Haematologica 2003 - Supplements

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Serum osteocalcin Urinary aminoterminal telopeptide of bone collagen (NTx) Urinary deoxypyridinoline (DPD) Skeletal survey Patients with elevated levels of serum or urinary markers of bone turnover went on to have a bone mineral density (BMD) test. The study was discussed with 15 potentially eligible patients. Of these, 7 declined to participate. Therefore, 8 patients underwent assessment between July 2002 and February <strong>2003</strong>. Of these 8 patients: 5 had neither abnormal bone markers nor osteopenia. 1 had both elevated bone markers and bony lytic lesions that indicated that her disease had progressed to multiple myeloma. 1 had elevated deoxypyridinoline (DPD), suggesting bone resorption, but no evidence of osteopenia on bone mineral density tests. 1 had elevated deoxypyridinoline (DPD), suggesting bone resorption, and at the time of writing, we are waiting on the results of a BMD test. The treatment phase of the study requires patients to have abnormalities suggesting bone resorption (raised urinary NTx or DPD or serum ostase or osteocalcin) and at least two sites of osteopenia. No patients have been identified who meet these criteria. From this limited study (to date) we can conclude that the incidence of bone disease in MGUS and smouldering myeloma is low. It is unclear if the introduction of zoledronic acid will prevent subsequent progression to myeloma but patients will continue to be accrued and reassessed annually. 4.3 New criteria for differential diagnosis between MGUS and MM. 084 Expression of Angiogenic Cytokines by Plasma Cells: A Comparison of MGUS, Smoldering Myeloma and Newly Diagnosed Symptomatic Myeloma. Jessica L Haug, Shaji Kumar, Thomas E Witzig, Michael A Thompson, Linda Wellik, Michael M Timm, Philip R Greipp, and S. Vincent Rajkumar Division of Hematology, Mayo Clinic, Rochester, MN, 55905 Background: Bone marrow (BM) angiogenesis is a striking feature of multiple myeloma that correlates with plasma cell proliferation and overall survival. There is a progressive increase in the BM angiogenesis along the spectrum of plasma cell proliferative disorders from MGUS to smoldering myeloma (SMM) and newly diagnosed symptomatic myeloma (NMM). We studied the expression of VEGF, bFGF and their receptors on plasma cells from patients with MGUS, SMM, and NMM using various methods to address this question. Methods and Materials: BM angiogenesis was studied using immunohistochemical staining for CD34 and graded as previously described. Expression of VEGF, bFGF, flt1, KDR (flk-1), FGFR-2 and FGFR-3 were studied by immunohistochemical staining of BM biopsy sections from patients with MGUS, SMM and NMM; results were expressed as the percentage of total plasma cells with cytoplasmic staining for the cytokine. Plasma levels of VEGF, bFGF and IL-6 were estimated using ELISA. Expression of VEGF, bFGF, flt-1 and KDR were studied using quantitative RT-PCR on CD138 sorted plasma cells from patients with MGUS, SMM and NMM. Results: Angiogenesis and angiogenic cytokine expression were studied by immunohistochemistry on 57 bone marrow biopsy samples (15 MGUS, 19 MM, 23 SMM). Plasma cells in MGUS, SMM, and NMM expressed VEGF, bFGF and their receptors (Table1), however there was no statistically significant difference between the three groups.When the expression pattern was correlated with grade of angiogenesis, patients with low grade of angiogenesis had significantly lower % of PC's expressing VEGF, bFGF and flt1. There was no difference in VEGF and bFGF plasma levels between SMM and NMM, P=0.79 and 0.62, respectively. Plasma levels of VEGF and bFGF did not correlate significantly with BM microvessel density (MVD) except in patients with SMM where there was correlation between MVD and bFGF. There was no significant difference in the mRNA expression of VEGF, bFGF, flt1 and KDR between the three groups by quantitative RTPCR. Conclusion: Plasma cells express the angiogenic cytokines VEGF, bFGF and their receptors. We found trends correlating degree of BM angiogenesis with the expression of these cytokines/receptors. However, there was no significant difference in expression of VEGF, bFGF, and their receptors by plasma cells between MGUS, SMM and NMM. Increased angiogenesis along the spectrum of plasma cell disorders may therefore be a function of increased levels of VEGF and bFGF that occur as a result of increasing BM plasma cell % from MGUS to SMM to NMM. Percentage of cytokine positive plasma cells VEGF flk1 KDR bFGF FGFR-2 FGFR-3 MGUS 50 20 33 19 50 40 (0-100) (0-100) (0-100) (0-100) (0-100) (0-100) 33 38 25 13 33 25 SMM (4-100) (4-100) (4-100) (0-100) (0-100) (0-100) 50 50 40 20 37 30 NMM (6-100) (0-100) (0-100) (0-100) (0-73) (0-70) P NS NS NS NS NS NS All values expressed as median (range);pg/mL 085 UTILITY OF SERUM CYTOKINES IN THE STUDY OF MONOCLONAL GAMMOPATHIES AND BONE DISEASE OF MULTIPLE MYELOMA (MM) J.M. Hernández Martín*, R.M.Fisac*, J.A.Queizan*, C.Olivier*, B.Suquía**, R.García-Sanz**, M.J.Calmuntia*, J.A.Portero***, C.Aguilera****, J.J.Sanchez*****, J.F. San Miguel**. * Hospital General de Segovia, ** Hospital Clínico de Salamanca,*** R.S. “Virgen de la Concha”-Zamora, **** Hospital del Bierzo-Ponferrada, ***** Universidad Autónoma de Madrid.Cooperative Group