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

6544 General Poster Session (Board #15C), Mon, 1:15 PM-5:15 PM
Allogenic stem cell transplant (ASCT) as initial salvage for patients (pts)
with acute myeloid leukemia (AML) refractory to high-dose cytarabinebased
induction chemotherapy. Presenting Author: Naval Guastad Daver,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Outcomes of pts with AML who are refractory to High-dose
Cytarabine (HiDAC) based induction are dismal. ASCT as initial salvage
may be effective and potentially superior to repeat induction with combination
chemotherapies in such pts. Methods: 1597 AML pts were treated with
HiDAC-based induction at MD Anderson Cancer Center between 1995 and
2009. 285 primary refractory pts were identified. 28 (10%) of these
underwent ASCT as initial salvage and were reviewed. Results: Median age
was 56 years (36 to 77) and 50% were males. Median ECOG PS was 1
(0-2). Antecedent hematological disorders were present in 14 pts (50%).
Median white cell count, hemoglobin, platelet count and bone marrow (BM)
blast percentage at diagnosis were 3.5 x 109 /l (0.6 to 73.6), 7.8 g/l (6.5 to
11.4), 44 x 109 /l (9 to 615), and 43% (6-82), respectively. 9 pts (32%)
had complex cytogenetics. FLT3 mutations were identified in 2 (15%) of
13 evaluated pts. All pts were refractory to HiDAC-based induction. HiDAC
was combined with an anthracycline in 16 pts (57%) and nonanthracycline
in 12 pts (43%). Median time from induction to ASCT was
76 days (28 to 184). Median BM blast and peripheral blast at ASCT were
28% (3 to 82) and 4% (0 to 41). 21 pts (75%) had matched related donors
(18 sibling and 3 haploidentical) and 7 (25%) had matched unrelated
donors. Conditioning regimens were melphalan-based, busulfan-based,
fludarabine-based or others in 7 (25%), 10 (36%), 8 (29%) and 3 pts
(10%); respectively. Complete remission (CR) was achieved in 23 of 28 pts
undergoing ASCT (CR � 82%) with median time to CR of 31 days (26 to
134). 12 pts relapsed with median time to relapse of 5 months (2 to 19). 8
pts remain alive with median follow up of 80 months (28 to 118). Median
overall survival (OS) for the entire group is 20 months (5 to 118). In
historical series of pts with AML refractory to HiDAC-based induction,
salvage chemotherapies induced CR rates of 22% with median OS of 4
months. Conclusions: Initial salvage with allogenic SCT is feasible and
yields superior outcomes to salvage chemotherapy in primary HiDAC
refractory AML pts. Randomized studies are warranted to further explore
this treatment option.
6546 General Poster Session (Board #15E), Mon, 1:15 PM-5:15 PM
Neurotoxicity after high-dose melphalan. Presenting Author: Jose Eugenio
Najera, M. D. Anderson Cancer Center Orlando, Orlando, FL
Background: High dose melphalan (HDM) at 200 mg/m2 is the standard
preparative regimen for patients with multiple myeloma (MM) and lightchain
amyloidosis (AL) undergoing autologous hematopoietic stem cell
transplantation (auto-HCT). Neurotoxicity has been seen with HDM. In this
report we describe the incidence, clinical manifestations and outcome of
HDM- associated neurotoxicity. Methods: We performed a chart review of all
patients who received HDM and auto-HCT for MM or AL between January
2007 to December 2009 at the University of Texas MD Anderson Cancer
Center (MDACC). HDM- associated encephalopathy was defined as altered
mental status, seizure or unexplained loss of consciousness within 30 days
of auto-HCT. Patients with documented hemorrhagic or embolic stroke, or
metabolic abnormalities were excluded. Results: 451 patients were included.
Median age at auto-HCT was 59 years (range: 35-80). Thirty
patients (6.6%) had AL and 61 patients (13.5%) had a pre-transplant
serum creatinine of � 1.5 mg/dl. Nine patients (2.0%) developed HDMassociated
encephalopathy with a median of 13 days (range 4-22) from
auto-HCT. Among patients with encephalopathy, 8 (89%) developed
changes in mental status ranging from drowsiness and confusion to loss of
consciousness, while one patient had tonic-clonic seizures (11%). Of the
affected patients there were 6 (66%) females, 8 patients (89%) � 59 years
of age and only 2 patients (22%) had a creatinine clearance of � 60
ml/min. One patient was dialysis-dependent. A CT scan or MRI was
obtained in all 9 patients. Only one patient had imaging abnormalities
reported as posterior reversible encephalopathy syndrome (PRES). Electroencephalogram
(EEG) was performed on 6 patients. Epileptiform activity
was seen in one patient with clinical seizures. Mild generalized slowing was
noted in 2 other patients with mental status changes. Cerebrospinal fluid
was obtained in 2 patients and did not show any abnormalities. Complete
resolution of neurologic symptoms was seen in all patients prior to hospital
discharge, and there were no deaths. Conclusions: HDM-induced encephalopathy
was seen in only 2% patients, and it is associated with complete
neurologic recovery without any increase in transplant-related mortality.
