Barraco, F.

Chelghoum, Y.

Detrait, M.

Ducastelle, S.

Labussiere, H.

Michallet, M.

Morisset, S.

Nicolini, F.E.

Sobh, M.

Tedone, N.

Thomas, X.

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Poster Session II S327had worse engraftment compared to congenic wildtypemice. In con-
clusion, both, vacating of HSC niche space, and the effects of host
regulatory cells, that are activated during the TLI procedure appear
critical to permit donor HSC engraftment post-TLI/ATG. The dy-
namics of engraftment after TLI/ATGare unique. Further studies to
define the exact roles of host Tregs and NKT cells in engraftment
after TLI/ATG and other conditioning modalities are underway.330
IMMUNE RECONSTITUTION AND CLINICAL OUTCOME AFTER HSCT
INFUSION FOR SEVERE COMBINED IMMUNODEFICIENCY IN NEWCASTLE
Moreira, D.1, Slatter, M.1, Nademi, Z.1, Brigham, K.3, Barge, D.4,
Jackson, A.5, Flood, T.1, Cant, A.1, Abinun, M.1, Hambleton, S.2,
Gennery, A.2 1Newcastle upon Tyne Hospital NHS Foundation Trust,
Newcastle upon Tyne, United Kingdom; 2Newcastle University, Newcastle
upon Tyne, United Kingdom; 3Newcastle upon Tyne Hospital NHS Foun-
dation Trust, Newcastle upon Tyne, United Kingdom; 4Newcastle upon
Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United
Kingdom; 5Newcastle upon Tyne Hospital NHS Foundation Trust, New-
castle upon Tyne, United Kingdom
Background: Hematopoietic stem cell transplantation (HSCT) is
the treatment of choice for severe combined immunodeficiency
(SCID). There remains debate on whether to pre-condition with
chemotherapy prior to infusion of stem cells.We aimed to determine
the long-term progress of classic SCID patients who had undergone
HSCT infusion at our centre, with respect to clinical outcome and
immune comparing outcome based on transplant at \3 or .3
months of age, and molecular diagnosis.
Methods: A retrospective case notes review of patients undergoing
a first HSCT infusion for classic SCID from 01/1995 to 02/2011,
surviving. 2 months. Patients with previous HSCT were excluded.
Parameters analyzed included clinical outcome, chimerism, lympho-
cyte subsets including recent thymic emigrants, specific antibody
levels and Ig replacement. Statistical analysis was performed using
c 2 (Fisher exact test) and nonparametric wilcoxon rank sum. A 2-
sided p value\ 0.05 was considered significant.
Results: Twenty seven of 100 patients with SCID treated fulfilled
the study criteria; 10 had ADA deficiency, 7 had T-B-NK+ pheno-
type, 8 had CgC/JAK3 SCID, and 2 had other forms of SCID. 12
were transplanted\ 3 months of age, median age at HSCT was 3
months (range 0-8 months). Twenty had infection at diagnosis, all
. 3 months. Eleven had MSD, 1 MMSD, 5 MFD, 3 MMFD, 6
MUD, 1MMUD.Twenty receivedGvHDprophylaxis. Median fol-
low up was 80 months (2-187). Seven developed grade II-IV GvHD,
3 grade III. Five were re-transplanted, 2 received boost infusion for
poor engraftment (1 CgC, 1 T-B-NK+), 3 received a conditioned
HSCT (3 T-B-NK+). TRMwas 11% (1 ADA, 2T-B-NK+). Neuro-
logical and autoimmune complications were more common in the
ADA and T-B-NK+ groups. Recent thymic emigrants were most
commonly present in the CgC/JAK3 and ADA groups, and absent
from the T-B-NK+ group. The ADA group had the most complete
donor chimerism including myeloid chimerism, T-B-NK+ SCID
only achieved donor T cell chimerism. Most ADA patients discon-
tinued IVIG, compared to none with T-B-NK+ SCID.
Conclusion: HSCT infusion is an effective treatment for SCID.
Best results are obtained if transplanted\ 3 months of age. Estab-
lishment of donor B cell chimerism may require additional therapies
to achieve engraftment within the stem cell niche in all but ADA
SCID.331
DECITABINE IN COMBINATION WITH DONOR LYMPHOCYTE INFUSION
AS SALVAGE THERAPY FOR RELAPSED AML POST-ALLOGENEIC STEM
CELL TRANSPLANTATION
Kritharis, A., Donahue, L.L., Keyzner, A., Devoe, C., Bayer, R.L. Hofstra
University School of Medicine, North Shore LIJ Health System, Lake Suc-
cess, NY
Prognosis is extremely poor for AMLpatients who relapse after al-
logeneic stem cell transplantation. Donor Lymphocyte infusions
(DLI) can be used to salvage these patients with complete responserates reported to be 10-15% with an associated 40-60% chance of
developing clinically significant GVHD. The mechanism by which
DLI results in clinical responses is thought to be a T-cell mediated
