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90 Chapter 2: ALL CONCLUSIONS Molecular remission after induction and consolidation chemotherapy is rare in patients with BCR-ABL + ALL. This is consistent with the clinical experience of rapid relapse after discontinuing chemotherapy. The rationale for in vitro purging is based on the evidence of residual leukemic cells in unpurged grafts. Event-free survival after autologous transplantation in BCR-ABL-positive ALL ranges between 20 and 30%. Patients do significantly worse if autografted beyond CR1. Thus, patients without an allogeneic donor should receive an autograft in first morphologic remission. Double autologous transplants are feasible with acceptable toxicity, but longer follow-up is needed to conclude that this approach affects long- term leukemia-free survival. ACKNOWLEDGMENTS We acknowledge the contribution of the dedicated hematologists participating in the GMALL trials who referred BCR-ABL + patients for autologous transplan tation. This work was supported by the Deutsche Forschungsgemeinschaft (Ho 684/2-1). REFERENCES 1. Bloomfield CD, Goldman AI, Alimena G, Berger R, Borgstrom GH, Brandt L, Catovsky D, De la Chapelle A, Dewald GW, Garson OM, et al.: Chromosomal abnormalities iden tify high-risk and low-risk patients with acute lymphoblastic leukemia. Blood 67:415^120, 1986. 2. Hoelzer D: Treatment of acute lymphoblastic leukemia. Semin Hematol 31:1-15, 1994. 3. Seeker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV: Philadelphia positive acute lymphoblastic leukemia in adults: Age distribution, bcr breakpoint and prognostic sig nificance. Leukemia 5:196-199, 1990. 4. Maurer J, Jannsen JWG, Thiel E, van Denderen J, Ludwig WD, Aydemir Ü, Heinze B, Fonatsch C, Harbott J, Reiter A, Riehm H, Hoelzer D, Bartram CR: Detection of chimeric BCR-ABL genes in acute lymphoblastic leukemia by the polymerase chain reaction. Lancet 337:1055-1058, 1991. 5. Hoelzer D: Therapy of the newly diagnosed adult with acute lymphoblastic leukemia. Hematol Oncol Clin North Am 7:139-160, 1993. 6. Hoelzer D: The role of bone marrow transplantation in the management of Ph-positive acute lymphoblastic leukemia in adults. In: Dicke KA, Keating A (eds) Autologous Marrow and Blood Transplantation. Proceedings of the Eighth International Symposium, Arlington, Texas. Charlottesville, VA: Carden Jennings, 1997, p. 79-85. 7. Barrett AJ, Horowitz MM, Ash RC, Atkinson K, Gale RP, Goldman JM, Henslee-Downey PJ, Herzig RH, Speck B, Zwaan FE, et al.: Bone marrow transplantation for Philadelphia
Martin, Atta, and Hoelzer 91 chromosome-positive acute lymphoblastic leukemia. Blood 79:3067-3070, 1992. 8. Chao NJ, Blume KG, Forman SJ, Snyder DS: Long-term follow-up of allogeneic bone marrow recipients for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 85:3353-3354, 1995. 9. Radich J, Gehly G, Lee A, Avery R, Bryant E, Edmands S, Gooley T, Kessler P, Kirk J, Ladne P, Thomas ED, Appelbaum FR: Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood 89:2602-2609,1997. 10. Sierra J, Radich J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J, Bryant E, Nash RA, Sanders JE, Storb R, Sullivan KM, Appelbaum FR, Anasetti C: Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblas tic leukemia. Blood 90:1410-1414, 1997. 11. Martin H, Goekbuget N, Atta J, Hoelzer D: Treatment of Ph + and t(4; 11) acute lym phoblastic leukemia in adults. Haematol Blood Transf 39:771, 1998. 12. Atta J, Martin H, Bruecher J, Eisner S, Wassmann B, Rode C, Russ A, Kvalheim G, Hoelzer D: Residual disease and immunomagnetic bead purging in patients with BCR- ABL-positive acute lymphoblastic leukemia. Bone Marrow Transplant 18:541-548,1996 13. Atta J, Martin H, Rode C, Lippok G, Fauth F, Hoelzer D: Purging in BCR-ABL-acute lymphoblastic leukemia using immunomagnetic beads: Comparison of purging efficien cy in bone marrow versus peripheral blood stem cells by semiquantitative polymerase chain reaction, (submitted) 14. Martin H, Bergmann L, Bruecher J, Christ S, Schneider B, Wassmann B, Hoelzer D: Immunological response to IL-2 and a-IFN treatment after autologous BMT in patients with BCR-ABL-positive ALL. In: Hiddemann W, Büchner T (eds) Acute Leukemias V. Berlin: Springer-Verlag, 1995. 15. Martin H, Atta J, Fauth F, Hoelzer D: Autologous double stem cell transplantation in patients with BCR-ABL-positive acute lymphoblastic leukemia (Abstract). Ann Hematol 77:S88, 1998. 16. Martin H, Atta J, Fauth F, Wassmann B, Arnold R, Bergmann L, Bunjes D, Finkenstein F, Gramatzki M, Knauf W, Kuse R, Langer W, Rieder H, Rode C, Weiss A, Hoelzer D: Autologous transplantation with purging and r-IL2/a-IFN-maintenance in patients with BCR-ABL-positive acute lymphoblastic leukemia, (submitted). 17. Gehly GB, Bryant EM, Lee AM, Kidd PG, Thomas ED: Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 78:458-465,1991. 18. Brennan C, Weisdorf D, Kersey J, Haake R, Ramsay N: Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia (Abstract). ProcASCO 10:222,1991. 19. Miyamura K, Tanimoto M, Morishima Y, Horibe K, Yamamoto K, Akatsuka M, Kodera Y, Kojima S, Matsauyama K, Hirabayashi N, Yazaki M, Imai K, Onozawa Y, Kanamaru A, Mizutani S, Saito H: Detection of Philadelphia chromosome positive acute lym phoblastic leukemia by polymerase chain reaction: Possible eradication of minimal resid ual disease by marrow transplantation. Blood 79:1366-1370, 1992. 20. Annino L, Ferrari A, Cedrone M, Giona F, Lo Coco F, Meloni G, Arcese W, Mandelli F:
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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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Page 77 and 78: De Witte et al. hematopoietic engra
Page 79 and 80: De Witte et al. 23. Fenaux P, Laï
Page 81 and 82: Stein et al. and fever. No patient
Page 83 and 84: Stein et al. after doses 1, 3, and
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Page 87: autologous stem-cell rescue. / Clin
Page 91 and 92: Bone Marrow Transplantation for Acu
Page 93 and 94: Table 2. Autologous BMT in ALL in f
Page 95 and 96: Rowe 61 or adult patients with acut
Page 97 and 98: Hoelzer and Gôkbuget minitransplan
Page 99 and 100: Hoelzer and Gdkbuget 65 blood, earl
Page 101 and 102: Table 3. Risk factors for the defin
Page 103 and 104: Hoelzer and Gôkbuget treatment opt