of Castilla-León for study of Monoclonal Gammopathies The marrow microenvironment plays a fundamental role in the etio-pathogenesis of bone disease of Multiple Myeloma (MM), either through direct cell-to-cell stimulus or through the interaction of a network of cytokines produced by stromal, tumor or bone marrow cells. These cytokines are detectable in the patient’s serum. We investigate the value of a series of serum cytokines for the study of bone disease of Multiple Myeloma and the distinction between MM and Monoclonal Gammopathy of Unknown Significance (MGUS). MATERIALS AND METHODS: 176 newly diagnosed patients were included: 107 MM and 69 MGUS. As control groups we selected 25 patients with benign Osteoporosis (BO) and 32 healthy individuals (HI). In all patients, the serum levels of the following cytokines were measured by ELISA (Quantikine®- R&D System): IL-6, soluble IL-6 receptor (sIL-6R), Oncostatine- M (OSM), IL-1β, TNF-α and TNF-β, Vascular Endothelial S125
Growth Factor (VEGF), Hepatocyte Growth Factor (HGF) and IL-11. All values were expressed as pg/ml., except the OC which was analysed qualitatively (detectable vs. undetectable). We determined three bone resorption markers (BRM) in urine: Pyridinoline total (Pyrt), Deoxypyridinoline total (Dpyrt) and Deoxypiridinoline free (DPD-i), and two bone formation markers (BFM) in serum: Osteocalcin (OC) and Bone alkaline phosphatase (bAP). RESULTS: IL-6, sIL-6R, TNF-α and HGF presented values which were significantly higher in the MM group than they were in the MGUS group (4.2 vs. 3.2 (p
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Focussed Symposia Arsenic trioxide
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assess whether such a program will
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The overall response rate was noted
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Figure 5A Table 1: VEL + THAL for R
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naturally occurring OPG. Present tr
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0.505). Finally, the multiple event
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CLINICOPATHOLOGICAL DEFINITION OF W
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Plenary Sessions 1. Development of
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clonotypic IgH VDJ signature confir
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can be considered as two entities,
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immunofluorescence staining for DKK
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P2.3 DEVELOPMENT OF A MULTIPLE MYEL
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P2.5 MOLECULAR CYTOGENETICS OF MYEL
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clear that the biggest challenge fo
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esponse and have demonstrated that
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variable region of the idiotypic im
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4. From MGUS to symptomatic MM Fig.
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(MRI); some have claimed that level
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P4.5 CYTOKINES IN MGUS: THERAPEUTIC
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preventing phosphorylation of p70S6
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transducing component of the interl
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survive initial drug exposure and a
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quiescent counterpart, the human um
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transcriptional activity of NF-êB;
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manifestations and anomalous protei
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P7.4 ROLE OF SERUM FREE LIGHT CHAIN
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P7.6 IMMUNOPHENOTYPIC INVESTIGATION
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presumably through the circulation,
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9. Chemotherapy, maintenance treatm
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stratified according to their antim
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explore higher doses of zoledronic
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initial therapy. However, the role
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P10.2.2 SINGLE VERSUS TANDEM HIGH D
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With a median follow-up of 38 month
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cells could be harvested following
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11. What is the role of allogeneic
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found that 75% of patients who were
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patients with responsive disease 3
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9. Giralt S, Estey E, Albitar M, et
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Badros A, Barlogie B, Siegel E, et
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Figure 3b. Event-free Survival 4-Ye
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Page 89 and 90: P12.2.5 MONOCLONAL ANTIBODY THERAPY
Page 91 and 92: myeloma. Blood 2001; 98:210-216. 6.
