Haematologica 2003 - Supplements

was obtained. Results: Methylation of the FHIT gene was
observed in 21(44%) of the 48 patients. Statistical correlation
between the methylation of the FHIT gene and any clinical
variable was not seen. The estimated 50% survival time of FHIT
methylation group and unmethylation group were 20.2 months
and 30.0 months, respectively (p=0.0042). By using univariate
analysis, the following variables had adverse prognostic features:
methylation of FHIT gene (p=0.0042), advanced age (61 years
old, p=0.0384), bad performance status (ECOG performance
status α to χ, p=0.0004), advanced stage (β, p= 0.0040), low level
of hemoglobin (φ 8.5 g/dl, p=0.0042), low level of serum albumin
(φ 3.5 g/dl, p0.5mg/dl, p=0.0031), elevated level of serum β2-microglobulin
(>6.5 mg/l, p6.5 mg/l, p=0.0327) had statistical significance. Conclusion:
These findings suggest that aberrant methylation of the FHIT
gene may be an independent adverse prognostic factor for
patients with MM.
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SOCS-1 gene methylation is frequent but does not
appear to have prognostic value in patients with
multiple myeloma
S. Depil1,2, G. Guillerm2,3, X. Leleu1, D. Hétuin2, D.
Wolowiec4, F. Bauters1, T. Facon1, B. Quesnel1,2.
1-Service des maladies du Sang, CHU de Lille, France, 2-Unité
Inserm 524, IRCL, Lille, France, 3-Service de Cytogénétique, CHU
de Lille, France, 4-Service d’Hématologie, CHU de Brest, France,
5-Department of Haematology, Wroclaw Medical University,
Wroclaw, Poland.
Background. SOCS-1 is a negative regulator of the Jak/STAT
signalling pathway. Aberrant methylation of SOCS-1 was
initially shown in hepatocellular carcinoma (Yoshikawa, 2001).
Recently, Galm and co-workers found SOCS-1 hypermethylation
in 23/35 (63.9%) patients (pts) with multiple myeloma (MM)
(Galm, 2002). In order to investigate the possible influence of
SOCS-1 methylation on the clinical outcome of MM pts, we
analyzed SOCS-1 gene methylation using methylation specific
PCR (MSP) in a series of MM pts with long term follow-up.
Patients and Methods. Fifty-one previously untreated MM pts
were included in the study. Median age was 66 years (range 36-
81). There were 33 males and 18 females. Clinical staging was:
stage I, 8 (15.7%); II, 12 (23.5%); III, 31 (60.8%). M-component
was Ig G in 30 (58.8%), Ig A in 15 (29.4%), Ig G +Ig A in one,
Bence Jones in 3 (5.9%). Two pts (3.9%) had myeloma without
M-component. Thirty-one patients (60.8%) were treated with
melphalan-prednisone, 15 (29.4%) with intensive protocol, and 5
(9.8%) were not treated. Bone marrow mononuclear cells from
MM pts were isolated by Ficoll Hypaque sedimentation and
extracted DNA was modified by bisulfite. SOCS-1 gene promoter
regions were amplified with DNA methylated and unmethylated
specific primers as previously described (Yoshikawa, 2001).
Results. Fifty-one samples of MM bone marrow cells were
analyzed by MSP. Median time follow-up was 9 years. Selective
methylation of SOCS-1 was found in 38/51 pts (74.5%). No
correlation could be made between SOCS-1 methylation and
gender, age, isotype, level of M-component, stage of the disease,
serum levels of albumin, creatinin, calcium, β2-microglobulin,
LDH, C-reactive protein, or response to treatment. Overall
survival was not significantly different between pts with
methylated or unmethylated SOCS-1 gene (p= 0.58, log-rank
test). In contrast pts presenting an elevated β2-microglobulin
level had a significantly poorer prognosis (p= 0.033).
Conclusion. Methylation of SOCS-1 is frequent in MM,
occurring at frequencies of 75% in our series, and does not appear
to have any significant prognostic value.
184
Plasma Cell Proliferation Index As A Clinical
Prognosticator For Relapsed Multiple Myeloma
Scott Ely, Morton Coleman, Mendel Roth, Paul Cristos,
Vesna Najfeld, Larry Lyons, Michael W Schuster, Karen
Pekle and Ruben Niesvizky
The Center for Lymphoma and Myeloma, Weill Medical College of
Cornell University, New York Presbyterian Hospital
The plasma cell labeling index (PCLI) is a measure of plasma cell
proliferative activity and has been shown to predict poor
prognosis in newly diagnosed multiple myeloma (MM) patients.
Other reports have demonstrated that PCLI is an independent
prognostic indicator for patients with stable-plateau MM. Major
drawbacks of this technique are that it is time-consuming,
requires a degree of subjectivity in its interpretation, and is not
readily available at all institutions. The plasma cell proliferation
index (PCPI) is a double staining immunohistochemistry
technique that allows identification of proliferating malignant
plasma cells in a core biopsy by dual staining Ki-67/CD-138. It is
far less time- consuming and can be consistently performed by a
trained pathologist. High-dose pulsed dexamethasone (Dex) is
one of the preferred treatments for relapsed MM patients and is
currently the accepted gold standard against which investigational
drugs are being tested. The predictors of outcome for relapsed
patients while on Dex treatment have not been well established.
We are therefore prospectively evaluating the PCPI in patients
with relapsed MM receiving Dex in consecutive, prospective
clinical trials. We intend to test its value as a predictor of
response and time to progression (PD). Time to progression is
defined as date of PD - date of Dex initiation. PCPI and
cytogenetics results are being evaluated before Dex initiation in
all enrolled patients. Sixteen patients with relapsed MM were
evaluated. Eighty-one percent (n=13) and 19% (n=3) had IgG
and IgA subtypes, respectively. Of the 16 patients, 56% (n=9)
showed progressive disease at a median time of 87 days. The
median PCPI for those patients with PD was 2.8, while the PCPI
for those that did not show PD was 0.80. Cox-regression analysis
revealed a 1.5 times greater likelihood of progression per unit
increase in PCPI (p=0.07). In accordance with other studies, an
abnormal cytogenetics profile predicted a worse prognosis
(p=0.03). Our results, albeit in a small but homogeneous cohort
of patients, supports the clinical utility of the PCPI in predicting
which patients will progress after high-dose Dex treatment.
Accrual continues and further analysis will be presented at the
meeting.
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