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164 Chapter 4: Lymphoma purging. Since the trial has started to accrue patients, several centers have initiated transplantation of patients with relapsed follicular lymphoma, although data supporting this decision are not convincing. This trend has increased after the general implementation of peripheral blood stem cells with decreased morbidity and mortality. This has had a great impact on the accrual of patients in this trial, finally resulting in the premature closing of entry. With current follow-up, which indisputably is too short for this low-grade disease, the results suggest an improved relapse free survival rate in the transplanted patients, not yet reflected in improved survival. Protocol Writing Committee T. Chisesi, P. Colombat, B. Dorken, A. Goldstone, G. Kvalheim, R. Marcus, H. Schouten, B. Wormann National Coordinators A. Porcellini, P. Colombat, R. Heinz, H. Schouten, A. Goldstone, S. Kvaloy, B. Dôrken Purging Coordinator G. Kvalheim REFERENCES 1. Gallagher CJ, Gregory WM, Jones AE, Stansfeld AG, Richards MA, Dhaliwal HS, Malpas JS, Lister TA: Follicular lymphoma: Prognostic factors for response and survival. J Clin Oncol 4:1470-1480, 1986. 2. Colombat P, Donadio D, Fouillard L, Milpied N, Tilly H, Pico J, Abgrall JF, Coiffier B, Herbrecht R, Philip T: Value of autologous bone marrow transplantation in follicular lym phoma: A France Autogreffe retrospective study of 42 patients. Bone Marrow Transplant 13:157-162, 1994." 3. Vose JM, Bierman PJ, Armitage JO: High-dose chemotherapy with stem cell rescue for the treatment of follicular low grade non-Hodgkin's lymphoma. In: Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium. 1991, p. 479^185. 4. Schouten HC, Colombat P, Verdonck LF, Gorin NC, Bjorkstrand B, Taghipour G, Goldstone AH: Autologous bone marrow transplantation for low-grade non- Hodgkin's lymphoma: The European Bone Marrow Transplant Group experience. EBMT Working Party for Lymphoma. Ann Oncol 5 (Suppl 2): 147-149,1994. 5. Rohatiner A, Johnson P, Price C, Arnott SJ, Amess J, Norton AJ, Dorey E, Adams K, Whelan JS, Matthews J, MacCallum PK, Oza AM, Lister TA: Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. J Clin Oncol 12:1177-1185, 1994. 6. Schouten HC, Raemaekers JJ, Kluin-Nelemans HC, Van Kamp H, Mellink WA, van't Veer MB: High-dose therapy followed by bone marrow transplantation for relapsed fol-
Schouten et al. licular non-Hodgkin's lymphoma. Dutch HOVON Group. Ann Hematol 73:273-277, 1996. 7. Cervantes F, Shu XO, McGlave P: Autologous marrow transplantation for non-trans- formed low-grade non-Hodgkin's lymphoma. Bone Marrow Transplant 16:387-392, 1995. 8. Freedman AS, Ritz J, Neuberg D, Anderson KC, Rabinowe SN, Mauch P, Takvorian T, Soiffer R, Blake K, Yeap B, Coral F, Nadler LM: Autologous bone marrow transplanta tion in 69 patients with a history of low-grade B-cell non-Hodgkin's lymphoma. Blood 77:2524-2529,1991. 9. Freedman AS, Gribben JG, Neuberg D, Mauch P, Soiffer RJ, Anderson KC, Pandite L, Robertson MJ, Kroon M, Ritz J, Nadler LM: High-dose therapy and autologous bone mar row transplantation in patients with follicular lymphoma during first remission. Blood 88:2780-2786,1996. 10. Bastion Y, Brice P, Haioun C, Sonet A, Salles G, Marolleau JP, Espinouse D, Reyes F, Gisselbrecht C, Coiffier B: Intensive therapy with peripheral blood progenitor cell trans plantation in 60 patients with poor-prognosis follicular lymphoma. Blood 86:3257-3262, 1995. 11. Fouillard L, Gorin NC, Laporte JP, et al.: Feasibility of autologous bone marrow trans plantation for early consolidation of follicular non-Hodgkin's lymphoma. Eur J Haematol 46:279-284,1991. 12. Schouten HC, Bierman PJ, Vaughan WP, Weisenburger DD, Kessinger A, Armitage JO, Vose JM: Autologous bone marrow transplantation in follicular non- Hodgkin's lym phoma before and after histologic transformation. Blood 74:2579-2584, 1989. 13. Morel P, Laporte JP, Noel MP, et al.: Autologous bone marrow transplantation as con solidation therapy may prolong remission in newly diagnosed high-risk follicular lym phoma: A pilot study of 34 cases. Leukemia 9:576-582, 1995. 14. Verdonck LF, Dekker AW, Lokhorst HM, Petersen EJ, Nieuwenhuis HK: Allogeneic ver sus autologous bone marrow transplantation for refractory and recurrent low-grade non- Hodgkin's lymphoma. Blood 90:4201^205,1997. 15. Haas R, Moos M, Karcher A, Mohle R, Witt B, Goldschmidt H, Fruhauf S, Flentje M, Wannenmacher M, Hunstein W: Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma. J Clin Oncol 12:1685-1692,1994. 16. Gribben JG, Neuberg D, Freedman AS, et al.: Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood 81:3449-3457, 1993. 17. Kvalheim G, Wang MY, Pharo A, et al.: Purging of tumor cells from leukapheresis prod ucts: Experimental and clinical aspects. /Hematother 5:427^136, 1996. 165
