Haematologica 2003 - Supplements

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del 6q, 88% complex abnormalities). Cox regression showed that 1p/q was an independent unfavourable prognostic factor for OS, EFS, PFS and TTP (P 3 mg/L with del13/13q- and 1p/q prognostic groups could be defined with a significant impact on OS (P
With a median follow-up of 38 months from the start of VAD therapy, no statistically significant difference in OS was observed between the two groups (median, 56 months for Tx-1 vs. 60 months for Tx-2). Patients who died due to treatment-related causes were 3% in group A and 4.9% in group B. Compared to group A, patients assigned to the the double transplant arm of the study had a significantly longer duration of remission (median TTR, 27 vs. 44 months, respectively; p = .005) and extended EFS (median, 34 months for patients randomized to group B vs.25 months for those assigned to group A; p= .05). Results of the present analysis confirmed that double autotransplants as primary therapy for MM could be timely performed in slightly less than two thirds of patients aged below 60 with a risk of treatment-related mortality that did not exceed 5%. Nonhematological toxicity of sequential HDT consisting of MEL and Bu-Mel was minimal and no cumulative toxicity was observed in the Tx-2 arm of the study compared to Tx-1. Double autotransplants, albeit not correlated with significantly higher CR rates in comparison with Tx-1, effected responses of “better quality”. This finding ultimately resulted in extended duration of remission and longer EFS for patients assigned to receive double autotransplants in comparison with those randomized to a single autotransplant. With a median follow-up of approximately 3 years no difference in OS was disclosed between the two treatment groups. It is worthy of note that data similar to those herein described were reported by the French Myeloma Intergroup at a preliminary analysis of the IFM-94 trial of single versus double autologous transplants, both prepared with TBI and MEL, 140 mg/m², preceded by MEL in case of double transplants (8). More recently, the same group updated the results of the trial with a longer follow-up and found that double autotransplants significantly extended the 5-year projected probability of OS and EFS in comparison with a single transplant (9). Mature data derived from the final analysis of our study must be awaited before definite conclusions can be given concerning the impact of double autotransplants on the ultimate outcome of MM. Supported in part by Università di Bologna, Progetti di Ricerca ex-60% (M.C.) Appendix The following physicians actively participated in the “Bologna 96” study:R. Giustolisi, F. Di Raimondo, Catania; E. Volpe, Avellino; G. Broccia, M.G. Cabras, Cagliari; L. Gugliotta, L. Masini, Reggio Emilia; B. Rotoli, L. Catalano, Napoli; G. Torelli, F. Narni, Modena; F. Dammacco, V.M. Lauta, Bari; F. Lauria, P.Galieni, A. Gozzetti, Siena; L. Cavanna, G. Civardi, Piacenza; P. Leoni, M. Offidani, Ancona; M. Gobbi, F. Ballerini, Genova; D. Amadori, P. Gentilini, Forlì; D. Mamone, Messina; R. Battista, Chioggia; F. Ricciuti, D. Vertone, Potenza; L. Guardigni, S. Pasini, Cesena; L. Contu, A. Ledda, Cagliari; M. Longinotti, F. Dore, Sassari; M.G. Michieli, Aviano; A. Zaccaria, A.L. Molinari, Ravenna; R. Fanin, F. Patriarca, Udine. REFERENCES Attal M, Harousseau J-L, Stopa A-M, et al: A prospective randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91. Lenhoff S, Hjorth M, Holmberg E, et al: Impact of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Blood 2000; 95: 7. Bjorkstrand B, Ljungman P, Bird JM, Samson D, Gahrton G: Double high-dose chemoradiotherapy with autologous stem cell transplantation can induce molecular remissions in multiple myeloma. Bone Marrow transpl 1995; 15: 367. Barlogie B, Jagannath S, Desikan KR, et al: Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55. Barlogie B, Jagannath S, Vesole DH, et al: Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997; 89: 789. Vesole DH, Barlogie B, Jagannath S, et al: High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. Blood 1994; 84: 950. Bladé J, Samson D, Reece D, et al: criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haematopoietic stem cell transplantation. Br J Haematol 1998; 102: 115. Attal M, Payen C, Facon T, et al: Single versus double transplant in myeloma: a randomized trial of the Intergroupe Francaise du Myelome (IFM). Blood 1997; 90: 418a. Attal M, Harousseau J-L: Randomized trial experience of the Intergroupe Francophone du Myélome. Semin Hematol 2001; 38: 226. P10.2.5 SINGLE VS. TANDEM AUTOLOGOUS TRANSPLANTATION IN MULTIPLE MYELOMA: THE GMMG EXPERIENCE Goldschmidt H On behalf of the German-Speaking Myeloma Multicenter Group, GMMG High-dose (HD) therapy followed by autologous stem cell transplantation (ASCT) has improved event-free (EFS) and overall survival (OS) in multiple myeloma (MM), but nonetheless virtually all patients eventually relapse. Single center experience of the Arkansas group has indicated that total therapy including tandem ASCT improves clinical outcome further, and results of the French IFM-group have shown in a randomized trial that MM patients benefit from tandem ASCT. No significant benefit of double ASCT could be demonstrated in the studies performed by the HOVON-group, the Bologna-group and in the MAG95-study. Melphalan without total body irradiation is currently considered as the best high-dose therapy regimen. Between 1996 and 2000, patients with MM who had received no more than 6 previous cycles of conventional chemotherapy were included in the GMMG-HD2 trial. In the study two randomizations were possible. The first randomization was optional and compared standard VAD vs. vincristine, oral idarubicine and dexamethasone (VID) as induction treatment. Results showed no difference in response and number of stem cells mobilized. Hematological toxicity was higher after VID compared to VAD. The second randomization was obligatory and compared a single cycle of HD-melphalan vs. two sequential cycles of HD-melphalan, each followed by peripheral blood ASCT. Interferon-alpha was started as maintenance treatment for all patients at a dose of 13.5 million units per week. The median follow up of the patients in the study is 36 month. The GMMG will present results of the first trial comparing a single vs. two sequential cycles of HD-melphalan (200 mg/m 2 ) followed by ASCT. S61
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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
Page 15 and 16: Plenary Sessions 1. Development of
Page 17 and 18: clonotypic IgH VDJ signature confir
Page 19 and 20: can be considered as two entities,
Page 21 and 22: immunofluorescence staining for DKK
Page 23 and 24: P2.3 DEVELOPMENT OF A MULTIPLE MYEL
Page 25 and 26: P2.5 MOLECULAR CYTOGENETICS OF MYEL
Page 27 and 28: clear that the biggest challenge fo
Page 29 and 30: esponse and have demonstrated that
Page 31 and 32: variable region of the idiotypic im
Page 33 and 34: 4. From MGUS to symptomatic MM Fig.
