Haematologica 2003 - Supplements

newly diagnosed multiple myeloma as compared to the bone
marrow of healthy controls and of patients with MGUS. A few
studies, however, have documented bone marrow angiogenesis to
be a predictor of survival in patients with newly diagnosed
multiple myeloma.
The aims of the study were to:
evaluate three different techniques to estimate bone marrow
angiogenesis,
investigate the relation between pro-angiogenic cytokines and
bone marrow angiogenesis,
screen relations between bone marrow angiogenesis and known
prognostic factors in patients with multiple myeloma, and
look for prognostic impact of estimates of bone marrow
angiogenesis in these patients.
Material and Methods: Sixty-seven patients with newly
diagnosed multiple myeloma were included in this study. The
median follow-up time was 99 months (range 33-156 months).
Paraffin-embedded bone marrow samples, aspirates and/or
biopsies, from the time of diagnosis were investigated. Sections
of the specimens were stained with hematoxylin and eosin (HE),
and immunohistochemically stained for CD34 to identify micro
vessels. The marrow’s angiogenetic density was determined by
three separate methods: 1) vascular grading, 2) micro vessel
density (MVD), and 3) Chalkley counting.
The concentrations of interleukin-6 (IL-6), basic fibroblastic growth
factor (bFGF), hepatocyte growth factor (HGF) and Syndecan-1 in
blood and bone marrow were analysed using commercial kits.
Results: Positive correlations were found between the three different
methods for estimating bone marrow angiogenesis. The patients with
bone marrows showing a high vascular grade also demonstrated a
higher number of micro vessel profiles per mm2 and higher Chalkley
count than patients with bone marrow showing a low or an
intermediate vascular grade. No correlations were demonstrated
between the estimates of angiogenesis and the concentrations of IL-6,
bFGF and HGF in blood and bone marrow. A positive correlation
was seen between the estimates of angiogenesis and concentrations of
Syndecan-1 in blood. The overall survival was significantly poorer
for patients with bone marrows showing a high vascular grade or a
high MVD, and furthermore, all three estimates of angiogenesis
showed prognostic significance when tested in a multivariate Cox
analysis.
Conclusion: Our study documents that the simple technique of
vascular grading may represent an efficient alternative to MVD or
Chalkley estimation of bone marrow angiogenesis. Moreover, the
prognostic evaluation demonstrates that a high vascular grade, a high
MVD or a high Chalkley count may represent predictors of poor
survival in patients with newly diagnosed multiple myeloma.
according to disease phase: asymptomatic phase (asymptomatic
and untreated MM), initial symptomatic phase (from diagnosis of
symptomatic MM to end of first-line chemotherapy), remission
phase (remission after completion of first-line chemotherapy),
advanced phase (from 1st relapse to death).
Sixty five episodes of positive blood cultures were identified.
Twenty were considered contaminant and excluded. Forty five
episodes of BSI occurred in 35 pts (1 episode: 27 pts, 2 episodes:
6 pts, 3 episodes: 2 pts). Twenty three were community-acquired
and 22 were nosocomial. Microbiological isolates were gram
positive: 21, gram negative: 17, anaerobes: 3, yeast: 1,
polymicrobial: 3. Primary source of infection was lung in 20%,
urinary tract in 11.1%, other in 17.8%, unknown in 51.1%. Ten
episodes (22.2%) occurred during chemotherapy-induced
neutropenia (neutrophil count