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470 Treatment Strategies in Breast Cancer Q I I I I I I I I I I I I I 200 400 600 800 1000 1200 Days Figure 1. Time to treatment failure for patients receiving high-dose combination alkylating agents as initial chemotherapy for metastases or after previous treatment with standard chemotherapy. Days 1200 Figure 2. Duration of survival from time of transplantation of all patients receiving highdose combination alkylating agents as initial chemotherapy for metastatic disease or after previous treatment with standard chemotherapy.
Treatment Strategies in Breast Cancer 471 patients and survival for all treated patients. The median time to treatment failure for patients who had received previous chemotherapy was shorter than for patients who had received no chemotherapy (88 versus 225 days; P, .014). Similarly, the median survival for all treated patients was longer for those who had received no previous chemotherapy compared with previously treated patients (390 versus 102 days; P, .004). The toxicity associated with high-dose combination alkylating-agent therapy is substantial. Among the 33 treated patients, seven therapy-related deaths occurred—an overall treatment-related mortality rate of 2156. Toxicity seems to be increased by a patient's reduced performance status before therapy, extensive previous therapy, especially with doxorubicin and radiation, and the presence of bulk disease at the start of therapy. Late opportunistic infections occurred in seven patients, perhaps related to inversion of the T-cell subsets that have persisted beyond 1 year from therapy (18) (unpublished data). DISCUSSION Intensive chemotherapy with ABMS is capable of producing a high objective response rate in patients with metastatic breast cancer. Although the regimen may produce regression of disease in patients who have received previous chemotherapy, the duration of their response is short and therapyrelated complications are frequent. When used as initial treatment for metastatic disease, frequent, rapid, and complete responses occur. Relapse remains common, however, the median response duration being 7.5 months. Relapse occurs most often (according to data not presented here) at pretreatment sites of bulk disease, suggesting that additional surgery or radiation therapy may prove of benefit. The difference in time to treatment failure (Fig 1) between patients having received previous chemotherapy or not for metastatic disease most likely represents differences in the intrinsic resistance of extensively treated disease. The different treatment programs (cyclophosphamide, cisplatin, and carmustine compared with cyclophosphamide, cisplatin, and melphalan or thio-TEPA) may, however, be less effective. The major limitation of the therapeutic approach described here seems to be the timing of treatment. Treatment of patients with resistant, relapsed acute leukemia or lymphoma with intensive chemoradiation therapy and marrow transplantation produced few long-term survivors and a high toxicity rate. When this therapy was applied during remission, however, especially first remission, more patients were cured and the toxicity became less pronounced. The breast cancer patients described here represent patients in first relapse and resistant relapse. To be more effective, this therapy needs to be attempted at earlier or at least during more favorable disease states. Table 4 lists the extent of breast
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Autologous Bone Marrow Transplantat
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To our colleagues, Drs. R. Lee Clar
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via ABMT Autologous Bone Marrow Tra
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X ABMT Pharmacological Manipulation
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XII ABMT C. INTERNATIONAL RANDOMIZE
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xiu ABMT Session IV - Breast Cancer
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xui ABMT Panel Discussion: Session
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xuiii ABMT Effect of Interleukin 2
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Acknowledgments The publication of
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AML in First Remission 5 performed
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AML in First Remission 7 than 50% o
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10 BAVC + ABMT in Patients With AML
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BAVC + ABMT in Patients With AML in
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14 BAVC + ABMTin Patients With AML
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16 Purged ABMT in CR of Acute Leuke
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24 First-Remission Autograft forAML
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Transplantation in CRI AML 33 DISCU
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36 ABMT in ALL compared the results
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38 ABMT in ALL were administered un
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40 ABMT in ALL CR1 patients receive
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42 ABMT in ALL 19. Rizzoli V, Mango
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44 ABMTin CRI program in CR1 is the
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46 ABMTin CRI RESULTS The AML inves
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Leukemia: First Remission K A. Dick
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Panel Discussion: Session IA 51 DR.
