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152 Chapter 4: Lymphoma Mobilization and collection of PBPCs Patients began PBPC mobilization after registration, using a regimen reported previously. 18 The mobilization regimen consisted of cyclophosphamide (4.0 g/m 2 ) intravenously over 3-6 hours on the first day of mobilization along with 3.0 g/m 2 mesna within the cyclophosphamide dosing bag, then 500 mg every 3 hours by mouth or by vein for eight doses. Prednisone (2 mg/kg/d) was given orally for the first 4 days of mobilization. G-CSF (Amgen, Thousand Oaks, CA) (10 pg/kg/d) was given subcutaneously beginning between 36 and 48 hours after the completion of cyclophosphamide therapy and continuing until the last day of leukapheresis or until the white blood cell (WBC) count was >75,000/pL. On return of blood neutrophils >1000/pL and platelet count >30,000/pL (usually 12-15 days after cyclophosphamide therapy), PBPCs were collected using standard leukapheresis procedures (COBE SPECTRA, Lakewood, CO, or a similar machine). The target for the collection was to process 10-15 liters of whole blood (or three patient volumes). Leukapheresis continued for a maximum of 4 days until a combined minimum collection of >10.0X10 8 mononuclear cells/kg was achieved. Processing of the collection using the CEPRATE SC System was to yield a combined minimum of 2.0 X10 6 total CD34 + enriched cells/kg patient weight. If either of these minimum numbers was not reached in four or fewer leukaphereses, additional leukaphereses or alternative treatments were to be determined by the site investigator and the principal investigator. Overnight storage To evaluate the effect of overnight storage, patients were randomly assigned to the overnight storage or immediate-processing group at the initiation of the leukapheresis procedures. Leukapheresis products obtained from patients in the overnight storage group were maintained overnight at 4°C, while leukapheresis products procured from patients in the immediate group were processed using the CEPRATE SC System the same day. All subsequent collections for each patient were processed in the same fashion. None of the leukapheresis products were combined with the next leukapheresis product for CD34 selection. Positive selection of CD34+ cells from mobilized PBPCs Harvested mononuclear cells from each leukapheresis collection were prepared and passaged over the immunoaffinity column device (CEPRATE SC System) as directed by the manufacturer (CellPro, Bothell, WA). Adsorbed CD34 + cells were resuspended at 2X10 7 cells/mL and frozen using a controlled-rate liquid nitrogen freezer in the presence of 7.5% (final concentration) dimethylsulfoxide (DMSO)
Lazarus et al. 153 (Sigma, St Louis, MO). Aliquots of the unprocessed PBPCs enriched for CD34 + cells and nontarget (unbound) cells were analyzed for progenitor cell content by clonogenic assays and for CD34 + surface markers using flow cytometry. Flow cytometry Each site used institutional protocols for flow cytometry for enumerating CD34 + cell number. High-dose chemotherapy and stem cell support The protocol required administration of a high-dose BCNU (carmustine)containing chemotherapy regimen. It was suggested that the preparative regimen described by Lazarus et al. be used. 21 Each site used a different regimen 21-23 ; however, all patients at each site received the same regimen. Involved-field radiation therapy was given to active/previously bulky tumors (>5 cm) as 1500 to 2000 cGy in 200-cGy fractions in selected patients. All days referred to herein were calculated from the day of CD34 + cell infusion (day 0). Starting the first day after PBPC infusion (day 1), G-CSF was administered subcutaneously in single or divided injections at a dose of 10 ug/kg/d until the patient's blood absolute neutrophil count was >1000/pL for three consecutive days. Platelet engraftment was defined as the first of seven consecutive days that platelet count was >20,000/uL without transfusion support for low counts and no platelet count 25%, and irradiated platelet transfusions were given for platelet counts less than 10,000-20,000/uL or bleeding complications. Cytomegalovirus (CMV)-negative blood products were given to CMVseronegative patients. Statistical methods Unless otherwise stated, the statistical analyses presented are for the patients who received an autograft of CD34 selected cells only.
