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594 Chapter 10: Graft Manipulation hematopoietic reconstitution, we cannot exclude the possibility that small differences in disease-free survival may exist among the three groups of patients. Within the past few years, autologous hematopoietic cell transplant using BM has rapidly declined, being replaced by PBSC transplant. The results of our study and, also, the results of two other trials in which unstimulated BM has been compared with mobilized PBSC 19 - 20 indicate that the advantages of PBSC over BM for autotransplant are not as great as had been previously suspected. 4 There may still be significant roles for BM as a stem cell product for autotransplantation; for instance, in small children, as a target for gene transfer therapy, and as a source of stem cells for ex vivo expansion. The data from this study demonstrate the clinical equivalence of G-CSF-primed BM and G-CSF-mobilized PBSC when used for autotransplantation after three different high-dose chemotherapy regimens. This supports the hypothesis that the kinetics of stem cell engraftment is determined by the treatment given to the patient before collection of the stem cells rather than the anatomical compartment from which the stem cells are collected. However, these data should not be overinterpreted. Namely, it cannot be concluded that all PBSC mobilization methods will produce the same engraftment kinetics. Data from our program indicate that the PBSC mobilization regimen may profoundly affect the rate of hematopoietic 4 3 recovery a result that is supported by reports of differential cell recoveries in both animal 44 and human 4546 studies. REFERENCES 1. Thomas ED: Stem call transplantation: Past, present and future. Stem Cells 12:539-544, 1994. 2. Juttner CA, Fibbe WE, Nemunaitis J, Kanz L, Gianni AM: Blood cell transplantation: Report from an International Consensus Meeting. Bone Marrow Transplant 14:689-693, 1994. 3. Gale RP, Henon P, Juttner C: Blood stem cell transplants come of age. Bone Marrow Transplant 9:151-155, 1992. 4. Henon PR: Autologous blood stem-cell versus bone marrow transplantation: Comparison of cost-effectiveness and of clinical benefits. In: Levitt D, Mertelsmann R (eds) Hematopoietic Stem Cells: Biology and Therapeutic Applications. New York: Marcel Dekker, 1995, p. 421. 5. Henon PR: Peripheral blood stem cell transplantations: Past, present and future (Review). Stem Cells 11:154, 1993. 6. Barr RD, McBride JA: Hemopoietic engraftment with peripheral blood cells in the treat ment of malignant disease. Br J Haematol 51:181-187, 1982. 7. Sheridan WP, Begley CG, Juttner CA, et al.: Effect of peripheral-blood progenitor cells mobilized by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet 339:640-644, 1992.
Janssen et al. 595 8. Dercksen MW, Gerritsen WR, Rodenhuis S, Dirkson MKA, Slaper-Cortenbach ICM, Schaasberg WP, Pinedo HM, von dem Borne AEGK, van der Schoot CE: Expression of adhesion molecules on CD34 + cells: CD34 + L-selectin + cells predict a rapid platelet recovery after peripheral blood stem cell transplantation. Blood 85:3313-3319,1995. 9. Chao NJ, Schriber A Grimes K, et al.: Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high- dose chemotherapy. Blood 81:2031-2035, 1993. 10. To LB, Roberts MM, Haylock DN, et al.: Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant 9:211'-284, 1992. 11. Brugger W, Brass K, Frisch J, Dem P, Weber B, Mertelsmann R, Kanz L: Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and gran ulocyte-macrophage colony-stimulating-factor following polychemotherapy with etoposide, ifosfamide and cisplatin. Blood 79:1193-1200,1992. 12. Elias AD, Ayash L, Anderson KC, et al.: Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating-factor for hemato logic support after high-dose intensification for breast cancer. Blood 79:3036-3044,1992. 13. Bensinger W, Singer J, Appelbaum F, et al.: Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stim ulating factor. Blood 81:3158-3163,1993. 14. Vose JM, Bierman PJ, Anderson JR, et al.: High-dose chemotherapy with hematopoiet ic stem cell rescue for non-Hodgkin's lymphoma (NHL): Evaluation of event-free sur vival based on histologic subtype and rescue product (Abstract). Proc Annu Am Soc Clin Oncol 11 :A1080,1992. 15. Vose JM, Anderson JR, Kessinger A, Bierman PJ, Coccia P, Reed EC, Gordon B, Armitage JO: High-dose chemotherapy and autologous hematopoietic stem cell trans plantation for aggressive non-Hodgkin's lymphoma. J Clin Oncol 11:1846-1851,1993. 16. Janssen WE: Peripheral blood and bone marrow hematopoietic stem cells: Are they the same? Semin Oncol 20:19-27, 1993. 17. Kessinger A, Armitage JO, Landmark JD, Smith DM, Weisenburger DD: Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function fol lowing marrow ablative therapy. Blood 11 -.123-121, 1988. 18. Lobo F, Kessinger A, Landmark JD, Smith DM, Weisenburger DD, Wigton RS, Armitage JO: Addition of peripheral blood stem cells collected without mobilization techniques to transplanted autologous bone marrow did not hasten marrow recovery following mye- loablative therapy. Bone Marrow Transplant 8:389-392, 1991. 19. Beyer J, Schwella N, Zingsem J, Strohscheer I, Schwaner I, Oettle H, Serke S, Huhn D, Siegert W: Hematopoietic rescue after high-dose chemotherapy using autologous periph eral blood progenitor cells or bone marrow: A randomized comparison. J Clin Oncol 13:1328-1335,1995. 20. Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A, Demuynck HM, Link H, Zander A, Barge A, et al.: Randomised trial of filgrastim-mobilised periph eral blood progenitor cell transplantation versus autologous bone marrow transplantation
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AUTOLOGOUS BLOOD AND MARROW TRANSPL
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AUTOLOGOUS BLOOD AND MARROW TRANSPL
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ACKNOWLEDGMENTS We wish to thank Wi
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THE VAN BEKKUM STEM CELL AWARD Prof
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xii Table of Contents CHAPTER 2: AL
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xiv Table of Contents Late Non-Rela
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xvi Table of Contents Pretreatment
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xviii Table of Contents CHAPTER 7:
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XX Table of Contents Long-Term Obse
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xxii Table of Contents CHAPTER 13:
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0-9 LIST OF ABBREVIATIONS 2CDA 2-ch
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List of Abbreviations xxvii EFS eve
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List of Abbreviations MOPP mechlore
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VOD veno-occlusive disease VPC viru
