Annual Meeting Proceedings Part 1 - American Society of Clinical ...

432s Leukemia, Myelodysplasia, and Transplantation
6564 General Poster Session (Board #17G), Mon, 1:15 PM-5:15 PM
Prognostic implication of monosomal karyotype in patients with acute
myeloid leukemia who received allogeneic hematopoietic cell transplantation.
Presenting Author: Yunsuk Choi, Department of Hematology, Asan
Medical Center, University of Ulsan College of Medicine, Seoul, South
Korea
Background: Monosomal karyotype (MK), defined as at least two autosomal
monosomies or one single autosomal monosomy with one or more structural
cytogenetic abnormalities, has been associated with worse outcomes in
acute myeloid leukemia (AML). We evaluated the prognostic impact of MK
on outcomes after allogeneic hematopoietic cell transplantation (allo-HCT)
in AML. Methods: We retrospectively analyzed 169 adult patients with AML,
who received allo-HCT in the first complete remission (CR) between 2000
and 2009. All patients had cytogenetic results at the diagnosis of AML.
Patients were classified as having good, intermediate, or poor risk cytogenetics
according to the NCCN guideline, and MK status was also determined.
Results: MK was observed in 12 patients (7.1%); of whom, 11 patients also
had complex karyotype (CK). Compared to patients without MK, those with
MK had significantly lower overall survival (OS) (62.2% vs. 0%) and event
free survival (EFS) (58.9% vs. 0%), and higher relapse probability (RP)
(22.9% vs. 66.7%) at 5 years (all, p�0.001). 22 patients with CK also
showed inferior outcomes, but CK with MK was associated with more
inferior outcomes than CK without MK. Multivariate analysis showed that
MK had a significantly adverse impact on OS (hazard ratio [HR], 5.192;
p�0.001), EFS (HR, 4.531; p�0.001), and RP (HR, 6.558; p�0.001)
after allo-HCT (Table). Conclusions: MK is a major prognostic factor
predicting extremely worse outcomes in AML patients who underwent
allo-HCT in the first CR.
Multivariate analysis.
OS EFS RP
HR (95% CI) p HR (95% CI) p HR (95% CI) p
WBC count, >60
(x103 /�L)
1.990 (1.107-3.576) 0.021 1.885 (1.074-3.307) 0.027 -
Time from diagnosis to 2.621 (1.216-5.650)
HCT, >250, days
Cytogenetics
0.014 2.378 (1.115-5.071) 0.025 2.749 (1.140-6.629) 0.024
Good 0.755 (0.231-2.463) 0.634 (0.196-2.054) 0.447 0.766 (0.180-3.248) 0.717
Intermediate 1 1 1
Poor, CK- 1.286 (0.576-2.872) 0.539 1.098 (0.496-2.435) 0.817 3.199 (1.338-7.648) 0.009
Poor, CK�, MK- 1.686 (0.703-4.043) 0.242 2.171 (1.014-4.648) 0.046 3.525 (1.506-8.252) 0.004
Poor, CK�,MK� 5.192 (2.552-10.561) �0.001 4.531 (2.255-9.108) �0.001 6.558 (2.739-15.703) �0.001
6566 General Poster Session (Board #18A), Mon, 1:15 PM-5:15 PM
Bendamustine retreatment of CLL in the outpatient setting. Presenting
Author: Georg Guenther, Oncological Medical Practice, Potsdam, Germany
Background: Several studies have proven that bendamustine is a highly
active drug in the therapy of CLL (Knauf et al. J Clin Oncol. 2009;27:4378-
84; Fischer et al. J Clin Oncol. 2011;29:3559-3556). Nevertheless, only
few data exist about the real-life use and efficacy of bendamustinetherapies
in the non-trial setting. The project group of internal oncology
(p.i.o.) therefore implemented a registry for patients in the routine use of
bendamustine in the therapy of CLL (Sauer et al. Onkologie 2010;33(suppl
6):12). Since 2008 a total of 616 patients have been registered, out of
which 473 have been thoroughly documented. To evaluate whether a
retreatment with bendamustine in relapsed CLL is still active and well
tolerable we present comparative data on therapies in patients with (group
A) or without (group B) bendamustine pretreatment. Methods: 228 documented
patients in relapsed situation were retrospectively appointed to one
of two groups (see table below). Results: In Group A the ORR was 80 % and
the median PFS lasted 15.6 month. In the patients without prior bendamustine
treatment the ORR was 84% and the median PFS lasted 21.2 month.
In both groups the median OS has not been reached yet. The grade 3/4
toxicities were mostly hematologic and comparable in both groups. Similar
grade 3/4 toxicities were observed for neutropenia (about 25% of the
patients), thrombocytopenia (16%) and infections (5%). Conclusions:
Bendamustine is broadly used in the routine treatment of CLL. Bendamustine-therapies
show impressionable high activity and tolerability, even in an
advanced-line context with prior exposition to bendamustine. The treatment
results are comparable to results of clinical trials and underline the
quality and feasibility of bendamustine in the outpatient treatment.
Nevertheless, it is to note that this is a registry and that both groups
therefore are not composed of randomized patient-populations (cf. ECOG,
patients in lines and ratio of rituximab combinations).
