Armistead, P.M.

Champlin, R.

De Lima, M.

Estey, E.

Giralt, S.

Pierce, S.

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HCT-CI Comorbidities and their corresponding HCT-CI and CCI
scores
Comorbidity
Prevalence:
No. of pts
(%)
HCT-CI
score CCI score
Hepatic (mild) 11 (13.8) 1 1
Cardiac 12 (15) 1 1
Cerebrovascular disease 3 (3.8) 1 1
Arrhythmia 7 (8.8) 1 0
Pulmonary (moderate) 9 (11.3) 2 1
Pulmonary (severe) 6 (7.5) 3 1
Rheumatologic 4 (5) 2 1
Diabetes 18 (22.5) 1 1
Inflammatory bowel disease 2 (2.5) 1 0
Renal dysfunction
(moderate/severe) 1 (1.3) 2 2
Psychiatric disturbance 9 (11.3) 1
Not
included
Infection 5 (6.3) 1
Not
included
Obesity 9(11.3) 1
Not
included
Peptic ulcer disease 0(0) 2 1
Hepatic (moderate/severe) 0(0) 3 3
Heart valve disease 0(0) 3 0
55
ALLOANATIGENIC REACTIONS AFTER HEMATOPOIETIC CELL TRANS-
PLANTATION (HCT) INDUCE GENOMIC ALTERATIONS IN EPITHELIAL
CELLS AS SHOWN IN HUMAN STUDIES AND IN AN IN VITRO MODEL
Spyridonidis, A.1, Faber, P.2, Petrikkos, L.2, Bertz, H.2, Finke, J.2
1Hematology, Patras University Hospital, Rio-Patras, Greece; 2Hema-
tology-Oncology, Freiburg University Medical Center, Freiburg, Ger-
many.
We previously demonstrated frequent genomic alterations mea-
sured by microsatellite instability (MSI) in non-neoplastic epithe-
lial tissues of pts who underwent allogeneic HCT (Blood 2006;
107:3389-3396). These genomic alterations were found only after
allogeneic but not after autologous HCT, and therefore we hy-
pothesized that an allogeneic effect is substantially involved in the
mutation process. We extended our previous analyses by examin-
ing 210 bucall swabs obtained from 70 pts between day (d) 26 and
d3514 after allogeneic HCT for the presence of MSI. MSI was
found in the buccal smears of 38% allografted patients. In a
prospective trial, in which pts were followed from time before
HCT until d365, 5 out of 14 (35%) pts exhibited MSI post-HCT
although all showed stable microsatellites before transplantation.
Statistical analyses in order to identify which clinical factors inﬂu-
ence the presence of MS are in progress. To test the hypothesis
that an alloantigenic effect is responsible for th induction of MSI,
we developed a model system in which keratinocyte (HaCaT) cells
were transfected with a plasmid vector which carries a G418 se-
lectable marker and a microsatellite repeat (CA) that places the
sequence for Hygromycin Resistance (HygR) out of frame for
protein translation. DNA slippage mutations can restore the HygR
reading frame and become detectable as HygR colonies. Pools of
stably transfected HaCaT cells were treated with supernatant (SN)
of major histocompatibility complex nonmatched mixed lympho-
cyte cultures (MLC) and assayed for HygR colonies 48h later.
We found that HaCaT cells aquire hygromycin resistance after
treatment with supernatatant from MLC. Treatment of cells with
hydrogen hyperoxid which has been shown in a E. Coli system to
induce MSI generated HygR colonies at a 80% lower fre-
quency than the SN-MLC treatment. Control cells transfected
with an in-frame hygromycin B gene construct (p12) were grown
with high efﬁciency in the presence of hygromycin B. In summary,
our in vivo data conﬁrm our previous results and provide evidence
of genomic alterations after allogeneic HCT and our in vitro data
are compatible with the hypothesis that an alloantigenic factor is
the driving force in producing detectable MSI in the allografted
patients. Elucidating the ultimate mechanisms underlying the
genomic instability following allogeneic HCT may prove to be of
major therapeutic value.
LEUKEMIA
56
QUANTIFYING THE SURVIVAL BENEFIT OF ALLOGENEIC STEM CELL