Page 105 and 106: Hoeker and Gökbuget tical sibling
Page 107 and 108: Sierra et al. INTRODUCTION Two-thir
Page 109 and 110: Sierra et al. Table 2. Adverse char
Page 111 and 112: 1,0 0,0 J Sierra et al. 0 20 40 60
Page 113 and 114: Sierra et al. Months Figure 4 < 30,
Page 115 and 116: Sierra et al. No adverse factors (n
Page 117 and 118: 1994. Sierra et al. 83 10. Canals C
Page 119 and 120: Martin, Atta, and Hoelzer 85 adult
Page 121 and 122: Martin, Atta, and Hoelzer 87 Single
Page 123: 100. Martin, Atta, and Hoelzer 89 P
Page 127 and 128: Autologous vs. Unrelated Allogeneic
Page 129 and 130: Boyer and Yeager 95 outcomes after
Page 131 and 132: Boyer and Y eager 97 Table 2. Hypot
Page 133 and 134: Boyer and Y eager SUMMARY Most of t
Page 135: CHAPTER 3 CML
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Page 142 and 143: 108 Chapter 3: CML DISCUSSION Myelo
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Page 146 and 147: The Case for Manipulation of CML Au
Page 148 and 149: Toward a Cure by Drug Treatment? Th
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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
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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
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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
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210 Chapter 5: Myeloma Scandinavia,
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212 Chapter 5: Myeloma (0 n o B co
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214 Chapter 5: Myeloma B cq d ? o c
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216 Chapter 5: Myeloma patients wit
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218 Chapter 5: Myeloma PBSC transpl
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220 Chapter 5: Myeloma 25. Seiden M
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Autologous Transplantation in Multi
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224 Chapter 5: Myeloma 0 52 44 U §
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226 Chapter 5: Myeloma BM ^ (CD34±
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228 Chapter 5: Myeloma IFM 94 : OS
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230 Chapter 5: Myeloma two groups a
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232 Chapter 5: Myeloma increase bot
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234 Chapter 5: Myeloma REFERENCES 1
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236 Chapter 5: Myeloma Intensified
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238 Chapter 5: Myeloma of CD34 + ce
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Chapter 5: Myeloma Table 2. Descrip
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242 Chapter 5: Myeloma o 8H 0 2 4 6
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244 Chapter 5: Myeloma ated with sh
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The Presence of Micrometastases in
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Kvalheim et al. 249 Table 1. Immuno
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Kvalheim et al. 251 Figure 1. Sixty
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Kvalheim et al. 253 DISCUSSION In t
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Kvalheim et al. 255 Bastert G: Micr
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Hood et al. 257 In an effort to inc
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#CD34 + cells in blood = Hood et al
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Hood et al. 261 Table 3. Frequency
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Hood et al. 263 REFERENCES 1. Rill
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The Clinical Significance of Breast
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Moss et al. tests, and bilateral po
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Moss et al. 269 0 15 70 143 200 400
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Moss et al. 271 0 3 6 12 18 24 30 3
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Moss et al. 273 8. Passos-Coelho J,
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Autotransplantation for Men With Br
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McCarthy et al. 277 radiation, two
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High Dose Sequential Chemotherapy W
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Viens et al. 281 3 g/m 2 and doxoru
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Table 1. Tumor characteristics Exte
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Table 4. Response Viens et al. 285
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Viens et al. 287 Table 5. Pathologi
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Viens et al. 289 apy for inoperable
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Gliick et al. 291 INTRODUCTION The
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Gluck et al. 293 RESULTS Patient de
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Glück et al. 295 Table 3. Response
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Gluck et al. 297 Overall Survival O
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Gluck et al. 299 Sudbury patients w
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Gluck et al. 301 anthracycline or t
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Repetitive High-Dose Therapy With P
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Prince et al. paramagnetic separati
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Prince et al. Table 1. High-dose re
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Table 2. Patient characteristics (n
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Table 4. Hematopoietic recovery fol
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1.0- M C .S 0.8- a c *fe o o> 0.6-
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M 1.0 I 0.8H s? VI o.6H S 0.2 0.0 P
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a Prince et al. days to platelets >
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Table 5. Results of Isolex 300i CD3
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Prince et al. 321 Figure 5, continu