Group A Group B
n 83 145
Gender m/w 53/30 88 /57
Median age (range) 51-84 (74) 45-93 (72)
Ratio B/B�rituximab in % 57/43 51/49
ECOG 0/1/2 in % 11/64/25 21/64/15
Binet A/B/C in % 4/54/42 4/45/51
Line 2./3./4./5./6.� in % 30/30/22/13/5 56/26/10/6/2
Med. B-dose-intensity over 4 weeks 151,9 mg/m² 151,3 mg/m²
6565 General Poster Session (Board #17H), Mon, 1:15 PM-5:15 PM
Predicting outcome based on minimal residual disease (MRD) using
multiparameter flow cytometry (FC) in acute myeloid leukemia (AML)
patients (Pts). Presenting Author: Sagar D. Sardesai, Roswell Park Cancer
Institute, Buffalo, NY
Background: Most AML pts will experience relapse caused by persistent
leukemic cells during complete remission (CR). The aim of our study was to
predict outcome in AML pts in CR by assessing their MRD using standard
4-colour FC panels available at our institute. Methods: We queried our AML
database between 1/2004 to 10/2010 for newly diagnosed untreated AML
pts �18 years of age who achieved CR after one induction regimen.
Treatment included 7�3 or similar intensive approaches. The gating
strategy used a series of Boolean regions that best defined the diagnostic
abnormal population based on its expression patterns using three 4-colour
FC panels (F7-CD38,CD10,CD19,CD34; F9-C11b,CD33,CD13,CD34; F38-
CD15,CD56,CD7,CD34). The same regions were applied to post-induction
samples, and the number of residual events was determined. Results: 140
AML patients with a median age of 64 (range 24-93) years, including 74
females (52.8%) were analyzed; 67 (47.8%) patients relapsed. Eightyeight
(62.8%) pts were CD34-positive (CD34�) at diagnosis. Normal
karyotype was detected in 27 (30.7%): FLT-3 ITD was detected in 4/23
(17.4%) and NPM-1 mutation was detected in 1/15 (0.07%) samples.
Median follow-up for CD34� pts was 17.9 months. Forty-two (30%) pts
underwent stem cell transplantation (SCT) in first CR: 31 (22.1 %) were
allogeneic and 11 (7.9%) autologous. In multivariate analysis, a detectable
MRD in any of the 3 panels at or beyond week 16 among CD34� AML pts in
CR was significantly associated with inferior relapse free survival (F7:
P�0.035 , F9: P�0.027, F38: P�0.042). In addition, MRD � week 16
using panel F9 was also significantly associated with inferior overall
survival (P�0.0224). In pair-wise comparison, those who were MRDnegative
� week 16 did not benefit from SCT compared to the non-SCT
group. Similar analyses among CD34– AML pts did not achieve statistical
significance. Conclusions: MRD� by FC in CD34� AML is an independent
prognostic factor and can identify pts who may benefit from SCT/more
intensive therapy to maintain remission. However, the value of studying
MRD in CD34– AML requires further consideration. More effort is needed
to identify stem cells in CD34– AML.
6567 General Poster Session (Board #18B), Mon, 1:15 PM-5:15 PM
Effect of epitopes derived from the mutated region of cytoplasmatic
nucleophosmine 1 (NPM1) on CD4� and CD8� T-cell responses in
patients with acute myeloid leukemia. Presenting Author: Jochen Greiner,
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Background: Mutations of the nucleophosmin gene (NPM1mut) are one of
the most frequent molecular alterations in AML and constitute an important
prognostic marker. The impact of NPM1mut on leukemogenesis and
progression remains to be elucidated. Immune responses against NPM1mut
might contribute to the favourable prognosis of AML patients with
NPM1mut. Therefore, we examined T cell responses against NPM1mut.
Methods: NPM1 wildtype as well as NPM1mut were screened for HLA-
A*0201 binding T cell epitopes with the help of different algorithm
programs. Ten peptides with most favourable characteristics were tested
with ELISpot analysis for interferon-� and granzyme B in 33 healthy
volunteers and 30 AML patients. Tetramer assays against most interesting
epitopes were performed and chromium release assays were used to show
the cytotoxicity of peptide-specific CD8� T cells. Moreover, HLA-DRbinding
epitopes were used to test the role of CD4� T cells in NPM1
immunogenicity. Results: Two epitopes (#1 and #3) derived from NPM1mut
induced CD8� T cell responses in a high frequency. In healthy volunteers,
immune responses were detected in 39%/18% against #1 and #3, and in
33%/44% of NPM1mut AML patients against #1 and #3. NPM1-peptide
primed effector T cells showed specific lysis of pulsed T2 cells as well as
leukemic blasts in chromium release assays. In tetramer assays a significant
CD8� T cell population could be detected. To obtain a robust and
continuous T cell reaction, the help of CD4� T cells is indispensable.
Therefore, we investigated the increase of CD8� T cell responses by the
activation of CD4� T cells stimulated with longer peptides called overlapping
peptides (OL). Potent HLA-DR epitopes were predicted and several
favourable peptides (OL 1 to 8) were synthesized. OL8 showed favourable
results to activate both CD8� and CD4� T cells. Conclusions: Taken
together, NPM1mut represents a candidate for immunotherapeutic approaches
and we hypothesize that it is also potentially involved in
immunogenic rejection of NPM1mut leukemic blasts. Therefore, NPM1mut
is a promising target structure for specific immunotherapies in AML
patients.
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