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538 Chapter 10: Graft Manipulation ex vivo tumor cell depletion procedures. 232428 Considering the rapid progress in the field of stem cell mobilization and graft engineering, it is conceivable that a tumor cell-free autograft is becoming a reality. Thus, it is now time to perform controlled randomized studies to validate the clinical relevance of such highly efficient and rigorous but time-consuming and cost-intensive purging procedures. REFERENCES 1. Sharp JG, Kessinger A, Mann S, Crouse DA, Armitage JO, Bierman P, Weisenburger DD: Outcome of high-dose therapy and autologous transplantation in non-Hodgkin's lym phoma based on the presence of tumor in the marrow or infused hematopoietic harvest. J Clin Oncol 14:214-219, 1996. 2. Gribben JG, Freedman AS, Woo SD, Blake K, Shu RS, Freeman G, Longtine JA, Pinkus GS, Nadler LM: All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrange ment at evaluation and after treatment. Blood 78:3275, 1991. 3. Brenner MK, Rill DR, Moen RC, Krance RA, Mirro J, Anderson WF, Ihle JN: Gene-mark ing to trace origin of relapse after autologous bone marrow transplantation. Lancet 341:85, 1993. 4. Rill DR, Santana VM, Roberts WM, Nilson T, Bowman LC, Krance RA, Heslop HE, Moen RC, Ihle JN, Brenner MK: Direct demonstration that autologous bone marrow trans plantation for solid tumors can return a multiplicity of tumorigenic cells. Blood 84:380-383, 1994. 5. Santos GW, Colvin M: Pharmacological purging of bone marrow with reference to auto- grafting. Clin Haematol 15:67, 1986. 6. Kvalheim G, Fodstad O, Pihl A, Nustad K, Pharo A, Ugelstad J, Funderud S: Elimination of B-lymphoma cells from human bone marrow: Model experiments using monodisperse magnetic particles coated with primary monoclonal antibodies. Cancer Res 47:846,1987. 7. Kiesel S, Haas R, Moldenhauer G, Kvalheim G, Pezzutto A, Dôrken B: Removal of cells from a malignant B cell line from bone marrow with immunomagnetic beads and with complement and immunoglobulin switch variant mediated cytolysis. Leuk Res 11:1119-1125, 1987. 8. Shpall EJ, Jones RB, Bearman SI, Franklin WA, Archer PG, Curiel T, Bitter M, Claman HN, Stemmer SM, Purdy M, Myers SE, Taffs S, Heimfeld S, Hallagan J, Berenson RJ: Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: Influence of CD34-positive peripheral blood prog enitors and growth factors on engraftment. J Clin Oncol 12:28-36, 1994. 9. Brugger W, Henschler R, Heimfeld S, Berenson RJ, Mertelsmann R, Kanz L: Positively selected autologous blood CD34 + cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP-16, ifosfamide, carbo- platin and epirubicin. Blood 84:1421-1426, 1994. 10. Civin CJ, Trischmann T, Kadan NS, Davis J, Noga S, Cohen K, Duffy B, Groenewegen I, Wiley J, Law P, Hardwick A, Oldham F, Gee A: Highly purified CD34-positive cells reconstitute hematopoiesis. J Clin Oncol 14:2224-2233, 1996.
Mapara et al. 539 11. Shpall EJ, LeMaistre CF, Holland K, Ball E, Jones RB, Sarai R, Jacobs C, Heimfeld S, Berenson R, Champlin R: A prospective randomized trial of buffy coat versus CD34- selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy. Blood 90:4313^320, 1997. 12. Mapara MY, Körner IJ, Hildebrandt M, Bargou R, Krahl D, Reichardt P, Dörken B: Monitoring of tumor cell purging after highly efficient immunomagnetic selection of CD34 cells from leukapheresis products in breast cancer patients: Comparison of immuno- cytochemical tumor cell staining and RT-PCR. Blood 89:337-344,1997. 13. Kvalheim G, Wang MY, Pharo A, Holte H, Jacobsen E, Beiske K, Kvaloy S, Smeland E, Funderud S, Fodstad O: Purging of tumor cells from leukapheresis products: Experimental and clinical aspects. J Hematother 5:427—436, 1996. 14. Negrin R, Kusnierz-Glaz C, Still B, Schriber J, Chao N, Long G, Hoyle C, Hu W, Horning S, Brown B, Blume K, Strober S: Transplantation of enriched and purged peripheral blood progenitor cells from a single apheresis product in patients with non-Hodgkin's lymphoma. Blood 85:3334-3341,1995. 15. Myklebust AT, Godai A, Juell S, Pharo A, Fodstad O: Comparison of two antibody-based methods for elimination of breast cancer cells from human bone marrow. Cancer Res 54:209-214, 1994. 16. Gribben JG, Arnold MD, Freedman MD, Neuberg D, Roy DC, Blake K, Woo SD, Grossbard ML, Rabinowe SN, Coral F, Freeman GJ, Ritz J, Nadler LM: Immunologic purging of marrow assessed before autologous bone marrow transplantation for B cell lym phoma. NEngl J Med 325:1525, 1991. 17. Bertolini F, Thomas T, Battaglia M, Gibeiii N, Pedrazzoli P, Robustelli DCG: A new "two step" procedure for 4.5 log depletion of T and B cells in allogeneic transplantation and of neoplastic cells in autologous transplantation. Bone Marrow Transplant 19:615-619, 1997. 18. Frankel AE, Ring DB, Tringale F, Hsieh MS: Tissue distribution of breast cancer-asso ciated antigens defined by monoclonal antibodies. J Biol Response Mod4:273-286,1985. 19. Ring DB, Kassel JA, Hsieh MS, Björn MJ, Tringale F, Eaton AM, Reid SA, Frankel AE, Nadji M: Distribution and physical properties of BCA200, a Mr 200,000 glycoprotein selectively associated with human breast cancer. Cancer Res 49:3070-3080, 1989. 20. Hirschowitz EA, Ohwada A, Pascal WR, Russi TJ, Crystal RG: In vivo adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene to human colon car cinoma-derived tumors induces chemosensitivity to 5-fluorocytosine. Hum Gene Ther 6:1055-1063, 1995. 21. Hersh J, Crystal RG, Bewig B : Modulation of gene expression after replication-deficient, recombinant adenovirus-mediated gene transfer by the product of a second adenovirus vector. Gene Ther 2:124-131, 1995. 22. Rosenfeld MA, Siegfried W, Yoshimura K, Yoneyama K, Fukayama M, Stier LE, Paakko PK, Gilardi P, Stratford PL, Perricaudet M, et al.: Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science 252:431-434, 1991. 23. Mapara MY, Körner IJ, Lentzsch S, Krahl D, Reichardt, Dörken B: Combined posi tive/negative purging and transplantation of peripheral blood progenitor cell autografts
