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High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Ovarian Carcinoma: Comparisons to Conventional Therapy and Future Directions Patrick J. Stiff, Christine Kerger, Robert A. Bayer BMT Program, Loyola University Medical Center, Maywood, IL ABSTRACT High-dose chemotherapy and peripheral blood stem cell (PBSC) rescue is increasingly used to treat patients with advanced epithelial ovarian cancer. Its greatest benefit appears to be in patients responding to initial therapy or relapsed patients with platinum-sensitive disease and minimal tumor 1 cm. The median progression-free survival (PFS) and overall survival (OS) for the entire group is 7.7 and 17.3 months. Those with platinum-refractory disease appear not to benefit, with a 5.6-month PFS and 10.6-month OS. In contrast, patients with relapsed platinum-sensitive, low tumor bulk have a 16.0-month PFS and a 43.3-month OS, and approximately 20% remain progression-free up to 5 years. When treated with the paclitaxel regimen as consolidation therapy («=10), the PFS was 65% at 26 months from diagnosis. High-dose therapy is associated with an improvement in PFS and OS compared with conventional options for relapsed, responding, low tumor burden patients. Its role as consolidation therapy of an initial remission should be verified in a phase III trial. 377
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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
Page 359 and 360: Prince et al. 325 excessive to be u
Page 361 and 362: Prince et al. 327 eight patients ha
Page 363 and 364: Prince et al. 329 marrow transplant
Page 365 and 366: Prince et al. intensive chemotherap
Page 367 and 368: -Q CO .Q O 1.0 0.9 0.8 0.7 0.6 0.5
Page 369 and 370: .Q CD .Q O 1.0 0.9 0.8 0.7 0.6 0.5
Page 371 and 372: oba Q. 1.0 0.9 Dicke et al. Stage I
Page 373 and 374: Vahdat with peripheral blood progen
Page 375 and 376: Evaluation of Prognostic Factors fo
Page 377 and 378: Fields et al. 343 PATIENTS AND METH
Page 379 and 380: Table 1. Chemotherapy regimens. Fie
Page 381 and 382: Fields et al. Stage II; 4-9 Pos LN
Page 383 and 384: U U Fields et al.
Page 385 and 386: Fields et al. 351 between 1 and 2 y
Page 387 and 388: European Trends and the EBMT Databa
Page 389 and 390: 25% % 22% / 17% \ Rosti et al. 355
Page 391 and 392: Rosti et al. 357 The new Italian St
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Page 395 and 396: Rosti et al. 6. Haas R, Schmid H, H
Page 397 and 398: Bewick et al. 363 INTRODUCTION The
Page 399 and 400: Bewick et al. 365 Blood samples obt
Page 401 and 402: Bewick et al. 367 HDCT with ABSC su
Page 403 and 404: Bewick et al. Progression Free Surv
Page 405 and 406: Bewick et al. pression in MBC, i.e.
Page 407 and 408: Bewick et al. 14. Kandl HL, Seymour
Page 409: CHAPTER 7 OTHER SOLID TUMORS
Page 413 and 414: Stiff, Kerger, and Bayer 379 75 mg/
Page 415 and 416: Table 1. Clinical characteristics S
Page 417 and 418: Survival 1.00 .80 4 .60 i .40 1 .20
Page 419 and 420: Stiff, Kerger, and Bayer 385 patien
Page 421 and 422: 57:278-285,1995. Stiff, Kerger, and
Page 423 and 424: Abonour et al. 389 INTRODUCTION Wit
Page 425 and 426: Abonour et al. 391 A more recent ex
Page 427 and 428: Abonour et al. 393 DFS by Prognosti
Page 429 and 430: Abonour et al. 395 6. Motzer RJ, Co
Page 431 and 432: Leyvraz et al. 397 Table 1. Results
Page 433 and 434: Table 3. ICE toxicity (172 cycles)
Page 435 and 436: Leyvraz et al. 401 intensive treatm
Page 437 and 438: Elias et al. (CAV) and with etoposi
Page 439 and 440: Elias et al. tumor, or in the case
Page 441 and 442: Elias et al. selection of patients
Page 443 and 444: Elias et al. partial purge of the a
Page 445 and 446: ProcASCO 16:456a, 1997. Elias et al
Page 447 and 448: Elias et al. late dose intensificat
Page 449 and 450: Elias et al. G, McCauley M, Gaynes
Page 451 and 452: Transplantation With PBSC, Manipula
Page 453 and 454: Takaue et al. 419 transfusion (day
Page 455 and 456: Takaue et al. All tation, this proc
Page 457 and 458: Rodenhuis et al. 423 INTRODUCTION H
Page 459 and 460: mg/m 2 Rodenhuis et al. 425 in pati
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Rodenhuis et al. All interest. One
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Rodenhuis et al. 429 Figure 2. Prog
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c 1000 -I Rodenhuis et al. 0 4 8 Ti
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Rodenhuis et al. 433 First, a respo
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Epirubicin Plus G-CSF-Elicited Peri
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Carlo-Stella et al. 437 tissues fro
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Carlo-Stella et al. 439 Epi 1 20 mg
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A 140 -i 120- _i 100- CO 80 - O 60
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Carlo-Stella et al. immediately evi
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lastomas. Anticancer Drugs 8:174-18
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CHAPTER 8 AUTOIMMUNE DISEASE
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450 Chapter 8: Autoimmune Disease u
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Autologous Blood Stem Cell Therapy
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454 Chapter 8: Autoimmune Disease T
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456 Chapter 8: Autoimmune Disease w
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Page 498 and 499:
Hematopoietic Stem Ceil Transplanta
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466 Chapter 8: Autoimmune Disease i
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468 Chapter 8: Autoimmune Disease s
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470 Chapter 8: Autoimmune Disease 1
