Konference: 2007 49th ASH Annual Meeting - účast ČR
Maligní lymfomy a leukémie
Téma: Publikace ve sborníku
Číslo abstraktu: 4356
Autoři: prof. MUDr. Michael Doubek, Ph.D.; MUDr. Ivo Palásek; Pospisil Zdenek; Mgr. Soňa Štruncová; Ing. Dana Dvořáková, CSc.; Mgr. Marek Borský; prof. MUDr. Martin Klabusay, Ph.D.; MUDr. Yvona Brychtová, Ph.D.; Prof. MUDr. Marta Krejčí, Ph.D.; prof. MUDr. Jiří Mayer, CSc.
It seems that the population of leukemia stem
cells (LSCs) have fundamental importance in the origin and
maintenance of the acute myeloid leukaemia (AML). Eradication of
LSCs is a new goal of AML therapy. We hypothesized, that by
monitoring of minimal residual disease (MRD) and its dynamics in
different compartments (peripheral blood, PB; bone marrow, BM;
sorted CD34+ BM cells; and CD34- BM cells) it would be possible to
find some patterns reliably predicting clinical relapse.
To find which compartment is the best for MRD
monitoring and whether it would be possible to treat the disease in
the phase of molecular relapse in order to prevent the
hematological relapse. Methods.
MRD monitoring, in average
once or twice per month, was performed in all phases of treatment,
and was done even more frequently in the cases of unstable MRD. RQ
PCR for fusion transcripts (CBFB/MYH11, RUNX1(AML1)/ETO or fusion
transcripts of MLL gene) and WT1 gene was used. Molecular relapse
was defined as reappearance of the fusion transcript detection or
its 10-fold increase, repeatedly detected. Some patients with
already known MRD dynamics and high probability of imminent
hematological relapse were treated at the time of molecular
In 67 AML patients and 6 healthy
volunteers, 2352 BM or PB samples were examined, including 265
samples from CD34+ BM cells. Follow up was 31-287 weeks (median:
113 w). The correlation between the fusion transcripts levels in BM
and PB was excellent (r=0,9676). The correlation between WT1 PB and
BM levels was far less satisfactory. Since the WT1values did not
mostly reach zero values even if the level of fusion transcript was
0, we wanted to find some normal value for WT1. Using the ROC
curves, however, we were not able to find any WT1 level being a
confidential marker of molecular remission in either compartment
(PB, BM, CD34- or CD34+). In relapsed patients, the time from
molecular to haematological relapse was 8 - 79 days (median: 25 d).
In the cases of subsequent development of haematological relapses,
the levels of fusion transcript in CD34+ BM cells were one order of
magnitude higher than in the BM or PB, even in the case of CD34-
blasts. Nine patients were treated for 17 molecular relapses with
following results: chemotherapy, CR=2, PR=3, NR=1; gemtuzumab
ozogamicin, CR=3, PR=1, NR=3; IL-2DLI, CR=3, NR=1 (PR was defined
as a decrease in fusion transcript level at least 10-fold, CR as a
decrease to 0). Patients with CD33- blasts at diagnosis did not
respond to gentuzumab ozogamicin. Non-responsiveness to one
treatment option did not mean non-responsiveness to another
Frequent quantitative monitoring
(especially in CD34+ BM cells) of fusion transcripts (in contrast
to WT1) is useful for reliable prediction of haematological relapse
in AML patients. PB seems to be sufficient for frequent outpatient
MRD monitoring. Efficient targeting of LSCs will be essential for
AML cure, however, the best method is currently not known. Some now
available procedures are sometimes surprisingly successful.
Supported by Research Grant MSM 0021622430.
Abstract #4356 appears in Blood, Volume 110, issue 11, November 16,
Keywords: Acute Myeloid Leukemia|Molecular Relapse|Treatment.
Disclosure: Research Funding: Supported by Research Grant MSM
0021622430, Czech Republic. .
Off Label Use: Gentuzumab ozogamicin therapy for molecular
relapse of acute myeloid leukemia.
Datum přednesení příspěvku: 8. 12. 2007