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4HC-Purged Autologous Stem Cell Tra
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1.0-1 + 0.2 Miller et al. 5 Event F
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Miller et al. Adjusted probability
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Who Benefits From Autograft in AML
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Burnett 11 which to set the transpl
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Table 1. Outcome after relapse in M
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Immunotherapy in AML: No Positive E
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Simonsson et al. inhibit IL-2 induc
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Autologous Bone Marrow Transplantat
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Ball et al. 21 CD15) and AML-2-23 (
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Ball et al. 23 The ex vivo treatmen
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Ball et al. 25 Table 2. Factors inv
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Ball et al. Overall Survival for Pa
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Ball et al. Overall Survival for Pa
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Ball et al. 31 Overall Survival for
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Ball et al. Table 4. Actuarial over
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Ball et al. myeloid leukemia. The G
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Ball et al. 1993. 38. Mehta J, Powl
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Can Autologous Stem Cell Transplant
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De Witte et al. 41 novo AML. Auer r
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De Witte et al. hematopoietic engra
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De Witte et al. 23. Fenaux P, Laï
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Stein et al. and fever. No patient
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Stein et al. after doses 1, 3, and
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Stein et al. early after the transp
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autologous stem-cell rescue. / Clin
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Bone Marrow Transplantation for Acu
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Table 2. Autologous BMT in ALL in f
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Rowe 61 or adult patients with acut
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Hoelzer and Gôkbuget minitransplan
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Hoelzer and Gdkbuget 65 blood, earl
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Table 3. Risk factors for the defin
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Hoelzer and Gôkbuget treatment opt
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Hoeker and Gökbuget tical sibling
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Sierra et al. INTRODUCTION Two-thir
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Sierra et al. Table 2. Adverse char
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1,0 0,0 J Sierra et al. 0 20 40 60
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Sierra et al. Months Figure 4 < 30,
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Sierra et al. No adverse factors (n
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1994. Sierra et al. 83 10. Canals C
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Martin, Atta, and Hoelzer 85 adult
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Martin, Atta, and Hoelzer 87 Single
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100. Martin, Atta, and Hoelzer 89 P
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Martin, Atta, and Hoelzer 91 chromo
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Autologous vs. Unrelated Allogeneic
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Boyer and Yeager 95 outcomes after
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Boyer and Y eager 97 Table 2. Hypot
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Boyer and Y eager SUMMARY Most of t
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CHAPTER 3 CML
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Autograft Followed by Allograft Wit
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106 Chapter 3: CML (one low-grade a
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108 Chapter 3: CML DISCUSSION Myelo
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110 Chapter 3: CML Philadelphia-neg
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The Case for Manipulation of CML Au
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Toward a Cure by Drug Treatment? Th
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116 Chapter 3 :CML Table 1. Prolong
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118 Chapter 3: CML Table 3. German
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120 Chapter 3: CML Table 5. Normal
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122 Chapter 3: CML Table 8. Surviva
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124 Chapter 3: CML 88:3118-3122, 19
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126 Chapter 3: CML RK, Klingemann H
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The Tyrphostin AG957 Inhibits the I
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130 Chapter 3: CML mobilization. Al
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132 Chapter 3: CML A B 100 n 0 1 5
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134 Chapter 3: CML The in vitro sel
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136 Chapter 3: CML detecting leukem
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Progressive Hodglcin's Lymphoma Fol
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Reece et al. survival is observed i
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0.2 -I 0.0 0 Reece et al. 143 ii i
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Reece et al. Table 3. Causes of non
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Reece et al. carmustine, etoposide
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CD34 + Selection of Hematopoietic B
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Lazarus et al. 151 significantly de
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Lazarus et al. 153 (Sigma, St Louis
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Lazarus et al. 155 Table 2. Effect
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Lazarus et al. 157 difference. Furt
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Lazarus et al. 159 cells after myel
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The European CUP/UP Trial: A Prelim
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Table 1. Patient characteristics at