process. Data suggest that DLI normalizes the T-cell receptor rep-
ertoire and expands the anti-leukemic cell population. Hypomethy-
lating agents, which appear to foster the graft versus leukemia
phenomenon, were combined with DLI in attempt to enhance the
graft versus leukemia effect.
We report ten AML patients who received Decitabine +/- Eto-
poside with incremental DLI as salvage after relapse from alloge-
neic stem cell transplantation during the years 2007-2010. These
patients were between the ages of 26- 73 years. Six patients had
de novo AML. Three patients were transformed from MDS, and
one from essential thrombocythemia. Eight patients had reduced
intensity conditioning regimens. Two patients received a fully ab-
lative preparative regimen. Average time to progression post trans-
plant was 17 months.
Patients received Decitabine at 20mg/m2 for 5 - 10 days, some in
combination with Etoposide for 3-5days for disease control. Patients
received 1-4 courses of treatment approximately every 28 days with
DLI between days 14-21. Two patients who progressed while receiv-
ing Decitabine/Etoposide received Clofarabine at 20-52mg/m2 for 5
days, with subsequent DLI. Cell dose ranged from 1.27 to 31.7
CD3+ cells / kg. Two patients received a mobilized DLI.
Six out of ten patients regained full chimerism. One patient who
relapsed with extra medullary disease never lost his graft. Seven out
of ten patients achieved a complete remission. Only one patient de-
veloped Grade 2 GVHD of the skin. Overall survival in these pa-
tients after relapse from allogeneic transplantation was 10.8
months.
The combination of Decitabine and DLI is a well tolerated outpa-
tient therapeutic option for patients with relapsed AML post alloge-
neic stem cell transplantation. The majority of patients regained full
chimerism and achieved complete remission with little or no
GVHD.332
IS THE USE OF 9/10 HLA UNRELATED DONORS STILL ACCEPTABLE IN
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR
HEMATOLOGICAL MALIGNANCIES? COMPARISON WITH TRANSPLANTS
FROM 10/10 HLA UNRELATED DONORS AND SIBLINGS
Michallet, M., Sobh, M., Morisset, S., Detrait, M., Labussiere, H.,
Tedone, N., Ducastelle, S., Barraco, F., Chelghoum, Y., Thomas, X.,
Nicolini, F.E. Centre Hospitalier Lyon Sud, Pierre Benite, France
To evaluate the outcome of allo-HSCT from 9/10 HLA mis-
matched unrelated donors compared to those from 10/10HLA iden-
tical unrelated donors and siblings; we retrospectively studied the
outcome of 213 patients who received allo-HSCT for different he-
matological malignancies, 121 (57%) from HLA identical siblings,
63 (29%) from 10/10 HLA identical unrelated donors and 29
(14%) from 9/10 HLA mismatched unrelated donors between
2006 and 2011 at our institution. The different patient characteris-
tics and figures will be provided in the future during the presentation.
After HSCT, engraftment was significantly lower in the 9/10 HLA
group (90%) than in the 10/10 HLA group (95%) than in the sibling
group (99%), (p5 0.03); the cumulative incidence of acute GVHD.
5 2 at 3 months was 32% (23-41), 20% (15-26) and 27% (23-32) re-
spectively; the cumulative incidence of extensive chronic GVHD at
one year was 21% (13-30), 9% (5-13) and 17% (14-21) for the 3
groups respectively. After a median follow-up of 8 months (0-54)
in the 9/10 HLA group, 10 months (0-60) in the 10/10 HLA group
and 18 months in the siblings group, the median OS was 10 months
(5-21), 18months (11-NR) and 60months (31-NR) respectively with
a 2-years probability of 19% (8-44), 43% (31-59) and 63% (54-74)
respectively. There was a higher but not significant relapse incidence
at one year in the 9/10 HLA group compared to other groups while
the TRM was significantly higher with a cumulative incidence at 1
year of 45% (35-55) vs. 33% (27-39) for 10/10 and 12%(9-15) for
siblings, (p\0.001). In multivariate analysis, OS was negatively af-
fected by unrelated donors [9/10 HR 5 5 (2.7-10), p 5 0.0001;
10/10 HR 5 2 (1.2-4), p 5 0.01], female donors [HR 5 2 (1.4-4),
p 5 0.03] and disease status\CR1 or\chronic phase 1 [HR 5 3
(1.4-6), p 5 0.003]; while the TRM was negatively affected by
S328 Poster Session IIunrelated donors [9/10HR5 9 (4-20), p\0.001; 10/10HR5 4 (1.2-
10), p 5 0.03], female donors [HR 5 3 (1.2-7); p 5 0.01] and ABO
minor incompatibility [HR5 2.5 (1.2-5), p5 0.01].We showed that
