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218 Chapter 5: Myeloma PBSC transplantation; concomitantly, an ex vivo expansion of their T cells is undertaken, using CD40-activated "y-irradiated autologous MM cells as stimulators. Preliminary studies suggest that these T cells can be expanded effectively to the level of 10 8 —10 9 and safely administered as adoptive immunotherapy. In vitro studies show their reactivity with autologous MM cells, but not with autologous B cells, CD40-activated autologous B cells, or allogeneic MM cells. The clinical utility of this treatment is under active investigation. A second strategy for enhancing autologous immunity to MM posttransplant involves vaccines. One example at our institute involves vaccinations with fusions of MM cells with DCs (MM-DC fusions). We have pioneered vaccinations with MM-DC fusions or with transduced DCs in breast cancer models at our institute 44,45 and demonstrated both triggering of specific in vitro T cell reactivity and clinically significant in vivo responses in animal models. MM-DC fusions used as vaccines have similarly induced in vitro and in vivo specific responses in animal models; to date, prophylactic MM-DC vaccinations have inhibited the subsequent ability to induce MM in syngeneic mouse models; and in animals already bearing MM, MM- DC vaccinations appear to prolong survival. Trials are now underway to test the safety and efficacy of MM-DC vaccinations in humans. Finally, to facilitate these and other novel immune approaches using DCs, we and others have shown that it is possible to generate large numbers of DCs from both the BM and PB of patients with MM which retain normal phenotype and APC function (Chauhan et al. and Raje et al., manuscripts submitted). 46 - 47 This is true even though our studies suggest that a fraction of these DCs contain human herpesvirus 8 gene sequences(Chauhan et al. and Raje et al., manuscripts submitted). The stage is therefore set for posttransplant immune-based treatments in patients with MM. REFERENCES 1. Landis SH, Murray T, Bolden S, et al.: Cancer Statistics, 1998. CA—A Cancer Journal for Clinicians 48:10-11, 1998. 2. Gregory WM, Richards MA, Malpas JS: Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: An overview of published trials. / Clin Oncol 10:334-342, 1992. 3. Alexanian R, Dimopoulos M: The treatment of multiple myeloma. N Engl J Med 330:484-489,1994. 4. Ludwig H, Cohen AM, Polliack A, et al.: Interferon-alpha for induction and maintenance in multiple myeloma: Results of two multicenter randomized trials and summary of other studies. Ann Oncol 6:467^176, 1995. 5. Kyle RA: Multiple myeloma: Review of 869 cases. Mayo Clin Proc 50:29-40, 1975. 6. Anderson KC: Who benefits from high dose therapy for multiple myeloma? / Clin Oncol 13:1291-1296, 1995. 7. Kovacsovics TJ, Delaly A: Intensive treatment strategies in multiple myeloma. Semin
Schlossman et al. Hematol 34:49-60,1997. 8. Bensinger WI, Demirer T, Buckner CD, et al.: Syngeneic marrow transplantation in patients with multiple myeloma. Bone Marrow Transplant 18:527-531, 1996. 9. Gahrton G, Tura S, Ljungman P, et al.: Allogeneic bone marrow transplantation in mul tiple myeloma. N Engl J Med 325:1267-1273, 1991. 10. Gahrton G, Tura S, Ljungman P, et al.: Prognostic factors in allogeneic bone marrow trans plantation for multiple myeloma. J Clin Oncol 13:1312-1322, 1995. 11. Bjorkstrand B, Ljungman P, Svensson H, et al.: Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: A retrospective case- matched study from the European Group for Blood and Marrow Transplantation. Blood 88:4711-4718, 1996. 12. Bensinger WI, Buchner CD, Anasetti C, et al.: Allogeneic marrow transplantation for mul tiple myeloma: An analysis of risk factors on outcome. Blood 88:2787-2793,1996. 13. Anderson KC: Who benefits from high dose therapy for multiple myeloma? J Clin Oncol 13:1291-1296, 1995. 14. Harousseau J-L, Attal M: The role of autologous hematopoietic stem cell transplantation in multiple myeloma. Semin Hematol 34:61-66,1997. 15. Bjorkstrand B, Svensson H, Ljungman P, et al.: 2522 autotransplants in multiple myelo ma—a registry study from the European group for blood and marrow transplantation (EBMT) (Abstract). Blood 90:419a, 1997. 16. Bensinger WI, Rowley SD, Demirer T, et al.: High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma. J Clin Oncol 14:1447-1456, 1996. 17. Attal M, Harousseau JL, Stoppa AM, et al.: Autologous bone marrow transplantation ver sus conventional chemotherapy in multiple myeloma: A prospective, randomized trial. N EnglJMed 335:91-97, 1996. 18. Attal M, Payen C, Façon T, et al.: Single versus double transplant in myeloma: A ran domized trial of the Inter Groupe Français du Myelome (IFM) (Abstract). Blood 90:418a, 1997. 19. Blade J, San Miguel JF, Fontanillas M, et al.: Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/autotransplantation and who were conventionally treated. J Clin Oncol 14:2167-2173, 1996. 20. Soiffer RJ, Murray C, Mauch P, et al.: Prevention of graft-versus-host disease by selec tive depletion of CD6-positive T lymphocytes from donor bone marrow. J Clin Oncol 10:1191-1200, 1992. 21. Alyea EP, Soiffer RJ, Canning C, et al.: Toxicity and efficacy of defined doses of CD4 + donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 91:3671-3680, 1998. 22. Anderson KC, Barut BA, Ritz J, et al.: Autologous bone marrow transplantation therapy for multiple myeloma. Eur J Haematol 43:157-163, 1989. 23. Anderson KC, Barut BA, Ritz J, et al.: Monoclonal antibody purged autologous bone mar row transplantation therapy for multiple myeloma. Blood 77:712-720, 1991. 24. Anderson KC, Anderson J, Soiffer R, et al.: Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma. Blood 82:2568-2576, 1993. 219
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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
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
Page 248 and 249: 214 Chapter 5: Myeloma B cq d ? o c
Page 250 and 251: 216 Chapter 5: Myeloma patients wit
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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
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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.
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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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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
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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
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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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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
Page 476 and 477:
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
Page 483 and 484:
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
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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
Page 505 and 506:
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
Page 513 and 514:
Kuis, Wulffraat, and Sanders neousl
Page 515:
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
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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
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Page 552 and 553:
Page 554 and 555:
Page 556 and 557:
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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 635 and 636:
Canine Hematopoietic Stem Allograft
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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
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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
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McGuinness and Arced 641 in G418. T
Page 677 and 678:
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
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
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:
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Page 726 and 727:
Radioimmunotherapy of Common Epithe
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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
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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.
Page 776 and 777:
742 List of Participants Sergio A.
Page 778 and 779:
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
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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