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298 Chapter 6: Breast Cancer obtaining appropriate internal institutional consent to collect ORCC patient-related information, the population from which the control group would be selected was identified. This population was defined as all patients referred to the ORCC with a diagnosis of metastatic breast cancer treated with chemotherapy for metastatic disease at some point during the study period. This population was generated using a computerized search strategy within the Oncology Patient Information System (OPIS). This population was then sampled and individual patient charts reviewed to determine the patients deemed eligible for high-dose chemotherapy/stem cell transplantation, but who received conventional chemotherapy for their illness (the control group). The inclusion criteria were designed to approximate as closely as possible the same physiologic/biological characteristics as was represented by the experimental group to minimize the effects of selection bias. Also, to minimize the introduction of any possible bias incurred by a temporal or sequenced selection of patients, chart numbers were selected at random using numbers generated from a random number table (generated using the random number function in Microsoft Excel). TREATMENT PROTOCOLS Standard-dose chemotherapy For patients who received adjuvant chemotherapy, CMF, FAC, and FEC accounted for the vast majority of chemotherapy regimens. If a patient had not received prior adjuvant therapy, the first-line treatment for metastatic disease was most often anthracycline-based (FEC or FAC), although a few patients were treated with CMF. For patients who had received anthracycline-based therapy in the adjuvant setting, the first-line chemotherapy was most often single-agent paclitaxel or docetaxel. Other chemotherapy regimens included vinorelbine (generally as a single agent), 5-FU/folinic acid, 5-FU/folinic acid/mitoxantrone, etoposide/cisplatin, mitomycin-C, and vinblastine. Only the response and response duration of the first chemotherapy for metastatic disease were used to calculate the failure-free survival. The duration of chemotherapy (number of cycles) was at the treating physician's discretion and generally depended on tolerance of therapy as well as ongoing response. High-dose chemotherapy At UNMC, the high-dose chemotherapy regimen was as follows: cyclophosphamide 1.5 g/m 2 /day intravenously as a continuous infusion for 4 days; thiotepa 150 mg/m 2 /day intravenously as a continuous infusion for 4 days; hydroxyurea 1.5 g/m 2 orally q 6 hours for 12 doses; and stem cell infusion 72 hours after the last doses of thiotepa and cyclophosphamide.
Gluck et al. 299 Sudbury patients were treated on one of the two high-dose chemotherapy regimens. Regimen 1: cyclophosphamide 3 g/m 2 /day intravenously for 2 days; mitoxantrone 23 mg/m 2 /day intravenously for 3 days; vinblastine 12 mg/m 2 intravenously as continuous infusion over 5 days. Regimen 2: cyclophosphamide 3 g/m 2 /day intravenously for 2 days; mitoxantrone 23 mg/m 2 /day intravenously for 3 days; carboplatin 800 mg/m 2 intravenously for 1 day; and stem cell infusion 48-72 hours postchemotherapy. RESULTS Patients The datasets consisted of patients treated between 1 January 1991 and 31 December 1995. The UNMC high-dose chemotherapy dataset contained 77 eligible évaluable UNMC patients. The NEORCC high-dose dataset consisted of 77 eligible patients, for a total of 154 patients. The ORCC standard-dose chemotherapy database consisted of 154 patients. Overall survival outcomes The median survival of all patients after the development of overt recurrent/metastatic disease was 27.4 months (95% CI 25.6-33.1). When grouped by treatment, the median survival of patients treated with standard chemotherapy was 25.6 months (95% CI 23.1-33.2), and for patients treated with high-dose chemotherapy, 28.1 months (95% CI 26.4-36.1). This difference was not statistically significant by univariate testing (unadjusted P=0.39 by log-rank, P=0.43 by Tarone-Ware). Using the Cox proportional hazards model with stepwise regression analysis to adjust for the effects of multiple potential confounding variables, a highly significant treatment effect was found in favor of high-dose therapy (/ > =0.0076, hazard ratio 0.62, 95% CI 0.27-0.97). Failure-free survival; all patients The median duration of failure-free survival for all patients after chemotherapy was 12.4 months (95% CI 11.2-14.3). Using the Cox proportional hazards model and stepwise regression analysis to adjust for the effects of multiple potential confounding variables (excluding type of treatment), factors that had an independent effect on failure-free survival were determined. When grouped by type of treatment, the median failure-free survival of patients treated with standard chemotherapy was 9.8 months (95% CI 8.8-11.4), and for patients treated with
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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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Page 283 and 284: Kvalheim et al. 249 Table 1. Immuno
Page 285 and 286: Kvalheim et al. 251 Figure 1. Sixty
Page 287 and 288: Kvalheim et al. 253 DISCUSSION In t
Page 289 and 290: Kvalheim et al. 255 Bastert G: Micr
Page 291 and 292: Hood et al. 257 In an effort to inc
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Page 295 and 296: Hood et al. 261 Table 3. Frequency
Page 297 and 298: Hood et al. 263 REFERENCES 1. Rill
Page 299 and 300: The Clinical Significance of Breast
Page 301 and 302: Moss et al. tests, and bilateral po
Page 303 and 304: Moss et al. 269 0 15 70 143 200 400
Page 305 and 306: Moss et al. 271 0 3 6 12 18 24 30 3
Page 307 and 308: Moss et al. 273 8. Passos-Coelho J,
Page 309 and 310: Autotransplantation for Men With Br
Page 311 and 312: McCarthy et al. 277 radiation, two
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Page 315 and 316: Viens et al. 281 3 g/m 2 and doxoru
Page 317 and 318: Table 1. Tumor characteristics Exte
Page 319 and 320: Table 4. Response Viens et al. 285
Page 321 and 322: Viens et al. 287 Table 5. Pathologi
Page 323 and 324: Viens et al. 289 apy for inoperable
Page 325 and 326: Gliick et al. 291 INTRODUCTION The
Page 327 and 328: Gluck et al. 293 RESULTS Patient de
Page 329 and 330: Glück et al. 295 Table 3. Response
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Page 335 and 336: Gluck et al. 301 anthracycline or t
Page 337 and 338: Repetitive High-Dose Therapy With P
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Page 355 and 356: Prince et al. 321 Figure 5, continu
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Page 359 and 360: Prince et al. 325 excessive to be u
Page 361 and 362: Prince et al. 327 eight patients ha
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Page 365 and 366: Prince et al. intensive chemotherap
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Page 371 and 372: oba Q. 1.0 0.9 Dicke et al. Stage I
Page 373 and 374: Vahdat with peripheral blood progen
Page 375 and 376: Evaluation of Prognostic Factors fo
Page 377 and 378: Fields et al. 343 PATIENTS AND METH
Page 379 and 380: Table 1. Chemotherapy regimens. Fie
Page 381 and 382: Fields et al. Stage II; 4-9 Pos LN
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U U Fields et al.
