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462 Chapter 8: Autoimmune Disease TBI (1200 cGy) for conditioning, which was well tolerated, and ex vivo T cell-depleted grafts. Functional improvement occurred in all three patients. AutoSCT cannot possibly provide definite cure of MS. Three of our patients continued to deteriorate and, on MRI analysis, four new active lesions were found to have developed in two patients who had evidence of active MRI lesions at enrollment. However, it seems that autoSCT may induce prolonged stabilization, or may bring the disease to a lower level of activity, in the four patients who had disease flares without generalized progression. Longer follow-up of the patients is necessary, not only to confirm any beneficial effect but also to determine long-term toxicity. At present, it would seem reasonable to conclude that autoSCT in MS warrants further study, with well-designed phase II and, eventually, comparative trials. REFERENCES 1. Matthews WB: Course and prognosis. In: Matthews WB, Compston A, Allen IV, Martyn CN (eds) McAlpines's Multiple Sclerosis, 2nd ed. Singapore: Churchill Livingstone, 1991, p. 139-163. 2. Rudich R, Cohen JA, Weinstock-Guttman B, et al.: Management of multiple sclerosis. N Engl J Med 337:1604-1611, 1997. 3. Marmont AM, van Bekkum DW: Stem cell transplantation for severe autoimmune diseases. Bone Marrow Transplant 16:497-498, 1995. 4. Snowden JA, Brooks PM, Biggs JC: Haemopoietic stem cell transplantation for autoimmune diseases. Br J Haematol 99:9-22, 1997. 5. van Gelder M, van Bekkum DW: Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain. Bone Marrow Transplant 16:343-351, 1995. 6. Karussis DM, Vourka-Karussis U, Lehmann D, et al.: Prevention and reversal of adop tively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplan tation. J Clin Invest 92:765-772, 1993. 7. van Gelder M, Kinwell-Bohre EPM, van Bekkum DW: Treatment of experimental aller gic encephalomyelitis in rats with total body irradiation and syngeneic BMT. Bone Marrow Transplant 11:233-241, 1993. 8. van Gelder M, van Bekkum DW: Effective treatment of relapsing experimental autoim mune encephalomyelitis with pseudoautologous bone marrow transplantation. Bone Marrow Transplant 18:1029-1034, 1996. 9. Snowden JA, Patton WN, O'Donnell J, et al.: Prolonged remission of longstanding systemic lupus erythematosus following autologous bone marrow transplantation for non- Hodgkin's lymphoma. Bone Marrow Transplant 19:1247-1250, 1997. 10. Euler HH, Marmont AM, Bacigalupo A, et al.: Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation. Blood 88:3621-3625, 1996. 11. Slavin S, Karussis D, Weiss L, et al.: Immunohematopoietic reconstitution by allogène-
Fassas et al. ic or autologous bone marrow grafts as a means for induction of specific unresponsive ness to donor specific allografts and modified self in autoimmune disorders. Transplant Proc 25:121'4-1275, 1993. 12. Burt RK; Burns W, Ruvolo P, et al.: Syngeneic bone marrow transplantation eliminates autoreactive Vâ8.2 T lymphocytes from the spinal cord of Lewis rats with experimental allergic encephalomyelitis. JNeurosci Res 41:526-531,1995. 13. Talmadge JE, Reed EC, Kessinger A, et al: Immunologic attributes of cytokine mobilised peripheral blood and recovery following transplantation. Bone Marrow Transplant 17:101-109,1996. 14. Fassas A, Anagnostopoulos A, Kazis A, et al.: Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: First results of a pilot study. Bone Marrow Transplant 20:631-638, 1997. 15. Tyndall A, Gratwohl A: Consensus statement: Blood and marrow stem cell transplants in autoimmune disease. A consensus report written on behalf of the European League Against Rheumatism and the European Group for Blood and Marrow Transplantation (EBMT). Br J Rheumatol 36:390-392, 1997. 16. Shots R, Verbruggen LA, Demanet C: G-CSF in Felty's syndrome: Correction of neu tropenia and effects on cytokine release. Clin Rheumatol 14:116-118, 1995. 17. Vidarsson B, Geirsson A, Onundarsson PT: Reactivation of rheumatoid arthritis and development of leukocytoclastic vasculitis in a patient receiving granulocyte colony- stimulating factor for Felty's syndrome. Am J Med 98:589-591, 1995. 18. Snowden JA, Milliken ST, Brooks PM, Biggs JC: High dose cyclophosphamide with autologous stem cell rescue in severe active rheumatoid arthritis: A dose escalation study (Abstract). Bone Marrow Transplant 21 (Suppl 1):S52, 1998. 19. Fouillard L, Miossec P, Leon A, et al.: Autologous peripheral blood CD34 positive stem cell transplantation in the treatment of severe systemic lupus erythematosus: A case report (Abstract). Bone Marrow Transplant 21 (Suppl 1):S53, 1998. 20. Fassas A, Anagnostopoulos A, Giannaki E, et al.: Autologous blood stem cell therapy for autoimmune pancytopenia due to systemic lupus erythematosus (Abstract). Bone Marrow Transplant 21 (Suppl 1):S53, 1998. 21. Miyamoto T, Gondo H, Miyoshi Y, et al.: Early viral complications following CD34- selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lym phoma. Br J Haematol 100:348-350, 1997. 22. Burt RK, Traynor AE, Cohen B, et al.: T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: Report on the first three patients. Bone Marrow Transplant 21:537-541,1998. 463
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AUTOLOGOUS BLOOD AND MARROW TRANSPL
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AUTOLOGOUS BLOOD AND MARROW TRANSPL
