Haematologica 2003 - Supplements

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of 4590 single subset determinations in 601 controls. We did no found statistically significant differences in the number of reinfused CD34+cells/Kg between patients receiving selected or unselected CD34+ PBSC. All patients achieved lymphocyte engraftment; median time to achieve a count of 500x106/l was 14 days for HD, 22 for MM and 20 for NHL. Total lymphocytes count was significantly higher in HD group (730x106/l) than in MM (270x106/l) and NHL (220x106/l) on day 15; then, from day 60, it reached stable values beyond 1000x106/l in all groups. CD3 cells recovery was similar in the 3 groups without reaching normal values but with a trend toward normalization until the 3rd year; thereafter the values returned into the normal range. CD4+ counts remained below the normal value throughout the observation period with a trend toward normalization in the 3 groups. Normal values were reaching for HD and NHL on the 6th year and on the 7th year for the MM. Suppressor (CD8) T-cells, decreased after transplant, as from day 60 returned to normal values or beyond the normal range without statistical differences among the groups. The persistent reduction in CD4 cells and the recovery of the CD8 cells subset determed a persistent reduction of the CD4/CD8 ratio. CD19 B cells recovered from day 30, achieving normal range on day 120 in the 3 groups; after 1 year all values settled beyond the normal range; only at baseline time the MM-group showed significant increase of CD19 lymphocytes in comparison with the others two groups. Effector cells, including CD3/HLA-DR and CD16/56, showed a similar trend during the study period. CD16/56 remained below the normal range until day 15 in the 3 groups and increased markedly reaching values beyond the normal range from day 30 with the maximum value on the 5th year in MM and on the 6th year in HD and NHL groups. The immunological recovery after PBSCT was similar in the 3 groups of lymphoprolipherative disorders. These data suggest that CD4 and CD4/CD8 could reach stable normal value resulting in a complete lymphocyte recovery in a longer follow-up. 278 Peripheral Blood Stem Cell (PBSC) Mobilization for Autologous Transplantation in Multiple Myeloma (MM): Comparison of four different schemes in 115 patients from a single center. A. Alegre, A. Granda, , B.Aguado, C. Aláez, C. Blázquez, J. Cannata, E. Martí, S. Nistal, S.Osorio, A. Figuera, M.J. Fernández-Villalta and J.M. Fernández-Rañada. Hematology Department. Hospital Universitario de la Princesa. Madrid.Spain Introduction and Objectives: Autologous PBSC transplantation is the treatment of choice for symptomatic MM patients under 70 years of age as intensification after induction treatment. However, the best method to mobilizing and collecting progenitor cells is not well defined the collecteons results could be influenzed by several variables related with disease status and with the technical procedures used. Patients and Methods: We present our single Centre experience comparing four methods used for PBSC mobilization and collection cell for autologous PBSCT in MM. From 1989 we have included 115 patients with MM (58M/57F). median of age was 50 years (28-70): 6 stage I, 24 stage II and 85 stage III . Median interval between diagnosis and mobilization was 9.5 months (2-142). Moblization schemes were as follows: Group I: Cyclophosphamide 4 g/m2 iv + GM-CSF 8 mcrg/Kg/d sc (Molgramostim, Leucomax®- Schering Plough); Group 2: Cyclophosphamide 2-4 g/m2 iv + G-CSF(filgrastim, Neupogen®,Amgen) sc; Group 3: G-CSF alone 10 mcrg/Kg/d sc x 5 (Group 3A) y 20 mcrg/Kg/d sc x 5 (Group 3b). Group 4: Cyclophosphamide 2 g/m2 iv + G-CSF 10 mcgr/Kg/d sc + SCF 20 mcgr/Kg/d sc. Lymphocitopheresis were started on day 5 in the cytokine alone schemes and after leucocyte recovery > 4x10e9/L in the chemotherapya+cytokine schemes. Resultas: Different results are showe in the table. ( Patients characteristics included in each group did not show significant differences ) Group N Pheresis number CD34 x106/kg Global 115 2 (1-13) 3.1 (1- 16.4) 1 21 6 (4-13) 6.8(1.8- 34.8)* 2 20 3 (2-5) 3.9 (0.5- 14.7) 3 67 2 (1-4) 3.2 (0.04- 14) 3A 56 2 (1-4) 3.4 (0.04- 14) 3B 11 2 (1-3) 3.2 (1.64- 5.9) 4 7 2 (2-4) 4.4 (1.4- 16.4)* MNC x108/kg CFU x104/kg 7.7 (2-15) 4.8 (0.5- 66.5) 7.6 (5- 11.6) 6.6 (2- 14.8) 8.3 (2- 15.2) 8.2 (2.4- 13.9) 8.3 (2.7- 15.2) 3.7 (2.4- 9.12) Graft > 0.5 neutr x 109/L 12 (7- 25) 4 (0-66.5) 13 (9- 20) 13.8 (0.5- 11 (8- 37) 14) 4 (0-25.5) 12 (7- 25) 4 (0-25.5) 12 (7- 25) - 13.5 (11-20) 16.7 (8.5- 11 (9- 38.5) 13) Graft >20 plq. x109/L 12 (7- 71) 11 (7- 42) 12 (7- 42) 12 (8- 71) 12 (8- 71) 11 (10- 36) 12 (8- 18) *p< 0.005 The main variables that influence the results, apart from mobilization scheme, were previous treatment with melphalant and the number of lines of previous chemotherapy.These two variables showed the major negative impact. Comments and Conclusions: The methods with best results regarding rates of CD34+/kg harvesting include chemotherapy followed by the cytokine G-CSF. However, the use of G-CSF alone is enough to reach the minimal CD34/kg targetted rate of 2x10e6/Kg. This