J. Jurlander et al., PERSISTENCE OF THE AML1 ETO FUSION TRANSCRIPT IN PATIENTS TREATED WITH ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR T(8-21) LEUKEMIA/, Blood, 88(6), 1996, pp. 2183-2191
The AML1/ETO fusion transcript is expressed in virtually all patients
with t(8;21)(q22;q22) acute myeloid leukemia (AML). The fusion transcr
ipt can be detected by reverse transcription-polymerase chain reaction
(RT-PCR) in most of these patients in long-term complete remission (C
R) following conventional chemotherapy or autologous bone marrow trans
plantation (BMT). However, AML1/ETO expression has mot been analyzed i
n a series of patients following allogeneic BMT. We examined CR bone m
arrow (BM) samples and, in some cases, blood samples from 10 patients
with t(8;21) leukemia who underwent allogeneic BMT in either first or
second remission or first or second relapse. A variety of myeloablativ
e regimens were used. Eight patients received non-T-cell depleted BM f
rom matched sibling donors, one patient received a T-cell depleted hap
loidentical BM, and one patient received a non-T-cell depleted BM from
a matched unrelated donor (MUD). Five patients developed acute and/or
chronic graft versus host disease (GVHD). The furthest time points an
alyzed for the AML1/ETO transcript in the 10 patients in CR following
allogeneic BMT ranged from 7.5 to 83.0 months. Sufficient RNA was extr
acted from the most recent BM or BM and blood samples from nine patien
ts to assay for presence or absence of the AML1/ETO fusion transcript
by RT-PCR. The fusion transcript was detected by RT-PCR in all nine of
these patient samples; eight were positive in BM and one was negative
in BM, but positive in blood. The fusion transcript could not be dete
cted in a BM sample from the tenth patient obtained 7.5 months after B
MT, but the amount of RNA available was suboptimal. Hematopoietic chim
erism could be demonstrated in sorted CD34(+) BM cells from two of fou
r patient CR BM samples with RT-PCR evidence of the fusion transcript.
Additionally, in one of the two cases with chimerism, we demonstrated
an abnormal clonal population of recipient cells in the CR BM sample
by fluorescence in situ hybridization. One patient died of complicatio
ns from GVHD, while the other nine patients remain alive without evide
nce of relapse, with a median follow-up time of 27 (range, 7.5 to 87)
months post-BMT. These data suggest that allogeneic BMT, like conventi
onal chemotherapy and autologous BMT, is not sufficient to eradicate c
ells expressing AML1/ETO, and that a positive RT-PCR for the fusion tr
anscript post allogeneic BMT is compatible with continued CR. (C) 1996
by The American Society of Hematology.