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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
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CHAPTER 3 CML
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Autograft Followed by Allograft Wit
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106 Chapter 3: CML (one low-grade a
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108 Chapter 3: CML DISCUSSION Myelo
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110 Chapter 3: CML Philadelphia-neg
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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 and 186: Lazarus et al. 151 significantly de
Page 187 and 188: Lazarus et al. 153 (Sigma, St Louis
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: Table 1. Patient characteristics at
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
Page 237: CHAPTER 5 MYELOMA
Page 240 and 241: 206 Chapter 5: Myeloma independent
Page 242 and 243: 208 Chapter 5: Myeloma disease (MRD
Page 244 and 245: 210 Chapter 5: Myeloma Scandinavia,
Page 246 and 247: 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
Page 283 and 284:
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
Page 297 and 298:
Hood et al. 263 REFERENCES 1. Rill
Page 299 and 300:
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
Page 428 and 429:
394 Chapter 7: Solid Tumors (mucosi
Page 430 and 431:
Three-Fold Intensification by Seque
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Page 434 and 435:
Page 436 and 437:
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
Page 458 and 459:
424 Chapter 7: Solid Tumors and the
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426 Chapter 7: Solid Tumors Thiotep
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Page 464 and 465:
430 Chapter 7: Solid Tumors E 100 0
Page 466 and 467:
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
Page 474 and 475:
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,
Page 487 and 488:
Fassas et al. 453 INTRODUCTION Mult
Page 489 and 490:
Fassas et al. Table 2. Stem cell mo
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Table 3. Toxicity after stem cell i
Page 493 and 494:
Fassas et al. Table 5. Trial 1: cha
Page 495 and 496:
Fassas et al. MS PROGRESSION FREE S
Page 497 and 498:
Fassas et al. ic or autologous bone
Page 499 and 500:
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
Page 505 and 506:
Burt et dl. All 23. Mor F, Cohen IR
Page 507 and 508:
Hasler, Gratwohl, and Tyndall an ev
Page 509 and 510:
Hasler, Gratwohl, and Tyndall 475 B
Page 511 and 512:
Kuis, Wulffraat, and Sanders 477 st
Page 513 and 514:
Kuis, Wulffraat, and Sanders neousl
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CHAPTER 9 LONG-TERM EFFECTS
Page 518 and 519:
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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Page 532 and 533:
498 Chapter 9: Long-Term Effects En
Page 534 and 535:
500 Chapter 9: Long-Term Effects Rl
Page 536 and 537:
502 Chapter 9: Long-Term Effects RE
Page 538 and 539:
504 Chapter 9: Long-Term Effects A,
Page 540 and 541:
Long-Term Follow-Up of Autologous T
Page 542 and 543:
Page 545:
CHAPTER 10 GRAFT MANIPULATION
Page 548 and 549:
514 Chapter 10: Graft Manipulation
Page 550 and 551:
Page 552 and 553:
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Page 556 and 557:
Page 558 and 559:
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Stem Cell Reinfusion Over Two Conse
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Page 610 and 611:
Page 612 and 613:
Page 614 and 615:
Final Report of the First Prospecti
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Page 628 and 629:
Page 630 and 631:
Page 632 and 633:
Page 635 and 636:
Canine Hematopoietic Stem Allograft
Page 637 and 638:
Sandmaier et al. 603 The resultant
Page 639 and 640:
Sandmaier et al. 605 synthesis path
Page 641 and 642:
Sandmaier et al. 607 interactions o
Page 643 and 644:
Sandmaier et al. 1991. 2. Burchenal
Page 645 and 646:
87:3508-3513,1996. Sandmaier et al.