method simplifes the collections, reducing the morbidity and the cost of the global procedure. Patients with previous treatment including alkilants as melphalan may have compromised the hemopoietic reserve for PBSC mobilization. The increase of G-CSF dose , until 20 g/kg, did not showed in our experience a significant increase in the CD34+ cells collected, although new studies with much cases are needed to define this point. SCF after chemotherapy and G-CSF was a scheme that showed optimal results although more experience and much cases, including testing ambulatory administration, are also needed, considering its secondary effects and the scarce experience with this drug. 279 Intermediate-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor (G-CSF) is a Valid Alternative to High Dose Cyclophosphamide for Mobilizing Peripheral Blood CD34+ Cells in Patients with Multiple Myeloma. Maria Teresa Petrucci, *Giuseppe Avvisati, Giacinto La Verde, Vincenza Martini, Anna Levi, *Cristina Tirindelli, Pasqualino Amaranto Giovanna Meloni, Franco Mandelli Dipartimento di Biotecnologie Cellulari ed Ematologia University "La Sapienza”, *Ematologia University “Campus Bio-Medico”, Rome- Italy High doses (7g/m2) cyclophosphamide (CTX) followed by recombinant human granulocyte colony-stimulating factor (G- CSF) is an effective mobilizing regimen for collecting peripheral blood stem cells (PBSC). However, this regimen can cause severe toxicity requiring hospitalization and increasing costs. In this study, we retrospectively evaluated the efficacy and safety of a S211
PBSC mobilizing regimen utilizing CTX at 1.2 gr/m2 on days 1 and 3 associated to dexametasone 40 mg daily (from day 1 to day 4) in 38 newly diagnosed MM patients (group A). Results were compared with those obtained in a previous cohort of 25 newly diagnosed MM patients (group B) in whom PBSC were mobilized using 7 gr/m2 of CTX. Subcutaneous administration of G-CSF (5 µg/kg/day) was started in all patients 24 hours after the last dose of dexametasone (group A) or CTX (group B) administration. Both consecutive cohorts of patients were comparable for age, immunoglobulins subtype, stage, disease status, time from diagnosis, previous chemo radiotherapy regimens. The efficacy of the two different mobilizing regimens as for the number of CD34+ collected cells was evaluated only after the first leukapheresis considering that, differently from patients of group B, a target of ≥ 2 x 106 CD34+ cells/Kg for patients of group A was required. This target was reached after a median of 1 (range 1-3) and 2 (range 1-5) leukapheresis in patients of group A and B, respectively. Failure of mobilization was observed in 2 patients of the group A and 1 of the B. The median number of CD34+ cells collected at the time of the first leukapheresis was not significant different between the two groups. A statistically significant reduction in G-CSF utilization was observed in group A as compared to Group B. No deaths in both groups were observed during mobilization and all patients of group B were hospitalized. The median duration of neutropenia (< 0.5 x 109/L) and thrombocytopenia (< 20 x 109/L) was 5 (range 3-8) vs 9 days (range 5-14) and 6 (range 5-10) vs 13 days (range 9-18) for patients of group A and B, respectively. Severe hepatotoxicity after 5 days from CD34+ cells reinfusion was the cause of death in one patient of group B. As for fever, 15/38 (39.5%) patients in group A and 20/25(80%) in group B had a body temperature > 38° C (χ2: 10.03; 2P < 0.02). The duration of neutropenia and thrombocytopenia following PBSC infusion as well as the hospitalization time and the response rate were the same in both groups. Noteworthy, for the relevant economic implications, all patients in group A required no hospitalization and all but two collected a satisfactory number of PBSC. However, a longer follow-up is required for clarifying whether or not survival duration will be different between the two groups. This will be relevant for planning future mobilization strategies . 280 DCEP IS MORE EFFECTIVE THAN hd-CTX AS MOBILIZING REGIMEN in multiple myeloma WITH GOOD antitumor activity P. Zappasodi, S. Mangiacavalli, A. Corso, C. Pascutto, A. Lorenzi, C. Rusconi, M. Varettoni, C. Castagnola, M. Bonfichi, L. Barbarano*, E. Morra*, M. Lazzarino Division of Hematology, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy and *Division of Hematology, Ospedale Niguarda, Milano, Italy Introduction. We previously reported the higher efficacy in mobilizing PBSC and the lower toxicity of DCEP (dexamethasone 40 mg x 4 d and 4-day continuous infusion of daily doses of cyclophosphamide 400 mg/m2, etoposide 40 mg/m2, and cisplatin 10 mg/m2), with respect to HD-CTX. Few information, however, are available about its anti-tumor activity. Aims of the study. 