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

49% for PCR positive patients (95% CI, 20-67), (p=0.17). For the same
patients, the cumulative incidence of relapse was 0% for PCR negative
patients and 46% in MRD positive patients (p=0.027). Moreover, the
relapse rate of patients with PCR negativity at day +100 after transplantation
was remarkably low (7%) as compared to patients who proved
PCR positive (80%, p=0.0006). By multivariate analysis, only the molecular
CR before conditioning proved to be a significant predictor for the
achievement of a molecular negativity at day 100 after transplantation.
Conclusions. These observations may help in identifying patients at high
risk of leukemia relapse after allogeneic stem cell transplantation. More
importantly, our results strongly suggest that patients not achieving an
early molecular remission after transplantation require timely and appropriate
preemptive treatments such as immunosuppression modulation,
infusions of donor lymphocytes or new experimental drugs.
0424
DIRECT INTRA BONE TRANSPLANT OF UNRELATED CORD BLOOD CELLS IS ASSOCIATED
WITH FAST AND COMPLETE HEMATOLOGIC RECOVERY
F. Frassoni, 1 A. Ibatici, 1 A.M. Raiola, 1 F. Gualandi, 2 N. Sessarego, 1
A. Parodi, 1 S. Pozzi, 1 M. Gobbi, 3 M. Corselli, 1 M. Podestà, 1 G. Piaggio, 2
A. Bacigalupo, 2 F. Frassoni1 1 Centro Cellule Staminali, GENOA; 2 Ematologia e Trapianto AO S Martino,
GENOVA; 3Clinica Ematologica, GENOVA, Italy
Background. Cord blood transplants (CBT) are associated with delayed
or failed engraftment in a significant proportion of patients. Two previous
our observations suggested (i) that, in the animal model, direct intrabone
(i.b.) injection of hematopoietic cells improves seeding efficiency
and (ii) that the delayed engraftment was not related to an insufficient
number of hematopoietic stem cells but rather to a reluctance to differentiation
and maturation. Methods. Unrelated CB (4/6 or 5/6 HLA antigen
matched) were selected for 19 consecutive patients. Median cell
dose was 2.6×10 7 /kg (range 1.6-3.5). CB cells were concentrated in a
total volume of 20 mL and infused in the supero-posterior iliac crest
(SPIC) under rapid general anesthesia (10 minutes with propofol).
Patients median age was 40 years (18-60), 15 had acute leukemia, 2
chronic myeloid leukemia, 2 Hodgkin disease. Fifteen patients had
refractory or advanced disease, whereas 4 had high risk first remission
leukemia. Most patients (n=15) were prepared with conventional CY-
TBI. Results. The infusion of cells i.b. in supero-posterior iliac rest (SPIC),
in the operating room, under short general anaesthesia, was uneventful.
All patients engrafted. Cumulative incidence of neutrophil and platelet
engraftment was 100% at 50 days. Median for neutrophil engraftment
(>0.5×10 9 /L) was day 23 (14-40), whereas for platelets (>20×10 9 /L) it was
day 38 (range 22-47). Three patients are not evaluable because died within
day 10 from transplant. Two patients relapsed and two died of infection
and multiorgan failure. Twelve patients are alive and well in hematologic
remission at a median follow up of 6 months (range 2-11). 100%
donor chimerism was documented since 30 days onward after transplant,
including those in which CB cells were injected monolaterally in
one SPIC. From day +60, CFC and LTC-IC had already reached the lower
values of the range of normal individuals in bilateral sites. This is particularly
relevant considering that hemopoietic progenitor reconstitution
remains deficient years after allo-transplant. Thus, direct injection
of CB cells in the bone marrow spaces, produces in situ proliferation and
maturation, rapid recovery of peripheral blood counts, and early recirculation
of stem cells to other un-injected bone marrow sites. Acute
GvHD grade II was seen in 1/20 patient (5%). Since lymphocyte trafficking
is known to be an essential part of immune response, two combined
factors might contribute: (i) injected T cells come immediately in direct
contact with mesenchymal stem cells (MSC) and osteoblasts which are
known to be potent immunomodulators; (ii) the T cells present in the
graft do not reach primarily in the lymphatic organs, where they would
be immediately confronted with host antigen presenting cells, as it probably
occurs after intra-venous injection. Conclusions. This study shows
that CB cells injected directly into the iliac crests are associated with fast
and complete hematologic recovery and almost absent acute GvHD.
