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124 Chapter 3: CML 88:3118-3122, 1995. 14. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV: The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: Biologic signifi cance and implications for the assessment of minimal residual disease. Blood 92:3362-3367, 1998. 15. Simonsson B, Oberg G, Killander A, Bjoreman M, Borkholm M, Gahrton G, Hast R, Turesson I, Uden AM, Malm C, et al.: Intensive treatment to minimize the Ph-positive clone in chronic myelogenic leukemia. Stem Cells Dayt 11 (Suppl 3):73-76,1993. 16. Goldman JM, Johnson SA, Catovsky D, Wareham NJ, Galton DAG: Autografting for chronic granulocytic leukemia. N Engl J Med 305:700, 1981. 17. Carella AM, Podesta M, Frassoni F, Raffo MR, Pollicardo N, Pungolino E, Vimercati R, Sessarego M, Parodi C, Rabitti C, et al.: Collection of "normal" blood repopulating cells during early hemopoietic recovery after intensive conventional chemotherapy in chron ic myelogenous leukemia. Bone Marrow Transplant 12:267-271, 1993. 18. McGlave PB, De Fabritiis P, Deisseroth A, Goldman J, Barnett M, Reiffers J, Simonsson B, Carella A, Aeppli D: Autologous transplants for chronic myelogenous leukaemia: Results from eight transplant groups. Lancet 343:1486-1488, 1994. 19. Hehlmann R, Heimpel H, Hossfeld DK, Hasford J, Kolb HJ, Löffler H, Pralle H, Queisser W, Hochhaus A, Tichelli A, Fett W, Schmitz N, Reiter A, Griesshammer M, Pfeifer W, Bäumler M, Kamp T, Tobler A, Eimermacher H, Kuse R, Berger U, Ansari H, and the German CML Study Group: Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). Bone Marrow Transplant 17 (Suppl 3):S21-S24, 1996. 20. Hehlmann R, Heimpel H: Current aspects of drug therapy in Philadelphia-positive CML: Correlation of tumor burden with survival. Leuk Lymphoma 22:161-167, 1996. 21. Kantarjian HM, Talpaz M, Kurzrock R, Keating MJ, McCredie KB, Gutterman J, Freireich EJ: Intensive combination chemotherapy and interferons in the management of chronic myelogenous leukemia. Acta Haematol 78:70-74, 1987. 22. Zhang MJ, Baccarani M, Gale RP, McGlave PB, Atkinson K, Champlin RE, Dicke KA, Giralt S, Gluckman E, Goldman JM, Klein JP, Herzig RH, Masaoka T, O'Reilly RJ, Rozman C, Rowlings PA, Sobocinski KA, Speck B, Zwaan FE, Horowitz MM: Survival of patients with chronic myelogenous leukaemia relapsing after bone marrow transplan tation: Comparison with patients receiving conventional chemotherapy. Br J Haematol 99:23-29,1997. 23. Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, Bouabdallah R, Guyotat D, Cheron N, Nicolini F, Abgrall JF, Tanzer J: Interferon alpha2b (IFN) com bined with cytarabine versus interferon alone in chronic myelogenous leukemia. N Engl J Med 337:223-229, 1997. 24. Tura S: Cytarabine increases karyotypic response in alpha-IFN treated chronic myeloid leukemia patients: Results of a national prospective randomized trial (Abstract). Blood 92:317a, 1998. 25. Finney R, McDonald GA, Baikie AG, Douglas AS: Chronic granulocytic leukaemia with Ph 1 negative cells in bone marrow and a ten year remission after busulphan hypoplasia.
Br J Haematol 23:283-288,1972. Hehlmann et al. 125 26. Coulombel L, Kalousek DK, Eaves CJ, Gupta CM, Eaves AC: Long-term marrow cul ture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. N Engl J Med 308:1493-1498,1983. 27. Bhatia R, Verfaillie CM, Miller JS, McGlave PB: Autologous transplantation therapy for chronic myelogenous leukemia. Blood 89:2623-2634, 1997. 28. Clift RA, Appelbaum FR, Thomas ED: Treatment of chronic myeloid leukemia by mar row transplantation. Blood 82:1954-1956, 1993. 29. Carella AM, Frassoni F: Ice, mini-ice or high-dose hydroxyurea to mobilize Philadelphia (Phl)-negative PBPC in chronic myelogenous leukaemia. Br J Haematol 95:213-214, 1996. 30. Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C: Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia in chronic phase. N Engl J Med 338:962-968,1998. 31. Appelbaum FR, Clift R, Radich J, Anasetti C, Buckner CD: Bone marrow transplanta tion for chronic myelogenous leukemia. Semin Oncol 22:405-411, 1995. 32. van Rhee F, Szydlo RM, Hermans J, Devergie A, Frassoni F, Arcese W, de Witte T, Kolb HJ, Niederwiser D, Jacobsen N, Gahrton G, Bandini G, Carreras E, Bacigalupo A, Michallet M, Ruutu T, Reiffers J, Goldman JM, Apperley J, Gratwohl A, Apperley JF, Labopin M, Madrigal A, Prentice HG, Jouet JP, Hertenstein B, Evensen SA, Ljungman P, Nagler A, Clark RE: Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: A report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 20:11-19, 1997. 33. Goldman JM: Autografting for CML: Overview and perspectives. Bone Marrow Transplant 17 (Suppl 3):S71-S74, 1996. 34. Cunningham I, Gee T, Dowling M, Chaganti R, Bailey R, Hopfan S, Bowden L, Turnbull A, Knapper W, Clarkson B: Results of treatment of Ph 1+ chronic myelogenous leukemia with an intensive treatment regimen (L-5 protocol). Blood 53:375-395,1979. 35. Sharp JC, Joyner MV, Wayne AW, Kemp J, Crofts M, Birch ADJ, McArthur G, Lai S, Sterndale H, Williams Y: Karyotypic conversion in Ph'-positive chronic myeloid leukaemia with combination chemotherapy. Lancet i:1370—1372, 1979. 36. Kolitz JE, Kempin SJ, Schluger A, Wong GY, Berman E, Jhanwar S, Arlin ZA, Gee T, Clarkson BD: A phase II pilot trial of high-dose hydroxyurea in chronic myelogenous leukemia. Semin Oncol 19 (Suppl 9):27-33, 1992. 37. Verfaillie CM, Miller WJ, Boylan K, McGlave PB: Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR anti gen expression. Blood 79:1003-1010, 1992. 38. Barnett MJ, Eaves CJ, Phillips GL, Gascoyne RD, Hogge DE, Horsman DE, Humphries