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AUTOLOGOUS BLOOD AND MARROW TRANSPL
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AUTOLOGOUS BLOOD AND MARROW TRANSPL
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ACKNOWLEDGMENTS We wish to thank Wi
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THE VAN BEKKUM STEM CELL AWARD Prof
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xii Table of Contents CHAPTER 2: AL
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xiv Table of Contents Late Non-Rela
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xvi Table of Contents Pretreatment
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xviii Table of Contents CHAPTER 7:
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XX Table of Contents Long-Term Obse
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xxii Table of Contents CHAPTER 13:
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0-9 LIST OF ABBREVIATIONS 2CDA 2-ch
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List of Abbreviations xxvii EFS eve
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List of Abbreviations MOPP mechlore
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VOD veno-occlusive disease VPC viru
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4HC-Purged Autologous Stem Cell Tra
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1.0-1 + 0.2 Miller et al. 5 Event F
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Miller et al. Adjusted probability
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Who Benefits From Autograft in AML
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Burnett 11 which to set the transpl
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Table 1. Outcome after relapse in M
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Immunotherapy in AML: No Positive E
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Simonsson et al. inhibit IL-2 induc
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Autologous Bone Marrow Transplantat
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Ball et al. 21 CD15) and AML-2-23 (
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Ball et al. 23 The ex vivo treatmen
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Ball et al. 25 Table 2. Factors inv
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Ball et al. Overall Survival for Pa
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Ball et al. Overall Survival for Pa
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Ball et al. 31 Overall Survival for
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Ball et al. Table 4. Actuarial over
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Ball et al. myeloid leukemia. The G
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Ball et al. 1993. 38. Mehta J, Powl
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Can Autologous Stem Cell Transplant
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De Witte et al. 41 novo AML. Auer r
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De Witte et al. hematopoietic engra
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De Witte et al. 23. Fenaux P, Laï
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Stein et al. and fever. No patient
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Stein et al. after doses 1, 3, and
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Stein et al. early after the transp
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autologous stem-cell rescue. / Clin
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Bone Marrow Transplantation for Acu
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Table 2. Autologous BMT in ALL in f
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Rowe 61 or adult patients with acut
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Hoelzer and Gôkbuget minitransplan
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Hoelzer and Gdkbuget 65 blood, earl
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Table 3. Risk factors for the defin
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Hoelzer and Gôkbuget treatment opt
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Hoeker and Gökbuget tical sibling
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Sierra et al. INTRODUCTION Two-thir
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Sierra et al. Table 2. Adverse char
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1,0 0,0 J Sierra et al. 0 20 40 60
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Sierra et al. Months Figure 4 < 30,
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Sierra et al. No adverse factors (n
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1994. Sierra et al. 83 10. Canals C
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Martin, Atta, and Hoelzer 85 adult
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Martin, Atta, and Hoelzer 87 Single
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100. Martin, Atta, and Hoelzer 89 P
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Martin, Atta, and Hoelzer 91 chromo
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Autologous vs. Unrelated Allogeneic
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Boyer and Yeager 95 outcomes after
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Boyer and Y eager 97 Table 2. Hypot
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Boyer and Y eager SUMMARY Most of t
Page 135: CHAPTER 3 CML
Page 138 and 139: Autograft Followed by Allograft Wit
Page 140 and 141: 106 Chapter 3: CML (one low-grade a
Page 142 and 143: 108 Chapter 3: CML DISCUSSION Myelo
Page 144 and 145: 110 Chapter 3: CML Philadelphia-neg
Page 146 and 147: The Case for Manipulation of CML Au
Page 148 and 149: Toward a Cure by Drug Treatment? Th
Page 150 and 151: 116 Chapter 3 :CML Table 1. Prolong
Page 152 and 153: 118 Chapter 3: CML Table 3. German
Page 154 and 155: 120 Chapter 3: CML Table 5. Normal
Page 156 and 157: 122 Chapter 3: CML Table 8. Surviva
Page 158 and 159: 124 Chapter 3: CML 88:3118-3122, 19
Page 160 and 161: 126 Chapter 3: CML RK, Klingemann H
Page 162 and 163: The Tyrphostin AG957 Inhibits the I
Page 164 and 165: 130 Chapter 3: CML mobilization. Al
Page 166 and 167: 132 Chapter 3: CML A B 100 n 0 1 5
Page 168 and 169: 134 Chapter 3: CML The in vitro sel
Page 170 and 171: 136 Chapter 3: CML detecting leukem
Page 173 and 174: Progressive Hodglcin's Lymphoma Fol
Page 175 and 176: Reece et al. survival is observed i
Page 177 and 178: 0.2 -I 0.0 0 Reece et al. 143 ii i
Page 179 and 180: Reece et al. Table 3. Causes of non
Page 181 and 182: Reece et al. carmustine, etoposide
Page 183 and 184: CD34 + Selection of Hematopoietic B
