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502 Chapter 9: Long-Term Effects REFERENCES 1. Gorin NC, Najman A, Duhamel G: Autologous bone-marrow transplantation in acute myelocytic leukemia (Letter). Lancet i: 1050, 1977. 2. Appelbaum FR, Herzig GP, Ziegler JL, Graw RGG, Levine AS, Deisseroth AB: Successful engraftment of cryopreserved autologous bone marrow in patients with malig nant lymphoma. Blood 52: 85-95, 1978. 3. Dicke KA, Spitzer G, Peters L, Mac Credie KC, Zander A, Verma DS, Vellekoop L, Hester J: Autologous bone-marrow transplantation in relapsed adult acute leukaemia. Lancet i:514—517, 1979. 4. Gorin NC: Autologous stem cell transplantation in acute myelocytic leukemia. Blood 92:1073-1090, 1998. 5. Korbling M, Hunstein W, Fliedner TM, Cayeux S, Dorken B, Fehrentz D, Haas R, Ho AD, Keilholz U, Knauf W, et al.: Disease-free survival after autologous bone marrow transplantation in patients with acute myelogenous leukemia. Blood 74:1898-1904,1989. 6. Cassileth PA, Andersen J, Lazarus HM, Colvin OM, Bennett JM, Stadtmauer EA, Kaizer H, Weiner RS, Edelstein M, Oken MM: Autologous bone marrow transplant in acute myeloid leukemia in first remission. J Clin Oncol 11:314-319, 1993. 7. Linker CA, Ries CA, Damon LE, Rugo HS, Wolf JL: Autologous bone marrow trans plantation for acute myeloid leukemia using 4-hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: A follow up report. Bone Marrow Transplant 22:865-872, 1998. 8. Gorin NC, Douay L, Laporte JP, Lopez M, Mary JY, Najman A, Salmon C, Aegerter P, Stachowiak J, David R, Pene F, Kankor G, Deloux J, Duhamel E, Van Der Akker J, Gerota Y, Parker Y, Duhamel G: Autologous bone marrow transplantation using marrow incu bated with ASTA-Z 7557 in adult acute leukemia. Blood 67:1367-1376, 1986. 9. Laporte JP, Douay L, Lopez M, Labopin M, Jouet JP, Lesage S, Stachowiak J, Fouillard L, Isnard F, Noel-Walter MP, Pene F, Deloux J, Van Den Akker J, Grande M, Bauters F, Najman A, Gorin NC: One hundred twenty-five adult patients with primary acute leukemia autografted with marrow purged by mafosfamide: A 10 year single institution experience. Blood 84:3810-3818, 1994. 10. Gulati S, Acaba L, Yalahom J, Reich L, Motzer R, Crown J, Doherty M, Clarkson B, Berman E, Atzpodien J, Andreeff M, Gee T: Autologous bone marrow transplantation for acute myelogenous leukemia, using 4 hydroperoxycyclophosphamide and VP-16 purged bone marrow. Bone Marrow Transplant 10:129-134, 1992. 11. Selvaggi KJ, Wilson JW, Mills LE, Corwell GG, Hurd D, Dodge W, Gingrich R, Martin SE, McMillan R, Miller W, et al.: Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow. Blood 83:1698-1705, 1994. 12. Yeager AM, Kaizer H, Santos GW, Sarai R, Colvin ON, Stuart RK, Brain HG, Burke PJ, Ambinder RF, Burns WH, Fuller DJ, Davis JM, Karp JE, May WS, Rowley SD, Sensenbrenner LL, Vogelsang GB, Wingard JR: Autologous bone marrow transplanta tion in patients with acute non lymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide. N EnglJ Med 315A41-141, 1986. 13. Carella AM, Gaozza E, Santini G, Martinengo M, Pungolino E, Piatti G, Congiu A, Nati
Gorin 503 S, Carlier P, Giordano D, Cerri R, Risso M, Miceli S, Raffo MR, Scarpati D, Corvo R, Franzone P, Vitale V, Vimercati AR, D'Amico T, Marmont A: Autologous unpurged bone marrow transplantation for acute non-lymphoblastic leukaemia in first remission. Bone Marrow Transplant 3:537'-541, 1988. 14. Dicke K, Jagannafh S, Walters RS, Horwitz LJ, Spitzer G: The role of autologous bone marrow transplantation in acute leukemia. Ann N Y Acad Sei 511:468^172,1987. 15. McMillan AK, Goldstone AH, Linch DC, Gribben JG, Patterson KG, Richards JDM, Franklin I, Boughton BJ, Milligan DW, Leyland M, Hutchison RM, Newland AC: High dose chemotherapy and autologous bone marrow transplantation in acute myeloid leukemia. Blood 76:480-488,1990. 16. Stein AS, O'Donnell MR, Chai A, Schmidt GM, Nademanee A, Parker PM, Smith EP, Snyder DS, Molina A, Stepan DE, Spielberger R, Somlo G, Margolin KA, Vora N, Lipsett J, Lee J, Niland J, Forman SJ: In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission. J Clin Oncol 14:2206-2216,1996. 