1) to confirm on a large population the efficacy of DCEP as mobilizing regimen; 2) to compare its antitumor activity with that of HD-CTX in previously untreated MM patients. Patients and methods. From 1996 to 2002, 203 MM patients were consecutively enrolled in high-dose programs including single or double autologous transplantation. Two different mobilizing regimens were used: from 1996 to 1999 patients (n=61) were mobilized with HD-CTX (group I); from January 2000 we adopted the DCEP protocol as mobilizing regimen in all MM patients for whom high-dose therapy was indicated (n=142; group II). We evaluated the mobilizing capacity of DCEP on 142 MM pts (M 74, F 68, median age 55 yrs), and the toxicity related to this regimen. We compared the response to the induction/mobilizing phase on a total of 142 evaluable pts: 40 pts of group 1 treated with VAD chemotherapy (3 cycles) followed by a single cycle of HD-CTX (4 g/mq) and 102 pts of group 2 treated with VAD chemotherapy (2 cycles) followed by DCEP (2 cycles). Results. At the start of mobilization with DCEP, 101 pts (71%) were responsive to VAD; 11 pts (7%) were previously treated with alkylating agents; the median interval from first treatment was 3 mos (range1-54). First leukapheresis was performed after a median of 13 days (8-18) from chemotherapy. The patients collecting ≥4x106/kg were 92 (64.8%), while poor mobilizers (≤2x106/kg) were 5 (3.5%). The analysis of toxicity showed thrombocytopenia (PLT
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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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improve patient outcome in MM. Impo
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myeloma and in 40% of previously un
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degrade OPG in the same way as myel
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P12.2.5 MONOCLONAL ANTIBODY THERAPY
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myeloma. Blood 2001; 98:210-216. 6.
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MHC molecules, in effectively prese
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mice demonstrate that class II-spec
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detected in 293 and NIH3T3 cells. S
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hypothesis that (1) CCND1 and FGFR3
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patient samples. In addition, the p
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016 NEUTRAL ENDOPEPTIDASE (CD10) KN
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2. Genetic heterogeneity in MM: imp
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evidence from two t(11;14) cases wh
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immunoglobulin heavy chain (IgH) lo
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034 Instability of Pericentromeric
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clusters were found, the first was
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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
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
Page 183 and 184: vivo detected resonances was invest
Page 185 and 186: Support Unit (CTSU) with flexibilit
Page 187 and 188: (β2m) & C reactive protein (CRP).
Page 189 and 190: plasmids carrying the clonotypic in
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Page 193 and 194: 216 Transgenic expression of Myc an
Page 195 and 196: 221 Prolonged survival in the 5T2MM
Page 197 and 198: 9. Chemotherapy, maintenance, treat
Page 199 and 200: 229 EFFECTIVENESS OF STANDARD CHEMO
Page 201 and 202: 234 Melphalan and Dexamethasone- Is
Page 203 and 204: Methods. We investigated the VECD p
Page 205 and 206: 9.2 Renal complications. 243 MERIT
Page 207 and 208: cost of SRE-related care was $10,24
Page 209 and 210: those with Hb >13 g/dL. Analysis of
Page 211 and 212: sustained response, lasting from 52
Page 213 and 214: proportion of bone abnormality. IgD
Page 215 and 216: disease. The lack of response to in
Page 217 and 218: yielding a median of 3x106/kg CD34
Page 219: patients(pts) aged ≥60 yrs. We co
Page 223 and 224: their leukocytes and platelets. No
Page 225 and 226: 25 Gy to marrow. The tracer dose wa
Page 227 and 228: non-CR after the first transplant a
Page 229 and 230: 296 PERIPHERAL BLOOD STEM CELL TRAN
Page 231 and 232: References Effect of dose-intensive
Page 233 and 234: with cyclosporine A and methotrexat
Page 235 and 236: 11.Role of novel therapies targetin
Page 237 and 238: 312 Thalidomide as Rescue of Relaps
Page 239 and 240: patients, light chain in 1 patients
Page 241 and 242: platelets of 207 (76-402), B2M of 3
Page 243 and 244: 325 Low Dose Thalidomide plus Dexam
Page 245 and 246: in 5 pts (11%), M protein decreased
Page 247 and 248: time from diagnosis was 3.7 years a
Page 249 and 250: 339 Thalidomide, Clarithromycin and
Page 251 and 252: 344 COMBINATION OF THALIDOMIDE, DEX
Page 253 and 254: experienced early death during the
Page 255 and 256: untreated patients with high tumor
Page 257 and 258: 357 Thalidomide protects endothelia
Page 259 and 260: 362 EOSINOPHILIA IS A VERY COMMON F
Page 261 and 262: 11.5 CC 4047, PS 341 and arsenic tr
Page 263 and 264: without chromosome 13. Mean IC50 fo
Page 265 and 266: myeloma patients. Phase I data indi
Page 267 and 268: 11.6 Other drugs 380 EFFECT OF STI5
Page 269 and 270: 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
Page 291 and 292:
Siegel D 70 115 250 Sierra J 304 30
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