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

12 th Congress of the European Hematology Association
also looked the role donor lymphocyte infusions (DLI) for post-transplant
relapse in the absence of clinically significant graft versus host disease
(GVHD). Methods.METHODS Six patients were enrolled into our
programme of HLA matched sibling allogeneic haematopoietic stem cell
transplantation (HSCT) for Sézary syndrome and advanced cutaneous
T-cell lymphoma (CTCL). Sézary syndrome n=3, tumour stage MF n=2,
and the erythrodermic variant of MF n=1. All six patients were in
advanced stage disease (stage IIIA or above) at time of transplant conditioning.
All patients were conditioned with a reduced intensity regime
using Campath-1H Fludarabine and Cyclophosphamide. Disease status
pre and post-transplant was monitored clinically, radiologically and molecularly
by PCR for TCR gene rearrangement. Upon disease relapse
post-transplant, and in the absence of graft versus host disease (GVHD)
a programme of escalating dose DLI with a starting dose of 10×10 6 /kg
CD3 positive T-cells was commenced. Results. Of the six patients who
had a RIC SCT, five demonstrated a clinical complete remission (CR),
four of those also experienced a molecular CR. One patient died in CR
of transplant related mortality (invasive aspergillosis). One patient developed
autologous reconstitution and died of disease progression while
four patients experienced early relapse with cutaneous disease and the
re-emergence of a T-cell clone (median time to relapse 82.2 days (range:
28-100). One patient developed acute GVHD after withdrawal of
immunosuppression and entered a molecular CR. Three patients
received DLI. All three developed acute skin GVHD, and regression of
the relapsed disease occurred concurrently. All three remain alive (median
32 months, range: 12-24 months) in clinical and molecular CR. The
minimum dose to induce GVHD and result in CR2 was 10×10 6 /kg CD3
T-cells. Conclusions. RIC-SCT can result in clinical and molecular remissions
post-transplant in the majority of patients. However, most patients
experience early relapse. Reduction of immunosuppression and donor
lymphocyte infusions induce GVHD which is followed by regression of
the relapsed disease and subsequent clinical and molecular complete
remission. We believe that this is clear evidence of a graft versus tumour
effect in patients with cutaneous T-cell lymphoma.
0457
MULTI-DONOR STEM CELL TRANSPLANTATION (MDT) FROM HAPLOIDENTICAL
MISMATCHED DONORS ENGRAFTMENT AND SAFETY DATA
M.Y Shapira, I.B. Resnick, B. Gesundheit, M. Bitan, S. Samuel, L. Dry,
Y. Verkholevsky, S. Slavin, R. Or
Hadassah Hebrew University Medical Cen, JERUSALEM, Israel
Introduction. The aim of stem-cell-transplantation (SCT) is to combine
tumor cytoreduction and to replace host with donor cells. For patients
with no matched sibling available for allogeneic SCT (approximately
70% of patients) an alternative treatment option is SCT from a relative
carrying only one identical HLA haplotype (haplo-SCT), which may
provide a donor for almost every patient in need at optimal timing.
Mandatory T-cell depletion (TCD) increases the risk of graft rejection
and decreases the intensity and efficacy of GVT effect. In umbilical cord
blood transplant, in order to overcome the delayed engraftment, the
possibility of using several cord-blood units to increase the stem cell
dose was investigated. In the small number of multi-cord transplants
reported, it was found that usually only one unit engrafted faster, while
the others were rejected. We hypothesized that multi-donors may
improve the engraftment, GVT effect and immune reconstitution following
haplo-SCT. Patients and Methods. Eleven ultra high-risk patients
(median age 38 years, 9-54, mostly after 1-2 previous SCTs) were included.
Conditioning regimen was fludarabine-TBI (n=8) or TLI-CY (n=3)
based. All grafts were T-cell depleted. Results. All nine evaluable patients
engrafted but one of them later rejected the graft. The time for neutrophil
engraftment (0.5 and 1.0×109 /L) was fast, 11 days (9-23) and 12
days (10-17) respectively. Platelets engrafted earlier (20 and 50×109 /L), 9.5
days (8-11) and 11 days (9-14) respectively. Of 6 evaluable patients, all
converted to single donor hematopoiesis within a median of 33 days (21-
49). In 2 patients in-which the leukemia persisted throughout the conditioning,
there was a noteworthy disappearance of leukemic cells during
the conversion to single donor chimerism. Despite major blood type
differences between the recipient and the 2 donor, no hemolysis related
side-effects were noted. Two patients developed GVHD (grade 2 and
3). Conclusions. MDT is safe and induces fast and durable engraftment
of both myeloid and thrombocyte lineages in patients undergoing haplo-SCT.
Further studies should follow this report.
