Bensinger, W.I.

Gooley, T.

Holmberg, L.A.

Maloney, D.

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wk4) and all patients IFRT (20-30 Gy) post AutoSCT. Three
patients did not proceed onto RI AlloSCT (1 HD parental with-
drawal, 1 Burkitts PD, and 1 Burkitts too early post autoSCT) 9/12
proceeded to RI AlloSCT.. RI: Fludarabine 30 mg/m2  5d,
Busulfan 3.2 mg/kg  2d, and R ATG 2 mg/kg  4d (UCB
recipients)  AlloSCT (1 related 6/6 PBSC, 1 related 5/6 PBSC, 1
8/10 MUD, 1 5/6 UCB, 5 4/6 UCB). GVHD prophylaxis: tacroli-
mus (0.03 mg/kg CIVI) on day-1- 60 and MMF (15 mg/kg
IV/PO q12h) day 1 &luAmn;28 as previously reported (Os-
unkwo/Cairo et al BBMT 2004). Six HD (3 stage IIA, 1 stage IIB,
1 stage IIIB, 1 stage IVB) and 3 NHL ( ALCL n 1, lymphoblastic
n  1, DLBCL n  1, ) have been treated. MA AutoSCT  RI
AlloSCT were well tolerated in all patients. Median time to RI
AlloSCT after MA AutoSCT was 130 days. Median F/U is 924
days. Toxicity: grade 3 hematuria (n  1), grade 3/4 infection
without neutropenia (n  4), grade 4 infection with neutropenia
(n  2), grade 4 pulmonary ﬁbrosis (n  1), grade 4 hearing loss
(n  1), and grade 4 thrombocytopenia (n  1), grade 4 neuro-
toxicity (n  1). All patients achieved 100% donor chimerism.
GVHD: grade II-III aGVHD (2/8), cGVHD (3/8). Four of 6 HD
patients: are NED; 2 patients died; PD n  1 and cGVHD n  1.
Two of 3 NHL: are NED, 1 died of PD. There has been one death
(NRM) from infection day 632. The estimated OS at 1 year is
56.2%. In summary, MA AutoSCT followed by IFRT, targeted
monoclonal antibody therapy, and RI AlloSCT is feasible and well
tolerated in pediatric patients with relapsed HD/NHL. A larger
controlled study with longer follow up is required to determine if
this approach will reduce relapse, MDS, long-term toxicity, and
improve EFS.
331
BORTEZOMIB PRIOR TO AUTOLOGOUS TRANSPLANT IN MULTIPLE
MYELOMA: EFFECTS ON MOBILIZATION, ENGRAFTMENT, AND MARK-
ERS OF IMMUNE FUNCTION
Uy, G.L.1, Peles, S.1, Fisher, N.M.1, Tomasson, M.H.1, DiPersio, J.F.1,
Vij, R.1 Washington University School of Medicine, St. Louis, MO.
To explore the potential role of bortezomib (VELCADE®) in
the frontline treatment of multiple myeloma, we conducted a study
of bortezomib administered prior to autologous transplant. The
primary objective was to determine the effects of bortezomib on
cytokine based mobilization and engraftment. Given the critical
role NF-B in lymphocyte development and survival, we also
sought to determine the effects of bortezomib on markers of
immune function. Following induction, two cycles of bortezomib
1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day
treatment cycle. Peripheral blood stem cells were mobilized with
G-CSF 10 mcg/kg/day for 5 days and harvested by large volume
apheresis (20 L/day) until a minimum of 2.5  106 CD34
cells/kg were collected. High-dose melphalan 200 mg/m2 was
administered followed by autologous stem cell transplant with
GM-CSF 250 mcg/m2/day support until neutrophil engraftment.
Peripheral blood was collected at baseline (cycle 1, day 1) and after
treatment with bortezomib (cycle 2, day 18) for analysis of lym-
phocyte subsets and serum cytokines. Forty patients were enrolled
with 37 continuing on to autologous transplant. Prior to receiving
bortezomib, 20 patients had been previously treated with an an-
thracycline, 22 with thalidomide, and two patients had no induc-
tion therapy. Stem cell collection was successful in 37 of 38 patients
(97%) with the median ﬁrst collection of 4.24  106 CD34cells/
kg. Following transplant, all patients engrafted with a median time
to neutrophil engraftment (ANC  500/mm3) of 11 days (range
9-14 days) and platelet engraftment (platelet count 20,000/mm3)
of 11 days (range 9-31 days). In an intention-to-treat analysis at
100 days post-transplant, we observed a CR in 6 patients (15%), a
near CR in 10 patients (25%) and a PR in an additional 19 patients
(48%) for an overall response rate of 88%. Following treatment
with bortezomib, we observed a 38% decrease in CD56 NK cells
(P  .02) and a 26% increase in CD4/CD8 ratio (P  .0006) with
a 18% decrease in CD8 cytotoxic T-cells (P  .054). No signif-
icant changes were detected in either Th1 or Th2 serum cytokine
levels: IL-2 (P  .116), TNF-alpha (P  .854), IFN- (P  .070),
IL-4 (P  .240), IL-6 (0.236), IL-10 (0.151). We conclude that
pretransplant bortezomib does not adversely impair stem cell mo-
bilization or engraftment. Bortezomib also decreases NK and cy-
