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xii Table of Contents CHAPTER 2: ALL Bone Marrow Transplantation for Acute Lymphoblastic 57 Leukemia (ALL) in First Complete Remission Jacob M. Rowe Adult ALL: BMT in First Remission for Selected Patients 62 Dieter Hoelzer, Nicola Gökbuget Autologous Hematopoietic Stem Cell Transplantation as 72 Treatment for Adult Acute Lymphoblastic Leukemia Jorge Sierra, Montserrat Rovira, Luz Muñoz, Carmen Canals, Pedro Marín, Gregorio Martin-Henao, Alvaro Urbano-Ispizua, Joan García, Anna Sureda, Enric Carreras, Salut Brunet, Emilio Montserrat Autologous BMT/PBSCT in BCR-ABL-positive ALL: 84 Rationale for Purging Hans Martin, Johannes Atta, Dieter Hoelzer Autologous vs. Unrelated Allogeneic Bone Marrow 93 Transplantation (AlloBMT) for Acute Lymphoblastic Leukemia (ALL) Michael W. Boyer, Andrew M. Yeager CHAPTER 3: CML Donor Lymphocyte Infusions Produce Durable Molecular 103 Remission in Patients Who Relapse After Allografting for CML in Chronic Phase: The Consequent Need to Reassess the Definition of Leukemia-Free Survival C. Craddock, F. Dazzi, R.M. Szydlo, E. Olavarria, N.C.P. Cross, F. van Rhee, E. Kanfer, J.F. Apperley, J.M. Goldman Autograft Followed by Allograft Without Myeloablative 104 Conditioning Regimen: A New Approach for Resistant Hematologic Neoplasia and Breast Cancer Angelo M. Carella, Enrica Lerma, Anna Dejana, Maria T. Corsetti, Lidia Celesti, Federica Benvenuto, Osvaldo Figari, Caterina Parodi, Mauro Valbonesi, Lucia Casarino, Francesco De Stefano, Andrea Bacigalupo
Table of Contents Autografting for Chronic Myeloid Leukemia in Chronic 111 Phase: EBMT Retrospective Analysis and Proposals for a Prospective Study J.M. Goldman, J. Reiffers, J.F. Apperley, A.M. Carella The Case for Manipulation of CML Autografts 112 Michael Barnett, Connie Eaves, Allen Eaves Preclinical Evaluation of an Inhibitor of the ABL Tyrosine 113 Kinase as a Therapeutic Agent for Chronic Myelogenous Leukemia B.J. Dinker, E. Buchdunger, S. Ohno-Jones, N.B. Lydon Toward a Cure by Drug Treatment? The German CML 114 Study Group Experience R. Hehlmann, U. Berger, A. Hochhaus, C. Huber, T. Fischer, H. Heimpel, J. Hasford, D. K. Hossfeld, H.-J. Kolb, H. Löffler, H. Pralle, W. Queißer, A. Gratwohl, A. Tobler, P. Oppenhoff, M. Grießhammer, S. Valsamas, H. Eimermacher, T. Südhoff, S. Müller-Hagen, C. Elser, C. Scheid, M. Steins, C. Falge, T. Hoffmann, B. Koch, S. Kremers, K. Geissler, C. R. Meier, B. Waßmann, K. Tischmann, J. Eggert, K. Zutavern-Bechtold, D. Hempel, H.-P. Lohrmann, M. Bargetzi, H.-F. Hinrichs, S. Scheding, B. Bieniaszewska, S. W. Krause, H.-J. Tischler, D. Kata, B. Emmerich, H. Wolf, E. Krahulcova, N. Brack, J. Mohm, A. C. Mayr, L. Labedzki, E. -D. Kreuser, O. Rosen, A. A. Fauser, H. G. Sayer, C. Busemann, K. Spiekermann, J. Gmür, F. Schneller, O. Klein, W. Grimminger, R. Mück, C. Neri, A. Neubauer, M. Pfirrmann, A. Carella, J. M. Goldman and the German CML Study Group The Tyrphostin AG957 Inhibits the In Vitro Growth of 128 CD34+ Chronic Myelogenous Leukemia Progenitor Cells Carmelo Carlo-Stella, Ester Regazzi, Daniela Garau, Aviv Gazit, Gabriella Sammarelli, Barbara Savoldo, Daniela Cilloni, Antonio Tabilio, Alexander Levitzki, Vittorio Rizzoli CHAPTER 4: LYMPHOMA Progressive Hodgkin's Lymphoma Following High-Dose 139 Chemotherapy J. Shamash, S.M. Lee, W.D.J. Ryder, G.R. Mogenstern, J. Chang, J.H. Scarffe, A.Z.S. Rohatiner, R.K. Gupta, T.A. Lister, J.A. Radford xiii
Page 1: AUTOLOGOUS BLOOD AND MARROW TRANSPL
Page 5 and 6: AUTOLOGOUS BLOOD AND MARROW TRANSPL
Page 7: ACKNOWLEDGMENTS We wish to thank Wi
Page 11: THE VAN BEKKUM STEM CELL AWARD Prof
Page 16 and 17: xiv Table of Contents Late Non-Rela
Page 18 and 19: xvi Table of Contents Pretreatment
Page 20 and 21: xviii Table of Contents CHAPTER 7:
Page 22 and 23: XX Table of Contents Long-Term Obse
Page 24 and 25: xxii Table of Contents CHAPTER 13:
Page 27 and 28: 0-9 LIST OF ABBREVIATIONS 2CDA 2-ch
Page 29 and 30: List of Abbreviations xxvii EFS eve
Page 31 and 32: List of Abbreviations MOPP mechlore
Page 33: VOD veno-occlusive disease VPC viru
Page 37 and 38: 4HC-Purged Autologous Stem Cell Tra
Page 39 and 40: 1.0-1 + 0.2 Miller et al. 5 Event F
Page 41 and 42: Miller et al. Adjusted probability
Page 43 and 44: Who Benefits From Autograft in AML
Page 45 and 46: Burnett 11 which to set the transpl
Page 47 and 48: Table 1. Outcome after relapse in M
Page 49 and 50: Immunotherapy in AML: No Positive E
Page 51 and 52: Simonsson et al. inhibit IL-2 induc
Page 53 and 54: Autologous Bone Marrow Transplantat
