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Persistence of the AML1/ETO fusion transcript in patients treated with
allogeneic bone marrow transplantation for t(8;21) leukemia
J Jurlander, MA Caligiuri, T Ruutu, MR Baer, MP Strout, AR Oberkircher, L Hoffmann, ED Ball, DA Frei-Lahr, NP Christiansen, AM Block, S Knuutila, GP Herzig and CD Bloomfield
Department of Hematologic Oncology, Roswell Park Cancer Institute, Buffalo,
NY 14263, USA.
The AML1/ETO fusion transcript is expressed in virtually all patients with
t(8;21) (q22;q22) acute myeloid leukemia (AML). The fusion transcript can
be detected by reverse transcription-polymerase chain reaction (RT-PCR) in
most of these patients in long-term complete remission (CR) following
conventional chemotherapy or autologous bone marrow transplantation (BMT).
However, AML1/ETO expression has not been analyzed in a series of patients
following allogeneic BMT. We examined CR bone marrow (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 myeloablative regimens were used. Eight
patients received non-T-cell depleted BM from matched sibling donors, one
patient received a T-cell depleted haploidentical 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 analyzed 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 extracted from the most recent BM or BM and
blood samples from nine patients 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 detected in a BM sample from the tenth patient obtained 7.5 months
after BMT, but the amount of RNA available was suboptimal. Hematopoietic
chimerism could be demonstrated in sorted CD34+ BM cells from two of four
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 complications from
GVHD, while the other nine patients remain alive without evidence 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 conventional
chemotherapy and autologous BMT, is not sufficient to eradicate cells
expressing AML1/ETO, and that a positive RT-PCR for the fusion transcript
post allogeneic BMT is compatible with continued CR.
Volume 88,
Issue 6,
pp. 2183-2191,
09/15/1996
Copyright © 1996 by The American Society of Hematology
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