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

426s Leukemia, Myelodysplasia, and Transplantation
6540 General Poster Session (Board #14G), Mon, 1:15 PM-5:15 PM
Outcomes of second allogeneic hematopoietic stem cell transplantation
(SCT) for patients with acute lymphoblastic leukemia (ALL). Presenting
Author: L. M. Poon, University of Texas M. D. Anderson Cancer Center,
Houston, TX
Background: Disease relapse is the major cause of failure after allogeneic
hematopoietic stem cell transplantation (SCT) for acute lymphoblastic
leukemia (ALL). Treatment options for these patients (pts) are limited and
only a second SCT provides a realistic chance for long term disease
remission. Methods: We retrospectively analyzed the outcomes of 31 pts
with ALL who relapsed following their first allogeneic SCT, and went on to
receive a second allogeneic SCT. Univariate analysis was used to assess for
risk factors which influenced treatment-related mortality (TRM), and
progression free survival (PFS) following second SCT. Results: 31 pts were
evaluable for response with 2 early deaths within 30 days of SCT. The
median age of the pts was 26 years (range 7- 49), and the median duration
between their first SCT (SCT1) to relapse was 9.5 months (range 2.2-32.6
months). 39% of pts were transplanted in active disease (n�12). The
complete remission (CR) rate post SCT was 89%; 83% of pts transplanted
with active disease attained CR. With a median follow-up of 3 years among
survivors, PFS, and OS rates at 1 year were estimated at 23%. The TRM
rate was 41% at 12 months. We did not identify any factors that impacted
TRM through univariate analysis. We found a significant relationship
between the time to progression following SCT 1 and PFS following SCT 2
(p�0.02, HR�0.93/month). Conclusions: In summary, a second transplant
remains an effective method for achieving response in a highly refractory
patient population. Pts with longer PFS following SCT1 have a better PFS
following SCT2. While long-term survival is limited, a significant proportion
of pts remain disease-free for up to one year following SCT2, providing a
window of time to administer preventive interventions. Notably, our 4
long-term survivors, received novel therapies in the form of a single
umbilical cord blood unit in addition to the PBSC to augment the immune
response (n�2), a change in the stem cell source for the SCT from cord to
mismatched adult unrelated (n�1), and post SCT maintenance therapy
with 5-azacytidine (n�1), underscoring the need for a fundamental change
with the methods for the second transplant to improve outcome.
6542 General Poster Session (Board #15A), Mon, 1:15 PM-5:15 PM
Impact of antithymocyte globulin (ATG)-containing conditioning regimens
on patients undergoing allogeneic stem cell transplantation (allo-CST) for
poor risk cytogenetic IPSS myelodysplastic syndrome (PRC-MDS): A report
from the French Society of Stem Cell Transplantation and Cell Therapy
(SFGM-TC). Presenting Author: Ibrahim Yakoub-Agha, University Hospital,
Lille, France
Background: Due to a risk of relapse of underlying disease in patients with
PRC-MDS, the use of ATG, incorporated within the conditioning regimen
prior to allo-SCT, is still controversial. Methods: Inclusion criteria included
patients aged over 18 (n�101) who received allo-SCT transplanted
between 1999 and 2009 from either a sibling (n�68) or HLA-allele-MUD
(10/10) (n�33) for PRC-MDS. HLA matching was double-checked by the
national Bone Marrow Donor Registry. Results: According to the FAB/WHO
classification at diagnosis, 22 pts had RA/RARS/RCMD, 40 RAEB1, 30
REAB2 and 9 RAEB-t/AML. 34 pts had progressed to a more advanced
disease before allo-SCT. At diagnosis, 89 patients had an IPSS int-2 or
higher. At transplant, 36 pts were responders (CR, PR, CRm) and 62 with
progressive disease (relapsed/refractory, untreated or stable disease without
hematological improvement). Median age at transplantation was 54
years (range, 22-69). Pts received myeloablative conditioning (n�46) and
nonmyeloablative (n�55). In this series, 48 patients received ATG as part
of conditioning (’ATG’ group), whereas 53 did not (’no-ATG’ group). As of
April 1st 2011, 44 patients died of relapse and 22 of TRM. 3-year relapse,
overall and event-free survival rates were not significantly different between
the two groups. In contrast, the cumulative incidence of grade 2-4 acute
GVHD was 48% in the no-ATG group and 30% ATG group (P �.005).
Although the cumulative incidence of chronic GVHD was similar in the
no-ATG and ATG groups, a trend for a lower TRM was observed in the ATG
group (p�.06). In multivariate analysis, the absence of use of ATG was
associated with an increased risk of acute grade 2-4 [HR � 1.92, p�.044].
Conclusions: The addition of ATG to the conditioning regimen resulted in a
decreased incidence of acute GVHD without increasing relapse rates and
compromising survival of patients undergoing allo-SCT for poor risk
cytogenetic MDS.
