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704 Chapter 15: New Avenues myeloid leukemia following allogeneic bone marrow transplantation. Bone Marrow Transplant 19:927-932, 1997. 21. Rondón G, Giralt S, Huh Y, Khouri I, Andersson B, Andreeff M, Champlin R: Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplant 18:669-672, 1996. 22. Van Besien KW, De Lima M, Giralt SA, Moore DF Jr, Khouri IF, Rondón G, Mehra R, Andersson BS, Dyer C, Cleary K, Przepiorka D, Gajewski JL, Champlin RE: Management of lymphoma recurrence after allogeneic transplantation: The relevance of graft-versus- lymphoma effect. Bone Marrow Transplant 19:977-982, 1997. 23. Khouri I, Keating MJ, Przepiorka D, O'Brien S, Giralt S, Korbling M, Champlin R: Engraftment and induction of GVL with fludarabine-based non-ablative preparative reg imen in patients with chronic lymphocytic leukemia (Abstract). Blood 88 (Suppl l):301a, 1996. 24. Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LLM, Verdonck LF: Donor leuko cyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 90:4206^1211, 1997. 25. Tricot G, Vesole DH. Jagannath S, Hilton J, Munshi N, Barlogie B: Graft-versus-myeloma effect: Proof of principle. Blood 87:1196-1198, 1996. 26. Verdonck LF, Lokhorst HM, Dekker AW, Nieuwenhuis HK, Petersen EJ: Graft-versus- myeloma effect in two cases. Lancet 347:800-801, 1996. 27. Ueno NT, Rondón G, Mirza NQ, Geisler DK, Anderlini P, Giralt SA, Andersson BS, Claxton DF, Gajewski JL, Khouri IF, Kôrbling M, Mehra RC, Przepiorka D, Rahman Z, Samuels BI, Van Besien K, Hortobagyi GN, Champlin RE: Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 16:986-993, 1998. 28. Eibl B, Schwaighofer H, Nachbaur D, Marth C, Gàchter A, Knapp R, Bock G, Gassner C, Schiller L, Petersen F, Niederwieser D: Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow trans plantation for breast cancer. Blood 88:1501-1508, 1996 29. Korngold R, Sprent J: T cell subsets and graft-versus-host disease. Transplantation 44:335-339,1987. 30. Korngold R, Sprent J: Variable capacity of L3T4 + T cells to cause lethal graft-versus- host disease across minor histocompatibility barriers in mice. J Exp Med 165:1552-1564, 1987. 31. Ferrara JLM, Deeg HJ: Mechanisms of disease: Graft-versus-host disease. N Engl J Med 324:667-674, 1991. 32. Sakamoto H, Michaelson J, Jones WK, Bhan AK, Abhyankar S, Silverstein M, Golan DE, Burakoff SJ, Ferrara JLM: Lymphocytes with a CD4 + CD8 2 CD3 2 phenotype are effec tors of experimental cutaneous graft-versus-host disease. Proc Natl Acad Sci USA 88:10890-10894,1991. 33. Ferrara JLM, Guillen FJ, vanDijken PJ, Marion A, Murphy GF, Burakoff SJ: Evidence that large granular lymphocytes of donor origin mediate acute graft-versus-host disease. Transplantation 47:50-54, 1989. 34. Ferrara JLM, Abhyankar S, Gilliland DG: Cytokine storm of graft-versus-host disease:
Champlin, Khouri, and Giralt 705 A critical effector role for interleukin-1. Transplant Proc 25:1216-1217, 1993. 35. Faber LM, Van Luxemburg-Heijs SAP, Willemze R, Falkenburg JHF: Generation of leukemia-reactive cytotoxic T lymphocyte clones from the HLA-identical bone marrow donor of a patient with leukemia. J Exp Med 176:1283-1289, 1992. 36. Faber LM, Van der Hoeven J, Goulmy E, Hooftmàn-den Otter AL, Van Luxemburg-Heijs SAP, Willemze R, Falkenburg JHF: Recognition of clonogenic leukemic cells, remission bone marrow and HLA-identical donor bone marrow by CD8 + or CD4 + minor histo compatibility antigen-specific cytotoxic T lymphocytes. J Clin Invest 96:877-883,1995. 37. Van der Harst D, Goulmy E, Falkenburg JHF, Kooij-Winkelaar YMC, Van Luxemburg- Heijs SAP, Goselink HM, Brand A: Recognition of minor histocompatibility antigens on lymphocytic and myeloid leukemic cells by cytotoxic T-cell clones. Blood 83:1060-1066, 1994. 38. Truitt RL, Atasoylu AA: Contribution of CD4 + and CD8 + T cells to graft-versus-host dis ease and graft-versus-leukemia reactivity after transplantation of MHC-compatible bone marrow. Bone Marrow Transplant 8:51-58, 1991. 39. Okunewick JP, Kociban DL, Machen LL, Buffo MJ: The role of CD4 and CD8 T cells in the graft-versus-leukemia response in Rauscher murine leukemia. Bone Marrow Transplant 8:445^152, 1991. 40. Okunewick JP, Kociban DL, Machen LL, Buffo MJ: Evidence for a possible role of Asialo-GMl-positive cells in the graft-versus-leukemia repression of a murine type-C retroviral leukemia. Bone Marrow Transplant 16:451-456,1995. 41. Jiang Y-Z, Barrett AJ: Cellular and cytokine-mediated effects of CD4-positive lympho cyte lines generated in vitro against chronic myelogenous leukemia. Exp Hematol 23:1167-1172, 1995. 42. Jiang YZ, Mavroudis D, Dermime S, Hensel N, Couriel D, Molldrem J, Barrett AJ: Alloreactive CD4 + T lymphocytes can exert cytotoxicity to chronic myeloid leukaemia cells processing and presenting exogenous antigen. Br J Haematol 93:606-612, 1996. 