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

424s Leukemia, Myelodysplasia, and Transplantation
6532 Poster Discussion Session (Board #24), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Outcomes of patients older than 60 years with acute lymphoblastic
leukemia: Survey from the Surveillance, Epidemiology, and End Results
(SEER) program. Presenting Author: Jae Hong Park, Leukemia Service,
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: The cure rate of pediatric acute lymphoblastic leukemia (ALL)
has increased over the last 4 decades to above 80%, compared to a much
smaller improvement in adults aged � 60 years. However, outcome
information on older ALL patients (age � 60 years) is limited. Only a few
clinical trials include the older patients, apply the same regimens developed
for adults of all ages, and report a very poor outcome with no
improvement over time. We therefore conducted a population-based survey
of older ALL patients focusing on early death (ED) rates and changes in
outcome over the last 30 years. Methods: Data from 9 population-based
cancer registries that participate in the National Cancer Institute’s SEERprogram
were used to identify patients aged 60 or older with a diagnosis of
ALL. Survival rates at 1, 6, 12 and 24 months were estimated using
actuarial methods for 4 calendar periods: 1980-1985, 1986-1992,
1993-1999, and 2000-2006. ED was defined as death occurring within
one month of ALL diagnosis. Results: A total of 1066 ALL patients were
identified. The ED rate significantly improved over the four study time
periods from 20.2% in 1980-1985 to 13.2% in 2000-2006 (p�0.03).
The overall survival (OS) at 6 months improved from 32.8% in 1980-1985
to 45.3% in 2000-2006, but at 24 months, only a modest difference in OS
was noted across the time period (13.1% in 1980-85 vs. 17.5% in
2000-06). The median survival increased from 3 months to 6 months from
the period 1980-1999 to 2000-2006. Conclusions: Although the longterm
OS for patients aged 60 and over remains poor, there has been a slight
improvement in early mortality and median OS from 1980s to the early 21st century. While the progress in reducing ED and increasing survival at 6
months is encouraging, and may be reflecting better supportive care
measures, the limited improvement indicates poor tolerance and lack of
efficacy of the toxic, long and complex chemotherapy regimens designed
for younger adults. Therefore, future studies should be designed specifically
for older ALL patients, focusing on novel, effective, but less toxic
therapies, to further improve the short-term OS seen in the past decades
and possibly a better overall outcome.
6534 General Poster Session (Board #14A), Mon, 1:15 PM-5:15 PM
Impact of treatment prior to allogeneic stem cell transplantation for
myelodysplastic syndromes: A study on behalf of the SFGM-TC and the
GFM groups. Presenting Author: Gandhi Laurent Damaj, Centre Hospitalier
Universitaire Amiens Sud, Amiens, France
Background: Until the early 2000s, treatment prior to SCT varied according
to cytogenetics and % BM blasts and was mainly induction-type chemotherapy
(ICT). The role of Azacitidine (AZA) prior to transplant remains
uncertain. Methods: 163 consecutive pts (M/F�104/67; age � 18)
underwent alloSCT between 2005 and 2009 from sibling (n�96) or HLAallele-MUD
(10/10) (n�67). The SC source was blood (n�142) or marrow
(n�21) and conditionings were myeloablative (n�33); nonmyeloablative
(n�130). Pts who did not received neither prior ICT nor AZA were excluded
since the main objective of this study was to investigate the impact of prior
therapy on pts’ outcome. Results: At diagnosis, FAB/WHO was: 24 RA/RARS/
RCMD, 52 RAEB-1, 74 RAEB-2, 13 RAEB-t/AML; Cytogenetic: fav
(n�93), int (n�32), unfav (n�37). 98 pts received prior ICT (ICT-group)
and 65 had received AZA, either alone (AZA-group; n�48) or AZA preceded
or followed by intensive CT (AZA-chemo-group; n�17). In AZA groups, the
drug was started 38 to 941 days from transplant and discontinued 6 to 438
days before transplant with a median number of 4 cycles (range 1-26).
Overall, 119 pts were considered responders at SCT (CR, PR, mCR),
including 33 (69%) treated with AZA-alone, 9 (53%) with AZA-chemo and
77(78%) with ICT.While there were no differences between AZA-group and
ICT-group in terms of OS, EFS, relapse and NRM, having a poor risk
cytogenetic and receiving AZA-chemo prior to SCT were, in multivariate
analyses, the most important factors that adversely influenced OS with
[HR�3.03; 95% CI 1.84-4.96] (p�.0001) and [HR�2.72; 95% CI,
1.38-5.35] (p�.004), respectively. Pts of AZA-chemo group had the same
rate of relapse but significantly higher NRM rate (p�.059) than those who
received either AZA or ICT alone. Conclusions: With the goal of downstaging
underlying disease before allo-SCT, AZA treatment appears to be a
valid therapeutic approach, but mainly in pts receiving AZA alone with an
outcome at least equivalent to pts receiving ICT prior to SCT. Allo-SCT in
pts who required both AZA and chemotherapy had less satisfactory
outcomes, possibly reflecting additional toxicity and/or more resistant
disease.
