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424 Chapter 7: Solid Tumors and the study was approved by the Committee on Medical Ethics of the Netherlands Cancer Institute. Treatment plan Therapy was started with two courses of FE, 20C (fluorouracil 500 mg/m 2 , epirubicin 120 mg/m 2 , and cyclophosphamide 500 mg/m 2 , all given as intravenous push on day 0 and repeated on day 21). This is a relatively intensive anthracyclinebased regimen that we previously reported to be highly efficacious in locally advanced breast cancer. 8 The second of these FE120C courses was used to mobilize stem cells (see below). In patients with at least a minimal response to chemotherapy, the first high-dose therapy course (tiny CTC) was begun 3 weeks later, to be followed by the second and third after 4-5 weeks each. After recovery from the last high-dose therapy course, resection or irradiation of residual disease was attempted and, when possible, prior sites of disease were irradiated. Delays and dose adaptations of the chemotherapy courses were executed as described previously for full-dose CTC. 7 Evaluable patients who did not respond to a FE I 2 0C or tCTC course were taken off study. PBPC mobilization and harvest For stem cell mobilization, the FE, 20C chemotherapy regimen was used, all given as intravenous push on day 1. Filgrastim (5 pg/kg/d subcutaneously) was started on day 2. Leukaphereses began when the white blood cell (WBC) count exceeded 3.0X10 9 /L and the CD34 + cell count in the peripheral blood was at least 0.5%. To facilitate apheresis, all patients had 13.5 French double-lumen Hickman catheters. A continuous-flow blood cell separator was employed (Fenwal CS 3000; Baxter Deutschland GmbH, Germany). Both the number of CD34 + cells and the number of granulocyte-macrophage colony-forming units (GM-CFU) were determined in the cell collections. All methods employed in the stem cell harvests have been described previously. 9 Based on earlier findings, 10 we considered a graft size of 3.0X10 6 CD34 + cells/kg body weight sufficient for sustained bone marrow recovery and 1.0X10 6 CD34 + cells/kg sufficient for rapid (but possibly transient) granulocyte recovery after high-dose therapy. High-dose chemotherapy regimen: tCTC The high-dose chemotherapy regimen tCTC was administered as published previously. 7 Briefly, carboplatin was administered intravenously as daily 1-hour infusions on days -6, -5, -4, and -3. The total dose of carboplatin was 1060
mg/m 2 Rodenhuis et al. 425 in patients with normal renal function, but in those with creatinine clearances of 110 ml/min or less, it was determined by the following formula: dose (mg) = 13.3 X (creatinine clearance + 25) Cyclophosphamide (total dose 4000 mg/m 2 ) was divided over 4 daily 1-hour infusions, and thiotepa (total dose 320 mg/m 2 ) was divided over 8 twice-daily half- hour infusions. Both agents were given on days -6, —5, -4, and -3. Mesnum (500 mg per dose) was given six times a day for a total of 36 doses, beginning 1 hour before the first cyclophosphamide infusion. All infusions were administered through double-lumen Hickman catheters inserted in a subclavian vein. The peripheral blood progenitor cells were reinfused on day 0. Antiemetics were employed both prophylactically and as needed and usually included dexamethasone and granisetron. All patients received prophylactic antibiotics, including ciprofloxacin and itraconazole orally. In addition, all patients received acyclovir in an oral dose of 400 mg twice a day. To prevent gram-positive infections, roxitromycin was given orally from day 0 and was discontinued when the neutrophil count exceeded 0.5 X10 9 cells/L. Irradiated platelet transfusions were administered to maintain platelet counts of at least 10 X10 9 /L, and leukocyte- free irradiated red blood cells were given to maintain hemoglobin levels >5.5 mmol/L. Whenever possible, patients were discharged from the hospital on the day following PBPC reinfusion, but returned daily to the clinic for check-ups. G-CSF (filgrastim; a gift from Amgen-Roche, Breda, The Netherlands) was administered as a daily subcutaneous injection of 300 ug, regardless of body weight, from day 1 until the WBC count exceeded 5.0X10 9 /L. Sample collection for pharmacokinetic monitoring Samples were collected before the infusions on all days of chemotherapy, and on days 1 and 4 at 30 minutes after start of the cyclophosphamide infusion (i=0) and at i=60, 90, 120, 150, 180, 210, 285, 390, and 660 min. The infusion sequence was cyclophosphamide (1 hour), carboplatin (1 hour), thiotepa (30 minutes). After sample collection, blood samples were placed on ice and plasma was separated immediately by centrifuging the sample for 3 min at 3,000g at 4°C. Plasma ultrafiltrate was prepared without delay using the MPS-1 system (Amicon Division, Dan vers, MA) by centrifugation (10 min, 1500g) of 1.0 mL plasma. Carboplatin assay Free, ultrafiltrable carboplatin was measured using Zeeman atomic absorption spectrometry as described earlier. 11