Page 55 and 56: Ball et al. 21 CD15) and AML-2-23 (
Page 57 and 58: Ball et al. 23 The ex vivo treatmen
Page 59 and 60: Ball et al. 25 Table 2. Factors inv
Page 61 and 62: Ball et al. Overall Survival for Pa
Page 63 and 64: Ball et al. Overall Survival for Pa
Page 65 and 66:
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
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Toward a Cure by Drug Treatment? Th
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116 Chapter 3 :CML Table 1. Prolong
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118 Chapter 3: CML Table 3. German
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120 Chapter 3: CML Table 5. Normal
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122 Chapter 3: CML Table 8. Surviva
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124 Chapter 3: CML 88:3118-3122, 19
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126 Chapter 3: CML RK, Klingemann H
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The Tyrphostin AG957 Inhibits the I
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130 Chapter 3: CML mobilization. Al
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132 Chapter 3: CML A B 100 n 0 1 5
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134 Chapter 3: CML The in vitro sel
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136 Chapter 3: CML detecting leukem
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Progressive Hodglcin's Lymphoma Fol
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Reece et al. survival is observed i
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0.2 -I 0.0 0 Reece et al. 143 ii i
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Reece et al. Table 3. Causes of non
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Reece et al. carmustine, etoposide
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CD34 + Selection of Hematopoietic B
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Lazarus et al. 151 significantly de
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Lazarus et al. 153 (Sigma, St Louis
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Lazarus et al. 155 Table 2. Effect
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Lazarus et al. 157 difference. Furt
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Lazarus et al. 159 cells after myel
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The European CUP/UP Trial: A Prelim
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Table 1. Patient characteristics at
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Schouten et al. licular non-Hodgkin
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Sweetenham et al. vs. autologous pe
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Table 1. Patient characteristics, g
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Table 2. Patient characteristics, g
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Table 3. Sites of relapse, group A
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Table 4. Patterns of relapse, group
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A 100 80 %OS 60 40 20 B 100 %OS | S
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Sweetenham et al. new sites, and fi
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Sweetenham et al. Treatment options
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Molecular Remission: A Worthwhile A
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Early or Late Autotransplant in Hig
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Schenkein et al. 187 PATIENTS AND M
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Schenkein et al. 189 Toxicity Toxic
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Schenkein et al. 191 16. Glick JH,
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Santini et al. 193 to evaluate the
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Table 1. Continued Santini et al. 1
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Santini et al. 197 cytosine arabino
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1 0 0 1 90- 80- 70- (0 u. 60' o so-
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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
Page 244 and 245:
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
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
Page 295 and 296:
Hood et al. 261 Table 3. Frequency
Page 297 and 298:
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
Page 327 and 328:
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.
