12th Congress of the European Hematology ... - Haematologica

ly received melphalan-based chemotherapy collected a median number
of 4.4×10 6 CD34 + /kg (range 0.5-19×10 6 CD34 + /kg). The cytarabine-based
regimens were generally well tolerated. According to the NCI CTC version
3 scale, grade 3-5 toxicity was observed in two cases (7%): a patient
reactivated Herpes Zoster infection, and a patient affected by a severe
form of Churg Strauss vasculitis with kidney and lung involvement, and
a long history of immunesuppression, died of septic shock. After PBSC
collection, 4 (14%) patients received a single ASCT, 21 (75%) a double
ASCT, one (4%) patient three ASCT, and 2 (7%) were not transplanted.
All patients engrafted. The median time to neutrophil count >500×10 6 /L
was 11 days (range 9-12) and to platelet count >20×10 9 /L was 10 days
(range 0-14). Conclusions. Cytarabine-based regimens are a feasible option
to collect PBSC in MM patients. Despite one (4%) chemotherapy related
death, the treatment was well tolerated. While not active against
MM, cytarabine-based regimens allowed the collection of an adequate
number of PBSC to support a double ASCT in most patients, with a
hematopoietic recovery comparable with other series.
0502
HUMAN UMBILICAL CORD BLOOD CELLS REGENERATE HEPATOCYTES BY FUSION IN A
NON-MYELOABLATIVE SETTING
R. Wong, 1 G. Cheng, 1 K. Tsang, 1 D. Lau, 1 N.P. Chan, 1 W.S. Wong, 1
M.H Ng, 1 C. Tong, 1 A. Chan, 2 J. Tang,2 S. Kok, 2 C.H. Chui2 1 The Chinese University of Hong Kong, HONG KONG, Hongkong; 2 Polytechnic
University of Hong Kong, HONG KONG, Hongkong, China
Background. Many studies have shown that haematopoietic stem cells
can regenerate hepatocytes. Human umbilical cord blood (UCB) is a rich
source of hematopoietic stem cells and mesenchymal progenitor cells
which might be used for tissue or organ repair. Aims. We evaluated the
possibility and mechanism of hepatocyte regeneration by administration
of human UCB cells following non-myeloablative conditioning after
acute liver injury in an immunocompetent mouse model. Methods.
Female C57Bl6 mice were administered toxic dose of acetaminophen.
Six hours later, they were given fludarabine and cyclosporine followed
by infusion of human UCB mononuclear cells. Surviving mice were sacrificed
at two and four weeks post transplant. Immunohistochemistry,
fluorescence in-situ hybridization (FISH) using centromere enumeration
probe for human chromosome Y and FITC-labeled mouse pancentromeric
probe, and polymerase chain reaction (PCR) analysis of hepatic
DNA for α-satellite region of human chromosome 17 were used to
confirm the presence of hepatocytes from human origin and the mechanism
of regeneration. Results. Fifteen out of 24 mice received human
UCB cells infusion after non-myeloablative conditioning survived
beyond two weeks. Immunohistochemical analysis demonstrated the
presence of hepatocytes expressing human hepatocyte antigen and
human albumin in the hepatic sections of all but three of the surviving
mice. FISH confirmed the presence of human Y chromosome in 0.5-
20% of the hepatocytes. PCR analysis showed that 1-20% of the hepatic
DNA was of human origin. Fusion of human cell with mouse cell was
demonstrated by FISH (Figure 1).
Figure 1. Cell fusion demonstrated by FISH.
12 th Congress of the European Hematology Association
Conclusions. Our data suggested that human umbilical cord blood can
regenerate functional hepatocytes by fusion after acetaminophen
induced acute hepatic injury in a non-myeloablative setting. This may
be an effective approach in the management of patients with inherited
diseases by using UCB cells for gene therapy.