43. Sosman JA, Oettel KR, Smith SD, Hank JA, Fisch P, Sondel PM: Specific recognition of human leukemic cells by allogeneic T cells: II. Evidence for HLA-D restricted deter minants on leukemic cells that are crossreactive with determinants present on unrelated nonleukemic cells. Blood 75:2005-2016, 1990. 44. Jiang YZ, Barrett AJ, Goldman JM, Mavroudis DA: Association of natural killer cell immune recovery with a graft-versus-leukemia effect independent of graft-versus-host dis ease following allogeneic bone marrow transplantation. Ann Hematol 74:1-6,1997. 45. Zeis M, Uharek L, Glass B, Gaska T, Steinmann J, Gassmann W, Lôffler H, Muller- Ruchholtz W: Allogeneic NK cells as potent antileukemic effector cells after allogeneic bone marrow transplantation in mice. Transplantation 59:1734-1736,1995. 46. Glass B, Uharek L, Zeis M, Loeffler H, Mueller-Ruchholtz W, Gassmann W: Graft-versus-leukaemia activity can be predicted by natural cytotoxicity against leukaemia. Br J Haematol 93:412-420, 1996. 47. Hauch M, Gazzola MV, Small T, Bordignon C, Barnett L, Cunningham I, Castro- Malaspinia H, O'Reilly RJ, Keever CA: Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. Blood 75:2250-2262, 1990.
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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
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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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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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Canine Hematopoietic Stem Allograft
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Sandmaier et al. 603 The resultant
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Sandmaier et al. 605 synthesis path
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Sandmaier et al. 607 interactions o
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Sandmaier et al. 1991. 2. Burchenal
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87:3508-3513,1996. Sandmaier et al.
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Giralt, Khouri, and Champlin Table
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Giralt, Khouri, and Champlin seven
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1.0 3 0.2 Giralt, Khouri, and Champ
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CHAPTER 12 GENE THERAPY
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622 Chapter 12: Gene Therapy INTROD
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624 Chapter 12: Gene Therapy RESULT
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626 Chapter 12: Gene Therapy envisi
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628 Chapter 12: Gene Therapy cer in
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A Vaccine of Melanoma Peptide Loade
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B43(anti-CD 19)-Gen i stein Immunot
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Targeting Immunotherapy for the Tre
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McGuinness andArceci 637 modified m
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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
Page 687 and 688: McGuinness andArceci 75. Jubinsky F
Page 689 and 690: Slavin et al. 655 up suggests, as p
Page 691 and 692: Slavin et al. 657 was a phase lib c
Page 693 and 694: Slavin et al. presented, appears to
Page 695 and 696: Antitumor Immunotherapy in Autologo
Page 697 and 698: Klingemann et al. 663 Table 3. Meth
Page 699: CHAPTER 14 RADIOIMMUNOTHERAPY
Page 702 and 703: 668 Chapter 14: Radioimmunotherapy
Page 714 and 715: Selection of Radioisotopes, Chelate
Page 726 and 727: Radioimmunotherapy of Common Epithe
Page 729: CHAPTER 15 NEW AVENUES
Page 732 and 733: 698 Chapter 15: New Avenues Table 1
Page 734 and 735: 700 Chapter 15: New Avenues An alte
Page 736 and 737: 702 Chapter 15: New Avenues who can
Page 740 and 741: 706 Chapter 15: New Avenues 48. Gir
Page 742 and 743: Emerging Viral Infections in Blood
Page 744 and 745: 710 Chapter 15: New Avenues influen
Page 746 and 747: 712 Chapter 15: New Avenues Among a
Page 748 and 749: 714 Chapter 15: New Avenues physica
Page 750 and 751: 716 Chapter 15: New Avenues respira
Page 752 and 753: Minimal Therapy Models of Transplan
Page 755: CHAPTER 16 SUMMARIES
Page 758 and 759: 724 Chapter 16: Summaries although
Page 760 and 761: 726 Chapter 16: Summaries use of po
Page 762 and 763: 728 Chapter 16: Summaries Table 1.
Page 770 and 771: 736 Chapter 16: Summaries IL-15. Th
Page 772 and 773: 738 Chapter 16: Summaries Patterns
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
Page 782 and 783: 748 List of Participants AUTHOR IND
Page 784 and 785: 750 Author Index Hurd, D.D. 483 Kui
Page 786 and 787: 752 Author Index Stiff, Patrick J.
Page 788 and 789:
754 Key Word Index Hematologic mali
Page 792:
ISBN 1-891524-04-6
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