Haematologica 2003 - Supplements

evaluated at diagnosis and at various time points during therapy.
By study design, all patients received four months of combined
thalidomide (100mg/d for two weeks and 200mg/d thereafter) and
dexamethasone (40mg/d, on d 1-4, 9-12, 17-20/28 d on odd
cycles and on d 1-4/28 d on even cycles) therapy (THAL-DEX)
as induction of remission before peripheral blood stem cell
(PBSC) collection with high-dose cyclophosphamide and
subsequent double autotransplants upon treatment with melphalan
200mg/sqm. Zoledronic acid (ZOLE acid) was administered at
4mg/28d for at least 9 months. Data from 21 patients (10M, 11F,
median age = 53 years) have been collected so far. At diagnosis,
all bone resorption markers were increased in more than half of
the patients, while BAP and osteocalcin were decreased in 29%
and 18% of the patients, respectively. Both urinary NTX
(p=0.039) and serum crosslaps (p=0.000) were positively
correlated with the extent of skeletal involvement, graded
according to the number and the size of osteolytic bone lesions
assessed in whole skeleton X-ray. After 4 months of therapy with
THAL-DEX and ZOLE acid a significant decrease in mean
urinary NTX (58.6 ±9.5SE nmol/mmol crea vs 21.2±5.1SE,
p=0.003) and serum crosslaps ( 5992±1213SE pmol/L vs 2239±
589SE ) was observed. Other resorption markers were also
reduced, though not significantly. In patients who responded
favorably to THAL-DEX, reduction in bone resorption markers
paralleled the decrease in M protein concentration. A slight
decrease in bone formation markers was also detected, possibly
as a result of DEX therapy; however, this finding needs to be
confirmed at a subsequent analysis performed at the end of the
whole treatment program. It is concluded that among all the
markers of bone turnover, serum crosslaps and urinary NTX are
the ones most strictly related to actual bone resorption and to the
extent of bone involvement, as evaluated at X-ray survey.
Combined THAL-DEX and ZOLE acid administered as primary
therapy for patients with newly diagnosed and symptomatic MM
seem to be highly effective in reducing bone resorption, although
the relative merits of each of these drugs cannot yet be
determined.
Supported in part by MIUR, FIRB project RBAU012E9A_001
(M. Cavo)
diagnosed active (MM) and 26 with relapsed multiple myeloma
(RMM).
Results: Serum levels of FGF-2 and HGF were significantly
higher in active newly diagnosed or relapsed multiple myeloma
in comparison to SMM (P