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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
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 and 124: 100. Martin, Atta, and Hoelzer 89 P
Page 125 and 126: Martin, Atta, and Hoelzer 91 chromo
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
Page 138 and 139: Autograft Followed by Allograft Wit
Page 140 and 141: 106 Chapter 3: CML (one low-grade a
Page 142 and 143: 108 Chapter 3: CML DISCUSSION Myelo
Page 144 and 145: 110 Chapter 3: CML Philadelphia-neg
Page 146 and 147: The Case for Manipulation of CML Au
Page 148 and 149: Toward a Cure by Drug Treatment? Th
Page 150 and 151: 116 Chapter 3 :CML Table 1. Prolong
Page 152 and 153: 118 Chapter 3: CML Table 3. German
Page 154 and 155: 120 Chapter 3: CML Table 5. Normal
Page 156 and 157: 122 Chapter 3: CML Table 8. Surviva
Page 160 and 161: 126 Chapter 3: CML RK, Klingemann H
Page 162 and 163: The Tyrphostin AG957 Inhibits the I
Page 164 and 165: 130 Chapter 3: CML mobilization. Al
Page 166 and 167: 132 Chapter 3: CML A B 100 n 0 1 5
Page 168 and 169: 134 Chapter 3: CML The in vitro sel
Page 170 and 171: 136 Chapter 3: CML detecting leukem
Page 173 and 174: Progressive Hodglcin's Lymphoma Fol
Page 175 and 176: Reece et al. survival is observed i
Page 177 and 178: 0.2 -I 0.0 0 Reece et al. 143 ii i
Page 179 and 180: Reece et al. Table 3. Causes of non
Page 181 and 182: Reece et al. carmustine, etoposide
Page 183 and 184: CD34 + Selection of Hematopoietic B
Page 185 and 186: Lazarus et al. 151 significantly de
Page 187 and 188: Lazarus et al. 153 (Sigma, St Louis
Page 189 and 190: Lazarus et al. 155 Table 2. Effect
Page 191 and 192: Lazarus et al. 157 difference. Furt
Page 193 and 194: Lazarus et al. 159 cells after myel
Page 195 and 196: The European CUP/UP Trial: A Prelim
Page 197 and 198: Table 1. Patient characteristics at
Page 199 and 200: 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
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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
Page 283 and 284:
Kvalheim et al. 249 Table 1. Immuno
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Kvalheim et al. 251 Figure 1. Sixty
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Kvalheim et al. 253 DISCUSSION In t
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Kvalheim et al. 255 Bastert G: Micr
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Hood et al. 257 In an effort to inc
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#CD34 + cells in blood = Hood et al
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Hood et al. 261 Table 3. Frequency
Page 297 and 298:
Hood et al. 263 REFERENCES 1. Rill
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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,
Page 487 and 488:
Fassas et al. 453 INTRODUCTION Mult
Page 489 and 490:
Fassas et al. Table 2. Stem cell mo
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Table 3. Toxicity after stem cell i
Page 493 and 494:
Fassas et al. Table 5. Trial 1: cha
Page 495 and 496:
Fassas et al. MS PROGRESSION FREE S
Page 497 and 498:
Fassas et al. ic or autologous bone
Page 499 and 500:
1 2 1 6 EAE. Burt et al. 465 Becaus
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Burt et al. Since cyclophosphamide
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Burt et al. 469 toxicity study, we
Page 505 and 506:
Burt et dl. All 23. Mor F, Cohen IR
Page 507 and 508:
Hasler, Gratwohl, and Tyndall an ev
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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.
Page 526 and 527:
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,
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Long-Term Follow-Up of Autologous T
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Page 545:
CHAPTER 10 GRAFT MANIPULATION
Page 548 and 549:
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
Page 746 and 747:
712 Chapter 15: New Avenues Among a
Page 748 and 749:
714 Chapter 15: New Avenues physica
Page 750 and 751:
716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
Page 755:
CHAPTER 16 SUMMARIES
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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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Page 766 and 767:
Page 768 and 769:
Page 770 and 771:
736 Chapter 16: Summaries IL-15. Th
Page 772 and 773:
738 Chapter 16: Summaries Patterns
Page 774 and 775:
740 List of Participants Thomas L.
Page 776 and 777:
742 List of Participants Sergio A.
Page 778 and 779:
744 List of Participants Hans Marti
Page 780 and 781:
746 List of Participants David P. S
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748 List of Participants AUTHOR IND
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750 Author Index Hurd, D.D. 483 Kui
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752 Author Index Stiff, Patrick J.
Page 788 and 789:
754 Key Word Index Hematologic mali
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ISBN 1-891524-04-6
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