The direct intra-bone transplant of CB cells could now be offered to
many more adult patients. This may change our policy of hemopoietic
cell transplants.
12 th Congress of the European Hematology Association
0425
THE ROLE FOR AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) IN THE TREATMENT
OF WALDENSTRMS MACROGLOBULINAEMIA PATIENTS. ANALYSIS OF 201 CASES FROM
THE EUROPEAN BONE MARROW TRANSPLANT REGISTRY (EBMT)
C. Kyriakou, 1 C. Kyriakou, 1 C. Canals, 2 G. Taghipour, 2
C. Gisselbrecht, 2 P. Mazza,2 M. Kazmi, 2 E. Montserrat,2 N. Milpied, 2
D. Niederwieser, 2 K. Indrak, 2 A. Neubauer, 2 A. Kolbe, 2 P. Biron, 2
J. Bay, 2 A. Levis, 2 A. Sureda, 2 N. Schmitz2 1 2 University College London, LONDON; Lymphoma WP of the EBMT, LON-
DON, United Kingdom
Background. Waldenström’s Macroglobulinaemia (WM) is a relatively
rare lymphoma, which primarily affects elderly patients. Standard doses
of alkylating agents, purine analogues and anti-CD20 monoclonal
antibody produce response rates of up to 60%. Nevertheless, complete
responses are infrequent and there is no cure. Due to the indolent nature
of the disease and the fact that patients are old and present with comorbidities,
the evaluation of the role of high-dose therapy with autologous
transplantation (ASCT) has been infrequent in the past. Aims.
Herein we report a retrospective multicenter analysis of 201 WM
patients (132 male, 69 female), who an ASCT between 1992 and 2005
were reported to the database of the Lymphoma WP of the EBMT. Patient
and Methods. Median age at transplantation was 53 years (22-73), the
median time from diagnosis to transplant was of 18 months (3-239) and
the patients had received a median number of 2 (1-10) lines of therapy
before ASCT. Forty patients (20%) were in CR1, 24 (12%) in CR2, 83
(41%) in PR1, 27 (13%) in PR2, 21(10%) with primary refractory at the
time of transplantation. Conditioning regimens used were BEAM in 44%
of the cases, the combination of cyclophosphamide or melphalan/TBI in
28% of the cases, high dose melphalan in 4% and other protocols in the
remaining 14% of the cases. Peripheral blood was used as the source of
stem cells in 188 patients, bone marrow in 10 patients and the combination
of both in 3 patients. Results. All patients but 3 had a successful
engraftment. With a median follow-up of 26 months (5-163), 112 (56%)
patients are alive and free of disease and 73 (36%) patients have relapsed
after a median of 14 months (1-110) post ASCT. Fifty-two patients have
died, 36 (18%) from disease progression and 16 (8%) from regimen toxicity.
Non- relapse mortality was 6% at 1 year. The actuarial overall survival
was 86% at 1 year, 75% at 3 years and 61% at 5 years. The probability
of relapse was 20% at 1 year, 38% at 3 years and 55% at 5 years
and the estimated progression free survival of 74%, 54% and 33% at 1,
3 and 5 years, respectively. Conclusions. In conclusion, this study shows
that ASCT is a safe procedure and is able to rescue a significant proportion
of heavily pre-treated patients with WM.
haematologica/the hematology journal | 2007; 92(s1) | 157