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

6536 General Poster Session (Board #14C), Mon, 1:15 PM-5:15 PM
Impact of ATG on new HLA groups for unrelated donor allogeneic stem cell
transplantation. Presenting Author: Soo Jung Lee, Department of Hematology/Oncology
and Stem Cell Transplantation Unit, Kyungpook National
University Hospital, Kyungpook National University School of Medicine,
Daegu, South Korea
Background: The outcomes of unrelated donor transplantation have improved
with refinements in HLA testing. Recently, grouping of HLA
matching for unrelated donor was suggested, defining by well-matched,
partially-matched, and mismatched. In the current study, the role of ATG
for each group was evaluated. Methods: A total of 92 patients diagnosed as
hematologic diseases and received allogeneic stem cell transplantation
(SCT) from unrelated donor were retrospectively analyzed. Results: Nineteen
patients were classified as well-matched, 42 as partially-matched,
and 31 as mismatched. Among them, 57 patients received anti-thymocyte
globulin (ATG) as graft-versus-host disease (GVHD) prophylaxis. The overall
survival (OS) rate was higher for well-matched group (83%) compared to
partially-matched (54%) and mismatched (34%, p�0.076). For partiallymatched
group, the OS was significantly improved with ATG (83.3% vs.
38.6%, p�0.018). But, the OS was not different between groups with or
without ATG for well-matched (87.5% vs. 66.7%, p�0.487) and mismatched
(32.4% vs. 41.7%, p�0.215). ATG decreased the cumulative
incidence of grade 3-4 acute GVHD (10% vs. 40.2%, p�0.068) and severe
chronic GVHD (21.2% vs. 52.2%, p�0.037). The use of ATG (HR�0.248,
p�0.029) was related with favorable OS for partially-matched group.
However, the favorable effect of ATG was not observed in well-matched and
mismatched groups. Conclusions: ATG effectively improved survival rate for
partially-matched group in unrelated donor transplantation. However, the
positive effect of ATG was not observed in well-matched and mismatched
group.
6538 General Poster Session (Board #14E), Mon, 1:15 PM-5:15 PM
The outcomes of allogeneic stem cell transplantation in AML patients with
monosomal karyotypes. Presenting Author: Sang Kyun Sohn, Department
of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook
National University School of Medicine, Daegu, South Korea
Background: The prognosis of acute myeloid leukemia (AML) with monosomal
karyotype (MK) was reported extremely poor. We investigated the role
of allogeneic stem cell transplantation (allo-SCT) for those with MK.
Methods: A total of 114 patients who received allo-SCT for treatment of
AML were retrospectively analyzed. All patients were treated with standard
induction chemotherapy with anthracycline and cytarabine. Cytogenetic
abnormalties were grouped according to recently published MRC criteria
and MK was defined as at least two autosomal monosomies or one
monosomy plus one or more structural abnormality. Results: Thirteen
patients had favorable cytogenetic risk, 78 intermediate, 11 adverse
without MK, and 12 adverse with MK at the time of diagnosis. Among 12
patients with MK, 5 (41.7%) achieved CR after induction therapy, 1
(8.3%) relapsed and 6 (50.0%) refractory at the time of allo-SCT. The
2-year overall survival (OS) was significantly lower for patients with MK
(17.5%) compared to favorable (76.9%), intermediate (61.0%), and
adverse without MK (36.4%, p�0.017). In the multivariate analysis, those
with MK was related with extremely poor outcomes (HR 6.02, p�0.008),
which was independent risk factor for OS. Survival benefit was observed in
MK group with chronic GVHD compared to those without chronic GVHD.
The median survival was 272 days with chronic GVHD (95% CI 204-339
days) compared to 159 days (95% CI 76-172 days) without chronic GVHD
(p�0.010). Conclusions: The prognosis remained poor in patients with MK
despite of allo-SCT. Innovative approaches to induce GLV effects are
needed to improve SCT outcomes in patients with MK.
Leukemia, Myelodysplasia, and Transplantation
425s
6537 General Poster Session (Board #14D), Mon, 1:15 PM-5:15 PM
Low day 100 transplant-related mortality (TRM) and relapse rate following
clofarabine (CLO) in combination with cytarabine, total body irradiation
(TBI), and allogeneic stem cell transplantation (AlloSCT) in children,
adolescents, and young adults (CAYA) with poor-risk acute leukemia.
Presenting Author: Kavita Radhakrishnan, New York Medical College,
Valhalla, NY
Background: CAYA with ALL or AML in third complete remission (CR3),
refractory relapse (RR) or induction failure (IF) have an extremely poor
prognosis, �20% EFS (Gaynon, BJH, 2005;Wells, JCO, 2003). CLO, an
inhibitor of DNA polymerase and ribonucleotide reductase, has significant
activity in CAYA with relapsed ALL/AML (Jeha, JCO 2006,2009) and
synergy with cytarabine (Faderl, Blood, 2005). We sought to determine
safety, day-100 TRM, and overall survival (OS) associated with CLO,
cytarabine and TBI followed by AlloSCT in CAYA with poor-risk ALL/AML.
