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372 Chapter 6: Breast Cancer ACKNOWLEDGMENTS The authors would like to thank the clinical staff of the Northeastern Ontario Regional Cancer Centre for their contribution and dedication to the patient related work, Ms. Nadia Krane and Ms. Lorna Dixon for their excellent secretarial support, and the Northern Cancer Research Foundation, Sudbury, Ontario, and the Northern Ontario Heritage Fund, Sault Ste. Marie, Ontario, Canada for their grant support. Part of this paper was presented at the 39th Annual ASH Meeting, San Diego, California, December 1997, and also at the 20th Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, December 1997. REFERENCES 1. Maguire HC, Green MI: The neu (c-erbB-2) oncogene. Semin Oncol 16:148-155, 1989. 2. Earp HP, Dawson TL, Li X, et al.: Heterodimerization and functional interaction between EGF receptor family members: A new signalling paradigm with implications for breast cancer research. Breast Cancer Res Treat 35:115-132, 1995. 3. Reese DM, Slamon DI: HER-2/neu signal transduction in human breast and ovarian can cer. Stem Cells 15:1-8, 1997. 4. Sliwkowski MX, Schaefer G, Akita RW, et al.: Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 269:14661-14665, 1994. 5. Wallasch C, Weiss FU, Niederfellner G, et al.: Heregulin-dependent regulation of HER2/neu oncogenic signalling by heterodimerization with HER3. EMBO J 14:4267-4275, 1995. 6. Lewis GD, Lofgren, JA, McMurtrey AE, et al.: Growth regulation of human breast and ovarian tumour cells by heregulin: Evidence for the requirement of erbB2 as a critical com ponent in mediating heregulin responsiveness. Cancer Res 56:1457-1465, 1996. 7. De Potter CR, Schelfhout A-M: The neu protein and breast cancer. Virchows Archiv 426:107-115, 1995. 8. Singleton TP, Strickler JG: Clinical and pathological significance of the c-erbB-2 (HER- 2/neu) oncogene. Pathol Annu 27:165-190, 1992. 9. Perren TJ: C-erbB-2 oncogene as a prognostic marker in breast cancer. Br J Cancer 63:328-332, 1991. 10. Hynes NE, Stern DF: The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta 1198:165-184, 1994. 11. Slamon DJ, Godolphin W, Jones LA, et al.: Studies of the HER2/neu proto-oncogene in human breast and ovarian cancer. Science 24:707-712, 1989. 12. Slamon DJ: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu Oncogene. Science 235:177-182, 1989. 13. Kallioniemi OP, Holli K, Visakorpi T, et al.: Association of c-erbB-2 protein over-expres sion with high rate of cell proliferation, increased risk of visceral metastasis and poor long- term survival in breast cancer. Int J Cancer 49:650-655, 1991.
Bewick et al. 14. Kandl HL, Seymour L, Bezwoda WR: Soluble c-erbB-2 fragment in serum correlates with disease stage and predicts for shortened survival in patients with early- stage and advanced breast cancer. Br J Cancer 70:739-742, 1994. 15. Narita T, Funahashi H, Satoh Y, et al.: C-erbB-2 protein in the sera of breast cancer patients. Breast Cancer Res Treat 24:97-102, 1992. 16. Kynast B, Binder L, Marx D, et al.: Determination of the c-erbB2 translational product pl85 in serum of breast cancer patients. J Cancer Clin Oncol 119:249-252, 1993. 17. Revillion F, Hebbar M, Bonneterre J, et al.: Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients. Eur J Cancer 32A:231-234, 1996. 18. Molina R, Filella X, Zanon G, et al.: C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis. Anticancer Res 16:2295-2300, 1996. 19. Anderson TI, Paus E, Nesland JM, et al.: Detection of c-erbB-2 related protein in sera from breast cancer patients. Relationship to ERBB2 gene amplification and c-erbB-2 over- expression in tumour. Acta Oncol 34:499-504, 1995. 20. Volas Gena H, Leitzel K, Teramoto Y, et al.: Serial serum c-erbB-2 levels in patients with breast carcinoma. Cancer 78:267-272, 1996. 21. Hubbard AL, Doris CP, Thompson AM, et al.: Critical determination of the frequency of c-erbB-2 amplification in breast cancer. Br J Cancer 70:434-439, 1994. 22. Fehm T, Maimonis P, Wetz S, et al.: Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients. Breast Cancer Res Treat 43:87-95, 1997. 