allo-HSCTfrom9/10HLAmismatchedunrelated donors have a sig-
nificantly worse OS than those from matched unrelated donors and
siblings; this was mainly due to an increased TRM in this group. Pa-
tients in first CR or CP could benefit themore frommatched or 9/10
unrelated allo-HSCT while the use of transplants from 9/10 HLA
unrelated donors in patients not in CR1 should be limited to clinical
trials.
333
OUTCOMES OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLAN-
TATION IN PATIENTS WITH ACUTE MYELOID LEUKEMIA IN THIRD RE-
MISSION
Beitinjaneh, A.1,2, Jakob, J.2, Saliba, R.2, Chen, J.2, Rondon, G.2,
Giralt, S.2, Cortes, J.E.2, Champlin, R.2, De Lima, M.2 1University of
Virginia, Charlottesville, VA; 2University of Texas MD Anderson, Hous-
ton, TX
Introduction: A small minority of patients (pts) with AcuteMyeloid
Leukemia (AML) achieve complete remission (CR3) after a second
relapse. The role of allogeneic HCT (allo-HCT) for such patients
is unclear. Here we present the outcomes of CR3 AML patients
treated at the M D Anderson Cancer Center.
Methods: We conducted a retrospective analysis of prospectively
collected data on all AML pts (n 5 33) who received their allo-
HCT in $ CR3 between 11/2/1990- 7/1/2009.
Results:Median age was 40 years (range, 19-67) and 46% were fe-
male. CR3 pts comprised 2.7% of all pts with AML treated at the
same time period in our institution (n 5 1227). 3/33 had secondary
AML (2 with prior myelodysplastic syndrome and one with previ-
ous myeloproliferative disorder). Cytogenetics risk categories were
low in 24%, intermediate in 30%, high in 21% and unknown in
25%. Pts had a median of 4 chemotherapy lines prior to transplant.
Donor was matched unrelated in 48%, matched related in 24%,
mismatched related in 15% and mismatched unrelated 9%. Graft
source was peripheral blood (52%), marrow (39%) or umbilical
cord blood (9%). Ten pts had prior allo-HCT. Conditioning reg-
imen was of reduced intensity in 60% and myeloablative in 40% of
pts. and 84% of pts received Tacrolimus/Methotrexate +/- Pentos-
tatin for graft- versus-host disease (GVHD) prophylaxis. 97% of
the pts engrafted. Cumulative incidence rate of grade II-IV acute
GVHD was 26% and of chronic GVHD was 27%. Overall survival
was 19% (95 % CI: 7-34%) and progression-free survival (PFS)
was 12% (95% CI: 3-26%)[Figure below]. Relapse rate was 29%,
and cumulative incidence of non relapse mortality (NRM) was
46%. Less NRM was seen among pts who had allo-HCT after
year 2002, year in which molecular class I HLA typing was incor-
porated (32% vs. 64%; p 5 0.9); improved PFS was also observed
after 2002 (22% vs. 0% before 2002, p 5 0.5). Prior allo-HCT was
not a risk factor for adverse outcomes with PFS of 20% with prior
HCT vs. 7% for pts without prior allo-HCT (p 5 0.7) and NRM
rates were comparable (20% vs. 58%; p 5 0.3). Seven pts are alive,
with a median follow-up of 11.3 months. Causes of death (n 5 26)
were relapse (n 5 7), infections (n 5 8), GVHD (n 5 5), other (n 5
3), and unknown (n 5 3).
Conclusions: Pts in CR3may benefit from allo-HCT, but should be
considered for investigational approaches given high non-relapse
and relapse mortality.
334
BROAD EXPRESSION OF A MINOR HISTOCOMPATIBILITY ANTIGEN RE-
SULTS IN IMPAIRED ANTITUMOR IMMUNITY THAT CANNOT BE OVER-
COME WITH DENDRITIC CELL VACCINATION
Shand, J.C.1, Capitini, C.M.2, Qin, H.2, Fry, T.J.2 1Johns Hopkins Uni-
versity-National Cancer Institute Combined Fellowship, Baltimore and
Bethesda, MD; 2National Cancer Institute, Bethesda, MD
Although allogeneic transplant remains a potent immunotherapy
for high-risk hematopoetic malignancies, relapse is the main cause
of treatment failure. We, and others, have shown that alloreactivity
associated with minor histocompatibility antigen (miHA) mismatchreduces quantitative responses to vaccines targeting tumor-specific
antigens. The effect of miHA mismatch on the antitumor response
when the tumor also expresses the miHA has not been well-studied,
and could provide important insight into the biology of the graft-ver-
sus-tumor effect. We therefore utilized a murine allotransplant sys-
tem in which donors and recipients weremismatched at the clinically
relevant male miHA HY, followed by DLI with HY-specific T cells
and challenge with an HY-expressing tumor. Professional HY anti-
gen presentation was provided at the time of DLI using an activated