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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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Page 409: CHAPTER 7 OTHER SOLID TUMORS
Page 412 and 413: 378 Chapter 7: Solid Tumors INTRODU
Page 414 and 415: 380 Chapter 7: Solid Tumors Prepara
Page 416 and 417: 382 Chapter 7: Solid Tumors Surviva
Page 418 and 419: 384 Chapter 7: Solid Tumors months
Page 420 and 421: 386 Chapter 7: Solid Tumors have be
Page 422 and 423: High-Dose Chemotherapy in the Manag
Page 424 and 425: 390 Chapter 7: Solid Tumors followe
Page 426 and 427: 392 Chapter 7: Solid Tumors Table 1
Page 428 and 429: 394 Chapter 7: Solid Tumors (mucosi
Page 430 and 431: Three-Fold Intensification by Seque
Page 436 and 437: High-Dose Therapy for Small Cell Lu
Page 438 and 439: 404 Chapter 7: Solid Tumors chemoth
Page 440 and 441: 406 Chapter 7: Solid Tumors SCLC ha
Page 442 and 443: 408 Chapter 7: Solid Tumors relapse
Page 444 and 445: 410 Chapter 7: Solid Tumors 69:585-
Page 446 and 447: 412 Chapter 7: Solid Tumors ogous b
Page 448 and 449: 414 Chapter 7: Solid Tumors 64. Bru
Page 450 and 451: 416 Chapter 7: Solid Tumors Prignot
Page 452 and 453: 418 Chapter 7: Solid Tumors CO > CO
Page 454 and 455: 420 Chapter 7: Solid Tumors TANDEM
Page 456 and 457: Multiple Courses of Cyclophosphamid
Page 460 and 461: 426 Chapter 7: Solid Tumors Thiotep
Page 464 and 465: 430 Chapter 7: Solid Tumors E 100 0
Page 466 and 467: 432 Chapter 7: Solid Tumors course
Page 468 and 469: 434 Chapter 7: Solid Tumors boplati
Page 470 and 471: 436 Chapter 7: Solid Tumors INTRODU
Page 472 and 473: 438 - Chapter 7: Solid Tumors Table
Page 474 and 475: 440 Chapter 7: Solid Tumors seeded
Page 476 and 477: 442 Chapter 7: Solid Tumors DISCUSS
Page 478 and 479: 444 Chapter 7: Solid Tumors 10. Di
Page 480 and 481: 446 Chapter 7: Solid Tumors plasma
Page 483 and 484: 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
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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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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
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710 Chapter 15: New Avenues influen
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712 Chapter 15: New Avenues Among a
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714 Chapter 15: New Avenues physica
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716 Chapter 15: New Avenues respira
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Minimal Therapy Models of Transplan
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CHAPTER 16 SUMMARIES
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724 Chapter 16: Summaries although
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726 Chapter 16: Summaries use of po
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728 Chapter 16: Summaries Table 1.
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736 Chapter 16: Summaries IL-15. Th
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738 Chapter 16: Summaries Patterns
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740 List of Participants Thomas L.
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742 List of Participants Sergio A.
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744 List of Participants Hans Marti
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746 List of Participants David P. S
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748 List of Participants AUTHOR IND
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750 Author Index Hurd, D.D. 483 Kui
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752 Author Index Stiff, Patrick J.
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754 Key Word Index Hematologic mali
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ISBN 1-891524-04-6
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