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98 Chapter 2: ALL 5:01 2.5:1 1.25:1 0.6:1 E:T Ratio Figure 2. Bcl-2 overexpression inhibits LAK cytotoxicity of697 ALL. LAK cells were gen erated by incubation of random donor peripheral blood mononuclear cells at 10 6 lmL in RPMI with 10% fetal bovine serum (FBS) (CM) with addition of5000 U recombinant human IL-2/mL for 5 days. The growth inhibition assay is performed by proliferation of target cells both with and without addition of irradiated effector cells. Targets are placed in round-bottomed 96-well plates at 25,000 per well in triplicate in CM. Effectors are irradiated (30 Gy) and plated with targets at four different effector .target ratios in triplicate. Background proliferation from irra diated effectors is calculatedfrom parallel wells containing only effectors. Proliferation of tar gets only is performed with six replicates. After 4-hour coincubation, all wells are pulsed with 1 mCi [ 3 H]thymidine overnight and cpm obtained by standard liquid scintillation counting. Percentage growth inhibition is scored after subtraction of effectors alone and is based on cpm of targets alone. Shown are mean and standard deviation for five separate experiments. 5:01 2.5:1 1.25:1 E:T Ratio 1-2 -697Bcl-2 Figure 3. Bcl-2 overexpression has no effect on CTL cytotoxicity of 697 ALL. CTL were generated by incubation of random donor peripheral blood mononuclear cells at ItflmL in RPMI with 10% FBS (CM) with addition of 50 U recombinant human IL-2/mlfor 5 days with irradiated (60 Gy) 697 or 697Bcl-2 stimulators at a 3:1 responder-to-stimulator ratio. The growth inhibition assay is performed identically to that described in Fig. 2. Shown are mean and standard deviation for four separate experiments. .6:1 -697
Boyer and Y eager SUMMARY Most of the available data suggest that autoBMT and UD BMT are roughly equivalent for ALL patients in first remission, although no prospective studies have yet addressed this issue. For patients beyond first remission, the data seem to favor UD BMT, in both adults and children. This area will likely remain controversial, as both auto- and alloBMT are rapidly changing fields. Clearly, for both auto- and UD BMT, results are less than completely gratifying. In autoBMT, lack of effective in vivo purging probably overshadows effects of in vitro purging. In UD BMT, the mortality of GVHD probably overshadows much of the beneficial effects of a GVL reaction. Attempts to provide for a CTL-mediated GVL effect in the setting of an autoBMT may allow combining the benefits of both autologous and allogeneic BMT. REFERENCES 1. Attal M, Blaise D, Marit G, et al., for the BGMT Group: Consolidation treatment of adult acute lymphoblastic leukemia: A prospective, randomized trial comparing allogeneic vs. autologous bone marrow transplantation and testing the impact of recombinant interleukin- 2 after autologous bone marrow transplantation. Blood 86:1619,1995 2. Martino R, Bellido M, Brunet S, et al.: Allogeneic or autologous stem cell transplanta tion following salvage chemotherapy for adults with refractory or relapsed acute lym phoblastic leukemia. Bone Marrow Transplant 21:1023, 1998 3. Arcese W, Amadori S, Meloni G, et al.: Allogeneic or autologous bone marrow trans plantation for intensification of salvage therapy in patients with high-risk advanced acute lymphoblastic leukemia. Semin Hematol 3:116, 1991 4. Billet AL, Pollock BH, Abshire TC, Buchanan GR: Outcome of children with B-lineage acute lymphoblastic leukemia (ALL) in first bone marrow relapse. Blood 90:332a, 1997 5. Barrett AJ, Horowitz MM, Pollock BH, et al.: Bone marrow transplantation from HLA- identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission. N Engl J Med 331:1253, 1994 6. Szydlo R, Goldman JM, Klein JP, et al.: Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. / Clin Oncol 15:1767,1997 7. Ringden O, Labopin M, Gluckman E, et al.: Donor search or autografting in patients with acute leukemia who lack an HLA-identical sibling? A matched-pair analysis. Bone Marrow Transplant 19:963, 1997 8. Weisdorf DJ, Billet AL, Hannan P, et al.: Autologous vs. unrelated donor allogeneic mar row transplantation for acute lymphoblastic leukemia. Blood 90:2962,1997 9. Uckun F, Kersey J, Haake R, et al.: Pretransplant burden of leukemic progenitor cells as a predictor of relapse after bone marrow transplantation of acute lymphoblastic leukemia. NEnglJ Med 93:1296, 1993 10. Atta J, Martin H, Bruecher J, et al.: Residual leukemia and immunomagnetic bead purg ing in patients with BCR-ABL-positive acute lymphoblastic leukemia. Bone Marrow Transplant 18:541, 1996 99
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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
Page 81 and 82: Stein et al. and fever. No patient
Page 83 and 84: Stein et al. after doses 1, 3, and
Page 85 and 86: Stein et al. early after the transp
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 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: Boyer and Y eager 97 Table 2. Hypot
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 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
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
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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
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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.
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742 List of Participants Sergio A.
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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
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750 Author Index Hurd, D.D. 483 Kui
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752 Author Index Stiff, Patrick J.
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754 Key Word Index Hematologic mali
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ISBN 1-891524-04-6
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