male dendritic cell (DC) vaccine. Recipients were monitored for
clinical GVHD and antitumor responses measured by tumor-free
and overall survival. Further analysis of HY specific T-cells in sec-
ondary lymphoid organs was performed by flow cytometry using
congenic markers.WhenHY is expressed only on the tumor, follow-
ing syngeneic transplant of female (HY-naive) T-cell depleted mar-
row into female recipients, there is 100% tumor-free survival
following HY-specific DLI and male vaccination. However, when
HY is expressed in all nonhematopoetic tissues, following transplan-
tation of female marrow into male recipients, there is approximately
20% tumor-free survival regardless of whether an activatedmale DC
vaccine is given. Interestingly, expression of HY in both the non-
hematopoetic and hematopoetic (when male marrow is transplanted
into female recipients) compartments produces a robust expansion of
HY-specific T-cells, suggesting that the impaired antitumor immu-
nity is due to dysfunction, rather than clonal deletion. Indeed, nearly
100% of HY-specific T-cells from secondary lymphoid organs ex-
press high levels of PD-1 in the allogeneic transplant setting, com-
pared to low levels in syngeneic recipients and no expression in
lymphocytes reconstituted independently of the DLI. Studies are
underway to functionally characterize these exhausted alloreactive
T cells and and identify targets for therapeutic blockade to restore
the effectiveness of antitumor vaccination in the allotransplant set-
ting while minimizing GVHD.335
THE IMPACT OF HCV SERO-POSITIVITY OF RECIPIENTS ON CLINICAL
OUTCOMES FOLLOWING ALLOGENEIC HSCT IN JAPAN
Nakasone, H.1,15, Yakushijin, K.2,15, Kurosawa, S.3,15, Ogawa, H.4,
Ohashi, K.5, Eto, T.6, Sakamaki, H.5,7, Morishima, Y.8,9,
Nagamura, T.10,11, Suzuki, R.12,15, Murata, M.13, Taniguchi, S.14,15,
Fukuda, T.3,15 1Saitama Medical Center, Jichi Medical University;
2Kobe University Hospital; 3National Cancer Center Hospital; 4Hyogo
College of Medicine; 5Tokyo Metropolitan Cancer and Infectious Disease
Center, Komagome Hospital; 6Hamanomachi Hospital; 7The Japan Soci-
ety for Hematopoietic Cell Transplantation; 8Aichi Cancer Center Re-
search Institute; 9 Japan Marrow Donor Program; 10Research Hospital,
The institute of Medical Science, The University of Tokyo; 11 Japanse
Cord Blood Bank Network; 12Nagoya University School of Medicine;
13Nagoya University Graduate School of Medicine; 14Toranomon Hospi-
tal; 15Working Group for Complications Associated with SCT Other
Than GVHD
Background: It is estimated that over 2,000,000 people suffer from
hepatitis C virus (HCV) infection in Japan. Therefore, HCV infec-
tion is one of major liver diseases. In hematopoietic stem cell trans-
plantation (HSCT), HCV infections of recipients might induce
a transient liver dysfunction, and an increasing risk of veno-occlusive
disease (VOD), although these are controversial. In addition, the ge-
notypes of HCV in Japan are considered different from those in
Western countries. Therefore, we have assessed the impact of
HCV sero-positivity of recipients on clinical outcomes in Japan.
Patients: The population was based on TRUMP data confirmed in
2010. The eligible population included the all recipients who re-
ceived an initial allogeneic HSCT since 2006 and whose data about
age, gender, HCV sero-positivity of recipients and status of survival
at last observation were available.
Results: We identified 136 and 7720 recipients with and without
HCV, respectively. Although more recipients with HCV tended
to be male (p 5 0.054) and to receive female to male HSCT
(p 5 0.081), there were no differences in other background. The
recovery of more than 5x10^10/L platelet was significantly later
in recipients with HCV (38 vs 47 days, p 5 0.013), while there
was no significant difference in neutrophil engraftment. There
were no differences between groups without and with HCV in


Is the Use of 9/10 HLA Unrelated Donors Still Acceptable in Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies? Comparison with Transplants from 10/10 HLA Unrelated Donors and Siblings 

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Is the Use of 9/10 HLA Unrelated Donors Still Acceptable in Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies? Comparison with Transplants from 10/10 HLA Unrelated Donors and Siblings

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