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

446s Leukemia, Myelodysplasia, and Transplantation
6620 General Poster Session (Board #24G), Mon, 1:15 PM-5:15 PM
Azacitidine as induction therapy of elderly patients with acute myelogenous
leukemia. Presenting Author: Cyrus Khan, West Penn Allegheny Health
System, Pittsburgh, PA
Background: Effective alternative treatment of elderly patients (aged � 60
years) with acute myelogenous leukemia (AML) remains challenging.
Elderly patients with AML respond poorly to standard induction regimens
and have high treatment related mortality. In a prior retrospective analysis
of elderly patients with AML performed at our institution, azacitidine (AZA)
showed an overall response rate (ORR) of 60% with limited toxicity.
Methods: This is a prospective, phase II open-label study using AZA in
patients �60 years with AML. Inclusion criteria: Newly-diagnosed non-M3
AML and ECOG � 2. Patients with circulating blast count �30,000/mcl
were treated with hydroxyurea until � 30,000/mcl. AZA was administered
at 100 mg/m2 subcutaneously for 5 consecutive days every 28 days until
disease progression or significant toxicity. Results: In all, 15 patients were
enrolled last follow-up being 8/2/11. The mean age of patients is 74 years
(range: 64–82). Mean ECOG score was 1. Mean baseline bone marrow
blast count was 52% (range: 25–92%). ORR was 46% (n�7) with
complete response (CR) in 3 (20%) patients and partial response (PR) in 2
(13%) patients according to NCI response criteria, and hematologic
improvement (HI) in 2 (13%) patients according to IWG response criteria.
The mean number of days on treatment was 198 (range: 13–724). The
mean time to best response among responders was 95 days (range:
44-279). The mean number of days hospitalized for diagnosis plus
treatment or disease-related complication was 19 (range: 5–56), with the
majority of therapy administered in an outpatient setting. Mean overall
survival (OS) from diagnosis for all patients was 355 days (range: 13–908)
and mean OS for responders was 532 days (range: 120–908). Nonhematological
toxicity was limited to mild injection site skin reaction and
fatigue in 73% (11/15). No treatment-related deaths were observed. The
dose and schedule of AZA remained constant in a majority of the patients.
Conclusions: This study suggests that a 5-day schedule of SC AZA at 100
mg/m2 to elderly patients with newly-diagnosed AML is a feasible,
well-tolerated and effective alternative to standard induction chemotherapy.
6622 General Poster Session (Board #25A), Mon, 1:15 PM-5:15 PM
Use of granulocytes concentrates from a single high yield apheresis to
support more than one patient. Presenting Author: Fleur M. Aung, University
of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Allogeneic granulocyte transfusion therapy is sometimes the
only therapeutic option in immunocompromised neutropenic leukemic/
HSCT patients with life threatening bacterial and fungal infections.
Collection of larger cell doses of granulocyte concentrates (GC) by automated
apheresis following G-CSF/steroids administration has renewed
interest and its use has grown steadily. Methods: Donors were recruited from
family/friends of the patients and informed consent was obtained. GCs were
collected via donor stimulation with a single subcutaneous dose of G-CSF
(600 mcg). First time donors received an oral dose of dexamethasone (8
mg). GCs were harvested by Hetastarch-assisted leukapheresis 12 hours
later via peripheral venous access with the continuous flow cell separator
Spectra (COBE Caridian BCT, Lakewood, CO). Results: GCs were collected
from 93 donors (67M: 26F; age median 40 (19-73 years) and 1½xblood
volume processed median 7048 (3212-8085 mL). The pre/post wbc were
median 8.1 (4.1-22.8)/ 42.7 (22.4-77.5). The volume collected was
based on the post G-CSF wbc count (� 35 K/UL - 800 mL; �35 K/UL
between 600-700 mL). The original yield (10 x10e) was median 9.7
(5.1-17.2 units), volume median 718 (538-860 mL) and WBC median
132.7 (84.2 -241.6 K/UL per bag). The Split GCs were median 4.48
(2.70-7.72 units), with neutrophils median 87% (54-97% per bag). GCs
were transfused to 51 patients (31M: 20F; age median 58 [19-83 years])
who received median 3.5 (1-18 split units), containing wbcs median
10734.69 [5778-42 -162698.09 (x10^3/uL)/unit) and achieved a WBC
increment median 0.2 (0.0-8.3K/UL). Conclusions: The GCs were split due
to the primary care team’s reluctance to transfuse the entire volume of the
product due to volume restrictions or for some other medical reason. The
same rationale to split platelets from high yield single apheresis was used
to split our GC products. We found that GCs from each donor was utilized
maximally and also brought partial relief to other patients who lacked
donors. We would like to make the case that when adequate numbers of
GCs are collected it may be feasible to split the unit. This may offer a
glimmer of hope to other patients in need of GCs who lack a donor network
support.