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ACKNOWLEDGMENTS We wish to thank Wi
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THE VAN BEKKUM STEM CELL AWARD Prof
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xii Table of Contents CHAPTER 2: AL
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xiv Table of Contents Late Non-Rela
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xvi Table of Contents Pretreatment
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xviii Table of Contents CHAPTER 7:
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XX Table of Contents Long-Term Obse
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xxii Table of Contents CHAPTER 13:
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0-9 LIST OF ABBREVIATIONS 2CDA 2-ch
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List of Abbreviations xxvii EFS eve
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List of Abbreviations MOPP mechlore
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VOD veno-occlusive disease VPC viru
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4HC-Purged Autologous Stem Cell Tra
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1.0-1 + 0.2 Miller et al. 5 Event F
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Miller et al. Adjusted probability
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Who Benefits From Autograft in AML
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Burnett 11 which to set the transpl
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Table 1. Outcome after relapse in M
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Immunotherapy in AML: No Positive E
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Simonsson et al. inhibit IL-2 induc
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Autologous Bone Marrow Transplantat
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Ball et al. 21 CD15) and AML-2-23 (
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Ball et al. 23 The ex vivo treatmen
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Ball et al. 25 Table 2. Factors inv
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Ball et al. Overall Survival for Pa
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Ball et al. Overall Survival for Pa
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Ball et al. 31 Overall Survival for
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Ball et al. Table 4. Actuarial over
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Ball et al. myeloid leukemia. The G
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Ball et al. 1993. 38. Mehta J, Powl
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Can Autologous Stem Cell Transplant
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De Witte et al. 41 novo AML. Auer r
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De Witte et al. hematopoietic engra
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De Witte et al. 23. Fenaux P, Laï
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Stein et al. and fever. No patient
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Stein et al. after doses 1, 3, and
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Stein et al. early after the transp
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autologous stem-cell rescue. / Clin
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Bone Marrow Transplantation for Acu
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Table 2. Autologous BMT in ALL in f
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Rowe 61 or adult patients with acut
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Hoelzer and Gôkbuget minitransplan
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Hoelzer and Gdkbuget 65 blood, earl
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Table 3. Risk factors for the defin
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Hoelzer and Gôkbuget treatment opt
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Hoeker and Gökbuget tical sibling
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Sierra et al. INTRODUCTION Two-thir
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Sierra et al. Table 2. Adverse char
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1,0 0,0 J Sierra et al. 0 20 40 60
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Sierra et al. Months Figure 4 < 30,
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Sierra et al. No adverse factors (n
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1994. Sierra et al. 83 10. Canals C
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Martin, Atta, and Hoelzer 85 adult
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Martin, Atta, and Hoelzer 87 Single
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100. Martin, Atta, and Hoelzer 89 P
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Martin, Atta, and Hoelzer 91 chromo
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Autologous vs. Unrelated Allogeneic
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Boyer and Yeager 95 outcomes after
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Boyer and Y eager 97 Table 2. Hypot
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Boyer and Y eager SUMMARY Most of t
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CHAPTER 3 CML