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Prince et al. 323 months after tran
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Prince et al. 325 excessive to be u
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Prince et al. 327 eight patients ha
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Prince et al. 329 marrow transplant
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Prince et al. intensive chemotherap
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-Q CO .Q O 1.0 0.9 0.8 0.7 0.6 0.5
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.Q CD .Q O 1.0 0.9 0.8 0.7 0.6 0.5
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oba Q. 1.0 0.9 Dicke et al. Stage I
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Vahdat with peripheral blood progen
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Evaluation of Prognostic Factors fo
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Fields et al. 343 PATIENTS AND METH
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Table 1. Chemotherapy regimens. Fie
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Fields et al. Stage II; 4-9 Pos LN
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U U Fields et al.
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Fields et al. 351 between 1 and 2 y
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European Trends and the EBMT Databa
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25% % 22% / 17% \ Rosti et al. 355
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Rosti et al. 357 The new Italian St
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Rosti et al. 6. Haas R, Schmid H, H
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Bewick et al. 363 INTRODUCTION The
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Bewick et al. 365 Blood samples obt
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Bewick et al. 367 HDCT with ABSC su
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Bewick et al. Progression Free Surv
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Bewick et al. pression in MBC, i.e.
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Bewick et al. 14. Kandl HL, Seymour
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CHAPTER 7 OTHER SOLID TUMORS
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378 Chapter 7: Solid Tumors INTRODU
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380 Chapter 7: Solid Tumors Prepara
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382 Chapter 7: Solid Tumors Surviva
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384 Chapter 7: Solid Tumors months
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386 Chapter 7: Solid Tumors have be
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High-Dose Chemotherapy in the Manag
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390 Chapter 7: Solid Tumors followe
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392 Chapter 7: Solid Tumors Table 1
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394 Chapter 7: Solid Tumors (mucosi
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Three-Fold Intensification by Seque
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High-Dose Therapy for Small Cell Lu
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404 Chapter 7: Solid Tumors chemoth
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406 Chapter 7: Solid Tumors SCLC ha
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408 Chapter 7: Solid Tumors relapse
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410 Chapter 7: Solid Tumors 69:585-
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412 Chapter 7: Solid Tumors ogous b
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414 Chapter 7: Solid Tumors 64. Bru
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416 Chapter 7: Solid Tumors Prignot
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418 Chapter 7: Solid Tumors CO > CO
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420 Chapter 7: Solid Tumors TANDEM
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Multiple Courses of Cyclophosphamid
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424 Chapter 7: Solid Tumors and the
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426 Chapter 7: Solid Tumors Thiotep
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430 Chapter 7: Solid Tumors E 100 0
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432 Chapter 7: Solid Tumors course
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434 Chapter 7: Solid Tumors boplati
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436 Chapter 7: Solid Tumors INTRODU
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438 - Chapter 7: Solid Tumors Table
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440 Chapter 7: Solid Tumors seeded
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442 Chapter 7: Solid Tumors DISCUSS
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444 Chapter 7: Solid Tumors 10. Di
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446 Chapter 7: Solid Tumors plasma
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Autologous Stem Cell Transplantatio
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Keystone 451 hypertension, anemia,
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Fassas et al. 453 INTRODUCTION Mult
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Fassas et al. Table 2. Stem cell mo
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Table 3. Toxicity after stem cell i
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Fassas et al. Table 5. Trial 1: cha
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Fassas et al. MS PROGRESSION FREE S
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Fassas et al. ic or autologous bone
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1 2 1 6 EAE. Burt et al. 465 Becaus
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Burt et al. Since cyclophosphamide
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Burt et al. 469 toxicity study, we
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Burt et dl. All 23. Mor F, Cohen IR
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Hasler, Gratwohl, and Tyndall an ev
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Hasler, Gratwohl, and Tyndall 475 B