23. Molina R, Jo J, Zanon G, et al.: Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: Comparison with carcinoembryonic anti gen and CA 15.3. Br J Cancer 14:1126-1131. 24. Isola J, Holli K, Oksa H, et al.: Elevated erbB-2 oncoprotein levels in preoperative and follow-up serum samples define an aggressive disease course in patients with breast can cer. Cancer 73:652-658, 1994. 25. Leitzel K, Teramoto Y, Konrad K, et al.: Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J Clin Oncol 13:1129-1135, 1995. 26. Antman KH, Rowling PA, Vaughan WP, et al.: High-dose chemotherapy with autologous haematopoietic stem-cell support for breast cancer in North America. J Clin Oncol 15:1870-1879, 1997. 27. Gliick S, Porter K, Chadderton T, et al.: Depletion of DMSO (dimethylsulfoxide) prior to autografting after high-dose chemotherapy for metastatic breast cancer. Blood 82(Suppl. l):430a, 1993. 28. Bradford MM: A rapid and sensitive method for the quantitation of microgram quanti ties of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254, 1976. 29. Brugger W, Bross KJ, Glatt M, et al.: Mobilization of tumour cells and haematopoietic progenitor cells into peripheral blood of patients with solid tumours. Blood 83:636-640, 1994. 30. Shpall EJ, Jones RB: Release of tumour cells from bone marrow. Blood 83:623-625,1994. 31. Muss HB, Thor A, Berry DA, et al.: c-erbB-2 expression and response to adjuvant ther- 373
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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
Page 283 and 284:
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
Page 299 and 300:
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
Page 355 and 356: Prince et al. 321 Figure 5, continu
Page 357 and 358: 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
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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: Bewick et al. pression in MBC, i.e.
Page 409: CHAPTER 7 OTHER SOLID TUMORS
Page 412 and 413: 378 Chapter 7: Solid Tumors INTRODU
Page 414 and 415: 380 Chapter 7: Solid Tumors Prepara
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Page 418 and 419: 384 Chapter 7: Solid Tumors months
Page 420 and 421: 386 Chapter 7: Solid Tumors have be
Page 422 and 423: High-Dose Chemotherapy in the Manag
Page 424 and 425: 390 Chapter 7: Solid Tumors followe
Page 426 and 427: 392 Chapter 7: Solid Tumors Table 1
Page 428 and 429: 394 Chapter 7: Solid Tumors (mucosi
Page 430 and 431: Three-Fold Intensification by Seque
Page 436 and 437: High-Dose Therapy for Small Cell Lu
Page 438 and 439: 404 Chapter 7: Solid Tumors chemoth
Page 440 and 441: 406 Chapter 7: Solid Tumors SCLC ha
Page 442 and 443: 408 Chapter 7: Solid Tumors relapse
Page 444 and 445: 410 Chapter 7: Solid Tumors 69:585-
Page 446 and 447: 412 Chapter 7: Solid Tumors ogous b
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Page 454 and 455: 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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428 Chapter 7: Solid Tumors Table 2
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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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Page 545:
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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Page 635 and 636:
Canine Hematopoietic Stem Allograft
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Sandmaier et al. 603 The resultant
Page 639 and 640:
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
Page 649 and 650:
Giralt, Khouri, and Champlin seven
Page 651 and 652:
1.0 3 0.2 Giralt, Khouri, and Champ
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CHAPTER 12 GENE THERAPY
Page 656 and 657:
622 Chapter 12: Gene Therapy INTROD
Page 658 and 659:
624 Chapter 12: Gene Therapy RESULT
Page 660 and 661:
626 Chapter 12: Gene Therapy envisi
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628 Chapter 12: Gene Therapy cer in
Page 664 and 665:
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
Page 734 and 735:
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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