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Page 99 and 100: hypothesis that (1) CCND1 and FGFR3
Page 101 and 102: patient samples. In addition, the p
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Page 105 and 106: 2. Genetic heterogeneity in MM: imp
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Page 111 and 112: 034 Instability of Pericentromeric
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Page 115 and 116: MGUS but most likely not crucial fo
Page 117 and 118: Objective: To compare the impact on
Page 119 and 120: 4 patients had MMSET/IgH but did no
Page 121 and 122: and clonal PC from MGUS, MM and PCL
Page 123 and 124: 059 VEGF receptor expresion in Mult
Page 125 and 126: two HLA-A2+ myeloma patients with C
Page 127 and 128: molecules expressed on the surface
Page 129 and 130: Recognition of these antigens appea
Page 131 and 132: Diagnosis requires a single area of
Page 133: 081 Incidence of solid tumors in co
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Page 143 and 144: 103 Vascular amyloidosis induces se
Page 145 and 146: 5. Signal transduction pathways and
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Page 149 and 150: 118 IL-6- Induced Phosphorylation o
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Page 153 and 154: human myeloma cell line (HMCL) to a
Page 155 and 156: ligation or dexamethasone (Georgii-
Page 157 and 158: 6. Role of microenvironment 6.1 Cel
Page 159 and 160: 141 Human myeloma cells adhere to f
Page 161 and 162: 145 STUDY OF BONE MARROW ANGIOGENES
Page 163 and 164: patients, the growth of primary mye
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Page 167 and 168: 157 The Nitrogen-Containing Bisphos
Page 169 and 170: 7. New prognostic criteria for clas
Page 171 and 172: atio of >3. This system has subdivi
Page 173 and 174: Patient 1 (IgG/κ);IgG - 16.5 days,
Page 175 and 176: 176 Pro-inflammatory and angiogenic
Page 177 and 178: 180 Clinical study on the bone lesi
Page 179 and 180: 7.2 Imaging studies 185 99mTc-MIBI
Page 181 and 182: 189 Factors Predicting Occult Spina
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Support Unit (CTSU) with flexibilit
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(β2m) & C reactive protein (CRP).
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plasmids carrying the clonotypic in
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newly diagnosed multiple myeloma as
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216 Transgenic expression of Myc an
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221 Prolonged survival in the 5T2MM
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9. Chemotherapy, maintenance, treat
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229 EFFECTIVENESS OF STANDARD CHEMO
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234 Melphalan and Dexamethasone- Is
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Methods. We investigated the VECD p
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9.2 Renal complications. 243 MERIT
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cost of SRE-related care was $10,24
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those with Hb >13 g/dL. Analysis of
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sustained response, lasting from 52
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proportion of bone abnormality. IgD
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disease. The lack of response to in
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yielding a median of 3x106/kg CD34
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patients(pts) aged ≥60 yrs. We co
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PBSC mobilizing regimen utilizing C
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their leukocytes and platelets. No
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25 Gy to marrow. The tracer dose wa
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non-CR after the first transplant a
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296 PERIPHERAL BLOOD STEM CELL TRAN
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References Effect of dose-intensive
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with cyclosporine A and methotrexat
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11.Role of novel therapies targetin
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312 Thalidomide as Rescue of Relaps
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patients, light chain in 1 patients
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platelets of 207 (76-402), B2M of 3
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325 Low Dose Thalidomide plus Dexam
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in 5 pts (11%), M protein decreased
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time from diagnosis was 3.7 years a
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339 Thalidomide, Clarithromycin and
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344 COMBINATION OF THALIDOMIDE, DEX
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experienced early death during the
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untreated patients with high tumor
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357 Thalidomide protects endothelia
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362 EOSINOPHILIA IS A VERY COMMON F
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11.5 CC 4047, PS 341 and arsenic tr
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without chromosome 13. Mean IC50 fo
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myeloma patients. Phase I data indi
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11.6 Other drugs 380 EFFECT OF STI5
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significant inhibition of cell prol
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which acts to prevent the synthesis
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of B and its metabolites, however,
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and 10 months after start of therap
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terminal kinase (JNK) pathway which
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lymphocytes was tested by Ellispot.
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411 Dendritic Cell-Based Idiotype V
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Author Index Abe M 74 160 Abelman W
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De La Serna J 291 De Laurenzi A P11
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Hull DR 338 Hullen C P10.2.1 Humes
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Morra E 249 280 359 Morris CM 226 M
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Siegel D 70 115 250 Sierra J 304 30
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