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

one marrow and peripheral blood stem cell donors who were recruited,
screened, harvested and followed at our institution and the associated
donor registry. 40% were females and 60% males, with a median
age of 37 years (range: 1-71 years). 318 were family donors and 278
unrelated volunteer donors. 110 donated bone marrow, 472 peripheral
blood stem cells after mobilisation with G-CSF, and 14 both. 33 donors
underwent two harvests, four donors even three. Our preparative procedure
consisted of a medical work-up including history, examination,
blood and clinical chemistry tests, infectious disease markers, electrocardiogram,
chest X-ray, lung function test, and abdominal ultrasound. Follow-up
was scheduled at 1 and 6 months, as well as 1, 2, 5, and 10 years
after donation of hematopoietic stem cells. Results. Within the twelve
year period of evaluation, no donor death was recorded, no single case
of leukemia has been reported, and no splenic rupture occurred in any
of our donors. Five donors experienced severe adverse events: In one
female bone marrow donor, post-harvesting pain persisted for more than
twelve months. A 42 year old female donor developed breast cancer 3
years after G-CSF mobilised stem cell apheresis; however, this was not
considered to be of causal relationship. In two donors of peripheral blood
stem cells, vascular complications occurred: one donor had to be admitted
to hospital during G-CSF mobilisation for symptoms and signs of pulmonary
embolus (which, however, could be ruled out), and subsequently
was able to donate bone marrow. Another donor had recurrence of a
deep vein thrombosis eleven days after stem cell apheresis, despite sufficient
anticoagulation with low molecular weight heparin during G-
CSF stimulation. Finally, a donor with sporadic epilepsy, who donated
twice, had a generalised seizure few days after each G-CSF mobilised
harvest. This is particularly interesting in view of recent in vitro and animal
findings of G-CSF receptors on neural tissues and pleiotrophic neurostimulatory
functions of G-CSF. Conclusions. In our experience, bone
marrow and peripheral blood stem cell donations are safe and generally
well tolerated, with very few early and virtually no late complications.
0369
ALLOGENEIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH WALDENSTRMS
MACROGLOBULINAEMIA. ANALYSIS OF 106 CASES FROM THE EUROPEAN BONE
MARROW REGISTRY (EBMT)
C. Kyriakou, 1 C. Kyriakou, 1 C. Canals, 2 G. Taghipour, 2
J. Cornelissen, 2 R. Willemze, 2 G. Socie, 2 K. Thompson, 2 H. Greinix, 2
J. Harousseau, 2 N. Ifrah, 2 J. Kienast, 2 R. Hamladji, 2 M. Kazmi, 2
P. Jacobs, 2 A. Sureda, 2 N. Schmitz2 1 2 University College London, LONDON; Lymphoma WP of the EBMT, LON-
DON, United Kingdom
Background. Despite effectiveness of standard chemotherapy regimens,
complete response is infrequent in Waldenström’s Macroglobulinaemia
(WM) patients and there is no cure. The role of allogeneic stem cell transplantation
(Allo-SCT) has not been explored extensively and the available
data are limited. Aims. We retrospectively analyzed the results and
long-term outcome of a group of 106 WM patients from 65 European
centres who underwent an Allo-SCT between 1989 and 2005 and were
reported to the database of the Lymphoma WP of the EBMT. Patients and
Methods. There were 69 males and median age at transplantation was of
49 years (range, 21-65). Time interval between diagnosis and Allo-SCT
was 34 months (5-310) and the median number of lines of therapy prior
to Allo-SCT was 3. Nineteen patients (18%) had failed a prior autograft.