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Fields et al. 351 between 1 and 2 y
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European Trends and the EBMT Databa
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25% % 22% / 17% \ Rosti et al. 355
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Rosti et al. 357 The new Italian St
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Rosti et al. 6. Haas R, Schmid H, H
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Bewick et al. 363 INTRODUCTION The
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Bewick et al. 365 Blood samples obt
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Bewick et al. 367 HDCT with ABSC su
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Bewick et al. Progression Free Surv
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Bewick et al. pression in MBC, i.e.
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Bewick et al. 14. Kandl HL, Seymour
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CHAPTER 7 OTHER SOLID TUMORS
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378 Chapter 7: Solid Tumors INTRODU
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380 Chapter 7: Solid Tumors Prepara
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382 Chapter 7: Solid Tumors Surviva
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384 Chapter 7: Solid Tumors months
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386 Chapter 7: Solid Tumors have be
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High-Dose Chemotherapy in the Manag
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390 Chapter 7: Solid Tumors followe
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392 Chapter 7: Solid Tumors Table 1
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394 Chapter 7: Solid Tumors (mucosi
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Three-Fold Intensification by Seque
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High-Dose Therapy for Small Cell Lu
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404 Chapter 7: Solid Tumors chemoth
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406 Chapter 7: Solid Tumors SCLC ha
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408 Chapter 7: Solid Tumors relapse
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410 Chapter 7: Solid Tumors 69:585-
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412 Chapter 7: Solid Tumors ogous b
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414 Chapter 7: Solid Tumors 64. Bru
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416 Chapter 7: Solid Tumors Prignot
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418 Chapter 7: Solid Tumors CO > CO
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420 Chapter 7: Solid Tumors TANDEM
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Multiple Courses of Cyclophosphamid
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424 Chapter 7: Solid Tumors and the
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426 Chapter 7: Solid Tumors Thiotep
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430 Chapter 7: Solid Tumors E 100 0
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432 Chapter 7: Solid Tumors course
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434 Chapter 7: Solid Tumors boplati
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436 Chapter 7: Solid Tumors INTRODU
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438 - Chapter 7: Solid Tumors Table
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440 Chapter 7: Solid Tumors seeded
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442 Chapter 7: Solid Tumors DISCUSS
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444 Chapter 7: Solid Tumors 10. Di
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446 Chapter 7: Solid Tumors plasma
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Autologous Stem Cell Transplantatio
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Keystone 451 hypertension, anemia,
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Fassas et al. 453 INTRODUCTION Mult
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Fassas et al. Table 2. Stem cell mo
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Table 3. Toxicity after stem cell i
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Fassas et al. Table 5. Trial 1: cha
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Fassas et al. MS PROGRESSION FREE S
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Fassas et al. ic or autologous bone
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1 2 1 6 EAE. Burt et al. 465 Becaus
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Burt et al. Since cyclophosphamide
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Burt et al. 469 toxicity study, we
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Burt et dl. All 23. Mor F, Cohen IR
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Hasler, Gratwohl, and Tyndall an ev
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Hasler, Gratwohl, and Tyndall 475 B
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Kuis, Wulffraat, and Sanders 477 st
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Kuis, Wulffraat, and Sanders neousl
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CHAPTER 9 LONG-TERM EFFECTS
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484 Chapter 9: Long-Term Effects po
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486 Chapter 9: Long-Term Effects Ta
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488 Chapter 9: Long-Term Effects ml
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490 Chapter 9: Long-Term Effects 4.
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492 Chapter 9: Long-Term Effects us
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494 Chapter 9: Long-Term Effects AB
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498 Chapter 9: Long-Term Effects En
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500 Chapter 9: Long-Term Effects Rl
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502 Chapter 9: Long-Term Effects RE
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504 Chapter 9: Long-Term Effects A,
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Long-Term Follow-Up of Autologous T
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CHAPTER 10 GRAFT MANIPULATION
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514 Chapter 10: Graft Manipulation
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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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