6533 Poster Discussion Session (Board #25), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Impact of donor source on allogeneic stem cell transplantation for Philadelphia
chromosome-negative acute lymphoblastic leukemia. Presenting Author:
Satoshi Nishiwaki, Department of Hematology and Oncology, Nagoya
University Graduate School of Medicine, Nagoya, Japan
Background: Although allogeneic stem cell transplantation (allo-SCT) could
improve the outcome of adult Philadelphia chromosome-negative acute
lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source,
particularly the position of cord blood (CB) transplantation, is still uncertain.
Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients
transplanted at the first time between 1998 and 2009 with myeloablative
preparative regimens who were registered in the Japan Society for Hematopoietic
Cell Transplantation database. Two hundred and thirty-three
received CB transplantation [first complete remission (CR1): 95, subsequent
CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor
(URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received
allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR:
207). Results: Overall survival (OS) in patients after CB transplantation in
CR1 was comparable with that after allo-SCT from URD or RD [57% in CB,
64% in URD, and 65% in RD at 4 years, respectively, P�0.11]. Donor
source was not a significant risk factor for OS in multivariate analysis.
Although URD was a favorable factor for relapse and an unfavorable factor
for non-relapse mortality (NRM), CB was not a significant factor for them
[Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively
(P�0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years,
respectively (P�0.0001)]. Among CB recipients in CR1, age at allo-SCT
(45 years or older) was solely a significant adverse prognostic factor in
multivariate analysis. Among patients younger than 45 years who received
allo-SCT in CR1, OS after CB transplantation was significantly better than
that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%,
P�0.04). Similarly, OS was not different by donor source in subsequent CR
or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD,
P�0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P�0.20 at 4
years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes
as either RD or URD in any disease status. CB transplantation is a
good alternative for adult Ph(-) ALL patients without a suitable RD or URD.
6535^ General Poster Session (Board #14B), Mon, 1:15 PM-5:15 PM
Immune-reconstitution after combined haploidentical and umbilical cord
blood transplantation. Presenting Author: Koen van Besien, Weill Cornell
Medical College, New York, NY
Background: Umbilical cord blood (UCB) stem cells are frequently employed
for allogeneic stem cell transplantation. However, delayed myeloid
and lymphoid immune-reconstitution with UCB transplantation leads to
increased risk of infections. We recently reported a pilot study combining
UCB with a HLA haploidentical donor (Liu et al. Blood. 2011). Here, we
report the immune reconstitution after the haploidentical-cord blood
transplantation. Methods: Pts received reduced-intensity conditioning with
fludarabine/melphalan/rATG and were assessed for lymphocyte subsets,
serological response to pneumococcal vaccination, Cylex Immuknow assay
which measures amount of ATP secreted by CD4 lymphocytes on stimulation
by PHA, and T-cell spectratyping. Results: 45 pts, enrolled between
01/2007 and 04/2011, are included in this analysis. The median absolute
lymphocyte subset counts at serial time-points are shown in the Table. The
median absolute values of CD3, CD4 and CD8 counts remained below the
normal range throughout the 1st year post-transplant. The NK-cells and
B-cells reached normal range by day 30 and day 100, respectively.
Serological response to pneumococcal vaccination was seen in 7/17
(defined as seroconversion or �3 fold rise in titers of serotype 14, 19F and
23F) evaluable pts at a median 74 days after vaccination. Immuknow assay
showed that 6/6 pts tested within first 30 days of transplant had low values
whereas 5/8 tested �1yr had normal/high values. Of the 9 pts who were
assessed for T-cell receptor repertoire by T-cell spectratyping, 7 had a
polyclonal, complex T cell repertoire similar to healthy controls. CMV
viremia requiring treatment occurred in 14 patients. EBV reactivation
occurred in 18 pts and 5 developed PTLD 68 to 314 days after transplant.
Conclusions: Haploidentical cord blood transplantation leads to rapid
myeloid recovery and recovery of B-cell and NK cell numbers. T-cell
recovery is more delayed, but at 1-year most pts have a polyclonal T cell
repertoire and robust T-cell responses.
Absolute count, median
Day 30
N�28
Day 100
N�31
Day 180
N�23
Day 365
N�15
Total lymphocyte 256 747 959 1,354*
CD3 3.5 25 114 447
CD4 2 6 70 194
CD8 2.5 8 30 146
CD19 1 297* 401 439
CD56 (CD3-)
* Within normal range.
220* 228 267 150
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