Page 35 and 36: (MRI); some have claimed that level
Page 37 and 38: P4.5 CYTOKINES IN MGUS: THERAPEUTIC
Page 39 and 40: preventing phosphorylation of p70S6
Page 41 and 42: transducing component of the interl
Page 43 and 44: survive initial drug exposure and a
Page 45 and 46: quiescent counterpart, the human um
Page 47 and 48: transcriptional activity of NF-êB;
Page 49 and 50: manifestations and anomalous protei
Page 51 and 52: P7.4 ROLE OF SERUM FREE LIGHT CHAIN
Page 53 and 54: P7.6 IMMUNOPHENOTYPIC INVESTIGATION
Page 55 and 56: presumably through the circulation,
Page 57 and 58: 9. Chemotherapy, maintenance treatm
Page 59 and 60: stratified according to their antim
Page 61 and 62: explore higher doses of zoledronic
Page 63 and 64: initial therapy. However, the role
Page 65: P10.2.2 SINGLE VERSUS TANDEM HIGH D
Page 69 and 70: cells could be harvested following
Page 71 and 72: 11. What is the role of allogeneic
Page 73 and 74: found that 75% of patients who were
Page 75 and 76: patients with responsive disease 3
Page 77 and 78: 9. Giralt S, Estey E, Albitar M, et
Page 79 and 80: Badros A, Barlogie B, Siegel E, et
Page 81 and 82: Figure 3b. Event-free Survival 4-Ye
Page 83 and 84: improve patient outcome in MM. Impo
Page 85 and 86: myeloma and in 40% of previously un
Page 87 and 88: degrade OPG in the same way as myel
Page 89 and 90: P12.2.5 MONOCLONAL ANTIBODY THERAPY
Page 91 and 92: myeloma. Blood 2001; 98:210-216. 6.
Page 93 and 94: MHC molecules, in effectively prese
Page 95 and 96: mice demonstrate that class II-spec
Page 97 and 98: detected in 293 and NIH3T3 cells. S
Page 99 and 100: hypothesis that (1) CCND1 and FGFR3
Page 101 and 102: patient samples. In addition, the p
Page 103 and 104: 016 NEUTRAL ENDOPEPTIDASE (CD10) KN
Page 105 and 106: 2. Genetic heterogeneity in MM: imp
Page 107 and 108: evidence from two t(11;14) cases wh
Page 109 and 110: immunoglobulin heavy chain (IgH) lo
Page 111 and 112: 034 Instability of Pericentromeric
Page 113 and 114: clusters were found, the first was
Page 115 and 116: MGUS but most likely not crucial fo
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Objective: To compare the impact on
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4 patients had MMSET/IgH but did no
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and clonal PC from MGUS, MM and PCL
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059 VEGF receptor expresion in Mult
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two HLA-A2+ myeloma patients with C
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molecules expressed on the surface
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Recognition of these antigens appea
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Diagnosis requires a single area of
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081 Incidence of solid tumors in co
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Growth Factor (VEGF), Hepatocyte Gr
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PC-AI levels of MGUS and SMM patien
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093 The predominant pathway of tran
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was associated with I.V. line, whil
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103 Vascular amyloidosis induces se
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5. Signal transduction pathways and
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integrin in IGF-1-triggered MM cell
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118 IL-6- Induced Phosphorylation o
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123 THE IGF/IGF-1R SYSTEM IS A MAJO
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human myeloma cell line (HMCL) to a
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ligation or dexamethasone (Georgii-
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6. Role of microenvironment 6.1 Cel
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141 Human myeloma cells adhere to f
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145 STUDY OF BONE MARROW ANGIOGENES
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patients, the growth of primary mye
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tibia (con=49.1±0.7mg/cm2 vs 5T2=4
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157 The Nitrogen-Containing Bisphos
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7. New prognostic criteria for clas
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atio of >3. This system has subdivi
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Patient 1 (IgG/κ);IgG - 16.5 days,
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176 Pro-inflammatory and angiogenic
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180 Clinical study on the bone lesi
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7.2 Imaging studies 185 99mTc-MIBI
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189 Factors Predicting Occult Spina
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vivo detected resonances was invest
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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
Page 285 and 286:
De La Serna J 291 De Laurenzi A P11
Page 287 and 288:
Hull DR 338 Hullen C P10.2.1 Humes
Page 289 and 290:
Morra E 249 280 359 Morris CM 226 M
Page 291 and 292:
Siegel D 70 115 250 Sierra J 304 30
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