0503
CLINICAL RESULTS OF A NEW DOSING STRATEGY OF IV BUSULFAN AS PART OF BUMEL
HIGH-DOSE CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS STEM CEL
TRANSPLANTATION IN CHILDREN WITH HIGH-RISK SOLID TUMORS: REDUCED
REGIMEN-RELATED TOXICITY AND VENO-OCCLUSIVE DISEASE
D. Valteau-Couanet, 1 J.C. Gentet, 2 G. Vassal, 1 F. Doz, 3 C. Paillard, 4
N. Corradini, 4 D. Frappaz, 5 O. Hartmann, 1 V. Cadic, 6 H. Zouabi, 6
G. Michel2 1 Institut Gustave Roussy, VILLEJUIF; 2 Hopital La Timone, MARSEILLE; 3 Institut
Curie, PARIS; 4 Hopital Hotel Dieu, CLERMONT FERRAND; 5 Centre Leon
Berard, LYON; 6 Institut de Recherche Pierre Fabre, BOULOGNE, France
Background. Oral busulfan (Bu) and melphalan (Mel) has been extensively
used as a high-dose chemotherapy (HDC) regimen followed by
autologous hematopoietic stem cell transplantation (ASCT) in pediatric
patients (pts) with high-risk (HR) solid tumors. With the availability of
IV Bu, a new dosing strategy based on body weight (BW) has been
defined (Nguyen et al BMT 2004). We assessed prospectively this
approach. Pharmocokinetic results have been reported in children and
adolescents (Vassal et al BMT 2006) and we report here the final clinical
results. Patients and Methods. 31 children (17 boys/14 girls), median age
4 y (range 0.7 to 14.9 y) and weight 14.5 kg (range 7.2 to 62.5), respectively
were enrolled. Pts received IV Bu (Busilvex ® ) over 2 h at a dose of
1.0 mg/kg or 1.2 mg/kg or 1.1 mg/kg or 0.95 mg/kg or 0.8 mg/kg for 23-34 kg, and > 34 kg BW, respectively. Mel
140 mg/m 2 was then administered followed by HSCT. Clonazepam was
given as seizures prophylaxis. Indications for HSCT were : HR neuroblastoma
(NB), n = 27:9 CR1/ CR2, 11 VGPR, 7 PR1/PR2, Ewing sarcoma
(EW), n=4:2 CR1, 2 PR1. Regimen-related toxicity (RRT) was graded
according to NCI-CTC 2.0. Kaplan-Meier EFS and OS were calculated.
Results. No adverse effect was observed during IV Bu administration. Pts
received 5.8×10 6 CD34 + /kg (range 3-34.8) with post transplant G-CSF in
27/31. Neutrophils (>0.5×10 9 /L) and platelets (>50.0×10 9 /L) recovery
occurred at day 11 (range 10-15) and day 34 (range 11-133), respectively.
Digestive toxicity (mucositis) was the main RRT: grade I-II and grade
III occurred in 24 and 14 pts, respectively. Four pts (13%) had hepatic
veno-occlusive disease (VOD) but none was severe. No early or late regimen-related
death occurred. 15/31 pts had disease relapse/ progression
after a median time of 9 months (2.6-40.4), and 11/31 pts died. With a
median follow-up of 41.2 months (range 3.2-52.2) EFS and OS rates were
as follows: 42±22% and 57±20%, for HR-NB, respectively; it was 38%
and 67% for HR-EW, respectively. Discussions/Conclusions. Oral BuMel is
currently the standard HDC regimen in pts with HR-NB but its use is limited
by the toxicity, especially VOD (up to 40%). The current results suggest
that the IVBu has similar impact on efficacy of the BuMel regimen
but with reduced toxicity, especially VOD (13%). The IVBu schedule
could be an useful alternative in the ongoing prospective randomized trial
(HR-NBL-1/SIOPEN).
0504
THREE STRATEGIES OF IMMUNOABLATIVE THERAPY WITH AUTOLOGOUS STEM CELL
TRANSPLANTATION IN MULTIPLE SCLEROSIS PATIENTS
Y. Shevchenko, 1 A. Novik, 1 A. Kuznetcov, 1 B. Afanasiev, 2 I Lisukov, 3
O. Rykavicin, 4 A. Myasnikov, 5 T. Ionova, 6 V. Melnichenko, 1
D. Fedorenko, 1 A. Kishtovich, 6 R. Ivanov, 1 G. Gorodokin7 1 Pirogov National Medical Surgical Center, MOSCOW, Russian Federation;
2 Pavlov State Medical University, ST. PETERSBURG, Russian Federation;
3 Institute of Clinical Immunology, NOVOSIBIRSK, Russian Federation; 4 Burdenko
Central Military Hospital, MOSCOW, Russian Federation; 5 Republican
Hospital, PETROZAVODSK, Russian Federation; 6 Multinational Center of
QoL Research, ST. PETERSBURG, Russian Federation; 7 NJ Cent. for QoL and
Health Outcome Res., NEW JERSEY, USA
During the last decade immunoablative therapy with ASCT has been
used more often as a therapeutic option for MS patients. Among a number
of unclear questions are the terms of conducting immunoablative
therapy with ASCT. There are 3 strategies of immunoablative therapy
with ASCT depending on the terms of disease process: early, conventional
and salvage/late. We aimed to study the clinical and patient-reported
haematologica/the hematology journal | 2007; 92(s1) | 187