Haematologica 2003 - Supplements

atio of >3. This system has subdivided our patients into three
groups. The low-risk group included 26 patients (score 8). The 5-year probability of survival
for each group is illustrated in the Figure. We compared this
scoring system with that proposed by Bataille et al using beta2-
microglobulin and CRP as prognostic values. Our risk score
appears to be more discriminating in identifying a very good risk
group, and a superior intermediate risk group. Not only do these
results confirm for the first time in humans the importance of the
RANKL/OPG system in the development of bone disease but
they also highlight the role of this pathway in the biology of
plasma cell growth as reflected by its influence on survival.
167
Low serum level of soluble tumor necrosis factor
receptor p55 predicts for response to thalidomide in
advanced myeloma.
Anne-Tove Brenne, Lene Hejna Romstad, Peter Gimsing,
Gunnar Juliusson, Ingemar Turesson, Magne Borset,
Anders Sundan and Anders Waage
Inst. of Cancer Research and Molecular Medicine, NTNU,
Trondheim, Norway; Dep. of Hematology, National Hospital,
Copenhagen, Denmark; Dep. of Hematology, University Hospital,
Linkøping, Sweden;University Hospital, Malmø, Sweden.
65 patients with primary or secondary resistance to melphalan/
prednisone or other types of chemotherapy were treated with
thalidomide at doses escalating from 200 mg to 800 mg (Nordic
Myeloma Study Group trial #10). The mean age of the patients
was 63,4 +/- 11 years. Serum taken before start of treatment was
available from 34 patients and analyzed for soluble TNF
receptors (sTNFR) p55 and p75. In addititon, serum taken after 3,
12-16, and 20-24 weeks of treatment was available from 16
patients for analysis. Patients were grouped into immunoglobulin
responders and non-responders after 12 weeks of treatment.
Response was defined as a decrease in concentration of
monoclonal protein by >25 %. The control group consisted of 21
blood donors with a mean age of 42,7 +/-11 years.
The concentration of both sTNFR p55 and p75 in serum taken
before start of treatment was significantly higher in the patient
group than in the control group ( 2,37 +/-1,02 ng/ml vs. 1,80 +/-
0,42 ng/ml (p = 0,04) for sTNFp55 and 4,23 +/-1,68 ng/ml vs.
2,27 +/-0,78 ng/ml (p < 0,001) for sTNFRp75 ). In responders,
the concentration of sTNFR p55 taken before start of treatment
was significantly lower than in non-responders ( 1,80 +/-0,47
ng/ml vs. 2,86 +/-1,16 ng/ml (p = 0,004)). The same tendency
was seen with sTNFRp75, but here the difference was not
significant ( 3,78 +/-1,26 ng/ml in responders vs.4,66 +/-2,01
ng/ml in non-responders (p = 0,28) ). In the longitudinel analysis
of serum from 16 patients, a borderline significant decrease was
observed in the level of sTNFR p55. The level of sTNFRp75 did
not change during this interval.
Median survival of patients with a level of sTNFR p55 ≤2,64
ng/ml ( coresponds to mean level +2SD of control group ) was
404 days and median survival of those with sTNFR p55 >2,64
ng/ml was 57 days ( p = 0,007 ). Median survival of patients with
a level of sTNFR p75 ≤ 3,83 ng/ml ( coresponds to mean level
+2SD of control group ) was 380 days vs. 108 days for those with
sTNFR >3,83 ng/ml ( p = 0,45 ). Median follow up was 2 years
and 22 weeks.
We conclude that the level of both sTNFRs p55 and p75 is
elevated in patients with advanced myeloma where treatment
with chemotherapy has failed. There is a significant difference
between responders and non-responders to thalidomide with
respect to pretreatment levels of sTNFR p55. Levels of serum
sTNFRp55 have prognostic significance and predict for response
to thalidomide in advanced multiple myeloma.
168
Total soluble HLA class I (HLA-Is): a new prognostic
factor in Multiple Myeloma
X. Leleu*, G. Le Friec*, L. Amiot*, R. Fauchet*, J.L.
Faucompré*, C. Mathiot, R. Bataille, J.Y. Mary* and T.
Facon
1Service des Maladies du Sang and Laboratoire de Biochimie,
CHU, Lille; 2Laboratoire d'Hématologie, CHU, Rennes, Nantes;
3Institut Curie, Paris and 4INSERM U444, PARIS VII, France, on
behalf of the IFM group.
Assessment of survival prognostic factors in multiple myeloma
(MM) patients (pts) remains an important issue for the selection
of the best treatment. Serum beta-2 microglobulin (beta2m)
which is the light chain of the HLA class I molecular complex
(HLA-I) is still one of the most powerful survival prognostic
factor. The aim of this study was to assess the levels and
prognostic roles of total soluble class I (HLA-Is) and soluble
HLA-Gs in MM, especially relatively to beta2m.
Serum was collected from 101 pts before any treatment. HLA-Is,
and HLA-Gs concentrations were measured using a specific
sandwich ELISA using MEM-G/9, a monoclonal antibody (mAb)
detecting HLA-Gs (Exbio, Czech rep) or W6/32, a mAb
recognizing a determinant of beta2m associated HLA class I
heavy chains (Harlan Sera-Lab Ltd, England). Main pts
characteristics : median age = 63 y ; stage I, II, III, DS, 36, 19 and
45%, respectively ; 64, 27 and 6% with IgG, IgA and light chain
M-component, respectively ; 51% with at least one bone lesion ;
31% chromosome 13 deletion (n=70) ; median level of beta2m
and creatinine were 2.8 mg/L and 10 mg/L, respectively. Thirtyseven
pts received an intensive treatment (44%). Median +/- se of
the follow-up, overall survival and progression-free survival
times were 51.7 +/- 3.1, 48.7 +/- 7.3 and 30.0 +/- 4.0 months
(mo.), respectively. HLA-Is and HLA-Gs median values (range)
were 839ng/ml (206-7913) and 28ng/ml (4.8-124.5), respectively.
Both marker levels were not correlated to the creatinine level (P
>.400). The factors predictive of a poor survival in Cox model
univariate analysis were : high level of beta2m (2.5 and 4.0 mg/L,
P=.0001), stage II or III DS (P=.0001) ; Hb 13% (P=.0010) ;
chromosome 13 deletion (P=.0069) ; age > 65y (P=.0131). When
coupling HLA-Is and beta2m levels, a very efficient prognostic
score was derived (P = 2100, respectively. When
adding these scores, median +/- se of survival time was (mo.)
14.1 +/- 4.3 with an overall score of 3, 27.8 +/- 4.1 with 2, and
47.8 +/- 2.7 with 1. The median survival time was not reached at
95 mo. with score 0. For pts with a given level of beta2m, relative
risk of death was 2.2 (95% CI 1.6-3.0) for pts with HLA-Is >=
2100 as compared to those