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690 Chapter 14: Radioimmunotherapy SUMMARY AND CONCLUSIONS Red marrow dosimetry is subject to many assumptions, uncertainties, and everchanging dosimetric models. Despite these uncertainties and the difficulty of marrow dose calculations, studies have shown fair correlations between calculated dose and biologic response. Efforts are in progress to improve calculational internal dosimetry. Methods and parameters used in dose assessment should be consistent within an overall clinical study. Direct measurements of activity in marrow over time provide the most reliable data for marrow dosimetry. A marrow dose assessment will be more reliable if the residence time is determined from direct measurements of red marrow activity over time rather than by merely grouping marrow with remainder tissues as a target tissue. ACKNOWLEDGMENTS This work was supported in part by the U.S. Department of Energy under contract DE-AC06-76RLO 1830, by a support contract from NeoRx Corporation (Seattle, WA), and by National Institutes of Health/National Cancer Institute Grant CA44991 to the Fred Hutchinson Cancer Research Center (Seattle, WA). Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy. REFERENCES 1. Appelbaum FR, Sandmeier B, Brown P, et al.: Myelosuppression and mechanism of recov ery following administration of samarium-153-EDTMP. Antibody Immun Radiopharm 4:263-270, 1988. 2. Bayouth JE, Macey DJ: Dosimetry considerations of bone-seeking radionuclides for mar row ablation. MedPhys 20:1089-1096, 1993. 3. Matthews DC, Appelbaum FR, Eary JF, et al.: Development of a marrow transplant reg imen for acute leukemia using targeted hematopoietic irradiation delivered by 1-131- labeled anti-CD-45 antibody, combined with cyclophosphamide and total body irradiation. Blood 85:1122-1131, 1995. 4. Loevinger R, Budinger TF, Watson EE: MIRD Primer for Absorbed Dose Calculations. New York: The Society of Nuclear Medicine, 1991. 5. National Council on Radiation Protection and Measurements: The experimental basis for absorbed dose calculations, NCRP Report No. 83. Bethesda, MD: National Council on Radiation Protection and Measurements, 1985, p. 18-19. 6. Siegel JA, Wessels BW, Watson EE, et al.: Bone marrow dosimetry and toxicity for radioimmunotherapy. Antibody Immun Radiopharm 3:213-233, 1990. 7. Siegel JA, Lee RE, Pawlyk DA, et al.: Sacral scintigraphy for bone marrow dosimetry in radioimmunotherapy. Nucl Med Biol 16:553-559, 1989.
Fisher 8. Sgouros G: Bone marrow dosimetry for radioimmunotherapy: Theoretical considera tions. J Nucl Med 34:689-694, 1992. 9. Snyder WS, Ford MR, Watson SB, et al.: "S," absorbed dose per unit cumulated activi ty. MIRD pamphlet no. 11. New York: The Society of Nuclear Medicine, 1975. 10. Spiers FW: The influence of energy absorption and electron range on dosage in irradiat ed bone. Br J Radiol 12:521, 1949. 11. Spiers FW: Dosage in irradiated soft tissue and bone. Br J Radiol 26:38, 1953. 12. Spiers FW: Beta dosimetry in trabecular bone. In: Mays CW (ed) Delayed Effects of Bone- Seeking Radionuclides. Salt Lake City, UT: University of Utah Press, 1969, p. 95-108. 13. Whitwell JR, Spiers FW: Calculated beta-ray dose factors for trabecular bone. Phys Med Biol 21:16-38,1976. 14. International Commission on Radiological Protection: Limits for intakes of radionuclides by workers, ICRP Publication 30, Part 1. Oxford, U.K.: Pergamon Press, 1979. 15. International Commission on Radiological Protection: Radiation dose to patients from radiopharmaceuticals, ICRP Publication 53. Oxford, U.K.: Pergamon Press, 1987. 16. Eckerman KF: Aspects of the dosimetry of radionuclides within the skeleton with par ticular emphasis on the active marrow. Proceedings of 4th International Radiopharmaceutical Dosimetry Symposium, CONF-851113. Oak Ridge, TN: Oak Ridge Associated Universities, 1985, p. 514-534. 17. Stabin MG: MIRDOSE: Personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 37:538-546,1996. 18. Breitz HB, Fisher DR, Wessels BW: Correlation of marrow toxicity with bone marrow radiation absorbed dose estimates from Re-186-labeled monoclonal antibody. J Nucl Med In press. 691
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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-
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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
Page 673 and 674: McGuinness andArceci 639 leukemic c
Page 675 and 676: McGuinness and Arced 641 in G418. T
Page 677 and 678: McGuinness andArceci 643 Figure 2
Page 679 and 680: mRNA for hB7-1 (1491 bp) mRNA for C
Page 681 and 682: McGuinness and Arced CD80PE C080PE
Page 683 and 684: McGuinness andArceci 649 8. Robert
Page 685 and 686: McGuinness andArceci immune respons
Page 687 and 688: McGuinness andArceci 75. Jubinsky F
Page 689 and 690: Slavin et al. 655 up suggests, as p
Page 691 and 692: Slavin et al. 657 was a phase lib c
Page 693 and 694: Slavin et al. presented, appears to
Page 695 and 696: Antitumor Immunotherapy in Autologo
Page 697 and 698: Klingemann et al. 663 Table 3. Meth
Page 699: CHAPTER 14 RADIOIMMUNOTHERAPY
Page 702 and 703: 668 Chapter 14: Radioimmunotherapy
Page 714 and 715: Selection of Radioisotopes, Chelate
Page 726 and 727: Radioimmunotherapy of Common Epithe
Page 729: CHAPTER 15 NEW AVENUES
Page 732 and 733: 698 Chapter 15: New Avenues Table 1
Page 734 and 735: 700 Chapter 15: New Avenues An alte
Page 736 and 737: 702 Chapter 15: New Avenues who can
Page 738 and 739: 704 Chapter 15: New Avenues myeloid
Page 740 and 741: 706 Chapter 15: New Avenues 48. Gir
Page 742 and 743: Emerging Viral Infections in Blood
Page 744 and 745: 710 Chapter 15: New Avenues influen
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Page 748 and 749: 714 Chapter 15: New Avenues physica
Page 750 and 751: 716 Chapter 15: New Avenues respira
Page 752 and 753: Minimal Therapy Models of Transplan
Page 755: CHAPTER 16 SUMMARIES
Page 758 and 759: 724 Chapter 16: Summaries although
Page 760 and 761: 726 Chapter 16: Summaries use of po
Page 762 and 763: 728 Chapter 16: Summaries Table 1.
Page 770 and 771: 736 Chapter 16: Summaries IL-15. Th
Page 772 and 773: 738 Chapter 16: Summaries Patterns
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740 List of Participants Thomas L.
Page 776 and 777:
742 List of Participants Sergio A.
Page 778 and 779:
744 List of Participants Hans Marti
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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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