6621 General Poster Session (Board #24H), Mon, 1:15 PM-5:15 PM
Phase I dose escalation study of bortezomib in combination with lenalidomide
in patients with myelodysplastic syndromes (MDS) and acute myeloid
leukemia (AML). Presenting Author: Philip C. Amrein, Massachusetts
General Hospital/Harvard Medical School, Boston, MA
Background: Both bortezomib (Bz) and lenalidomide have clinical activity in
patients with MDS and AML. We conducted a phase I dose escalation study
to determine the maximal tolerated dose (MTD) of Bz in combination with
lenalidomide. Methods: Patients with MDS (IPSS score � 0.5 or therapyrelated)
received Bz by IV bolus on Days 1, 4, 8, and 11 and lenalidomide
10 mg/day PO on Days 1-21 in 28 day cycles for up to 9 cycles. Three doses
of Bz were tested (0.7, 1.0, or 1.3 mg/m2 ). Cohorts consisted of 3-6
patients; the dose of Bz was escalated if there were � 2 dose limiting
toxicities (DLTs). Growth factor support and transfusions were permitted.
Dose limiting toxicities (DLTs) were assessed during the first cycle and were
defined as severe neutropenia (absolute neutrophil count � 250/ul),
thrombocytopenia (platelet count � 10,000/ul), grade � 2 neurotoxicity,
or other grade � 3 non-hematologic toxicity. Following determination of the
MTD, enrollment opened to patients with relapsed and refractory AML and
those with untreated high risk disease for whom induction therapy was not
indicated. Responses were assessed by IWG 2006 criteria for MDS and
IWG 2003 criteria for AML. Results: 23 patients (14 men) were enrolled;
one patient was inevaluable due to disease progression prior to starting
protocol therapy. The median age was 73 years (range 54-87). There was 1
DLT observed, neutropenia, in 6 patients treated with 1.0 mg/m2 Bz and no
DLTs at 0.7 or 1.3 mg/m2 . The median number of cycles was 2 (range 2-9).
Grade � 3 toxicities possibly attributable to the treatment at any dose level
were: anemia (2), thrombocytopenia (10), leukopenia (3), infection (1),
rash (2), dyspnea (1), dizziness (1), hypotension (1), pneumonia (2) and
neuropathy (1). Among the 14 patients with MDS, 1 patient with RARS
experienced a CR and 2 with RAEB-2 experienced marrow CR (mCR).
Among the 8 patients with AML, there was 1 CR. Conclusions: The maximal
tested dose of Bz (1.3 mg/m2 ) in combination with lenalidomide is safe.
Responses were seen in MDS and high risk AML. Future testing of this
regimen is planned.
6623 General Poster Session (Board #25B), Mon, 1:15 PM-5:15 PM
Novel risk factors for osteonecrosis of the jaw in multiple myeloma: A
RADAR report. Presenting Author: Jaimee S. Holbrook, Department of
Dermatology, Northwestern University Feinberg School of Medicine, Chicago,
IL
Background: Osteonecrosis of the jaw (ONJ) was identified in 2001 and is
commonly seen in multiple myeloma (MM). The objective of this study is to
evaluate novel risk factors in MM cases from a retrospective database. We
hypothesized that ONJ may be related to stem cell transplant, chronic
kidney disease and active smoking. Methods: We conducted a retrospective
case-control study of 231 MM cases (from January 1, 1998 to September
30, 2010) identified from the electronic data warehouse (EDW) at
Northwestern University (NU). The EDW is cross-institutional and integrates
clinical data across NU. It comprises more than 2.3TB of data on
roughly 2 million patients. The search terms used were: bisphosphonates,
pamidronate, zoledronic acid, multiple myeloma, plasma cell disorders,
osteonecrosis of the jaw, jaw abscess, dental abscess, among other terms
described in literature. Data was abstracted onto a standardized form by 2
trained abstractors and validated by a clinician reviewer (BJE). Known and
hypothesized new risk factors were abstracted, including duration of
myeloma, treatment used, duration of bisphosphonate use, renal function
indices, chemotherapy (vincristine, doxorubicin (A), dexamethasone (D) ,
thalidomide (T), cisplatin (P), cyclophosphamide (C), etoposide (E), novel
agents [bevacizumab, sorafenib, angiostatin]) GCSF, smoking, and MM
clinical stage. Analyses included T test, Wilcoxon, and log rank analysis.
Results: ONJ occurring after MM diagnosis was identified in 33 cases out of
a total of 233 cases of MM. ZOL, VAD, DT-PACE, and diabetes were more
common in ONJ cases. Log rank analysis identified 2 risk factors for ONJ,
the use of DT-PACE (p� 0.003), and complete and partial remission
(p�0.007). Stem cell transplant and chronic kidney disease were not
associated with ONJ. Conclusions: We identified novel risk factors for ONJ
in MM, mainly partial or complete remission and use of DT-PACE. These
results should prompt clinicians to heightened awareness and increased
surveillance for the symptoms of ONJ for patients treated with DT-PACE.
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