At Allo-SCT, 10 patients (10%) were in CR?2, 35 patients (33%)
in PR1, 29 patients (27%) in PR?2 and 32 patients (30%) had relapsed or
refractory disease. Seventy-nine patients (74%) were allografted from an
HLA-identical sibling donor, 18 (17%) from a matched unrelated donor
and the remaining 9 patients from other donors. Conventional conditioning
protocols (CT) were used in 44 (41%) patients and reduced intensity
conditioning (RIC) regimens in 62 (59%) patients. Results. Forty-eight
(45%) patients developed acute graft versus host disease [Grade III-IV
(n=14)] with no statistically significant differences between CT and RIC
regimens. After a median follow up of 31 months (3 to 169), 17 (16%)
patients had relapsed at a median time of 8 (1-89) months post Allo-
SCT. The incidence of relapse at 3 years was 18%, 12% after CT and
25% after RIC. Thirty-five (33%) patients died, 5 (5%) from disease progression
and 30 (28%) from non-relapse mortality (NRM), with an incidence
of NRM of 27% and 31% at 1 and 3 years. The progression free
survival (PFS) rates were 61%, 50% and 48% at 1, 3 and 5 years and the
overall survival rates were of 69%, 63% and 63%, at 1, 3 and 5 years,
respectively. In a multivariate analysis, conditioning regimen had no
impact either on NRM or on relapse rate. Refractory patients presented
with a higher risk of relapse (p=0.03). The use of TBI in the condition-
12 th Congress of the European Hematology Association
ing regimen was associated with a lower relapse risk (p=0.02) and a
trend to a better PFS (p=0.1). Conclusions. Allogeneic stem cell transplantation
is a feasible and well tolerated procedure in this heavily pre-treated
group of patients. Relapse rate is low and long-term outcome seems
promising, with half of the patients being alive and disease-free 5 years
after the procedure.
0370
HEMATOPOIETIC STEM CELL TRANSPLANTATON FOR OSTEOPETROSIS
P.J. Orchard, 1 M. Eapen, 2 J. Tolar, 1 E. Horwitz, 3 P. Veys, 4 F. Fasth5 1 University of Minnesota, MINNEAPOLIS, USA; 2 CIBMTR/Medical College
of Wisconsin, MILWAUKEE, WI, USA; 3 St. Jude Children's Research Hospital,
MEMPHIS, TN, USA; 4 Great Ormond St Hospital for Children, LON-
DON, United Kingdom; 5 Göteborg University, GÖTEBORG, Sweden
Autosomal recessive osteopetrosis is a disorder of osteoclast function,
generally lethal in the first decade of life without allogeneic hematopoietic
stem cell transplantation (HCT). To determine the outcomes of
patients with this disorder undergoing transplantation, we examined
long-term survival after HCT in 124 children with infantile osteopetrosis
reported to the Center for International Blood and Marrow Transplant.
The data reflected outcomes of transplantation for patients with
osteopetrosis from 1978-1999. The median age at transplantation was 8
months and median time from diagnosis to transplantation 4 months.
Forty percent of allografts were from HLA-matched siblings, 34% from
unrelated donors and 26% from alternative related donors. Busulfan and
cyclophosphamide was the most commonly used conditioning regimen
(74%) and bone marrow the predominant graft source (87%). The cumulative
incidence of neutrophil recovery at day +100 was 75% (93/124)
with similar rates across the three donor sources. Fifty-four children are
alive with a median follow up of 7.5 years and an 8-year probability of
survival of 43%. The 8-year probabilities of survival were 54%, 39% and
35% after HLA-matched sibling, alternative related and unrelated donor
transplantation, respectively. Early mortality rates were high after HCT
regardless of donor type; 34% at day +100 and 50% at 1- year after
transplantation. Common causes of mortality were graft failure (33%),
interstitial pneumonitis or adult respiratory distress syndrome (34%),
infections (12%) and graft-versus-host disease (10%). Nineteen patients
underwent a second transplant for either primary or late graft failure. Six
of these patients are alive. Most second transplants occurred within 6
months from the first transplant (n=15) and the remaining 4 occurred at
4, 4.5, 5 and 9 years after the first transplant. We conclude that long
term survival for autosomal recessive osteopetrosis can be obtained with
HCT. Peri-transplant mortality and graft failure remain significant obstacles
in this population. Second transplantation is a viable option if
engraftment is not initially achieved.
haematologica/the hematology journal | 2007; 92(s1) | 133