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Schouten et al. licular non-Hodgkin
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Sweetenham et al. vs. autologous pe
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Table 1. Patient characteristics, g
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Table 2. Patient characteristics, g
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Table 3. Sites of relapse, group A
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Table 4. Patterns of relapse, group
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A 100 80 %OS 60 40 20 B 100 %OS | S
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Sweetenham et al. new sites, and fi
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Sweetenham et al. Treatment options
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Molecular Remission: A Worthwhile A
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Early or Late Autotransplant in Hig
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Schenkein et al. 187 PATIENTS AND M
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Schenkein et al. 189 Toxicity Toxic
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Schenkein et al. 191 16. Glick JH,
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Santini et al. 193 to evaluate the
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Table 1. Continued Santini et al. 1
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Santini et al. 197 cytosine arabino
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1 0 0 1 90- 80- 70- (0 u. 60' o so-
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Hodgkin's lymphoma. N EnglJ Med 333
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CHAPTER 5 MYELOMA
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206 Chapter 5: Myeloma independent
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208 Chapter 5: Myeloma disease (MRD
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210 Chapter 5: Myeloma Scandinavia,
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212 Chapter 5: Myeloma (0 n o B co
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214 Chapter 5: Myeloma B cq d ? o c
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216 Chapter 5: Myeloma patients wit
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218 Chapter 5: Myeloma PBSC transpl
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220 Chapter 5: Myeloma 25. Seiden M
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Autologous Transplantation in Multi
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224 Chapter 5: Myeloma 0 52 44 U §
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226 Chapter 5: Myeloma BM ^ (CD34±
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228 Chapter 5: Myeloma IFM 94 : OS
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230 Chapter 5: Myeloma two groups a
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232 Chapter 5: Myeloma increase bot
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234 Chapter 5: Myeloma REFERENCES 1
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236 Chapter 5: Myeloma Intensified
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238 Chapter 5: Myeloma of CD34 + ce
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Chapter 5: Myeloma Table 2. Descrip
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242 Chapter 5: Myeloma o 8H 0 2 4 6
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244 Chapter 5: Myeloma ated with sh
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The Presence of Micrometastases in
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Kvalheim et al. 249 Table 1. Immuno
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Kvalheim et al. 251 Figure 1. Sixty
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Kvalheim et al. 253 DISCUSSION In t
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Kvalheim et al. 255 Bastert G: Micr
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Hood et al. 257 In an effort to inc
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#CD34 + cells in blood = Hood et al
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Hood et al. 261 Table 3. Frequency
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Hood et al. 263 REFERENCES 1. Rill
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The Clinical Significance of Breast
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Moss et al. tests, and bilateral po
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Moss et al. 269 0 15 70 143 200 400
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Moss et al. 271 0 3 6 12 18 24 30 3
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Moss et al. 273 8. Passos-Coelho J,
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Autotransplantation for Men With Br
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McCarthy et al. 277 radiation, two
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High Dose Sequential Chemotherapy W
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Viens et al. 281 3 g/m 2 and doxoru
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Table 1. Tumor characteristics Exte
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Table 4. Response Viens et al. 285
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Viens et al. 287 Table 5. Pathologi
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Viens et al. 289 apy for inoperable
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Gliick et al. 291 INTRODUCTION The
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Gluck et al. 293 RESULTS Patient de
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Glück et al. 295 Table 3. Response
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Gluck et al. 297 Overall Survival O
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Gluck et al. 299 Sudbury patients w
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Gluck et al. 301 anthracycline or t
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Repetitive High-Dose Therapy With P
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Prince et al. paramagnetic separati
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Prince et al. Table 1. High-dose re
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Table 2. Patient characteristics (n
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Table 4. Hematopoietic recovery fol
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1.0- M C .S 0.8- a c *fe o o> 0.6-
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M 1.0 I 0.8H s? VI o.6H S 0.2 0.0 P
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a Prince et al. days to platelets >
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Table 5. Results of Isolex 300i CD3
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Prince et al. 321 Figure 5, continu
