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

12 th Congress of the European Hematology Association
GvHD - GvL - graft rejection
0578
LUNG TRANSPLANTATION AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL
TRANSPLANTATION
A. Dodds, 1 V. Potter, 1 K. Bradstock, 2 T. O'Brien, 3 A. Glanville1 1 St Vincents Hospital, SYDNEY; 2 Westmead Hospital, SYDNEY, Australia;
3 Sydney Children's Hospital, SYDNEY, Australia
Background and Aim. Pulmonary complications cause significant morbidity
and mortality after haematopoietic allogeneic stem cell transplant
(HSCT). We describe our experience with bilateral lung transplantation
as a therapeutic option in HSCT patients with end-stage lung disease.
Methods. Cases were identified via search of database information from
St Vincent’s Hospital and personal contact with lung transplant units in
Australia. Information from medical records of identified cases was
analysed. Pathology specimens of the end stage lung were reviewed.
Results. Five cases have been identified. All received HLA matched allogeneic
transplants from related donors (four sibling, one maternal) for
haematological disease (three CML, one AML, one aplastic anaemia).
Conditioning was with Cy/Bu in four patients and Cy/TBI in one. Graft
versus Host Disease (GVHD) prophylaxis was with CsA/MTX. Acute
GVHD (grades II-III) occurred in two patients. Chronic GVHD other
than lung occurred in three. Pathology review confirmed the diagnosis
of bronchiolitis obliterans (BO) in three patients, interstitial fibrosis in a
fourth, and a mixed process in the fifth. Time from HSCT to lung transplant
ranged from 23 to 125 months. Four of five patients are alive after
lung transplant with no evidence of relapse of haematological malignancy
(range +8 to+74 months). One patient died three years after lung
transplant from Post-Transplant Lymphoproliferative Disorder. The
remaining patients maintain normal pulmonary function. Morbidity in
the living patients includes gastro-oesopharangeal reflux disease, osteoporosis,
hypertension, mild renal impairment, and opportunistic infections
(CMV, aspergillus colonization, MAC reactivation, herpes zoster
and simplex). Marrow function is normal and performance status ECOG
0-1 in the surviving patients. Conclusions. Lung transplantation is a viable
therapeutic option for patients with prior HSCT and end-stage lung disease.
Interesting questions requiring further research include those related
to causative processes, HLA matching, stem cell dose, prevention
and therapy of end stage lung disease. Ongoing immunosuppression
does not appear to affect recipient bone marrow function or contribute
to relapse.
0579
THE GRAFT CONTENT OF DONOR T-CELLS EXPRESSING γ/δ TCR+ AND CD4+FOXP3+
PREDICTS THE RISK OF ACUTE GRAFT VERSUS HOST DISEASE AFTER TRANSPLANTATION
OF ALLOGENEIC PERIPHERAL BLOOD STEM CELLS FROM
UNRELATED DONORS
U. Platzbecker, C. Pabst, G. Ehninger, M. Bornhauser
Universitätsklinikum Carl Gustav Carus, DRESDEN, Germany
Purpose. Recently, high numbers of regulatory T-cells within the stem
cell graft were described to be associated with less graft versus host disease
(GVHD) after related peripheral blood stem cell transplantation
(PBSCT). Studies in mice also suggest a distinct role of γ/δ TCR+ T-cells
in mediating GVHD. Therefore, the aim of this study was to define the
yet unknown role of regulatory and gamma/delta TCR+ T-cells in
human PBSCT from unrelated donors. Experimental design. The frequency
of both T-cell subsets within the graft was analyzed in 63 patients
receiving unrelated allogeneic PBSCT. The respective amounts were
quantified by flowcytometry and PCR and further correlated with clinical
outcome. Results. The grafts contained a median of 11.2×106 /kg
CD4 + foxp3 + and 9.8 ×106 /kg γ/delta TCR + T-cells, respectively. Patients
receiving more CD4 + foxp3 + cells had a lower cumulative incidence of
acute GVHD II-IV (44% vs. 65%, p=0.03). Interestingly, in patients who
received higher concentrations of donor γ/delta TCR + T-cells acute
GVHD II-IV was more frequent (66% vs. 40%, p=0.02). In multivariate
analysis only the graft concentration of γ/δ TCR + T-cells (p=0.002) and
a positive CMV-status of the recipient (p=0.03) were significantly associated
with the occurrence of acute GVHD II-IV. Conclusions. Graft composition
of T-cell subsets seems to affect the outcome of patients receiving
allogeneic PBSCT from unrelated donors. Therefore, selective manipulation
or add-back of particular subsets might be a promising strategy
to reduce the incidence of GVHD.
