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220 Chapter 5: Myeloma 25. Seiden M, Schlossman R, Andersen J, et al.: Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma. LeukLymphoma 17:87-93, 1995. 26. Schiller G, Vescio R, Freytes C, et al.: Transplantation of CD34 positive peripheral blood progenitor cells following high dose chemotherapy for patients with advanced multiple myeloma. Blood 86:390-397, 1995. 27. Schiller G, Vescio R, Lee M, et al.: Long-term outcome of a phase II study of autologous CD34 + peripheral blood stem cell transplantation as treatment for multiple myeloma (Abstract). Blood 88:483a, 1996. 28. Vescio R, Schiller G, Stewart K, et al.: Multicenter phase III trial to evaluate CD34 + select ed vs. unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood In press. 29. Tricot G, Vesole DH, Jagannath S, et al.: Graft-versus myeloma effect: Proof of princi ple. Blood 87:1196-1198, 1996. 30. Verdonck LF, Lokhorst HM, Dekker AW, et al.: Graft-versus-myeloma effect in two cases. Lancet 347:800-801, 1996. 31. Lokhorst HM, Schattenberg JJ, Cornelissen JJ, et al.: Donor lymphocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 90:4206-4211, 1997. 32. Munshi NC, Govindarajan R, Drake R, et al.: Thymidine kinase (TK) gene-transduced human lymphocytes can be highly purified, remain fully functional and are killed effi ciently with ganciclovir. Blood 89:1334-1340, 1997. 33. Soiffer RJ, Gonin R, Murray C, et al.: Prediction of graft-versus-host disease by pheno- typic analysis of early immune reconstitution after CD6-depleted allogeneic bone mar row transplantation. Blood 82:2216-2223, 1993. 34. Champlin R, Ho W, Gajewski J, et al.: Selective depletion of CD8 + T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation. Blood 76:418^123, 1990. 35. Lemoli RM, Fortuna A, Motta MR, et al.: Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: Positive selection and transplantation of enriched CD34 + cells to remove circulating tumor cells. Blood 87:1625-1634, 1996. 36. Qing Y, Osterborg A: Idiotype-specific T cells in multiple myeloma: Targets for an immunotherapeutic intervention? Med Oncol 13:1-7, 1996. 37. Osterborg A, Yi Q, Henriksson L, et al.: Idiotype immunization combined with granulo cyte-macrophage colony-stimulating factor in myeloma patients induced type I, major his tocompatibility complex-restricted, CD8 and CD4 specific T cell responses. Blood 91:2459-2466, 1998. 38. Bergenbrant B, Yi Q, Osterborg A, et al.: Modulation of anti-idiotypic immune response by immunization with the autologous M component protein multiple myeloma patients. Br J Haematol 92:840-846, 1996. 39. Hsu FJ, Benike C, Fagnoni F, et al.: Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med 2:52-58, 1996. 40. Yi Q, Dabadghao S, Osterborg A, et al.: Myeloma bone marrow plasma cells: Evidence for their capacity as antigen-presenting cells. Blood 90:1960-1967, 1997.
Schlossman et al. 221 41. Giralt S, Weber D, Colome M, et al.: Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue. J Clin Oncol 15:667-673, 1997. 42. Urashima M, Chauhan D, Uchiyama H, et al.: CD40 ligand triggered interleukin-6 secre tion in multiple myeloma. Blood 85:1903-1912, 1995. 43. Schultze JL, Cardoso AA, Freeman GJ, et al.: Follicular lymphomas can be induced to present alloantigen efficiently: A conceptual model to improve their tumor immuno- genicity. Proc Natl Acad Sci USA 92:8200-8204, 1995. 44. Gong I, Chen D, Kufe D: Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nature Med 3:558-561, 1997. 45. Gong J, Chen L, Chen D, et al.: Induction of antigen-specific antitumor immunity with adenoviral-transduced dendritic cells. Gene Ther 4:1023-1028, 1997. 46. Tarte K, Lu ZY, Fiol G, et al.: Generation of virtually pure and potentially proliferating dendritic cells from non-CD34 apheresis cells from patients with multiple myeloma. Blood 90:3482-3495, 1997. 47. Tarte K, Olsen SJ, Lu ZY, et al.: Clinical grade functional dendritic cells from patients with multiple myeloma are not infected with Kaposi's sarcoma-associated herpesvirus. Blood 91:1852-1858, 1998.
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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
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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
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
Page 248 and 249: 214 Chapter 5: Myeloma B cq d ? o c
Page 250 and 251: 216 Chapter 5: Myeloma patients wit
Page 252 and 253: 218 Chapter 5: Myeloma PBSC transpl
Page 256 and 257: Autologous Transplantation in Multi
Page 258 and 259: 224 Chapter 5: Myeloma 0 52 44 U §
Page 260 and 261: 226 Chapter 5: Myeloma BM ^ (CD34±
Page 262 and 263: 228 Chapter 5: Myeloma IFM 94 : OS
Page 264 and 265: 230 Chapter 5: Myeloma two groups a
Page 266 and 267: 232 Chapter 5: Myeloma increase bot
Page 268 and 269: 234 Chapter 5: Myeloma REFERENCES 1
Page 270 and 271: 236 Chapter 5: Myeloma Intensified
Page 272 and 273: 238 Chapter 5: Myeloma of CD34 + ce
Page 274 and 275: Chapter 5: Myeloma Table 2. Descrip
Page 276 and 277: 242 Chapter 5: Myeloma o 8H 0 2 4 6
Page 278 and 279: 244 Chapter 5: Myeloma ated with sh
Page 281 and 282: The Presence of Micrometastases in
Page 283 and 284: Kvalheim et al. 249 Table 1. Immuno
Page 285 and 286: Kvalheim et al. 251 Figure 1. Sixty
Page 287 and 288: Kvalheim et al. 253 DISCUSSION In t
Page 289 and 290: Kvalheim et al. 255 Bastert G: Micr
Page 291 and 292: Hood et al. 257 In an effort to inc
Page 293 and 294: #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
Page 299 and 300: The Clinical Significance of Breast
Page 301 and 302: Moss et al. tests, and bilateral po
Page 303 and 304: 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.
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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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
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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
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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,
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
Page 493 and 494:
Fassas et al. Table 5. Trial 1: cha
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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
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
Page 522 and 523:
488 Chapter 9: Long-Term Effects ml
Page 524 and 525:
490 Chapter 9: Long-Term Effects 4.
Page 526 and 527:
492 Chapter 9: Long-Term Effects us
Page 528 and 529:
494 Chapter 9: Long-Term Effects AB
Page 530 and 531:
Page 532 and 533:
498 Chapter 9: Long-Term Effects En
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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:
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Stem Cell Reinfusion Over Two Conse
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Page 614 and 615:
Final Report of the First Prospecti
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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
Page 643 and 644:
Sandmaier et al. 1991. 2. Burchenal
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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
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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
Page 693 and 694:
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
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
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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
Page 746 and 747:
712 Chapter 15: New Avenues Among a
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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.
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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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