Page 185: Lazarus et al. 151 significantly de
Page 189 and 190: Lazarus et al. 155 Table 2. Effect
Page 191 and 192: Lazarus et al. 157 difference. Furt
Page 193 and 194: Lazarus et al. 159 cells after myel
Page 195 and 196: The European CUP/UP Trial: A Prelim
Page 197 and 198: Table 1. Patient characteristics at
Page 199 and 200: Schouten et al. licular non-Hodgkin
Page 201 and 202: Sweetenham et al. vs. autologous pe
Page 203 and 204: Table 1. Patient characteristics, g
Page 205 and 206: Table 2. Patient characteristics, g
Page 207 and 208: Table 3. Sites of relapse, group A
Page 209 and 210: Table 4. Patterns of relapse, group
Page 211 and 212: A 100 80 %OS 60 40 20 B 100 %OS | S
Page 213 and 214: Sweetenham et al. new sites, and fi
Page 215 and 216: Sweetenham et al. Treatment options
Page 217 and 218: Molecular Remission: A Worthwhile A
Page 219 and 220: Early or Late Autotransplant in Hig
Page 221 and 222: Schenkein et al. 187 PATIENTS AND M
Page 223 and 224: Schenkein et al. 189 Toxicity Toxic
Page 225 and 226: Schenkein et al. 191 16. Glick JH,
Page 227 and 228: Santini et al. 193 to evaluate the
Page 229 and 230: Table 1. Continued Santini et al. 1
Page 231 and 232: Santini et al. 197 cytosine arabino
Page 233 and 234: 1 0 0 1 90- 80- 70- (0 u. 60' o so-
Page 235 and 236: Hodgkin's lymphoma. N EnglJ Med 333
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CHAPTER 5 MYELOMA
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206 Chapter 5: Myeloma independent
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208 Chapter 5: Myeloma disease (MRD
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210 Chapter 5: Myeloma Scandinavia,
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212 Chapter 5: Myeloma (0 n o B co
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214 Chapter 5: Myeloma B cq d ? o c
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216 Chapter 5: Myeloma patients wit
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218 Chapter 5: Myeloma PBSC transpl
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220 Chapter 5: Myeloma 25. Seiden M
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Autologous Transplantation in Multi
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224 Chapter 5: Myeloma 0 52 44 U §
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226 Chapter 5: Myeloma BM ^ (CD34±
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228 Chapter 5: Myeloma IFM 94 : OS
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230 Chapter 5: Myeloma two groups a
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232 Chapter 5: Myeloma increase bot
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234 Chapter 5: Myeloma REFERENCES 1
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236 Chapter 5: Myeloma Intensified
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238 Chapter 5: Myeloma of CD34 + ce
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Chapter 5: Myeloma Table 2. Descrip
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242 Chapter 5: Myeloma o 8H 0 2 4 6
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244 Chapter 5: Myeloma ated with sh
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The Presence of Micrometastases in
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Kvalheim et al. 249 Table 1. Immuno
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Kvalheim et al. 251 Figure 1. Sixty
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Kvalheim et al. 253 DISCUSSION In t
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Kvalheim et al. 255 Bastert G: Micr
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Hood et al. 257 In an effort to inc
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#CD34 + cells in blood = Hood et al
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Hood et al. 261 Table 3. Frequency
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Hood et al. 263 REFERENCES 1. Rill
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The Clinical Significance of Breast
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Moss et al. tests, and bilateral po
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Moss et al. 269 0 15 70 143 200 400
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Moss et al. 271 0 3 6 12 18 24 30 3
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Moss et al. 273 8. Passos-Coelho J,
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Autotransplantation for Men With Br
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McCarthy et al. 277 radiation, two
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High Dose Sequential Chemotherapy W
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Viens et al. 281 3 g/m 2 and doxoru
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Table 1. Tumor characteristics Exte
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Table 4. Response Viens et al. 285
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Viens et al. 287 Table 5. Pathologi
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Viens et al. 289 apy for inoperable
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Gliick et al. 291 INTRODUCTION The
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Gluck et al. 293 RESULTS Patient de
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Glück et al. 295 Table 3. Response
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Gluck et al. 297 Overall Survival O
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Gluck et al. 299 Sudbury patients w
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Gluck et al. 301 anthracycline or t
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Repetitive High-Dose Therapy With P
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Prince et al. paramagnetic separati
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Prince et al. Table 1. High-dose re
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Table 2. Patient characteristics (n
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Table 4. Hematopoietic recovery fol
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1.0- M C .S 0.8- a c *fe o o> 0.6-
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M 1.0 I 0.8H s? VI o.6H S 0.2 0.0 P
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a Prince et al. days to platelets >
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Table 5. Results of Isolex 300i CD3
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Prince et al. 321 Figure 5, continu
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Prince et al. 323 months after tran
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Prince et al. 325 excessive to be u