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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
Page 522 and 523: 488 Chapter 9: Long-Term Effects ml
Page 524 and 525: 490 Chapter 9: Long-Term Effects 4.
Page 526 and 527: 492 Chapter 9: Long-Term Effects us
Page 528 and 529: 494 Chapter 9: Long-Term Effects AB
Page 530 and 531: 496 Chapter 9: Long-Term Effects Ta
Page 532 and 533: 498 Chapter 9: Long-Term Effects En
Page 534 and 535: 500 Chapter 9: Long-Term Effects Rl
Page 536 and 537: 502 Chapter 9: Long-Term Effects RE
Page 538 and 539: 504 Chapter 9: Long-Term Effects A,
Page 540 and 541: Long-Term Follow-Up of Autologous T
Page 542 and 543: 508 Chapter 9: Long-Term Effects Ta
Page 545: CHAPTER 10 GRAFT MANIPULATION
Page 548 and 549: 514 Chapter 10: Graft Manipulation
Page 606 and 607: Stem Cell Reinfusion Over Two Conse
Page 614 and 615: Final Report of the First Prospecti
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588 Chapter 10: Graft Manipulation
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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
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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
Page 658 and 659:
624 Chapter 12: Gene Therapy RESULT
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626 Chapter 12: Gene Therapy envisi
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628 Chapter 12: Gene Therapy cer in
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A Vaccine of Melanoma Peptide Loade
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B43(anti-CD 19)-Gen i stein Immunot
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Targeting Immunotherapy for the Tre
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McGuinness andArceci 637 modified m
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McGuinness andArceci 639 leukemic c
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McGuinness and Arced 641 in G418. T
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McGuinness andArceci 643 Figure 2
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mRNA for hB7-1 (1491 bp) mRNA for C
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McGuinness and Arced CD80PE C080PE
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McGuinness andArceci 649 8. Robert
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McGuinness andArceci immune respons
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McGuinness andArceci 75. Jubinsky F
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Slavin et al. 655 up suggests, as p
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Slavin et al. 657 was a phase lib c
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Slavin et al. presented, appears to
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Antitumor Immunotherapy in Autologo
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Klingemann et al. 663 Table 3. Meth
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CHAPTER 14 RADIOIMMUNOTHERAPY
Page 702 and 703:
668 Chapter 14: Radioimmunotherapy
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Page 710 and 711:
Page 712 and 713:
Page 714 and 715:
Selection of Radioisotopes, Chelate
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Radioimmunotherapy of Common Epithe
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CHAPTER 15 NEW AVENUES
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698 Chapter 15: New Avenues Table 1
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700 Chapter 15: New Avenues An alte
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702 Chapter 15: New Avenues who can
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704 Chapter 15: New Avenues myeloid
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706 Chapter 15: New Avenues 48. Gir
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Emerging Viral Infections in Blood
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710 Chapter 15: New Avenues influen
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712 Chapter 15: New Avenues Among a
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714 Chapter 15: New Avenues physica
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716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
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CHAPTER 16 SUMMARIES
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724 Chapter 16: Summaries although
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726 Chapter 16: Summaries use of po
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728 Chapter 16: Summaries Table 1.
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736 Chapter 16: Summaries IL-15. Th
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738 Chapter 16: Summaries Patterns
Page 774 and 775:
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
Page 780 and 781:
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
Page 792:
ISBN 1-891524-04-6
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