170 | haematologica/the hematology journal | 2007; 92(s1)
0458
FEASIBILITY AND OUTCOME OF ALLOGENEIC HEMATOPOIETIC STEM CELL
TRANSPLANTATION IN ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA AFTER A
FLUDARABINE-BASED INDUCTION PROGRAM
A. Candoni, 1 E. Simeone, 2 M. Battista, 2 F. Zaja, 2 F. Patriarca, 2
A. Sperotto, 2 M. Cerno, 2 A. Geromin, 2 R . Fanin2 1 Hematology Unit, UDINE; 2 Division of Hematology, UDINE, Italy
There are only limited data about allogeneic stem cell transplantation
(HSCT) in elderly patients (pts). In the present analysis we report
the feasibility and outcome of HSCT in elderly pts with acute myeloid
leukemia (AML) after a fludarabine-based induction program.
Between 2000 and 2006, 62 consecutive AML pts aged 50 years or older
(range 50-78) were treated with fludarabine-based induction regimen
[FLAI+Mylotarg 20/62 (32%), FLAIE 28/62 (45%), FLAI 14/62
(23%)]; the median age at diagnosis was 59 years (range 50-78), high
risk at onset 45/62 cases (76%). Thirty-eight of 62 pts (61%) achieved
complete remission after induction chemotherapy (death during
induction was only 3%). Twenty-four of these 62 pts (39%) underwent
HSCT. The median time from diagnosis to transplant was 6
months. Disease status at time of transplant: high-risk 21/24 cases
(88%), advanced disease 10/24 cases (42%), complete remission 14/24
cases (58%). Median age 60 years (range 50-69). Donor status: sibling
donor 50% (12/24), unrelated donor 37% (9/24), haploidentical donor
13% (3/24). Twelve of 24 pts (50%) received a reduced intensity conditioning
regimen (RIC). Conditioning regimen: Fludarabine + Busulfan
4/24 (17%), Thyotepa + Cyclophosphamide + ATG 8/24 (33%),
Busulfan + Cyclophosphamide + ATG 7/24 (29%) and other regimens
5/24 (21%). Outcome: all patients achieved engraftment. Acute GvHD
was observed in 11/24 pts (46%) with 8 having grades I-II and 3 having
grades III-IV. Data on chronic GvHD was available for 14/24 pts
(58%); of those 1/14 (7%) developed extensive chronic GvHD. Transplant-related
mortality occurred in 3/24 pts (12%). At the time of
analysis, after a median follow-up of 8 months (range 1-37), 14/24 pts
(58%) were alive and in complete remission while 10/24 (42%) have
died (leukemia relapse 7/10 and TRM 3/10). One and two year probability
of Overall Survival (OS) was 70% and 56% respectively. The
pts transplanted in complete remission have a significantly better OS
and DFS compared to those transplanted with relapsed or refractory
disease (log rank=0,01). These preliminary results are encouraging
and compare favourably with results after conventional chemotherapy
in elderly pts with AML. Related and unrelated donor HSCT is
feasible in elderly pts with AML, with outcomes that are similar to
younger pts. Favourable outcome was observed expecially in those
transplanted in complete remission and early in the course of disease.
Besides our data confirm the efficacy of fludarabide-based induction
regimen for AML pts older than 50 yrs (61% of complete remission
rate) allowing the treatment intensification with HSCT in a high proportion
of cases (39%, 24/62).
0459
IMPACT OF ALLOGENEIC STEM CELL TRANSPLANTATION IN CYTOGENETICALLY
NORMAL ACUTE MYELOID LEUKEMIA PATIENTS AND CORRELATIONS WITH PGP
EXPRESSION
M. Tiribelli, 1 D. Damiani, 2 A. Geromin, 2 A. Michelutti, 2 D. Russo, 3
C. Filì, 3 R. Fanin2 1 Azienda Ospedaliero-Universitaria, UDINE; 2 Division of Hematology and
BMT, UDINE; 3 Unit of Blood Diseases and Cell Ther., BRESCIA, Italy
Background. Patients with acute myeloid leukemia (AML) and normal
karyotype represent about 40-50% of all AML cases. Despite
being included in an 'intermediate' risk group, with a median 5-year
overall survival (OS) of 35%, they display an heterogeneous clinical
course. Different genetic abnormalities have been found to impact
on the clinical course of these patients. We have recently demonstrated
that Multidrug resistance (MDR) protein P-glycoprotein (PGP) is
related with a reduced survival also in cytogenetically normal (CN)
AML patients. Allogeneic hematopoietic stem cells transplantation
(HSCT) is recommended in patients with unfavourable karyotype
AML, while its role in CN AML cases is not yet established. Aims. We
have retrospectively analyzed 111 patients with high-risk CN AML.
We have evaluated the role of allogeneic HSCT in 51 patients who
underwent transplant procedure and its relationship with different
know prognostic factors, including PGP expression at diagnosis. We
also compared the survival in the transplanted patients with the 60
high-risk CN AML patients who did not received HSCT. Methods.