Methods: This is a multi-center phase I/II trial of a novel conditioning
regimen of CLO (dose escalation: 40mg/m2 [n�3], 46 mg/m2 [n�3], 52
mg/m2 [n�19]) x5d, sequential (4 hrs later) cytarabine 1000 mg/m2 x6d
and TBI (1200cGy) followed by AlloSCT from matched related or unrelated
donors in CAYA with ALL/AML in CR3, RR or IF. Patients with unrelated
donors received R-ATG. GVHD prophylaxis consisted of tacrolimus and
MMF (Bhatia/Cairo, BBMT, 2009). Kaplan-Meier method was used to
determine the probabilities of engraftment, GVHD, TRM and OS. Results:
25 pts, median age: 11.3 yrs (1.5-20.7); M:F: 19:6, ALL/AML: 22:3 (10
CR3, 3 RR, 12 IF), 10 related donors, 15 unrelated donors (9 BM/PBSCs,
6 UCB). Median TNC and CD34 dose was 4.47x108 /kg and 4.84x106 /kg
for BM/PBSCs and 4.0x107 /kg and 2.8x105 /kg for UCB, respectively.
Probabilities of neutrophil, platelet engraftment and grade II-IV aGVHD
were 100%, 92.9% and 47.5%, respectively. CLO dose was tolerable at
52mg/m2 /d x5d without dose limiting toxicity. Probability of Day 100 TRM
was only 4.3%. Probability of 1-yr PFS and OS were 51% (CI95: 28-71%),
and 43% (CI95: 22-63%) respectively. Conclusions: Preliminary results
suggest this novel regimen followed by AlloSCT is safe and well tolerated in
CAYA with poor-risk ALL/ AML with CLO dose 52 mg/m2 . Results are
encouraging with respect to low risk of day 100 TRM and leukemic relapse
associated with this conditioning regimen in this poor-risk population.
6539 General Poster Session (Board #14F), Mon, 1:15 PM-5:15 PM
Effect of IL-22 on intestinal stem cells, GVHD-related tissue damage, and
GVL. Presenting Author: Alan M. Hanash, Memorial Sloan-Kettering Cancer
Center, New York, NY
Background: Intestinal graft vs. host disease (GVHD) is a major complication
of allogeneic bone marrow transplantation (allo-BMT). Strategies to
limit GVHD by selective promotion of epithelial regeneration in the absence
of immunosuppression are largely unknown. Methods: We investigated the
role of IL-22 in allo-BMT by utilizing wild type and IL-22 knockout (KO)
mice as donors or recipients in allo-BMT. Results: We found that administration
of an anti-IL-22 neutralizing antibody to allo-BMT recipients during
the first month post-BMT led to increased GVHD mortality, indicating that
IL-22 functioned to reduce GVHD severity post-BMT. In contrast, use of
IL-22 KO donor T cells did not impair their ability to eliminate A20
lymphoma cells upon tumor challenge, thus indicating that IL-22 was not
essential for donor T cells to mediate graft vs. lymphoma (GVL) responses.
BMT with WT donors and recipients indicated that IL-22 levels in small and
large intestine were increased after BMT and after radiation injury (RI)
without BMT. IL-22 upregulation after RI was dependent on the presence
of IL-23p40. Although intestinal IL-22 levels were increased after T
cell-depleted (TCD) BMT, intestinal IL-22 was reduced by GVHD, as IL-22
production was mediated by host-derived innate lymphoid cells (ILC) that
were eliminated by GVHD. Furthermore, host-derived IL-22 was critical for
reduction of GVHD morbidity, mortality, and intestinal pathology. GVHD in
IL-22 KO mice led to increased apoptosis in epithelial crypts where the
intestinal epithelial stem/progenitor cell niche is located. Immunohistochemistry
and immunofluorescence demonstrated IL-22 receptor expression
on intestinal stem cells (ISC) and progenitors. Allo-BMT in Lgr5-LacZ
reporter mice indicated that ISC were targeted by GVHD, and GVHD in
IL-22 KO mice led to dramatic ISC depletion. Conclusions: IL-22 is critical
for protection of host epithelium during GVHD and critical for protection of
ISC, and it does not contribute to donor T cell GVL responses. These
findings may have broad relevance for protection of ISC and intestinal
epithelium in clinical GVHD and other inflammatory intestinal diseases,
and may be useful for clinical separation of pathologic GVH and therapeutic
GVL responses.
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