Konference: 2015 57th ASH Annual Meeting - účast ČR
Kategorie: Maligní lymfomy a leukémie
Téma: 618. Acute Lymphoblastic Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Poster
Číslo abstraktu: 1414
Autoři: MUDr. Ester Mejstříková, Ph.D.; Julie Irving; Dr. Leonid Karawajew, p; Marian Case; Jenny Jesson; Prof. Vaskar Saha, PhD, FRCP, FRCPath; Dr. Nicholas Goulden; Dr. Jeremy Hancock, Ph.D.; MD Arend von Stackelberg; Dr. Sarah Lawson; Prof. MD Michael Dworzak; MD Renate Panzer-Grümayer; MD Barbara Buldini; Lisa Eyre; MD Giuseppe Basso; Maddalena Paganin, Ph.D.; Prof.MUDr. Jan Trka, Ph.D.; Mgr. Daniela Kužílková; prof. MUDr. Jan Starý, DrSc.; MUDr. Lucie Šrámková; Doc. MUDr. Ondřej Hrušák, Ph.D.; Dr. Cornelia Eckert, PhD
Thus, prospective MRD quantification of patients entered onto the UKALLR3 and ALL-REZ BFM 2002 clinical trials was performed by a standardised, quality assured, 4-8colour Flow MRD assay in end of re-induction bone marrow aspirates, by laboratories in the IBFM FLOW consortium (n=221). Flow MRD in both treatment protocols was classed as a prospective biological add on study and not used for clinical decision making. Median MRD levels were 0.026 +/-9.9% SD for BFM versus 0.027+/-18% SD for UK protocols, with comparative MRD positivity rates of 45% versus 54%, respectively. Comparison with MRD levels as assessed by molecular analysis of antigen receptor gene rearrangements was performed in 170 samples (BFM,128; UK R3, 42). The Spearman rank correlation of all samples was 0.90 (p<0.0001) for patients treated on the BFM protocol, compared to 0.82 (p<0.0001) for those on UK ALL R3. Risk category concordance was 88% (ALL-REZ BFM) and 88% (UKALLR3). For the 21 discordant samples, 5 were MRD positive by flow but negative by PCR and 17 were negative by flow and positive by PCR. When analysing the accuracy, with which flow MRD classified specimens identically as PCR, the sensitivity of flow MRD in the ALL-REZ BFM protocol was 81% (cut off 0.1% ) and in UK ALL R3 was 79% (cut off 0.01%). Specificity values were 93% versus 100%, respectively.
Although sample processing and quantification of MRD differ between PCR and FC MRD, in both re-induction protocols, there was good correlation of MRD levels assessed by flow cytometry and PCR, validating the use of Flow MRD as a method of choice in patients without PCR targets in the IntReALL trial. Flow MRD also has the advantage of enabling levels of CD22 to be assayed on MRD cells, prior to treatment with Epratuzumab.
This research has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 278514 – IntReALL”, Deutsche Kinderkrebsstiftung for its funding support of the ALL-REZ BFM 2002 clinical trial and the minimal residual disease studies by PCR and the Deutsche Jose Carreras Leukämiestiftung for support of the international principal investigator, Leukaemia and Lymphoma Research and North East Children's Cancer Research Fund, NT 13462-4, NV15-28525A, NV15-26588A, UNCE 204012.
Datum přednesení příspěvku: 5. 12. 2015