TRANSPLANT IN THE MANAGEMENT OF RELAPSED ACUTE MYELOID
LEUKEMIA
Armistead, P.M.1, De Lima, M.1, Pierce, S.1, Giralt, S.1,
Champlin, R.1, Estey, E.1 1MD Anderson Cancer Center, Houston, TX.
Outcomes data comparing patients with relapsed acute myeloid
leukemia (AML) who undergo transplant versus traditional che-
motherapy alone are limited, due primarily to difﬁculty obtaining
adequate patient sample sizes. To address these issues, a retrospec-
tive chart review was performed on all AML patients (n600)
treated at ﬁrst relapse at MD Anderson Cancer Center from 1995
through 2004. Median age was 58 (range 15-85, 66% of patients
50), and poor risk cytogenetics (-5 or -7 deletions) were present
in 23%. 139 (23%) patients achieved a second complete remission
(CR2), 64 (11%) patients died during salvage chemotherapy, and
397 (66%) patients were resistant to therapy. Remission duration
and overall survival were compared between patients in second
remission who underwent allogeneic transplant and only those
patients who did not undergo transplant because of patient pref-
erence or lack of a suitable donor.
Of the 102 patients who achieved a CR2 and were evaluated for
tranplant, 72 (71%) underwent transplant and 30 (29%) did not.
Twenty-one of the 30 patients not undergoing transplant declined
the procedure or did not have a suitable donor. There was a
statistically signiﬁcant difference in remission duration favoring
the transplant cohort (2-year actuarial relapse-free survival of 46%
vs. 13%, p0.007), and a trend toward overall survival beneﬁt
(2-year actuarial survival 44% vs. 23%, p0.105). Differences is
relapse-free and overall survival for patients 50 years old (n24
patients transplanted vs. 14 patients not transplanted) were not
statistically signiﬁcant (2 year relapse-free survival 50% vs. 15%,
p0.373; 2-year overall survival 43% vs. 23%, p0.832).
Of the 239 patients resistant to their ﬁrst salvage regimen who
underwent a transplant evaluation, 105 (44%) patients underwent
allogeneic transplant while 71 (30%) patients did not because of
lack of an available donor. A signiﬁcant survival advantage was
noted in the cohort of patients undergoing transplant (2-year
actuarial survival 13% vs. 0%, p0.001). This beneﬁt was also
observed in patients in the cohort who were 50 years old (2-year
actuarial survival 12% vs. 0%, p0.001).
Allogeneic transplant at the time of second remission or failed
ﬁrst salvage is a feasible strategy in many patients (30% of patients
in this cohort). Given the large number of AML patients who will
need salvage therapy, greater efforts should be made in identifying
donors prior to the patient’s ﬁrst relapse.
57
OUTCOMES FOR ALLOGENEIC TRANSPLANTATION IN IMATINIB-RE-
FRACTORY CHRONIC MYELOID LEUKAEMIA (CML) ARE EQUIVALENT
TO OUTCOMES IN IMATINIB-RESPONSIVE/IMATINIB-NAIVE CML AND
CAN BE PREDICTED BY THE EBMT RISK SCORE
Durrant, S.T.1, Stylian, S.1, Western, R.J.1, Morton, J.P.1, Butler, J.1,
Hutchins, C.1, Hill, G.1, Kennedy, G.A.1 1Royal Brisbane Hospital,
Brisbane, Queensland, Australia.
Aims: To review the outcome of allogeneic stem cell transplan-
tation (SCT) in imatinib refractory chronic myeloid leukaemia
(CML).
Methods:Outcomes of all allogeneic transplants performed after
Oral Presentations 23


56: Quantifying the survival benefit of allogeneic stem cell transplant in the management of relapsed acute myeloid leukemia 

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56: Quantifying the survival benefit of allogeneic stem cell transplant in the management of relapsed acute myeloid leukemia

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