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

HSCT from the available Asian as well as Caucasian donors for AML.
Overall, 56 patients received unrelated donor bone marrow cells, and 18
patients received G-CSF mobilized peripheral blood stem cells. Results.
The median age of enrolled patients and donors was 36 (16-53) and 38
(20-51) years, respectively. The median follow-up duration was 24
months (range, 6-61). The majority of patients had intermediate (N=45)
or unfavourable (N=29) cytogenetic features. The main conditioning regimen
consisted in cyclophosphamide plus TBI with our standard GvHD
prophylaxis containing tacrolimus plus short course methotrexate.
Instead, some of patients (N=19) received additional 2-day course ATG
(thymoglobulin, Sangstat) in addition to the standard regimen. All transplanted
patients were engrafted. The incidence of acute GvHD was 52%,
with grade I (21%), grade II (20%), grade III (10%), and grade IV (1%).
Chronic GvHD developed in 52% of evaluable patients, and 17% had
extensive disease. Eight (11%) patients were relapsed so far. The 2-year
non-relapse TRM was 16%. In order to compare the results of DFS, EFS
by the development of GvHD, we compared the survival curves according
to the presence or absence of acute or chronic GvHD. Thus, in contrast
to improved overall survival results, notably improved DFS was
noted when acute GvHD was developed (p=0.0444), but there were no
statistical significance for EFS in this study. The comparison of overall
estimated probability of DFS and EFS at 5-year were 84%, 67%, respectively.
Conclusions. These results showed that multinational mismatched
unrelated donors for Korean AML patients were available to be performed
as possible. Our data revealed that development of acute GvHD
after unrelated donor HSCT for AML patients was closely related to better
long-term DFS and EFS.
0940
GENOTYPE SPECIFICITIES OF KILLER CELL IMMUNOGLOBULIN-LIKE RECEPTORS
IN HLA-MATCHED SIBLING DONOR-RECIPIENT PAIRS
H.-J. Kim, Y. Choi, W.-S. Min, C.-C. Kim
Catholic HSCT Center,St. Mary’s Hospital, SEOUL, South-Korea
Background. NK cell alloreactions against AML cells were first actively
investigated in a clinical setting of allogeneic HLA-mismatched
hematopoietic stem cell transplantation (HSCT). More recently, the novel
concept of infusing NK cells to promote and consolidate engraftment
after haploidentical HSCT has been introduced. The inherent heterogeneity
of the multigene killer cell immunoglobulin-like receptor complexes
(KIRs) may also be a key factor for the outcome of HLA-matched
sibling HSCT. Therefore, it is expected that other researchers will also
examine the role of ethnic differences in the KIR genotype in association
with NK alloreactivity. Aims. There is limited information on the influence
of donor-derived NK cells on various outcomes after HLA-matched
sibling allogeneic HSCT. Methods. We investigated the KIRs, based on the
genotypes of inhibitory or activating KIRs in 76 consecutive pairs of
stem cell recipients with AML, and their HLA-matched sibling donors.
All donor’recipient pairs were typed for the presence or absence of specific
KIRs genes. Evaluation for 19 different KIR genes and pseudogenes
was performed using the Pel-Freez kit, according to the manufacturer’s
protocol. PCR data representing KIR genotypes from the recipients and
donors were compared. Results. Genotyping performed prospectively
was perfectly matched in 38% of pairs. Unlike to Caucasians, the single
2DL3 allele without 2DL2 was the predominant pattern for the Korean
C1 allotype, either in donors or in recipients. 2DS2 (19% vs 11%,
p=0.044) and 2DS4 (75% vs 68%, p=0.044) were at a higher frequency
activating KIRs genes in the recipient group. Analysis of KIRs gene numbers
revealed that the recipient group usually had two to three more
genes than donors. Conclusions. Taken together, these factors may be
helpful to understand an immunogenetic specificity in different races in
association with a specific disease AML.
0941
GENOTYPES OF INHIBITORY AND ACTIVATING KILLER CELL IMMUNOGLOBULIN-LIKE
RECEPTORS IN HLA-MATCHED SIBLING DONOR-RECIPIENT PAIRS ARE IMPORTANT
DETERMINANTS OF ACUTE GRAFT-VERSUS-HOST DISEASE IN HEMATOPOIETIC STEM
CELL TRANSPLANTATION FOR ACUTE MYELOGENOUS LEUKEMIA
H.-J. Kim, W.-S. Min, K.-S. Eom, B.-S. Cho, S.-Y. Kim, C.-K. Min,
S. Lee, S.-G. Cho, J.-W. Lee, C.-C. Kim
Catholic HSCT Center,St. Mary’s Hospital, SEOUL, South-Korea
Background. Natural killer (NK) cell alloreactivity is regulated by killer
cell immunoglobulin-like receptors (KIR). Several studies have demonstrated
variable expression of KIRs in allogeneic hematopoietic stem cell
transplantation (HSCT) donor’recipient pairs. Aims. The influence of KIR
12 th Congress of the European Hematology Association
genes, in stem cell recipients with acute myelogenous leukemia and their
HLA-matched sibling donors, on acute graft-versus host disease
(aGvHD) after HSCT was investigated. Methods. We studied 53 donor'recipient
pairs to determine the impact of both donor and recipient KIR
genotypes, and their bidirectional KIR interactions. Evaluation for 19
different KIR genes and pseudogenes was performed. PCR data representing
KIR genotypes from the recipients and donors were compared.
