Haematologica 2003 - Supplements

thalidomide: RR 35% cf. 14% (P =0.084). Among the 20
responders, the median baseline CA 153 was 28 U/ml (range 5-
80), and fell to a significantly lower median of 19U/ml (range 6-
42) at first response (p=0.03) Among all 29 pts who developed
PD on thalidomide, including 9 who initially responded , there
was no significant difference between the median baseline level
and the median at PD.
Of the 9 pts who developed PD after initial response/SD to
thalidomide, there was a significant rise in CA15-3 at PD :
median at response = 13(6-34) cf median at PD = 25(8-52);
P=0.037. 18/62 pts (29%) had clinically significant changes in
CA153, meaning the serum level changed by >25% and fell or
rose in conjunction with other recognised markers of disease.
Conclusions: Our results suggest that elevated serum CA 15-3
levels are a useful and novel marker in high-risk MM pts that
may be predictive of response to thalidomide and may also be of
value in monitoring disease.
165
Serum C-terminal telopeptide of collagen type I (ICTP)
and urinary N-terminal telopeptide of collagen type I
(Ntx) are useful parameters for monitoring myeloma
bone disease
N. Abildgaard, K. Brixen, J.E. Kristensen, E.F. Eriksen, L.
Heickendorff & J.L. Nielsen
Departments of Haematology, Endocrinology, Diagnostic
Radiology, and Clinical Biochemistry, Aarhus University Hospital,
Amtssygehuset, Aarhus, Denmark.
Background: Within recent years, several serum and urine based
biochemical assays for markers of bone resorption and bone
formation have been introduced. In particular, assays of bone
resorption might be useful in multiple myeloma (MM), but few
studies have investigated their clinical value. Earlier, we have
shown that serum C-terminal telopeptide of collagen type I
(ICTP) and urinary N-terminal telopeptide of collagen type I
(Ntx) correlate with the histomorphometrically assessed bone
resorption activity in MM and that elevated pre-treatment levels
of S-ICTP and U-Ntx are predictive for early progression of the
bone disease in myeloma patients.
Aim: This study was performed to evaluate the clinical usefulness
of analyses of biochemical markers of bone metabolism in
monitoring the bone disease in MM.
Methods: Assays for measuring ICTP in serum and Ntx in urine
were employed for assessment of bone resorption, and assays for
measuring serum levels of the C-terminal and N-terminal
propeptides of procollagen type I (PICP and PINP, respectively),
bone-specific alkaline phosphatase (bAP), and osteocalcin were
measured as indicators of bone formation. Thirty patients with
newly diagnosed MM were included before start of treatment and
were followed for a median of 24 months. All patients received
standard cyclic melphalan-prednisone treatment. None of the
patients received prophylactic bisphosphonate treatment. Serum
and urine samples were collected each 6. weeks before initiating
chemotherapy. X-rays of the skeleton were performed each 6.
months and when indicated by symptoms. The X-rays were
scored blindly.
Results: Elevated levels of serum ICTP and urinary Ntx over
time were highly predictive for progression of the bone disease
within the observation period. The markers of bone formation
were less informative. In Cox proportional hazards model, serum
ICTP showed the highest predictive significance, but could be
replaced by Ntx, which should be preferable in patients with
impaired renal function. For prediction of bone events, S-ICTP
and U-Ntx were superior to the M component measurements,
which in fact did not correlate with progression of the bone
disease.
Discussion and Conclusion: The introduction of bisphosphonates,
osteoprotegerin, and proteasome inhibitors in the treatment of
MM bone disease highlightens the need of non-invasive methods
for monitoring end-organ damage in bone. A clinical valid noninvasive
marker of bone resorption would allow individualised
treatment. Our study indicates that S-ICTP and U-Ntx are
sensitive and predictive markers of the bone disease in MM.
166
Critical role of receptor activator of nuclear factor kB
ligand (RANKL)/osteoprotegerin (OPG) pathway on
bone disease and survival in patients with multiple
myeloma.
Evangelos Terpos1, Richard Szydlo1, Jane F. Apperley1,
Evdoxia Hatjiharissi2, Marianna Politou1, John Meletis3,
Nora Viniou3, Xenophon Yataganas3, John M. Goldman1,
and Amin Rahemtulla1.
1Department of Haematology, Faculty of Medicine Imperial
College, London, U.K., 2Department of Haematology,
Theageneion Anticancer Hospital, Thessaloniki, Greece, and 3First
Department of Medicine, University of Athens School of Medicine,
Laikon Hospital, Athens, Greece.
Bone disease is a major cause of morbidity in multiple myeloma
(MM). Through the interactions between myeloma and stromal
cells, osteoclasts are activated resulting in an increased resorptive
activity, which is illustrated by the elevated levels of N-
telopeptide of type-I collagen (NTX), and of tartrate-resistant
acid phosphatase isoform-5b (TRACP-5b), an enzyme which is
produced only by activated osteoclasts. The receptor activator of
nuclear factor-kB ligand (RANKL) and osteoprotegerin (OPG)
pathway has been found to be the dominant mediator of
osteoclastogenesis and possibly promotes growth of myeloma
cells. The aim of this study was to evaluate the role of soluble
RANKL (sRANKL), OPG and markers of bone remodelling
[NTX, TRACP-5b, bone-alkaline phosphatase (bALP), and
osteocalcin (OC)] in bone disease and survival in MM.
A total of 121 newly diagnosed patients (61M/60F; median age:
68 years) with MM were studied. Ten patients had no lytic
lesions or osteoporosis only; 28 patients had 1-3 osteolytic
lesions, while 83 patients had >3 osteolytic lesions and/or a
pathological fracture. The above markers were also measured in
46, age and sex matched, healthy controls. Patients with MM had
elevated mean sRANKL, TRACP-5b and NTX values and
decreased levels of OPG, OC and bALP compared with controls.
The ratio of sRANKL/OPG was also significantly higher in MM
patients. There was a strong correlation between the ratio
sRANKL/OPG and the extent of bone disease (p