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Kuis, Wulffraat, and Sanders 477 st
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Kuis, Wulffraat, and Sanders neousl
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CHAPTER 9 LONG-TERM EFFECTS
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484 Chapter 9: Long-Term Effects po
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486 Chapter 9: Long-Term Effects Ta
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488 Chapter 9: Long-Term Effects ml
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490 Chapter 9: Long-Term Effects 4.
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492 Chapter 9: Long-Term Effects us
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494 Chapter 9: Long-Term Effects AB
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498 Chapter 9: Long-Term Effects En
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500 Chapter 9: Long-Term Effects Rl
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502 Chapter 9: Long-Term Effects RE
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504 Chapter 9: Long-Term Effects A,
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Long-Term Follow-Up of Autologous T
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CHAPTER 10 GRAFT MANIPULATION
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514 Chapter 10: Graft Manipulation
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Stem Cell Reinfusion Over Two Conse
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Final Report of the First Prospecti
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Canine Hematopoietic Stem Allograft
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Sandmaier et al. 603 The resultant
Page 639 and 640:
Sandmaier et al. 605 synthesis path
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Sandmaier et al. 607 interactions o
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Sandmaier et al. 1991. 2. Burchenal
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87:3508-3513,1996. Sandmaier et al.
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Giralt, Khouri, and Champlin Table
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Giralt, Khouri, and Champlin seven
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1.0 3 0.2 Giralt, Khouri, and Champ
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CHAPTER 12 GENE THERAPY
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622 Chapter 12: Gene Therapy INTROD
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624 Chapter 12: Gene Therapy RESULT
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626 Chapter 12: Gene Therapy envisi
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628 Chapter 12: Gene Therapy cer in
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A Vaccine of Melanoma Peptide Loade
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B43(anti-CD 19)-Gen i stein Immunot
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Targeting Immunotherapy for the Tre
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McGuinness andArceci 637 modified m
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McGuinness andArceci 639 leukemic c
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McGuinness and Arced 641 in G418. T
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McGuinness andArceci 643 Figure 2
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mRNA for hB7-1 (1491 bp) mRNA for C
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McGuinness and Arced CD80PE C080PE
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McGuinness andArceci 649 8. Robert
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McGuinness andArceci immune respons
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McGuinness andArceci 75. Jubinsky F
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Slavin et al. 655 up suggests, as p
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Slavin et al. 657 was a phase lib c
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Slavin et al. presented, appears to
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Antitumor Immunotherapy in Autologo
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Klingemann et al. 663 Table 3. Meth
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CHAPTER 14 RADIOIMMUNOTHERAPY
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668 Chapter 14: Radioimmunotherapy
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Selection of Radioisotopes, Chelate
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Radioimmunotherapy of Common Epithe
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CHAPTER 15 NEW AVENUES
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698 Chapter 15: New Avenues Table 1
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700 Chapter 15: New Avenues An alte
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702 Chapter 15: New Avenues who can
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704 Chapter 15: New Avenues myeloid
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706 Chapter 15: New Avenues 48. Gir
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Emerging Viral Infections in Blood
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710 Chapter 15: New Avenues influen
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712 Chapter 15: New Avenues Among a
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714 Chapter 15: New Avenues physica
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716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
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CHAPTER 16 SUMMARIES
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724 Chapter 16: Summaries although
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726 Chapter 16: Summaries use of po
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728 Chapter 16: Summaries Table 1.
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736 Chapter 16: Summaries IL-15. Th
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738 Chapter 16: Summaries Patterns
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740 List of Participants Thomas L.
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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