216 | haematologica/the hematology journal | 2007; 92(s1)
0580
TREATMENT OF STEROID REFRACTORY GRAFT VS. HOST DISEASE BY INTRA-ARTERIAL
INFUSION
M.Y. Shapira, A.I. Bloom, R. Or, I.B. Resnick, M. Aker, M. Bitan,
S. Slavin, A. Verstandig
Hadassah Hebrew University Medical Cen, JERUSALEM, Israel
Introduction. Graft versus host disease (GVHD) still is the major
draw-back of allogeneic stem cell transplantation (SCT). In its resistant
form, it carries high morbidity and mortality. The mainstay of
GVHD therapy is preventive and once it is developed the first line
therapy is systematically high dose steroids, and cyclosporine or
tacrolimus. It has been shown by us and other groups, that intra-arterial
targeted steroid therapy may be useful even in steroid refractory
GVHD. Methods. A total 35 patients with 37 cases of steroid resistant/dependent
gastrointestinal (GI) (n=16), hepatic (n=15) or combined
(n=6) GVHD, were included and given intra-arterial treatment,
for one or more of the following arteries - the hepatic, gastro-duodenal,
superior mesenteric, inferior mesenteric, internal iliacs. We
defined GI partial response and complete response as the day that
symptoms decrease or resolved, respectively. Hepatic partial response
and complete response were defined as the day that bilirubin level
began to decrease or decreased below 30% of initial level, respectively.
Results. The procedure was safe with no major complications. We
found that Intra-arterial catheter guided steroid therapy was associated
with partial and complete remission among patients with steroid
resistant or dependent GI or Hepatic GVHD. Hepatic partial response
was observed in 14 (66.6%) patients among whom 7 (33.3%) reached
complete response. GI partial response was observed in 19 (86.4%)
patients among whom 12 (54.4%) reached complete response. An
early administration of the local therapy, female gender, myeloid basic
disease, and a non-active status of the basic disease at the day of
transplantation were found related for predicting a better response for
the intra-arterial treatment. Conclusions. Intra-arterial catheter guided
steroid therapy is safe and effective in steroid resistant or dependent
GVHD. A further research is warranted characterizing the patients
benefit most.
0581
TREATMENT OF CHRONIC EXTENSIVE GRAFT VERSUS HOST DISEASE WITH ALEFACEPT
M.Y. Shapira, I.B. Resnick, P. Tsirigotis, M. Aker, M. Bitan,
B. Gesundheit, S. Slavin, R. Or
Hadassah Hebrew University Medical Cen, JERUSALEM, Israel
Introduction. Alefacept (AMEVIVE ® ) is an immunosuppressive dimeric
fusion protein that consists of the extracellular CD2-binding portion
of the human leukocyte function antigen-3 (LFA-3) linked to the
Fc (hinge, CH2 and CH3 domains) portion of human IgG1. We have
recently shown its effect in acute, steroid resistant/dependent GVHD.
In this study, we describe the effect of alefacept treatment on chronic
extensive graft versus host disease (cGVHD). Patients and Methods.
A total of 12 patients (13 cGVHD episodes) were included in this
study, 7 males and 5 females with median age 27 years (range 3-60
years).
Figure 1. Pulmonary function test.