Haematologica 2003 - Supplements
Haematologica 2003 - Supplements 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. 183 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. S169
7.2 Imaging studies 185 99mTc-MIBI SCINTIGRAPHY PATTERNS IN MULTIPLE MIELOMA (MM) AND MONOCLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE (MGUS). M. Gutierrez*, T, Iturbe*, J.Banzo**, P. Razola**, M.T. Olave*, J.A. Moreno*, A. Arruga*, L.Palomera*, O.Gavín* and V. Dourdil* Hospital Cínico Universitario de Zaragoza. Department of Medicine . University of Zaragoza. Spain Aim of this study: This study has been designed in order to find out the usefulness of 99mTc-MIBI in determining the activity and extension of MM and to differentiate MM from MGUS. Materials and Methods: We have studied a total of 65 patients with the following diagnosis: MM (43), Waldenstr=F6m=B4s Macroglobulinemia(1), and M= GUS (21). In several patients two or more scintigraphies were performed (2-4) at different times. The first scan was made before therapy in 58 patients, post chemotherapy in 4 patients and post autologous peripheral stem cell transplantation in 3 patients. Stage disease was recorded according to Durie & Salmon criteria; for this purpose MGUS was classified as "no diagnostic criteria of MM". Bone radiographic lesions were classified as normal (0), osteoporosis (1), more than 4 osteolitic lesions (3) and between 1 and 3 (2).Whole body scans were obtained 10 minutes after injection of 740 MBq of 99mTc-MIBI , using dual head camera. Scans were classified (according L.Pace) into four patterns :Normal (N, only physiological uptake), diffuse (D, presence of bone marrow uptake), and diffuse plus focal (D+F). The diffuse uptake was scored according to extension and intensity. Other biochemical data with prognostic significance have been studied: Monoclonal protein, Beta2microglobuline, protein C, LDH and albumin. Results: Only 3 of 21 MGUS have been slightly positive (+) for 99mTcMIBI (1 F and 2 D). The difference of MIBI score among the different clinical stages (including MGUS) is significative (p< 0.0001, KW.test), but the sensitivity for positive diagnosis is only 72,5 %). The WM patient had ++ intensity score . One patient with non-secretory MM had normal intensity and pattern of MIBI uptake in two consecutive scans, even in the presence of active spine and paravertebral lesion, documented with CT and MNR. The highest intensity MIBI score (+++) has been observed only in osteolitic lesions grade two (4 patients) and three (5 patients). The difference of MIBI score among the different degrees of bone lesions is significative (p
- Page 127 and 128: molecules expressed on the surface
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7.2 Imaging studies<br />
185<br />
99mTc-MIBI SCINTIGRAPHY PATTERNS IN MULTIPLE<br />
MIELOMA (MM) AND MONOCLONAL GAMMOPATHY<br />
OF UNKNOWN SIGNIFICANCE (MGUS).<br />
M. Gutierrez*, T, Iturbe*, J.Banzo**, P. Razola**, M.T.<br />
Olave*, J.A. Moreno*, A. Arruga*, L.Palomera*, O.Gavín*<br />
and V. Dourdil*<br />
Hospital Cínico Universitario de Zaragoza. Department of<br />
Medicine . University of Zaragoza. Spain<br />
Aim of this study: This study has been designed in order to find<br />
out the usefulness of 99mTc-MIBI in determining the activity and<br />
extension of MM and to differentiate MM from MGUS.<br />
Materials and Methods: We have studied a total of 65 patients<br />
with the following diagnosis: MM (43), Waldenstr=F6m=B4s<br />
Macroglobulinemia(1), and M= GUS (21). In several patients two<br />
or more scintigraphies were performed (2-4) at different times.<br />
The first scan was made before therapy in 58 patients, post<br />
chemotherapy in 4 patients and post autologous peripheral stem<br />
cell transplantation in 3 patients. Stage disease was recorded<br />
according to Durie & Salmon criteria; for this purpose MGUS<br />
was classified as "no diagnostic criteria of MM". Bone<br />
radiographic lesions were classified as normal (0), osteoporosis<br />
(1), more than 4 osteolitic lesions (3) and between 1 and 3<br />
(2).Whole body scans were obtained 10 minutes after injection of<br />
740 MBq of 99mTc-MIBI , using dual head camera. Scans were<br />
classified (according L.Pace) into four patterns :Normal (N, only<br />
physiological uptake), diffuse (D, presence of bone marrow<br />
uptake), and diffuse plus focal (D+F). The diffuse uptake was<br />
scored according to extension and intensity. Other biochemical<br />
data with prognostic significance have been studied: Monoclonal<br />
protein, Beta2microglobuline, protein C, LDH and albumin.<br />
Results: Only 3 of 21 MGUS have been slightly positive (+) for<br />
99mTcMIBI (1 F and 2 D). The difference of MIBI score among<br />
the different clinical stages (including MGUS) is significative (p<<br />
0.0001, KW.test), but the sensitivity for positive diagnosis is only<br />
72,5 %). The WM patient had ++ intensity score . One patient<br />
with non-secretory MM had normal intensity and pattern of MIBI<br />
uptake in two consecutive scans, even in the presence of active<br />
spine and paravertebral lesion, documented with CT and MNR.<br />
The highest intensity MIBI score (+++) has been observed only<br />
in osteolitic lesions grade two (4 patients) and three (5 patients).<br />
The difference of MIBI score among the different degrees of<br />
bone lesions is significative (p
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