Various clinical factors associated with development of aGvHD in the
univariate analyses were used in the multivariate Cox proportional hazards
regression analysis. Results. All activating KIR genes in donors were
important factors for determining outcome in a manner distinctive for
each gene studied. Specifically, the 2DS2 gene and the 2DS4*003 allele
were closely correlated with aGvHD. The 2DS1 gene was associated
with a better long-term survival, even if present only in the donor and
not the recipient. The 2DS3-2DS5 dual genes were more often involved
in a variety of transplant-related complications. Lastly, when we compared
the specific association of the donor 2DS2-recipient 2DL2 genes
with acute and chronic GvHD, presence or absence of these genes
showed important correlations. Conclusions. As a pilot integrative NK-KIR
immunogenetic study in association with a variety of clinical outcomes,
even in the setting of sibling allogeneic HSCT in patients with AML; our
findings suggest that the genotypes of the inhibitory/activating NK-KIR
in donor cells, together with the interaction of the recipient NK-KIR
characteristics, may be, at least in part, critical for understanding
immunogenetic specificity. Further understanding of this process may
allow us to better predict transplant outcome, and aid in identifying the
best available donor in a specific transplant setting.
0942
PHASE II STUDY OF YTTRIUM-90 IBRITUMOMAB TIUXETAN (ZEVALIN) FOR PATIENTS
WITH UNTREATED STAGE I-II FOLLICULAR OR MARGINAL ZONE LYMPHOMA
F. Samaniego, B. Pro, R. Nunez, P. McLaughlin, M. Fanale, L. Kwak,
J. Romaguera
M.D. Anderson Cancer Center, HOUSTON, USA
Background. Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) is an
effective treatment for patients with relapsed follicular lymphoma. There
is no standard treatment for previously untreated stage I - II indolent lymphoma.
Methods. Patients with untreated CD20 positive lymphomas
including follicular lymphoma grade 1 - 2, and marginal zone B-cell lymphoma
of the mucosal (MALT) type were included in the study. Staging
included computed tomography (CT) of neck, thorax, abdomen and
pelvis, PET-CT and bone marrow biopsy. Eligibility criteria were performance
status of 2 or less, white blood count greater than 1500/mL,
platelet greater than 100,000/mL, and at least one lesion measuring 1.5 cm
in transverse dimension. Response was assessed 3 months after infusion.
Response evaluation of bowel disease required repeat biopsy of involved
tissues after completing therapy. Patients were treated with Zevalin, (0.3-
0.4 mCi 90Y/kg according to initial platelet count, caped at 32 mCi).
Results. Nine patients have been enrolled with a median age of 60 years
(range 37-71). Five are male, and 7 have follicular histology. With a median
follow-up of 5 months (range 3 to 9), seven patients have more than
3 months of follow up and are evaluable for response. Of these, 6 (85%)
have achieved a complete remission and one has stable disease. Two of
two patients with less than 3 months follow up have already achieved a
partial response and may continue to respond. Patients experienced a
nadir median platelet count of 50,000 (range 20,000-170,000) and a medium
neutrophil count of 1,323 (range 560-1,566) at four weeks from the
infusion of Zevalin. Nonhematologic toxicity included a rash associated
with rituximab/90Y ibritumomab tiuxetan administration. Conclusions.
This early preliminary data with Yttrium-90 ibritumomab tiuxetan is
encouraging; however long term follow-up will determine the clinical
utility of this simple convenient treatment.
0943
BONE MARROW TRANSPLANTATION FOR ALL
M. Khani, K. Alimoghadam, A. Karimi, A. Ghavamzadeh
Tehran University of Medical Science, TEHRAN, Iran
Introduction. Multiple myeloma (MM) is a clonal disorder of hematopoietic
stem cell. Treatment is based on supportive care, single or combination
chemotherapy and autologus or allogenic stem cell transplantation
(SCT). We are doing in-patient SCT in Iran since 1991 but this is the first
out-patient SCT. Material and Method. all patients who were candidate
for SCT received out-patient or in-patient SCT according to protocols.
In out-patient group, patient were discharged and followed by out-
haematologica/the hematology journal | 2007; 92(s1) | 351