Leukemia, Myelodysplasia, and Transplantation
427s
6545 General Poster Session (Board #15D), Mon, 1:15 PM-5:15 PM
A phase II trial 90y-ibritumomab tiuxetan in combination with reduced
intensity regimen of fludarabine (flu) and melphalan (mel) followed by
allo-HCT in patients with refractory B-cell lymphoma. Presenting Author:
Auayporn Nademanee, City of Hope, Duarte, CA
Background: RIC allo-HCT has reduced transplant-related mortality (TRM)
in patients with relapsed NHL. However, relapses do occur despite
potential graft vs. lymphoma (GVL) effect. We hypothesized that adding
Zevalin to Flu/Mel may improve disease control and reduce relapse post
allo-HCT. Methods: Patients received In- Zevalin on day -21 followed by
90 2 Y- Zevalin 0.4mCi/kg on day -14, flu 25 mg/m daily on days -9 to -5 and
mel 140 mg/m2 on day -4. Rituximab (R) level was measured on Day -22
and -15 and if the level was � 10 �g/ml, R was not given prior to In-Zevalin
or 90Y- Zevalin to enhance biodistribution. Tacrolimus and sirolimus was
used for GVHD prophylaxis. Between 10/2007 and 11/2011, 31 were
treated. Median age 55 (range 27-67), median regimen �3 (range 2-8).
Median time from diagnosis to HCT was 20 mo (range 5-105). Histology:
DLBCL (including transformed lymphoma)�14 (45%), MCL�7 (23%),
FL�5 (16%) and SLL/CLL�5 (16%). Disease status at HCT: 1CR�7,
Relapse�9, �2CR�5, primary refractory �10. Fifteen had chemoresistant
and 19 had FDG PET� at HCT. Donors: sib�13, URD�18. Results: All
patients engrafted with the median time to ANC �500 and platelet �
20,000 was 14 (range 10-28) and 13.5 days (range 11-28), respectively.
There were 10 deaths from disease progression (2) infection (5) GVHD (1)
and multi-organ failure (2). TRM at day �100 and at 1 yr was 6.5% and
17%, Five with DLBCL relapsed between 3-7 mos. Grade II-IV acute GVHD
was 65%, Grade III-IV was 16%, chronic GVHD was 65%. Fifteen became
PET- at day �100 while 4 remained PET� and relapsed. Twenty-one are
alive at a median followup of 24 mos (range 2-46). The 2 yrs OS and PFS
was 65% (95% CI, 51-75%) and 57% (95% CI, 46-67%), respectively.
Univariate analysis identified disease status predict for OS and PFS while
histology predict for PFS. Conclusions: This study demonstrates the
feasibility of adding Zevalin to flu/mel in the allo-HCT setting for B-cell NHL
and suggest that this approach could be used to provide early disease
control before GVL effect takes place. Innovative approaches should be
explored in DLBCL.
6547 General Poster Session (Board #15F), Mon, 1:15 PM-5:15 PM
Effect of radioimmunotherapy-based conditioning for autologous stem cell
transplantation on poor-risk molecular profiling in diffuse large B-cell
lymphoma. Presenting Author: Tanya Siddiqi, City of Hope, Duarte, CA
Background: Gene expression profiling has improved risk stratification of
diffuse large B-cell lymphoma (DLBCL) in the first line setting as shown by
DNA microarray analysis and immunohistochemistry (IHC). 5-year overall
survival (OS) for germinal center B-cell-like (GCB) DLBCL is significantly
better than that for non-GCB DLBCL in newly diagnosed patients. However,
in the relapsed/refractory setting, autologous stem cell transplant (ASCT)
appeared to overcome the poor prognosis of cell of origin as defined by IHC
using CD10, Bcl6 and MUM1 and there was no difference in survival
between GCB and non-GCB groups. Ibritumomab tiuxetan (Z)-BEAM
conditioning regimen for ASCT in DLBCL has produced promising response
rates and progression free survival (PFS). The role of poor risk molecular
markers in predicting outcome with the novel conditioning regimen
Z-BEAM is unknown. Methods: We evaluated cell of origin (GCB, non-GCB)
using IHC in 36 patients undergoing ASCT with Z-BEAM conditioning from
2002 to 2010. Median age of the patients was 54.5 years. There were 12
females and 24 males. 6 patients were in 1st CR/PR ( 17%), 12 had
induction failure disease (33%), 9 were in 1st relapse (25%), 1 in 2nd relapse (3%) and 8 were in �2nd CR (22%). 27 patients had chemosensitive
disease (75%) and all had prior rituximab exposure. Median number of
prior treatments was 2. IPI at transplant was mainly low risk (78%). 22
patients had GCB (61%) and 14 (39%) had non-GCB DLBCL. Results:
Median follow up is 25.6 months. 12 patients relapsed (33%) and 9 died
(25%). The major cause of death is relapse/disease progression. At 2 years,
median OS is 79% and median PFS is 64%. No significant difference in 2
year OS and PFS is noted between the GCB and non-GCB groups (p�0.07
and 0.06 respectively). Conclusions: Z-BEAM conditioning for ASCT may
overcome the poor prognostic effect of non-GCB DLBCL in relapsed/
refractory disease. Further evaluation of cell of origin using new markers
like GCET1, LMO2 and FOXP1 could confirm these results as there seems
to be better concordance of these markers with DNA microarray analysis.
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