem duplication -- n.i. not included -- KIT mast/stem cell growth factor receptor -- KRAS kirsten rat sarcoma viral oncogene homolog -- MLL mixed lineage leukemia -- NPM1 nucleophosmin 1 -- n.s. no significant association with prognosis -- NRAS Neuroblastoma rat sarcoma viral oncogene homolog -- PTD partial tandem duplication -- R140/R172 missense mutation in the codons encoding for the arginine residues on position 140/172 of the IDH2 gene -- RAD21 RAD21 cohesin complex component -- RUNX1 runt-related transcription factor 1 -- SF3B1 splicing factor 3b subunit 1 -- SRSF2 serine and srginine rich splicing factor 2 -- STAG2 stromal antigen 2 -- TET2 Tet methylcytosine dioxygenase 2 -- TKD tyrosine kinase domain mutation -- TP53 tumor protein p53 -- U2AF1 U2 small nuclear RNA auxiliary factor 1 -- ZRSR2 zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2; Acute myeloid leukaemia -- Elderly -- Randomization strategies -- Chemotherapy -- Epigenetic strategies -- Transplantation -- Genetics -- Targeted therapies; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2017.05.020
• Languages: English
• ISSNs: 0145-2126

Abstract

Highlights: The randomization strategy in randomized trials depends on the questions to answer. Various intensive and non-intensive therapies exist, each with unsatisfying results. Allotransplant is becoming increasingly feasible in elderly subjects with AML. The genetic and biological risk distribution does not sufficiently explain the age factor in AML. Toxicity can jeopardize the introduction of new compounds in this fragile population. Abstract: Most persons age ≥60 y with acute myeloid leukaemia (AML) die from their disease. When interpreting clinical trials data from these persons one must be aware of substantial selection biases. Randomized trials of post-remission treatments can be performed upfront or after achieving defined landmarks. Both strategies have important limitations. Selection of the appropriate treatment is critical. Age, performance score, co-morbidities and frailty provide useful data to treatment selection. If an intensive remission induction therapy is appropriate, therapy with cytarabine and an anthracycline is the most common regimen. Non-intensive therapies consist of the hypo-methylating drugs azacitidine and decitabine, low-dose cytarabine and supportive care. Feasibility of doing an allotransplant in older persons with AML is increasing. However, only very few qualify. Results of cytogenetic testing are risk factor in young and old persons with AML. Adverse abnormalities are more frequent in older persons. Although data about the frequency of mutations in older persons with AML is increasing their prognostic impact is less clear than in younger subjects. Neither differences in the distribution of cytogenetic risk, mutations, nor differences in clinical risk factors between younger and older persons with AML completely explain the age-dependent outcome. Many drugs are in clinical development in older persons with AML. Their potential role in the treatment of older persons with AML remains to be defined.