6541 General Poster Session (Board #14H), Mon, 1:15 PM-5:15 PM
Randomized phase III trial of haploidentical HCT with or without an add
back strategy of HSV-TK donor lymphocytes in patients with high-risk acute
leukemia. Presenting Author: Claudio Bordignon, Università Vita-Salute,
Istituto Scientifico San Raffaele; MolMed, Milan, Italy
Background: Suicide gene therapy applied to allogeneic stem cell transplantation
has been tested in several trials. When exposed to ganciclovir, donor
lymphocytes expressing herpes simplex thymidine kinase suicide gene (TK
cells) are selectively eliminated. In a phase I-II trial (Ciceri, Bonini, Lancet
Oncology 2009,489-500), TK cells were infused in patients after haploidentical
transplantation. Of 50 patients enrolled, 28 received transduced-TK
cells and 22 achieved rapid immune reconstitution, with a non-relapse
mortality of 14%. GvHD after DLI-TK infusion was reported in 30% of
patients and in all cases was fully controlled by ganciclovir treatment.
Methods: High risk leukemia patients in first or subsequent complete
remission are currently randomized in a 2-arm (3:1 ratio) phase III trial with
or without the add-back strategy of HSV-TK donor lymphocytes in patients
underwent T-depleted haploidentical stem cell transplant. Primary end
point is disease-free survival (DFS), while secondary end points included
overall survival, non-relapse mortality, immune reconstitution, acute and
chronic GvHD incidence, and relapse incidence. For the primary analysis of
DFS 170 patients (127 patients in the experimental group and 43 patients
in the control) are required to detect an hazard ratio of 0.55 with at least
80% power for 2-sided 0.05 level test. Patients are eligible for the study if
they are older than 18 years-old, absence of timely and suitable HLA
matched family or unrelated donor, and have a ECOG performance status �
2. Patients are stratified by state of disease, ECOG PS and country before
randomization. Results: Transduced lymphocytes are given to patients
between day �21 and day �49 after haploidentical HCT in the absence of
spontaneous immune reconstitution and/or development of GvHD. In
absence of immune reconstitution and GvHD after the first TK-cells
add-back further 3 infusions could be administered 30 days after the last
infusion. TK lymphocytes dose is 1 x10^7 CD3/Kg. Conclusions: The study
(TK008) is currently open to accrual in EU, US, Israel (clinicaltrials.gov:
00914628).
6543 General Poster Session (Board #15B), Mon, 1:15 PM-5:15 PM
Minimum tolerable interval of 90yttrium ibritumomab-tiuxetan to autologous
stem cell transplantation after high-dose chemotherapy with carmustin,
etoposide, cytarabine, and melphalan for relapsed or refractory
aggressive B-cell non-Hodgkin lymphoma. Presenting Author: Justin Hasenkamp,
University Medicine Goettingen, Goettingen, Germany
Background: High-dose therapy and autologous stem cell transplantation
(ASCT) in patients (pts) with aggressive B-NHL failing from immunochemotherapy
including rituximab show poor outcome with 3y PFS of 39%
(Gisselbrecht et al. JCO 2010). Combining BEAM with 90yttrium ibritumomab
tiuxetan is a promising option to enhance the efficacy of the
high-dose regimen. Methods: Pts without disease progression during
salvage therapy of relapsed or refractory CD20� aggressive B-NHL were
included in this prospective, multicenter, phase I/II trial. Primary endpoint
was the maximum tolerated dose of 90Yttrium ibritumomab tiuxetan given
as close as possible to ASCT defined as �2 pts with dose limiting toxicity in
a 6�6 pts cohort. First, we reduced the time interval of 90yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) to ASCT from 14 to 12 and
then 10 days. Subsequently it was planned to increase the 90yttrium ibritumomab tiuxetan dose. Results: From 2006 to 2009 26 pts, median
age 58y (34-66) were enrolled. Histology included 14 DLBCL, 6 FL III°, 5
transformed FL and 1 aggressive B-NHL without further subtyping. 11/26
pts had relapse/progression within 1y after diagnosis. Secondary IPI was
�1 in 14 pts. Response to salvage therapy was CR in 6/26 pts and PR in
12/26 pts. 20/26 pts achieved CR after ASCT. Engraftment showed no
significant differences in pts of different cohorts with median recovery of
leukocytes (�1/nl) and platelets (�25/nl) at d �10 and �13. Two early
deaths (d �7, �18) occurred due to infections. 90Yttrium ibritumomab
tiuxetan (0.4 mCi/kg body weight) at d -10 of ASCT was determined as
minimum tolerated interval of radioimmunotherapy to ASCT after BEAM.
Median follow-up of the survivors is 3.3 y. 3y PFS and OS is 67% (95% CI,
49%-85%) and 75% (95% CI, 58%-92%), respectively. Main cause of
death was relapse/progression with 27% (95% CI, 6%-38%) at 3y.
Conclusions: Z-BEAM followed by ASCT was safe and feasible and results in
a high response rate with durable remissions in rituximab pretreated
patients with aggressive B-NHL. Extended studies at the maximum
tolerated dose and confirmation of superiority compared to conventional
ASCT are warranted.
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