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Prince et al. 327 eight patients ha
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Prince et al. 329 marrow transplant
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Prince et al. intensive chemotherap
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-Q CO .Q O 1.0 0.9 0.8 0.7 0.6 0.5
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.Q CD .Q O 1.0 0.9 0.8 0.7 0.6 0.5
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oba Q. 1.0 0.9 Dicke et al. Stage I
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Vahdat with peripheral blood progen
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Evaluation of Prognostic Factors fo
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Fields et al. 343 PATIENTS AND METH
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Table 1. Chemotherapy regimens. Fie
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Fields et al. Stage II; 4-9 Pos LN
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U U Fields et al.
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Fields et al. 351 between 1 and 2 y
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European Trends and the EBMT Databa
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25% % 22% / 17% \ Rosti et al. 355
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Rosti et al. 357 The new Italian St
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Rosti et al. 6. Haas R, Schmid H, H
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Bewick et al. 363 INTRODUCTION The
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Bewick et al. 365 Blood samples obt
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Bewick et al. 367 HDCT with ABSC su
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Bewick et al. Progression Free Surv
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Bewick et al. pression in MBC, i.e.
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Bewick et al. 14. Kandl HL, Seymour
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CHAPTER 7 OTHER SOLID TUMORS
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378 Chapter 7: Solid Tumors INTRODU
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380 Chapter 7: Solid Tumors Prepara
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382 Chapter 7: Solid Tumors Surviva
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384 Chapter 7: Solid Tumors months
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386 Chapter 7: Solid Tumors have be
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High-Dose Chemotherapy in the Manag
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390 Chapter 7: Solid Tumors followe
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392 Chapter 7: Solid Tumors Table 1
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394 Chapter 7: Solid Tumors (mucosi
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Three-Fold Intensification by Seque
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High-Dose Therapy for Small Cell Lu
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404 Chapter 7: Solid Tumors chemoth
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406 Chapter 7: Solid Tumors SCLC ha
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408 Chapter 7: Solid Tumors relapse
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410 Chapter 7: Solid Tumors 69:585-
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412 Chapter 7: Solid Tumors ogous b
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414 Chapter 7: Solid Tumors 64. Bru
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416 Chapter 7: Solid Tumors Prignot
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418 Chapter 7: Solid Tumors CO > CO
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420 Chapter 7: Solid Tumors TANDEM
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Multiple Courses of Cyclophosphamid
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424 Chapter 7: Solid Tumors and the
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426 Chapter 7: Solid Tumors Thiotep
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430 Chapter 7: Solid Tumors E 100 0
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432 Chapter 7: Solid Tumors course
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434 Chapter 7: Solid Tumors boplati
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436 Chapter 7: Solid Tumors INTRODU
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438 - Chapter 7: Solid Tumors Table
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440 Chapter 7: Solid Tumors seeded
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442 Chapter 7: Solid Tumors DISCUSS
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444 Chapter 7: Solid Tumors 10. Di
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446 Chapter 7: Solid Tumors plasma
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Autologous Stem Cell Transplantatio
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Keystone 451 hypertension, anemia,
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Fassas et al. 453 INTRODUCTION Mult
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Fassas et al. Table 2. Stem cell mo
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Table 3. Toxicity after stem cell i
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Fassas et al. Table 5. Trial 1: cha
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Fassas et al. MS PROGRESSION FREE S
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Fassas et al. ic or autologous bone
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1 2 1 6 EAE. Burt et al. 465 Becaus
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Burt et al. Since cyclophosphamide
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Burt et al. 469 toxicity study, we
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Burt et dl. All 23. Mor F, Cohen IR
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Hasler, Gratwohl, and Tyndall an ev
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Hasler, Gratwohl, and Tyndall 475 B
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Kuis, Wulffraat, and Sanders 477 st
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Kuis, Wulffraat, and Sanders neousl
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CHAPTER 9 LONG-TERM EFFECTS
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484 Chapter 9: Long-Term Effects po
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486 Chapter 9: Long-Term Effects Ta
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488 Chapter 9: Long-Term Effects ml
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490 Chapter 9: Long-Term Effects 4.