totoxic T cell subsets without measurable change in serum Th1
and Th2 cytokines.
332
IMMUNOTHERAPY WITH RITUXIMAB/INTERLEUKIN 2 (IL-2) FOLLOW-
ING AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANT
(ASCT) AS TREATMENT FOR CD20 POSITIVE NON-HODGKIN’S LYM-
PHOMA
Holmberg, L.A.1,2,3, Maloney, D.1,2,3, Gooley, T.1,2, Bensinger,
W.I.1,2,3 1. Fred Hutchinson Cancer Research Center, Seattle, WA; 2.
University of Washington School of Medicine, Seattle, WA; 3. Puget
Sound Oncology Consortium, Seattle, WA.
Relapse of NHL remains a problem after ASCT. Early after
ASCT, the immune system is not very active and the addition of
immunotherapy may decrease the incidence of relapse and prolong
survival. In an initial phase I/II trial at our center, the immune-
modulator IL-2 increased NK and LAK activity in vitro. Since
Rituximab can lyse CD20 cells by ADCC, adding Rituximab to
IL-2 should boost its effectiveness. From January 2000, 20 patients
with CD20 NHL received ASCT followed by Rituximab/IL-2
therapy. The pathology at the time of ASCT included: follicular
small/large cleaved (n  2), diffuse large/T cell rich B cell (n  8),
mantle cell (n  4) and transformed from indolent to diffuse (n 
6). The disease status was primary refractory (n 3), relapse 1(PR)
(n  5), remission 1 (n  3), remission 2 (n  8) and relapse
2/refractory (n  1). The median age of the patients was 46 years
(range 31-70). The median time to initiation of the therapy was 79
days after transplant (range 49-100). The treatment schema was:
IL-2 0.6 106 IU/m2/day sc times 12 weeks, followed by 1.4 106
IU/m2 sc three times/week for an additional 12 weeks (for a total
of 24 weeks of IL-2 therapy). Rituximab was given iv at 375 mg/m2
for a total of 4 doses: beginning one day prior to starting IL-2, then
between days 25-30, 50-55 and 75-80 post beginning IL-2. NCI
Common Toxicity Criteria were used to evaluate adverse events.
Most common grade 3 /4 toxicities were neutropenia (n  9),
pneumonia (n  2), hypothyroidism (n  1), hypokalemia (n  1)
and pulmonary dysfunction (decreased DLCO) (n  1). Neutro-
penia responded to G-CSF. There were 11 infectious episodes,
pneumonia (inﬂuenza n  1) and pneumococcus strept (n  1),
oral thrush (n  2), herpes simplex (n  1), urinary tract infection
(n  1), zoster (n  1) and upper respiratory infection (n  4).
Most common side effects were fatigue, ertyheyma/indurationa/
discomfort at IL-2 injection sites and ﬂu-like symptoms. Seven
patients stopped therapy before completing 24 weeks due to sub-
dural hematoma and progression of NHL (n 1), pneumonia (n
2), decreased DLCO (n  1) and at own or physician’s choice
without grade 3/4 toxicity (n  3) at 9, 13, 14.5 weeks. With a
median follow-up of 45 months (range 14-64), 18 patients remain
alive and in compete remission. The combination of IL-2/ Ritux-
imab can be administered with acceptable toxicity and has a high
response rate. A randomized trial has been initiated to address
whether this combination therapy is beneﬁcial to patients.
333
HIGH RATES OF REACTIVATION OF VARICELLA ZOSTER VIRUS (VZV)
ASSOCIATED WITH BORTEZOMIB (VELCADE) WHEN GIVEN PRE AND
POST HIGH DOSE CHEMOTHERAPY (HDCT)
Peles, S.1, Uy, G.L.1, Fisher, N.M.1, Tomasson, M.H.1, DiPersio, J.F.1,
Vij, R.1 Washington University School of Medicine, St. Louis, MO.
We evaluated the tolerability and efﬁcacy of the proteasome
inhibitor bortezomib administered to multiple myeloma (MM)
patients both prior to, and as consolidation therapy following
HDCT, in a prospective pilot study. Patients received 2 cycles of
bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of every 21 days,
prior to stem cell collection and melphalan 200mg/m2, followed by
six cycles of consolidation bortezomib 1.3 mg/m2 given once
weekly for 4 of every 5 weeks, 90–120 days following transplanta-
tion. Of 40 enrolled patients, 33 have received at least one post
transplantation cycle of consolidation bortezomib. Patient and
Poster Session II
116


Immunotherapy with rituximab/interleukin 2 (IL-2) following autologous peripheral blood stem cell transplant (ASCT) as treatment for CD20 positive non-hodgkin’s lymphoma 

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Immunotherapy with rituximab/interleukin 2 (IL-2) following autologous peripheral blood stem cell transplant (ASCT) as treatment for CD20 positive non-hodgkin’s lymphoma

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