17. Meloni G, De Fabritiis P, Carella AM, Mangoni L, Porcellini A, Marmont A, Mandelli F: Autologous bone marrow transplantation in patients with AML in first complete remis sion. Results of two different conditioning regimens after the same induction and con solidation therapy. Bone Marrow Transplant 5:29-32, 1990. 18. Sierra J, Granena A, Garcia J, Vails A, Carreras E, Rovira M, Canals C, Martinez E, Punti C, Algara M, et al.: Autologous bone marrow transplantation for acute leukemia: Results and prognostic factors in 90 consecutive patients. Bone Marrow Transplant 12:517-523, 1993. 19. Mehta J, Powles R, Singhai S, Horton C, Tait D, Milan S, Meiler S, Pinkerton CR, Treleaven J: Autologous bone marrow transplantation for acute myeloid leukemia in first remission: Identification of modifiable prognostic factors. Bone Marrow Transplant 16:499-506, 1995. 20. Miggiano MC, Gherlinzoni F, Rosti G, Bandini G, Visani G, Fiacchini M, Ricci P, Testoni N, Motta MR, Geromin A, Rizzi S, Belardinelli A, Mangianti S, Manfroi S, Tura S: Autologous bone marrow transplantation in late first complete remission improves out come in acute myelogenous leukemia. Leukemia 10:402-409, 1996 21. Rizzoli V, Carlo-Stella C: Stem cell purging: An intriguing dilemma. Exp Hematol 23: 296-302, 1995. 22. Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, et al.: Autologous or allogeneic bone marrow transplantation com pared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med 332:217-223,1995. 23. Burnett AK, Goldstone AH, Stevens RMF, Hann IM, Gray RG, Rees JKH, Wheatley KW: Randomised comparison of autologous bone marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: Results of MRC-AML 10 trial. Lancet 351:700-708, 1998. 24. Sierra J, Brunet S, Granena A, Olive T, Bueno J, Ribera JM, Petit J, Besses C, Liorente
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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
Page 485 and 486: Keystone 451 hypertension, anemia,
Page 487 and 488: Fassas et al. 453 INTRODUCTION Mult
Page 489 and 490: Fassas et al. Table 2. Stem cell mo
Page 491 and 492: Table 3. Toxicity after stem cell i
Page 493 and 494: Fassas et al. Table 5. Trial 1: cha
Page 495 and 496: Fassas et al. MS PROGRESSION FREE S
Page 497 and 498: Fassas et al. ic or autologous bone
Page 499 and 500: 1 2 1 6 EAE. Burt et al. 465 Becaus
Page 501 and 502: Burt et al. Since cyclophosphamide
Page 503 and 504: Burt et al. 469 toxicity study, we
Page 505 and 506: Burt et dl. All 23. Mor F, Cohen IR
Page 507 and 508: Hasler, Gratwohl, and Tyndall an ev
Page 509 and 510: Hasler, Gratwohl, and Tyndall 475 B
Page 511 and 512: Kuis, Wulffraat, and Sanders 477 st
Page 513 and 514: Kuis, Wulffraat, and Sanders neousl
Page 515: CHAPTER 9 LONG-TERM EFFECTS
Page 518 and 519: 484 Chapter 9: Long-Term Effects po
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Page 528 and 529: 494 Chapter 9: Long-Term Effects AB
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Page 534 and 535: 500 Chapter 9: Long-Term Effects Rl
Page 538 and 539: 504 Chapter 9: Long-Term Effects A,
Page 540 and 541: Long-Term Follow-Up of Autologous T
Page 545: CHAPTER 10 GRAFT MANIPULATION
Page 548 and 549: 514 Chapter 10: Graft Manipulation
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552 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
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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
Page 744 and 745:
710 Chapter 15: New Avenues influen
Page 746 and 747:
712 Chapter 15: New Avenues Among a
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714 Chapter 15: New Avenues physica
Page 750 and 751:
716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
Page 755:
CHAPTER 16 SUMMARIES
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724 Chapter 16: Summaries although
Page 760 and 761:
726 Chapter 16: Summaries use of po
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728 Chapter 16: Summaries Table 1.
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Page 766 and 767:
Page 768 and 769:
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
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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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