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Autologous Stem Cell Therapy in Aut
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Autologous Hematopoietic Stem Cell
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480 Chapter 8: Autoimmune Disease r
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Presence in Pretransplant Marrow of
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Table 1. Study 1 patient characteri
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Radford et al. 487 1 2 3 4 5 6 7 8
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Radford et al. 489 transplantation,
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Importance of Marrow Doses and Mode
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Gorin TC 199 medium and finally fro
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Gorin 495 ABMT IN AL Engraftment on
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Gorin Table 5. Engraftment accordin
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Gorin 499 ABMT IN AL Outcome in rel
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OS% Gorin 501 1 1 1 • • 0 i 1 1
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Gorin 503 S, Carlier P, Giordano D,
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15:769-775, 1995. Gorin 505 35. Dou
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Long-Term Observations Following He
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Deeg et al 509 Table 2. Secondary m
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Gene Marking to Assess Tumor Contam
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Heslop et al. 515 clonogenic assays
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Heslop et al. 517 Disease Free Surv
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Heslop et al. 519 providing the cli
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Enrichment of Tumor Cells From Auto
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Ross et al. post-TEC fraction was c
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Ross et al. 525 Table 2. Results of
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Ross et al. that the capture antibo
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Combining Positive/Negative Selecti
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Mapara et al. 531 products of patie
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Mapara et al. 533 Hematopoietic col
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Mapara et al. 535 A i m : P u r g i
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Mapara et al. 537 A |_ «••«
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Mapara et al. 539 11. Shpall EJ, Le
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Tumor Purging Technologies: More Qu
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Gee 543 argued that these two patie
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Gee 545 immunomagnetic particles to
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Gee 547 POSITIVE OR NEGATIVE? Given
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Gee 549 autologous transplants of c
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Behavior of Hematopoietic Stem Cell
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Henschler et al. 553 MATERIALS AND
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Table 1. Engraftment of human CD34
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Henschler et al. 557 an increase of
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Henschler et dl. 559 plantation for
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CD34 Selection and Autografting in
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Table 1. Patient characteristics, n
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Voso et al. 565 The side scatter (S
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Table 3. Immunophenotype of CD34 +
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Voso et al. 569 neuroblastoma and a
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Voso et al. 571 transplantation for
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Neutrophils Days 100 Days to >500
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Dicke et al. 575 CD34 Labeling Samp
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Dicke et al. 577 Table 3. Platelet
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Dicke et al. 579 3. Ager S, Scott M
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Janssen et al. 581 PBSC products. H
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Janssen et al. Table 1. Characteris
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5X10 5 Janssen et ai. 585 In brief,
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Janssen et al. CD34+ CELLS INFUSED/
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1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2
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Janssen et al. RELAPSE FREE SURVIVA
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CD34 + Janssen et al. cells and CFU
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Janssen et al. 595 8. Dercksen MW,
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Janssen et al. 597 32. Sosman JA, S
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CHAPTER 11 MINITRANSPLANTS
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602 Chapter 11: Minitransplants to
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604 Chapter 11: Minitransplants Tab
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608 Chapter 11: Minitransplants tra
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610 Chapter 11: Minitransplants 14.
