title: The kinetics of relapse in DEK-NUP214-positive acute myeloid leukemia patients.
abstract: Preemptive treatment of relapse of acute myeloid leukemia (AML) holds the promise to improve the prognosis of this currently highly lethal condition. Proposed treatment modalities applicable in preemptive cytoreduction (e.g., demethylating agents or standard chemotherapy) differ substantially in interval from administration to antileukemic effect. The t(6;9) balanced translocation, producing the DEK-NUP214 fusion protein, is seen in only 1% of patients with AML. We hypothesized that in these patients, who relapse with a very high frequency, a more detailed knowledge of leukemic relapse growth kinetics would improve the personalized decision-making regarding re-administration of chemotherapy. Based on standardized quantitative PCR data, we therefore delineated the relapse kinetics in a cohort of 27 relapsing DEK-NUP214-positive patients treated in four different European countries. The prerelapse leukemic burden increased with a median doubling time of 13 d (range: 5-51 d, median: 0.71 logs/month, range: 0.18-1.91 logs/month), with FLT3-ITD-positive patients relapsing significantly faster than FLT3-ITD-negative ones (median: 0.9 vs. 0.6 logs/month, Wilcoxon rank sum test, P = 0.041). Peripheral blood and bone marrow were equally useful for minimal residual disease (MRD) detection, and thus, we found that with sampling intervals of 2 months, 94% of relapses would be detected with a median time from MRD detection to hematological relapse of 64 d. In conclusion, this data provide algorithms for handling the rare patients with DEK-NUP214-positive AML allowing for planning of both MRD follow-up and, upon molecular relapse, the timing of cytoreduction or possibly transplant procedures.
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans B
authors.initials: HB
authors.lastname: Ommen
authors.affiliation: Department of Hematology and CNRS UMR 8147, Hôpital Necker-Enfants-Malades, AP-HP, Université Paris 5 Descartes, Paris, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Touzart
authors.affiliation: Department of Hematology and CNRS UMR 8147, Hôpital Necker-Enfants-Malades, AP-HP, Université Paris 5 Descartes, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: MacIntyre
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.affiliation: Molecular Oncology Unit, Guy's Hospital, London, UK.
authors.forename: Khalid
authors.initials: K
authors.lastname: Tobal
authors.affiliation: Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics / Q000378:metabolism; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D012008:Recurrence; D015996:Survival Rate; D014178:Translocation, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D000075223:Poly-ADP-Ribose Binding Proteins
keywords: DEK-NUP214; minimal residual disease; preemptive treatment; relapse kinetics