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Relapse kinetics in acute myeloid leukaemias with MLL translocations or partial tandem duplications within the MLL gene
Author(s) -
Ommen Hans B.,
Hokland Peter,
Haferlach Torsten,
Abildgaard Lotte,
Alpermann Tamara,
Haferlach Claudia,
Kern Wolfgang,
Schnittger Susanne
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12792
Subject(s) - chromosomal translocation , oncology , medicine , immunology , biology , gastroenterology , genetics , gene
Summary Correct action upon re‐emergence of minimal residual disease in acute myeloid leukaemia ( AML ) patients has not yet been established. The applicability of demethylating agents and use of allogeneic stem cell transplantation will be dependent on pre‐relapse AML growth rates. We here delineate molecular growth kinetics of AML harbouring MLL partial tandem duplication ( MLL ‐ PTD ; 37 cases) compared to those harbouring MLL translocations (43 cases). The kinetics of MLL ‐ PTD relapses was both significantly slower than those of MLL translocation positive ones (median doubling time: MLL ‐ PTD : 24 d, MLL ‐ translocations: 12 d, P = 0·015, Wilcoxon rank sum test), and displayed greater variation depending on additional mutations. Thus, MLL ‐ PTD + cases with additional RUNX 1 mutations or FLT 3 ‐internal tandem duplication relapsed significantly faster than cases without one of those two mutations (Wilcoxon rank sum test, P = 0·042). As rapid relapses occurred in all MLL subgroups, frequent sampling are necessary to obtain acceptable relapse detection rates and times from molecular relapse to haematological relapse (blood sampling every second month: MLL ‐ PTD : 75%/50 d; MLL translocations: 85%/25 d). In conclusion, in this cohort relapse kinetics is heavily dependent on AML subtype as well as additional genetic aberrations, with possibly great consequences for the rational choice of pre‐emptive therapies.