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492 Chapter 9: Long-Term Effects us
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494 Chapter 9: Long-Term Effects AB
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498 Chapter 9: Long-Term Effects En
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500 Chapter 9: Long-Term Effects Rl
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502 Chapter 9: Long-Term Effects RE
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504 Chapter 9: Long-Term Effects A,
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Long-Term Follow-Up of Autologous T
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CHAPTER 10 GRAFT MANIPULATION
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514 Chapter 10: Graft Manipulation
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Stem Cell Reinfusion Over Two Conse
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Final Report of the First Prospecti
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Canine Hematopoietic Stem Allograft
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Sandmaier et al. 603 The resultant
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Sandmaier et al. 605 synthesis path
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Sandmaier et al. 607 interactions o
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Sandmaier et al. 1991. 2. Burchenal
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87:3508-3513,1996. Sandmaier et al.
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Giralt, Khouri, and Champlin Table
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Giralt, Khouri, and Champlin seven
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1.0 3 0.2 Giralt, Khouri, and Champ
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CHAPTER 12 GENE THERAPY
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622 Chapter 12: Gene Therapy INTROD
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624 Chapter 12: Gene Therapy RESULT
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626 Chapter 12: Gene Therapy envisi
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628 Chapter 12: Gene Therapy cer in
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A Vaccine of Melanoma Peptide Loade
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B43(anti-CD 19)-Gen i stein Immunot
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Targeting Immunotherapy for the Tre
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McGuinness andArceci 637 modified m
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McGuinness andArceci 639 leukemic c
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McGuinness and Arced 641 in G418. T
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McGuinness andArceci 643 Figure 2
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mRNA for hB7-1 (1491 bp) mRNA for C
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McGuinness and Arced CD80PE C080PE
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McGuinness andArceci 649 8. Robert
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McGuinness andArceci immune respons
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McGuinness andArceci 75. Jubinsky F
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Slavin et al. 655 up suggests, as p
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Slavin et al. 657 was a phase lib c
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Slavin et al. presented, appears to
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Antitumor Immunotherapy in Autologo
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Klingemann et al. 663 Table 3. Meth
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CHAPTER 14 RADIOIMMUNOTHERAPY
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668 Chapter 14: Radioimmunotherapy
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Selection of Radioisotopes, Chelate
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Radioimmunotherapy of Common Epithe
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CHAPTER 15 NEW AVENUES
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698 Chapter 15: New Avenues Table 1
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700 Chapter 15: New Avenues An alte
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702 Chapter 15: New Avenues who can
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704 Chapter 15: New Avenues myeloid
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706 Chapter 15: New Avenues 48. Gir
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Emerging Viral Infections in Blood
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710 Chapter 15: New Avenues influen
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712 Chapter 15: New Avenues Among a
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714 Chapter 15: New Avenues physica
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716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
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CHAPTER 16 SUMMARIES
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724 Chapter 16: Summaries although
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726 Chapter 16: Summaries use of po
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728 Chapter 16: Summaries Table 1.
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736 Chapter 16: Summaries IL-15. Th
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738 Chapter 16: Summaries Patterns
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740 List of Participants Thomas L.
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742 List of Participants Sergio A.
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744 List of Participants Hans Marti
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746 List of Participants David P. S
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748 List of Participants AUTHOR IND
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750 Author Index Hurd, D.D. 483 Kui
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752 Author Index Stiff, Patrick J.
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754 Key Word Index Hematologic mali
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ISBN 1-891524-04-6
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