Haematologica 2003 - Supplements

180
Clinical study on the bone lesions for 93 patients with
multiple myeloma
M.Badea, Daniela Badea
University of Medicine and Pharmacy, Craiova, Romania
Background. Multiple Myeloma (MM) is an incurable
plasmocitic dyscrasia associated with bone lesions and having a
major impact on the quality of life of these patients.
Aims. We investigated the incidence of the bone lesions in
multiple myeloma (MM), the course of those lesions and we also
evaluated the relationships of skeletal symptoms with prognostic
factors.
Methods. The subjects were 93 patients, aged 45 years or more
(median age 62 ange 45-82 year), They consisted of 54 men and
39 women. According to the Durie-Salmon staging 72,05%
patients were in stage III. Regarding the type of plasma cell
morphology, the lot was shared as following: 9,09%
plasmablastic group, 18,18% immature group, 15,9%
intermediate group and 56,81% mature group (Greipp). 58,82%
patients had a monoclonal IgG, (23,52%) had IgA, 14,7% had
only light chain in urine, 1,47% had IgD and 1,47% was
nonsecretory myeloma. Skeletal symptoms were noticed in
77,41% patients and bone pain in 62,36% patients at the time of
the dyagnosis.
Results. The bone lesions were evaluated as only osteolytic
lesions in 15,6% patients, osteolytic lesions + osteoporosis in
60,3% patients, only osteoporosis in 6,6% patients. Pathologic
bone fractures were present in 39,13% patients. The life activities
were limitted in 53,76% patients because of the bone lesions.
The occurrence rate of osteoporosis plus osteolytic lesions was
higher in elderly patients over 65 years (69,3%) than that in nonelderly
patients (51.3%) (p < 0.045). The bone lesions were most
often observed in lumbar vertebrae (53,69%), cranial bone
(46.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The
occurrence rate of bone lesion in lumbar vertebrae was higher in
elderly patients (59.7%) than that in non-elderly patients (45.6%)
(p < 0.05). There was a significant difference in the rate of
plasma cells in the bone marrow between the patients with and
without pathologic fracture (p< 0.05). Significant differences of
survival times were found between non-elderly MM patients with
and wihthout pathological bone fractures (p < 0.05). The rate of
the bone lesions and their gravity is higher in the patients with
immature and plasmablastic morphology (p < 0.06).
Conclusions. The bone marrow represent an unsolved problem
with major impact on the life quality for the patients with MM.
Their incidence ans extension seem more important in elderly
patients and in those who have aggressive morphology.
E-mail: mbadea@craiova.pcnet.ro
181
FRECUENCY AND PROGNOSTIC RELEVANCE OF P53
EXPRESSION IN MYELOMA MULTIPLE (MM)
E. Tuset, J. Trapé, A. Asensio, M. García, G las Heras, JA.
Hernández, MJ. Herraiz, R. López, M. Prat, O. Ramón, JA.
Soler, R. Salinas
Spain
Objective: The aim of this study was to investigate the expression
of protein p53 in MM de novo and analysis the prognostic
influence in survival and response to treatment.
Patients and Methods: A total of 73 new patients with MM were
included. In aspirate of bone marrow from MM we study the
immunochemistry expression of p53 in plasma cells and
considered positive when more than 5% of plasma cells were
nuclear positive expression. The most important clinical and
biological parameters were included. The cumulative survival
probability and cumulative response probability into positive
cases were calculated by men Kaplan Meier estimator.
Univariante and multivariate Cox models were used to identify
possible predictor of poor survival and resistance to treatment.
Results: Mean age (SD) 77y. (11). Males 59%. Histological
subtypes: Bence-Jones MM (n=13), Non-Secretor (n=2), IgG-κ
(n=17), IgG-λ (n=15), IgA-κ (n=13), IgA-λ (n=13). 46% (n=24)
were positive for p53 expression. Different schedules of
treatment were administrated: MFL+PDN (n=39), VCMP/VBAD
(n=21), VAD (n=4) and no treated 9 cases. Response was 63%
(33% objective, 11% complete and 19% partial). Mean survival
32m (0,5-54) and cumulative survival probability at 3y. was 43%
(IC95% 36-51%). Multivariate Cox model LDH> 5 µkat/L,
albumin < 30g/L and Durie stage III were independent factors for
shortened survival. Multivariate analysis to resistance to
treatment albumin< 30 g/L and positive expression of protein p53
were significantly.
Conclusion: These findings suggest that p53 immunostaininig in
routine bone marrow aspirate may be helpful for detection of MM
with potentially resistance to treatment.
182
Methylation status of FHIT and its clinical impact
Satoru Takada (1)Kimio Morita (2)Kunihiko Hayashi
(3)Nahoko Hatsumi (1)Morio Matsumoto (1)Takahumi
Matsushima (4)Hirokazu Murakami (3)
(1)Department of Internal Medicine, National Nishi Gunma
Hospital; (2)Department of Internal Medicine, Koshigaya Hospital,
Dokkyo University School of Medicine; (3)School of Health
Science, Facalty of Medicine, Gunma University; (4)Third
Department of Internal Medicine, Gunma University School of
Medicine
Introduction: Hypermethylation of CpG island is one of the
mechanisms for gene inactivation. Aberrant methylation of tumor
suppressor genes (TSG) has been reported in multiple myeloma
(MM), and has been discussed about its relationship to
pathogenesis, disease progression and prognosis. For example, it
has been reported that methylation of p16 or DAP kinase gene
was related to poor prognosis. We investigated methylation status
of FHIT (fragile histidine triad) gene, which was a putative TSG,
and evaluated the clinical impact of its methylation in MM.
Patients: Forty-eight patients were investigated in this study.
Forty of 48 patients were de novo cases, and the other 8 patients
were transferred from other hospitals, where they had already
received one to three courses of chemotherapy. The
characteristics of patients were as follows: gender; male vs.
female=26 vs. 22, age; 42 to 82 years (median 63), clinical stage;
I=2, II=13, III=23, immunoglobulin class of M-protein; IgG=29,
IgA=9, Bence-Jones type=8, IgD=1, non-secretary type=1, types
of light chain; κ=34, λ=14. Materials and method: Bone marrow
(BM) was obtained before treatment, or at administration to our
institution in the patients who had already received
chemotherapy. Mononuclear cells in BM were separated by a
density-gradient centrifugation, and stored at -150C. Genomic
DNA was extracted from the above mononuclear cells, and
detected methylation of the FHIT gene by using the methylationspecific
PCR. Briefly, DNA was treated with sodium bisulfite,
and then, amplified using two sets of primers. One set was for
unmethylated FHIT alleles, while another for methylated FHIT
alleles. If the FHIT gene in a sample was methylated, the sample
was able to be amplified by the primer set for the methylated
alleles. The survival time was calculated from the day when BM
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