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Prince et al. 323 months after tran
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Prince et al. 325 excessive to be u
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Prince et al. 327 eight patients ha
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Prince et al. 329 marrow transplant
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Prince et al. intensive chemotherap
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-Q CO .Q O 1.0 0.9 0.8 0.7 0.6 0.5
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.Q CD .Q O 1.0 0.9 0.8 0.7 0.6 0.5
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oba Q. 1.0 0.9 Dicke et al. Stage I
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Vahdat with peripheral blood progen
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Evaluation of Prognostic Factors fo
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Fields et al. 343 PATIENTS AND METH
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Table 1. Chemotherapy regimens. Fie
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Fields et al. Stage II; 4-9 Pos LN
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U U Fields et al.
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Fields et al. 351 between 1 and 2 y
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European Trends and the EBMT Databa
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25% % 22% / 17% \ Rosti et al. 355
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Rosti et al. 357 The new Italian St
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Rosti et al. 6. Haas R, Schmid H, H
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Bewick et al. 363 INTRODUCTION The
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Bewick et al. 365 Blood samples obt
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Bewick et al. 367 HDCT with ABSC su
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Bewick et al. Progression Free Surv
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Bewick et al. pression in MBC, i.e.
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Bewick et al. 14. Kandl HL, Seymour
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CHAPTER 7 OTHER SOLID TUMORS
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378 Chapter 7: Solid Tumors INTRODU
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380 Chapter 7: Solid Tumors Prepara
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382 Chapter 7: Solid Tumors Surviva
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384 Chapter 7: Solid Tumors months
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386 Chapter 7: Solid Tumors have be
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High-Dose Chemotherapy in the Manag
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390 Chapter 7: Solid Tumors followe
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392 Chapter 7: Solid Tumors Table 1
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394 Chapter 7: Solid Tumors (mucosi
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Three-Fold Intensification by Seque
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High-Dose Therapy for Small Cell Lu
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404 Chapter 7: Solid Tumors chemoth
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406 Chapter 7: Solid Tumors SCLC ha
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408 Chapter 7: Solid Tumors relapse
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410 Chapter 7: Solid Tumors 69:585-
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412 Chapter 7: Solid Tumors ogous b
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414 Chapter 7: Solid Tumors 64. Bru
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416 Chapter 7: Solid Tumors Prignot
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418 Chapter 7: Solid Tumors CO > CO
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420 Chapter 7: Solid Tumors TANDEM
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Multiple Courses of Cyclophosphamid
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424 Chapter 7: Solid Tumors and the
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426 Chapter 7: Solid Tumors Thiotep
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430 Chapter 7: Solid Tumors E 100 0
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432 Chapter 7: Solid Tumors course
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434 Chapter 7: Solid Tumors boplati
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436 Chapter 7: Solid Tumors INTRODU
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438 - Chapter 7: Solid Tumors Table
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440 Chapter 7: Solid Tumors seeded
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442 Chapter 7: Solid Tumors DISCUSS
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444 Chapter 7: Solid Tumors 10. Di
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446 Chapter 7: Solid Tumors plasma
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Autologous Stem Cell Transplantatio
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Keystone 451 hypertension, anemia,
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Fassas et al. 453 INTRODUCTION Mult
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Fassas et al. Table 2. Stem cell mo
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Table 3. Toxicity after stem cell i
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Fassas et al. Table 5. Trial 1: cha
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Fassas et al. MS PROGRESSION FREE S
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Fassas et al. ic or autologous bone
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1 2 1 6 EAE. Burt et al. 465 Becaus
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Burt et al. Since cyclophosphamide
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Burt et al. 469 toxicity study, we
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Burt et dl. All 23. Mor F, Cohen IR
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Hasler, Gratwohl, and Tyndall an ev
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Hasler, Gratwohl, and Tyndall 475 B
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Kuis, Wulffraat, and Sanders 477 st
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Kuis, Wulffraat, and Sanders neousl
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CHAPTER 9 LONG-TERM EFFECTS
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484 Chapter 9: Long-Term Effects po
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486 Chapter 9: Long-Term Effects Ta
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488 Chapter 9: Long-Term Effects ml
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490 Chapter 9: Long-Term Effects 4.