Page 647 and 648:
Giralt, Khouri, and Champlin Table
Page 649 and 650:
Giralt, Khouri, and Champlin seven
Page 651 and 652:
1.0 3 0.2 Giralt, Khouri, and Champ
Page 653:
CHAPTER 12 GENE THERAPY
Page 656 and 657:
622 Chapter 12: Gene Therapy INTROD
Page 658 and 659:
624 Chapter 12: Gene Therapy RESULT
Page 660 and 661:
626 Chapter 12: Gene Therapy envisi
Page 662 and 663:
628 Chapter 12: Gene Therapy cer in
Page 664 and 665:
A Vaccine of Melanoma Peptide Loade
Page 667 and 668:
B43(anti-CD 19)-Gen i stein Immunot
Page 669 and 670:
Targeting Immunotherapy for the Tre
Page 671 and 672:
McGuinness andArceci 637 modified m
Page 673 and 674:
McGuinness andArceci 639 leukemic c
Page 675 and 676:
McGuinness and Arced 641 in G418. T
Page 677 and 678:
McGuinness andArceci 643 Figure 2
Page 679 and 680:
mRNA for hB7-1 (1491 bp) mRNA for C
Page 681 and 682:
McGuinness and Arced CD80PE C080PE
Page 683 and 684:
McGuinness andArceci 649 8. Robert
Page 685 and 686:
McGuinness andArceci immune respons
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McGuinness andArceci 75. Jubinsky F
Page 689 and 690:
Slavin et al. 655 up suggests, as p
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Slavin et al. 657 was a phase lib c
Page 693 and 694:
Slavin et al. presented, appears to
Page 695 and 696:
Antitumor Immunotherapy in Autologo
Page 697 and 698:
Klingemann et al. 663 Table 3. Meth
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CHAPTER 14 RADIOIMMUNOTHERAPY
Page 702 and 703:
668 Chapter 14: Radioimmunotherapy
Page 704 and 705:
Page 706 and 707:
Page 708 and 709:
Page 710 and 711:
Page 712 and 713:
Page 714 and 715:
Selection of Radioisotopes, Chelate
Page 716 and 717:
Page 718 and 719:
Page 720 and 721:
Page 722 and 723:
Page 724 and 725:
Page 726 and 727:
Radioimmunotherapy of Common Epithe
Page 729:
CHAPTER 15 NEW AVENUES
Page 732 and 733:
698 Chapter 15: New Avenues Table 1
Page 734 and 735:
700 Chapter 15: New Avenues An alte
Page 736 and 737:
702 Chapter 15: New Avenues who can
Page 738 and 739:
704 Chapter 15: New Avenues myeloid
Page 740 and 741:
706 Chapter 15: New Avenues 48. Gir
Page 742 and 743:
Emerging Viral Infections in Blood
Page 744 and 745:
710 Chapter 15: New Avenues influen
Page 746 and 747:
712 Chapter 15: New Avenues Among a
Page 748 and 749:
714 Chapter 15: New Avenues physica
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716 Chapter 15: New Avenues respira
Page 752 and 753:
Minimal Therapy Models of Transplan
Page 755:
CHAPTER 16 SUMMARIES
Page 758 and 759:
724 Chapter 16: Summaries although
Page 760 and 761:
726 Chapter 16: Summaries use of po
Page 762 and 763:
728 Chapter 16: Summaries Table 1.
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Page 768 and 769:
Page 770 and 771:
736 Chapter 16: Summaries IL-15. Th
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738 Chapter 16: Summaries Patterns
Page 774 and 775:
740 List of Participants Thomas L.
Page 776 and 777:
742 List of Participants Sergio A.
Page 778 and 779:
744 List of Participants Hans Marti
Page 780 and 781:
746 List of Participants David P. S
Page 782 and 783:
748 List of Participants AUTHOR IND
Page 784 and 785:
750 Author Index Hurd, D.D. 483 Kui
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752 Author Index Stiff, Patrick J.
Page 788 and 789:
754 Key Word Index Hematologic mali
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