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Allogeneic Progenitor Cell Transpla
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614 Chapter 11: Minitransplants 100
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Page 652 and 653:
618 Chapter 11: Minitransplants all
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Transduction of Primitive Hematopoi
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Jordan et al. shown that such a hyb
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Table 1. Initial findings with seve
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Jordan et al. In preclinical studie
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Molecular Intervention in Myeloma A
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CHAPTER 13 IMMUNOTHERAPY
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Immune-toxins Containing Pokeweed A
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636 Chapter 13: Immunotherapy tumor
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638 Chapter 13: Immunotherapy unide
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640 Chapter 13: Immunotherapy lymph
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642 Chapter 13: Immunotherapy accom
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644 Chapter 13: Immunotherapy Figur
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646 Chapter 13: Immunotherapy CD80P
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648 Chapter 13: Immunotherapy are o
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650 Chapter 13: Immunotherapy 23. F
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652 Chapter 13: Immunotherapy 57. T
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Adjuvant Immunotherapy in Conjuncti
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656 Chapter 13: Immunotherapy mg/m
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658 Chapter 13: Immunotherapy NHL a
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660 Chapter 13: Immunotherapy tion
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662 Chapter 13: Immunotherapy Table
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664 Chapter 13: Immunotherapy leuke
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The Brambell Receptor (FcRB) and th
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5h P 11- V Junghans 669 o I 1 1 1 1
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Junghans 10 20 30 40 IgG Concentrat
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1001- 90 80 E 70 § 60 K g 50 u z 8
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Junghans 675 Time, days Figure 8. B
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Junghans 677 The site on Fc for int
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Junghans 679 1969. 20. Junghans RP,
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Approaches to the Radiation Dosimet
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Fisher 683 bution to marrow dose is
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Fisher 685 organ k per unit cumulat
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Fisher 687 acetabulum. The curve is
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Fisher 689 Table 2. Correlations be
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Fisher 8. Sgouros G: Bone marrow do
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Radioimmunotherapy for Malignant Ly
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Induction of Graft-vs.-Malignancy a
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Champlin, Khouri, and Giralt 699 is
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Champlin, Khouri, and Girat 701 and
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Champlin, Khouri, and Giralt 703 ti
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Champlin, Khouri, and Giralt 705 A
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Champlin, Khouri, and Giralt 707 E,
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Whimbey 709 INTRODUCTION Infectious
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Whimbey 711 CRVs are a common cause
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Whimbey 713 antibody titers to RSV
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Whimbey 715 toxic, less costly, and
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Asymmetric Division as Measurable P
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Neuropoiesis Peter Quesenberry, Car
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Summary: Leukemia John Barrett Bone
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Barrett New directions A role for i
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Autologous Blood and Marrow Transpl
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across page) Elfenbein 729 Examples
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Elfenbein 731 Examples Contributors
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Table 3. Types of clinical trials i
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Strategies in Autologous Bone Marro
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Summary: Lymphoma Armand Keating On
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Rafat Abonour Indiana Univ. Cancer
Page 775 and 776:
H-Joachim Deeg Fred Hutchinson Canc
Page 777 and 778:
Richard P. Junghans Division of Hem
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Peter J. Quesenberry Univ. of Massa
Page 781 and 782:
Linda T. Vahdat Columbia Presbyteri
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DiStefano, Alfred 332 Dodero, Anna
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Author Index 751 Ohno-Jones, S. 113
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KEY WORD INDEX 4-HC 1 Brambell rece
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Refractory anemia with excess blast
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