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492 Chapter 9: Long-Term Effects us
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494 Chapter 9: Long-Term Effects AB
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498 Chapter 9: Long-Term Effects En
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500 Chapter 9: Long-Term Effects Rl
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502 Chapter 9: Long-Term Effects RE
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504 Chapter 9: Long-Term Effects A,
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Long-Term Follow-Up of Autologous T
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CHAPTER 10 GRAFT MANIPULATION
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514 Chapter 10: Graft Manipulation
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Page 578 and 579: 544 Chapter 10: Graft Manipulation
Page 606 and 607: Stem Cell Reinfusion Over Two Conse
Page 614 and 615: Final Report of the First Prospecti
Page 635 and 636: Canine Hematopoietic Stem Allograft
Page 637 and 638: Sandmaier et al. 603 The resultant
Page 639 and 640: Sandmaier et al. 605 synthesis path
Page 641 and 642: Sandmaier et al. 607 interactions o
Page 643 and 644: Sandmaier et al. 1991. 2. Burchenal
Page 645 and 646: 87:3508-3513,1996. Sandmaier et al.
Page 647 and 648: 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
Page 653: 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
Page 662 and 663: 628 Chapter 12: Gene Therapy cer in
Page 664 and 665: A Vaccine of Melanoma Peptide Loade
Page 667 and 668: B43(anti-CD 19)-Gen i stein Immunot
Page 669 and 670: Targeting Immunotherapy for the Tre
Page 671 and 672: McGuinness andArceci 637 modified m
Page 673 and 674: McGuinness andArceci 639 leukemic c
Page 675 and 676: McGuinness and Arced 641 in G418. T
Page 677 and 678: McGuinness andArceci 643 Figure 2
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mRNA for hB7-1 (1491 bp) mRNA for C
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McGuinness and Arced CD80PE C080PE
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McGuinness andArceci 649 8. Robert
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McGuinness andArceci immune respons
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McGuinness andArceci 75. Jubinsky F
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Slavin et al. 655 up suggests, as p
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Slavin et al. 657 was a phase lib c
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Slavin et al. presented, appears to
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Antitumor Immunotherapy in Autologo
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Klingemann et al. 663 Table 3. Meth
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CHAPTER 14 RADIOIMMUNOTHERAPY
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668 Chapter 14: Radioimmunotherapy
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Selection of Radioisotopes, Chelate
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Radioimmunotherapy of Common Epithe
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CHAPTER 15 NEW AVENUES
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698 Chapter 15: New Avenues Table 1
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700 Chapter 15: New Avenues An alte
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702 Chapter 15: New Avenues who can
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704 Chapter 15: New Avenues myeloid
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706 Chapter 15: New Avenues 48. Gir
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Emerging Viral Infections in Blood
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710 Chapter 15: New Avenues influen
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712 Chapter 15: New Avenues Among a
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714 Chapter 15: New Avenues physica
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716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
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CHAPTER 16 SUMMARIES
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724 Chapter 16: Summaries although
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726 Chapter 16: Summaries use of po
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728 Chapter 16: Summaries Table 1.
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736 Chapter 16: Summaries IL-15. Th
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738 Chapter 16: Summaries Patterns
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
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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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