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

12 th Congress of the European Hematology Association
Red cells and iron
0913
PLASMA LIPOCALIN-2 LEVELS IN PATIENTS WITH THALASSEMIA INTERMEDIA:
CORRELATION WITH IRON METABOLISM AND ERYTHROPOIESIS
I. Papassotiriou, 1 A. Margeli, 1 V. Ladis, 2 S. Sophia, 1 K. Kassiou, 1
A. Kattamis 2
1 Aghia Sophia Children’s Hospital, ATHENS; 2 Athens University, Medical
School, ATHENS, Greece
Background and Aims. Members of the lipocalin protein family are
small, secreted proteins with a variety of functions. Although the physiological
role of lipocalin-2 has not been fully elucidated, a few pivotal
functions have recently been reported, namely the regulation of the
apoptosis of leukocytes. Unexpectedly, lipocalin-2 is abundantly
expressed in erythroid progenitor cells. in vitro culture experiments
demonstrated that lipocalin-2 induces apoptosis and inhibits differentiation
of erythroid progenitor cells. During acute anemia, the expression
of lipocalin-2 was reduced in erythroid cells by a feedback system.
Furthermore, injection of recombinant lipocalin-2 in mice suffering from
acute anemia retarded the recovery of red blood cell (RBC), suggesting
the importance of reduced expression of lipocalin-2 for accelerated erythropoiesis.
Lipocalin-2 is, also, an iron trafficking protein, a member
of the non-transferrin-bound iron (NTBI) pool and an alternative to the
transferrin-mediated iron-delivery pathway. Of note is, NTBI, which is
elevated in thalassemic patients, induces cellular toxicity. In this study
we investigated the possible association of lipocalin-2 with parameters
of iron overload and erythropoiesis in patients with Thalassemia
Intermedia (TI). Methods. Forty patients with TI were included in the
study. In terms of clinical severity, 16 of them were never transfused,
while 24 patients were of severe phenotype and only 8 of them were
rarely transfused. Twenty healthy individuals served as controls.
Patients and controls were evaluated for a possible renal impairment as
lipocalin-2 has been implicated in renal dysfunction. Lipocalin-2 levels
were determined in plasma using an immunoassay technique. NTBI
levels were determined using graphite furnace atomic absorption spectrometry.
Erythroid marrow activity was estimated by measuring soluble
transferrin receptors (sTfR) levels with a turbidimetric technique.
Results. The main results of the study showed: a) lipocalin-2 levels were
significantly higher in patients with TI compared to controls
(139.1±86.1 vs 51.2±11.8 mg/L, p0.66, p>0.67 and p>0.81 respectively),
nor with those of iron metabolism ferritin and NTBI (p>0.90 and p>0.95
respectively). Conclusions. The increased lipocalin-2 levels observed in
TI patients in this study are in agreement with the elevated expression
of lipocalin-2 observed in thalassemia mouse models. We postulate
that the induction of lipocalin-2 in these patients may represent either
a survival response, facilitating the survival of the less damaged thalassemic
erythroid precursors or a consequence of the abnormal iron
regulation in TI.
0914
ZOLEDRONIC ACID INCREASES BONE MINERAL DENSITY IN PATIENTS
WITH THALASSEMIA INTERMEDIA-INDUCED OSTEOPOROSIS DESPITE
THE CONTINUOUS BONE MARROW EXPANSION
E. Voskaridou, 1 D. Christoulas, 2 L. Antoniadou, 3 P. Tsaftaridis, 1
E. Plata, 1 E. Terpos2 1 Thalassemia Center, Laikon General Hosp., ATHENS; 2 251 General Airforce
Hospital, ATHENS; 3 Bioiatriki Medical Center, ATHENS, Greece
Background. Osteoporosis represents an important cause of morbidity
in adult patients with thalassemia. The pathogenesis of osteoporosis
in thalassemia is multifactorial, and includes mainly bone marrow
expansion, endocrine dysfunction and iron overload. Patients with thalassaemia
intermedia (TI) seem to have a more expanded bone marrow
with pressure on cortical bone, which causes pain and bone loss in several
cases. Soluble transferrin receptor (sTfR) and erythropoietin (Epo)
serum levels are considered as accurate markers of erythropoietic activity
in thalassemia. Bisphosphonates are potent inhibitors of osteoclast
activity and have been used for the management of thalassemiainduced
osteoporosis. The aim of this study was to evaluate the effect
of zoledronic acid, the most potent aminobisphosphonate, on bone
342 | haematologica/the hematology journal | 2007; 92(s1)
mineral density (BMD) of patients with TI and osteopenia/osteoporosis
and explore possible correlations with bone marrow expansion and
erythropoietic activity. Patients and Methods. Thirty-five patients with
TI and osteopenia/osteoporosis (13M/22F, median age 45 years) were
evaluated. Twenty-three were randomized to receive zoledronic acid,
4 mg, IV, every 3 months (n=12) or every 6 months (n=11), while 12
patients received placebo every 3 months. There was no difference in
terms of the presence of gonadal dysfunction between the three studied
groups. BMD of the lumbar spine (L), femoral neck and forearm was
determined in all patients, using DEXA, before and 12 months after
treatment. Bone marrow expansion was assessed by the measurement
of sTfR and Epo serum levels, using an ELISA methodology (R&D Systems,
Minneapolis, MN, USA), before and 12 months post zoledronic
acid or placebo administration. In all patients markers of bone remodelling,
such as C-telopeptide of collagen type-I (CTX) and bone specific
alkaline phosphatase (ALP) were also measured by ELISA (serum
CrossLaps ® , Nordic Bioscience Diagnostics A/S, Herlev, Denmark, &
Metra ® BAP, Quidel Corporation, San Diego, CA, USA, respectively).
Patients were asked to quantify their degree of bone pain on
Huskisson’s visual analogue scale (VAS) and the McGill’Melzack scoring
system (MGM) before and 12 months post-therapy. Results. All
patients had increased values of sTfR, Epo, CTX, & bALP compared
with 40 controls of similar age and gender (p