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64 Chapter 2: ALL leukemia) appears to be present in ALL, although it is less pronounced than in CML or AML. Age is another significant prognostic factor for survival after alloBMT. In patients >40 years old, TRM (37 vs. 28%) as well as relapse incidence (38 vs. 29%) are higher compared with younger patients, 5 leading to a less favorable LFS. RESULTS OF AUTOLOGOUS BMT IN CR1 The LFS after autoBMT in CR1 of approximately 42% (15-75%) is somewhat inferior compared to alloBMT (Table 1). Several trials comparing alio- and autoBMT demonstrated an advantage of alloBMT in terms of LFS and RI, whereas TRM after autoBMT was clearly lower. 67 AutoBMT can be employed in elderly patients up to approximately 65 years of age due to its low TRM (2-8%). The major disadvantage of autoBMT is the high RI (51%) probably caused to a lesser extent by the reinfusion of leukemic blasts but more by the lack of GVL effects. Purging of the marrow graft with monoclonal antibodies, chemotherapeutic drugs or immunomagnetic beads is of interest since it may reduce the leukemia cell burden. Thus, purging with immunomagnetic beads can reduce tumor load by 2 log either for BM or for PB grafts in ALL. 8 However, no comparative studies with purged and unpurged autoBMT have been reported to date. In addition to purging, the administration of maintenance treatment after autoBMT may contribute to a reduction of RI. A favorable LFS of 53% has been achieved in a single-center trial with autoBMT or PBSCT in 50 adult ALL patients in first CR followed by a 2-year maintenance treatment with 6-mercaptopurine and methotrexate. 9 Other options for maintenance therapy after autoBMT are biological response modifiers such as interferon-a or interleukin-2. The reported results, however, are not conclusive. AutoBMT is a reasonable treatment option for a substantial number of Ph + patients >50 years old without a sibling donor, for whom a MUD transplant is not considered. Thus, a large proportion of Ph + ALL patients remain candidates for autologous transplants. The LFS in 37 patients after autoBMT from several small series was 37% (Table 1). RESULTS OF PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT) IN CRI Transplantation of PBSC instead of bone marrow is increasingly employed in adult ALL since TRM may be reduced due to faster bone marrow recovery. Even more importantly, experience in Ph + ALL shows that the tumor load is lower in PBSC grafts compared to bone marrow. Since in heavily pretreated ALL patients, it may be difficult to collect a sufficient number of stem cells from the peripheral
Hoelzer and Gdkbuget 65 blood, early scheduling of stem cell apheresis after induction/consolidation treatment is recommended. In a preliminary report from the EBMT, in ALL patients in first remission, LFS was 41% after autoPBSCT compared with 35% after autoBMT with a similar RI of 60%. 10 RESULTS OF MISMATCHED AND MATCHED UNRELATED BMT Mismatched (MM) BMT from related donors or MUD BMT has been increasingly employed to extend the possibilities of alloBMT by enlarging the number of bone marrow donors available. With BMT from partially MM family donors, two groups have reported quite favorable results (LFS 38-53%) in pediatric and adult patients with relapsed ALL. Comparing results of fully matched and partially MM alloBMT in ALL >CR1 (including children), the LFS was similar (38 vs. 38%), whereas TRM was higher (38 vs. 31%) and RI lower (31 vs. 25%) after MM BMT. It remains an open question as to whether MM BMT may be a treatment option in adult patients without a matched sibling or unrelated donor. 11 In retrospective analyses of MUD transplants in adult ALL, the weighted means for LFS, TRM, and RI were 34, 59, and 22%, respectively (Table 1). However, adult ALL patients with all stages of disease were included, and the median age was low. In one retrospective analysis with a higher median age of 35 years (18-51) in patients with high-risk ALL, the overall LFS was 20% with a TRM of 65%. Outcome was clearly better in patients transplanted in CR1, with an LFS of 42% compared with 7% in those transplanted in subsequent disease stages. 12 Results of MUD BMT in Ph + ALL are only available from small patient cohorts. In the largest report on 18 patients (age 1.5-51 years) in CR1, the LFS was 48%, which is quite promising. 13 RESULTS OF TRIALS COMPARING BMT AND CHEMOTHERAPY The overall LFS after alloBMT is superior to that obtained with chemotherapy alone. However, when these results were adjusted for age, risk factors, and time to BMT (thereby excluding early relapses), the differences between BMT and chemotherapy were no longer statistically significant, although there was a trend toward better results for alloBMT. In a comparative analysis of BMT patients from the IBMTR and chemotherapy patients treated according to the GMALL (German Multicenter Adult ALL Studies) protocol, results for alloBMT and chemotherapy were comparable (34 vs. 32%). This was predominantly due to a higher TRM in the transplant group (53 vs. 5%), whereas RI was higher in the chemotherapy group (30 vs. 66%). 14 Similar results were reported for chemotherapy results of the JALSG chemotherapy protocol compared with BMT results of the IBMTR. 15 A
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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
Page 47 and 48: Table 1. Outcome after relapse in M
Page 49 and 50: Immunotherapy in AML: No Positive E
Page 51 and 52: Simonsson et al. inhibit IL-2 induc
Page 53 and 54: Autologous Bone Marrow Transplantat
Page 55 and 56: Ball et al. 21 CD15) and AML-2-23 (
Page 57 and 58: Ball et al. 23 The ex vivo treatmen
Page 59 and 60: Ball et al. 25 Table 2. Factors inv
Page 61 and 62: Ball et al. Overall Survival for Pa
Page 63 and 64: Ball et al. Overall Survival for Pa
Page 65 and 66: Ball et al. 31 Overall Survival for
Page 67 and 68: Ball et al. Table 4. Actuarial over
Page 69 and 70: Ball et al. myeloid leukemia. The G
Page 71 and 72: Ball et al. 1993. 38. Mehta J, Powl
Page 73 and 74: Can Autologous Stem Cell Transplant
Page 75 and 76: De Witte et al. 41 novo AML. Auer r
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
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: Hoelzer and Gôkbuget minitransplan
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 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
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Toward a Cure by Drug Treatment? Th
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116 Chapter 3 :CML Table 1. Prolong
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118 Chapter 3: CML Table 3. German
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120 Chapter 3: CML Table 5. Normal
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122 Chapter 3: CML Table 8. Surviva
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124 Chapter 3: CML 88:3118-3122, 19
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126 Chapter 3: CML RK, Klingemann H
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The Tyrphostin AG957 Inhibits the I
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130 Chapter 3: CML mobilization. Al
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132 Chapter 3: CML A B 100 n 0 1 5
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134 Chapter 3: CML The in vitro sel
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136 Chapter 3: CML detecting leukem
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Progressive Hodglcin's Lymphoma Fol
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Reece et al. survival is observed i
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0.2 -I 0.0 0 Reece et al. 143 ii i
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Reece et al. Table 3. Causes of non
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Reece et al. carmustine, etoposide
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CD34 + Selection of Hematopoietic B
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Lazarus et al. 151 significantly de
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Lazarus et al. 153 (Sigma, St Louis
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Lazarus et al. 155 Table 2. Effect
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Lazarus et al. 157 difference. Furt
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Lazarus et al. 159 cells after myel
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The European CUP/UP Trial: A Prelim
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Table 1. Patient characteristics at
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Schouten et al. licular non-Hodgkin
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Sweetenham et al. vs. autologous pe
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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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