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Autograft Followed by Allograft Wit
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106 Chapter 3: CML (one low-grade a
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108 Chapter 3: CML DISCUSSION Myelo
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110 Chapter 3: CML Philadelphia-neg
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The Case for Manipulation of CML Au
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Toward a Cure by Drug Treatment? Th
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116 Chapter 3 :CML Table 1. Prolong
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118 Chapter 3: CML Table 3. German
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120 Chapter 3: CML Table 5. Normal
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122 Chapter 3: CML Table 8. Surviva
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124 Chapter 3: CML 88:3118-3122, 19
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126 Chapter 3: CML RK, Klingemann H
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The Tyrphostin AG957 Inhibits the I
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130 Chapter 3: CML mobilization. Al
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132 Chapter 3: CML A B 100 n 0 1 5
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134 Chapter 3: CML The in vitro sel
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136 Chapter 3: CML detecting leukem
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Progressive Hodglcin's Lymphoma Fol
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Reece et al. survival is observed i
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0.2 -I 0.0 0 Reece et al. 143 ii i
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Reece et al. Table 3. Causes of non
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Reece et al. carmustine, etoposide
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CD34 + Selection of Hematopoietic B
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Lazarus et al. 151 significantly de
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Lazarus et al. 153 (Sigma, St Louis
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Lazarus et al. 155 Table 2. Effect
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Lazarus et al. 157 difference. Furt
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Lazarus et al. 159 cells after myel
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The European CUP/UP Trial: A Prelim
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Table 1. Patient characteristics at
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Schouten et al. licular non-Hodgkin
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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-
Page 446 and 447: 412 Chapter 7: Solid Tumors ogous b
Page 448 and 449: 414 Chapter 7: Solid Tumors 64. Bru
Page 450 and 451: 416 Chapter 7: Solid Tumors Prignot
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Page 454 and 455: 420 Chapter 7: Solid Tumors TANDEM
Page 456 and 457: Multiple Courses of Cyclophosphamid
Page 458 and 459: 424 Chapter 7: Solid Tumors and the
Page 460 and 461: 426 Chapter 7: Solid Tumors Thiotep
Page 462 and 463: 428 Chapter 7: Solid Tumors Table 2
Page 464 and 465: 430 Chapter 7: Solid Tumors E 100 0
Page 466 and 467: 432 Chapter 7: Solid Tumors course
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Page 470 and 471: 436 Chapter 7: Solid Tumors INTRODU
Page 472 and 473: 438 - Chapter 7: Solid Tumors Table
Page 474 and 475: 440 Chapter 7: Solid Tumors seeded
Page 476 and 477: 442 Chapter 7: Solid Tumors DISCUSS
Page 478 and 479: 444 Chapter 7: Solid Tumors 10. Di
Page 480 and 481: 446 Chapter 7: Solid Tumors plasma
Page 483 and 484: Autologous Stem Cell Transplantatio
Page 485 and 486: Keystone 451 hypertension, anemia,
Page 487 and 488: Fassas et al. 453 INTRODUCTION Mult
Page 489 and 490: Fassas et al. Table 2. Stem cell mo
Page 491 and 492: Table 3. Toxicity after stem cell i
Page 493 and 494: Fassas et al. Table 5. Trial 1: cha
Page 495: Fassas et al. MS PROGRESSION FREE S
Page 499 and 500: 1 2 1 6 EAE. Burt et al. 465 Becaus
Page 501 and 502: Burt et al. Since cyclophosphamide
Page 503 and 504: 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
Page 509 and 510: Hasler, Gratwohl, and Tyndall 475 B
Page 511 and 512: Kuis, Wulffraat, and Sanders 477 st
Page 513 and 514: Kuis, Wulffraat, and Sanders neousl
Page 515: CHAPTER 9 LONG-TERM EFFECTS
Page 518 and 519: 484 Chapter 9: Long-Term Effects po
Page 520 and 521: 486 Chapter 9: Long-Term Effects Ta
Page 522 and 523: 488 Chapter 9: Long-Term Effects ml
Page 524 and 525: 490 Chapter 9: Long-Term Effects 4.
Page 526 and 527: 492 Chapter 9: Long-Term Effects us
Page 528 and 529: 494 Chapter 9: Long-Term Effects AB
Page 532 and 533: 498 Chapter 9: Long-Term Effects En
Page 534 and 535: 500 Chapter 9: Long-Term Effects Rl
Page 536 and 537: 502 Chapter 9: Long-Term Effects RE
Page 538 and 539: 504 Chapter 9: Long-Term Effects A,
Page 540 and 541: Long-Term Follow-Up of Autologous T
Page 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
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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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