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426 Chapter 7: Solid Tumors Thiotepa, TEPA, and 2-dechloroethyl cyclophosphamide assays ThioTEPA, TEPA, cyclophosphamide and 2-dechloroethyl cyclophosphamide levels in plasma were determined using capillary gas chromatography with nitrogen/phosphorous selective detection after liquid-liquid extraction of the samples with chloroform. 12 RESULTS Feasibility of scheduled treatment A total of 41 patients were entered on the protocol. Pertinent patient characteristics are given in Table 1. Not all patients proceeded to high-dose therapy: seven patients had progressive disease or no sign of response at all to FE 12QC and were taken off protocol since high-dose therapy was not considered to be in their best Table 1. Characteristics of the 41 patients on study Age (years) 44 (27-55) Hormone responsiveness ER negative ER +, failed FLHT1 ER +, failed SLHT2 ER unknown, failed FLHT Number of sites of disease 1 site 2 sites 3 sites 4 or more sites Sites of disease Lymph nodes Bone Liver Lung Prior therapy Radiation therapy 28 7 5 11 20 6 4 23 18 11 11 Adjuvant 20 For advanced disease Chemotherapy Adjuvant 8 For advanced disease FLHT, first-line hormonal therapy; SLHT, second-line hormonal therapy. 2 13
Rodenhuis et al. All interest. One patient did respond to FE 120C, but had estrogen receptor-positive lobular carcinoma. The authors believed that high-dose therapy was not the best treatment option, and she was taken off protocol as a protocol violation. The treatment of one further patient was too early for evaluation and will be reported in a later publication. A total of 80 tCTC courses were administered. Thirty-two patients received a first tCTC course, 28 patients a second, and 20 patients completed the full planned sequence of three tCTC courses. Two patients are still undergoing treatment after tCTC-1 and will be reported elsewhere. The other two patients were taken off protocol after tCTC-1 either because of lack of response (one patient) or because of prolonged abnormalities of liver function tests (one patient). Six of eight patients who did not proceed to a third course of tCTC after tCTC-2 stopped treatment because of excessive toxicity (one unexplained death, three hemorrhagic cystitis, one veno-occlusive disease, one refractory thrombocytopenia). A seventh patient showed no further disease regression after the second tCTC course and was advised to discontinue protocol treatment. The eighth patient was still on protocol at the time of this writing. The protocol required that second and third courses of tCTC be started on day 22-29 after the previous PBPC transplantation; the earliest time point of 22 days was preferred. Following this policy, the median day after PBPC reinfusion on which tCTC-2 was begun was 28 (range 21-53). This was day 35 (range 20-42) for the third tCTC course. In addition, dose adaptations were required in three of the third courses. Major toxicity The tCTC regimen was well tolerated by most patients, and the large majority were able to leave the hospital on the first day after PBPC transplantation. Details of the outpatient management of these transplantation patients will be published elsewhere (A.M.W., et al., manuscript submitted); this section will focus on major toxicities, such as grade IV gastrointestinal (GI) toxicity, organ toxicity (liver, kidney, lung, heart, or lung), hemorrhagic cystitis, and other complications that are important for the feasibility and acceptability of the triple tCTC regimen. One patient died on the day 18 after reinfusion while apparently recovering from her second tCTC course. Her death was sudden and in her sleep, at a time when the neutrophil count had returned to normal but platelet transfusion dependence had not yet resolved. Unfortunately, no autopsy permission could be obtained and the cause of death remains unclear. The major (organ) toxicity of tCTC is presented in Table 2. Although none of this toxicity was life-threatening, it is clear that major organ toxicity such as hemorrhagic cystitis and veno-occlusive disease of the liver do occur with some
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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
Page 409: CHAPTER 7 OTHER SOLID TUMORS
Page 412 and 413: 378 Chapter 7: Solid Tumors INTRODU
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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
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Page 446 and 447: 412 Chapter 7: Solid Tumors ogous b
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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
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Page 464 and 465: 430 Chapter 7: Solid Tumors E 100 0
Page 466 and 467: 432 Chapter 7: Solid Tumors course
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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
Page 509 and 510: 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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