12th Congress of the European Hematology ... - Haematologica

0497
SINGLE AGENT CLORETAZINE (VNP40101M) IN ELDERLY AML PATIENTS WITH
UNFAVORABLE CYTOGENETICS: RESULTS FROM A PHASE II MULTI-CENTER STUDY
N. Vey, 1 D. Rizzieri, 2 J. Karp, 3 V. Karsten, 4 A. Cahill, 4 F. Gile s5
1 Paoli-Calmettes, MARSEILLE CEDEX 9, France; 2 Duke University,
DURHAM, NC, USA; 3 Johns Hopkins University, BALTIMORE, MD, USA;
4 Vion Pharmaceuticals, NEW HAVEN, CT, USA; 5 UT MD Anderson Dept of
Leukemia, HOUSTON, TX, USA
Background. Outcomes for elderly patients with AML are poor, and it
has been shown that elderly patients with unfavorable cytogenetics have
a particularly poor prognosis. Additionally, a large number of these
patients are considered unfit for intensive chemotherapy due to coexisting
comorbidities, and are given best supportive care or low-dose AraC.
However, no complete remissions are observed with this treatment and
median overall survival is approximately 1 month (Burnett et al., Cancer
2007). Patients with unfavorable cytogenetics who do receive cytotoxic
induction treatment achieve complete response rates between 23-33%
with very low 5-year survival rates (2-4%) (Grimwade et al Blood 2001,
Rowe et al Blood 2004, Farag et al Blood 2006, Buechner et al JCO 2006).
Methods. We present a subset analysis of patients with unfavorable cytogenetics
in a Phase II study of Cloretazine ® as a single agent (Vion Study
CLI-033). Cloretazine? is a new alkylating agent that causes DNA crosslinks
and cell death. The study was designed for untreated patients with
AML or high-risk MDS over the age of 60. Treatment consisted of Cloretazine
® (VNP40101M) 600 mg/m 2 administered as a short IV infusion on
day 1 (second cycle allowed) and an additional 400 mg/m 2 as consolidation
for responders (CR or CRp). The primary endpoint was overall
response (CR or CRp). Overall survival and relapse-free survival were
also analyzed. Results. The study treated 128 patients of age 60 or older.
Fifty-eight patients (45%) had unfavorable cytogenetics (-7, del5q,
abnl11q, abnl9q, abnl20q, abnl13q, complex (≥ 3 abnormalities)). Of
these 58 patients, 28 (48%) had secondary AML, 19 (33%) had de novo
AML and 11 (19%) had high-risk MDS. Twenty-three (40%) patients in
the unfavorable group had a complex karyotype. The response rate in
patients with unfavorable cytogenetics was 26% (15/58). Response by
diagnosis: 53% in de novo AML, 27% in MDS and 7% in secondary
AML. Median overall survival in patients with unfavorable cytogenetics
was 3 months (range 0.1-28). In patients achieving CR or CRp, median
overall survival was 5 months (range 2-28) and relapse-free survival
was 3.5 months (range 1-20). In non-responders, overall survival was 2
months (range 0.1-9). Twelve (21%) patients died within 30 days of
receiving induction treatment. Conclusions. Cloretazine ® has the ability
to induce remissions in elderly AML patients with unfavorable cytogenetics.
Survival in this group is improved compared to that reported for
supportive care or low dose AraC. Cloretazine ® may provide an important
treatment option for poor prognosis patients with AML.
12 th Congress of the European Hematology Association
Autologous stem cell transplantation
0498
THE ROLE OF HIGH DOSE CHEMOTHERAPY AND PERIPHERAL BLOOD STEM CELL
SUPPORT IN REFRACTORY TROPHOBLASTIC DISEASE AND NON-GESTATIONAL
CHORIOCARCINOMA: A REVIEW OF EIGHT PATIENTS
I. Gabriel, 1 A. Chaidos, 1 C. Giles, 1 J. Apperley, 1 M. Seckl, 2 M. Bower, 3
E Kanfer1 1 Hammersmith Hospital NHS Trust, LONDON; 2 Charing Cross Hospital,
LONDON; 3 Chelsea and Westminster Hospital, LONDON, United Kingdom
Objective. To evaluate the role of high dose therapy (HDT) with autologous
peripheral blood stem cell support (ASCT) refractory advanced
trophoblastic disease and non gestational choriocarcinoma. Methods.
Eight patients (gestational trophoblastic neoplasia n =6, choriocarcinoma
post complete hydatidiform mole n=1, possible non-gestational
choriocarcinoma n=1 and germ cell tumour with choriocarcinoma differentiation
n=1) were treated with HDT with ASCT. Median age was
33 years. All patients received a conditioning regimen of CarboPEC-Taxol
(Paclitaxel 75 mg/m 2 on days -7, -5, and -3, Etoposide 450 mg/m 2 days
-7, -5, and -3, Carboplatin 10 mg x glomerular filtration rate (GFR) +25
on days -7, -5,and -3, and Cyclophosphamide 60 mg/kg/day days -5,
and -3). Four patients received this regimen as a tandem ASCT, receiving
50% dose of the conditioning regimen drugs with stem cell infusion
twice, twelve weeks apart, to limit toxicity. All eight patients had multiply
relapsed disease and had received more than two different prior
treatments (median number of prior therapies was 3.5 range, 2-5) at time
of ASCT. Two patients had cerebral metastases. At transplant four
patients were in a partial remission (PR) and four had progressive
metastatic disease. Results. The regimen was well tolerated. Seven
patients showed an initial response immediately post ASCT, one patient
demonstrated disease progression throughout. Five patients achieved a
complete remission (CR) demonstrated by a reduction in serum tumour
markers to normal (