Page 385 and 386:
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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Page 395 and 396:
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
Page 401 and 402:
Bewick et al. 367 HDCT with ABSC su
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Bewick et al. Progression Free Surv
Page 405 and 406:
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
Page 412 and 413:
378 Chapter 7: Solid Tumors INTRODU
Page 414 and 415:
380 Chapter 7: Solid Tumors Prepara
Page 416 and 417:
382 Chapter 7: Solid Tumors Surviva
Page 418 and 419:
384 Chapter 7: Solid Tumors months
Page 420 and 421:
386 Chapter 7: Solid Tumors have be
Page 422 and 423:
High-Dose Chemotherapy in the Manag
Page 424 and 425:
390 Chapter 7: Solid Tumors followe
Page 426 and 427:
392 Chapter 7: Solid Tumors Table 1
Page 428 and 429:
394 Chapter 7: Solid Tumors (mucosi
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Three-Fold Intensification by Seque
Page 432 and 433:
Page 434 and 435:
Page 436 and 437:
High-Dose Therapy for Small Cell Lu
Page 438 and 439:
404 Chapter 7: Solid Tumors chemoth
Page 440 and 441:
406 Chapter 7: Solid Tumors SCLC ha
Page 442 and 443:
408 Chapter 7: Solid Tumors relapse
Page 444 and 445:
410 Chapter 7: Solid Tumors 69:585-
Page 446 and 447:
412 Chapter 7: Solid Tumors ogous b
Page 448 and 449:
414 Chapter 7: Solid Tumors 64. Bru
Page 450 and 451:
416 Chapter 7: Solid Tumors Prignot
Page 452 and 453:
418 Chapter 7: Solid Tumors CO > CO
Page 454 and 455:
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
Page 468 and 469:
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,
Page 487 and 488:
Fassas et al. 453 INTRODUCTION Mult
Page 489 and 490:
Fassas et al. Table 2. Stem cell mo
Page 491 and 492:
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
Page 503 and 504:
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
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Hasler, Gratwohl, and Tyndall 475 B
Page 511 and 512:
Kuis, Wulffraat, and Sanders 477 st
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Kuis, Wulffraat, and Sanders neousl
Page 515:
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
Page 524 and 525:
490 Chapter 9: Long-Term Effects 4.
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492 Chapter 9: Long-Term Effects us
Page 528 and 529:
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:
Page 554 and 555:
Page 556 and 557:
Page 558 and 559:
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Page 602 and 603:
Page 604 and 605:
Page 606 and 607:
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:
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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
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Sandmaier et al. 1991. 2. Burchenal
Page 645 and 646:
87:3508-3513,1996. Sandmaier et al.
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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
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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
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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
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
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Slavin et al. presented, appears to
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Antitumor Immunotherapy in Autologo
Page 697 and 698:
Klingemann et al. 663 Table 3. Meth
Page 699:
CHAPTER 14 RADIOIMMUNOTHERAPY
Page 702 and 703:
668 Chapter 14: Radioimmunotherapy
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Page 706 and 707:
Page 708 and 709:
Page 710 and 711:
Page 712 and 713:
Page 714 and 715:
Selection of Radioisotopes, Chelate
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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
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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
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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
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712 Chapter 15: New Avenues Among a
Page 748 and 749:
714 Chapter 15: New Avenues physica
Page 750 and 751:
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.
Page 764 and 765:
Page 766 and 767:
Page 768 and 769:
Page 770 and 771:
736 Chapter 16: Summaries IL-15. Th
Page 772 and 773:
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
Page 786 and 787:
752 Author Index Stiff, Patrick J.
Page 788 and 789:
754 Key Word Index Hematologic mali
Page 792:
ISBN 1-891524-04-6
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