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IB. Clinical Studies in Second- or
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56 ABMTIn CR2 RESULTS OF VARIOUS TR
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58 ABMTIn CR2 antibodies; for non-T
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60 ABMT in Acute Nonlymphocytic Leu
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70 ABMT in AML With Monoclonal Anti
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80 Mafosfamide Purging in Leukemia
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ABMT in CR2 Pediatric ALL 91 follow
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Ex Vivo Use of Monoclonal Antibodie
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Ex Vivo Marrow Purging 95 Table 1.
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De Viuo Marrow Purging 97 WBC-f- AN
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Conditioning Regimens Before Bone M
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Conditioning Regimens in AML 101 Le
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Conditioning Regimens in AML 103 co
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106 Double (Jnpurged ABMT in Leukem
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108 Double Unpurged ABMT in Leukemi
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770 Double (Jnpurged ABMT in Leukem
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7/2 Double Autografting in Acute Le
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114 Double Autografting in Acute Le
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120 Recovery After 4-Hydroperoxycyc
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122 Recovery After 4-Hydroperoxycyc
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Panel Discussion: Session IB 127 di
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Panel Discussion: Session IB 129 tu
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Magnetic Affinity Colloid Eliminati
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Magnetic Separation of Marrow Cells
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*r r- r» u. >>• O S ^ CO ai a> C
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4-Hydroperoxycyclophosphamide and V
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Chemopurging 145 incubation, the ce
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Chemopurging 147 To date, four pati
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Chemopurging 149 4-HC + VCR IC75 AM
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Decontaminating Bone Marrow With Me
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Merocyanine 540 Marrow Decontaminat
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Merocyanine 540 Marrow Decontaminat
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CALLA-Negative Clonogenic Cultures
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CALLA-Negatiœ Clonogenic BCell ALL
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CALLA-Negative Clonogenic BCell ALL
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164 Acetaldophosphamide Ex Vivo Che
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766 Acetaldophosphamide Ex Vivo Che
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168 Acetaldophosphamide Ex Viuo Che
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Detecting Residual Disease in Bone
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178 Pharmacological Manipulation an
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ID. Chronic Myelogenous Leukemia
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190 CML Chronic Phase Autografting
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196 CML Blast Crisis Autografting e
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Autologous Transplantation of Phila
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Autografting in Chronic Granulocyti
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Autografting in Chronic Granulocyti
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206 Panel Discussion: Session ID DR
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Natural History of Relapsed Hodgkin
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ABMT in Hodgkin's Disease 211 50%.
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ABMTin Hodgkin, 's Disease 213 (62%
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ABMT in Hodgkin's Disease 215 LLLLL
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Updated Results of CBV and Autologo
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CBV and ABMT in Hodgkin's Disease 2
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CBV and ABMT in Hodgkin 's Disease
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224 Chemotherapy and ABMT in Hodgki
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226 Chemotherapy and ABMTin Hodgkin
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232 ABMT for Advanced Hodgkin's Dis
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234 ABMTfor Advanced Hodgkin's Dise
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Hodgkin's Disease J. O. Armitage an
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Panel Discussion: Session IIA 239 D
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IIB. Non-Hodgkin's Lymphoma
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244 Salvage Chemotherapy for Lympho
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246 Salvage Chemotherapy for Lympho
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ABMT in Burkitt's Lymphoma 251 Tabl
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ABMT in Burkitt's Lymphoma 253 medi
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ABMT in Burkitt's Lymphoma 255 Heal
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ABMT in Burkitt's Lymphoma 257 •
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ABMT in Burkitt's Lymphoma 259 init
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ABMT in Burkitt's Lymphoma 261 11.
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264 Myeloma Biology and Therapy hig
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266 Myeloma Biology and Therapy mon
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265 Myeloma Biology and Therapy 5.
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270 BMT in Relapsed Diffuse Large C
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276 Transplantation for Malignant L
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Optimum Timing of Autologous Bone M
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ABMT Timing in Lymphoma 281 PATIENT
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3 o + + + + o LO T— T— LO co Tf
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ABMT Timing in Lymphoma 285 RESULTS
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co co I I I I I I I I I I 2 2 2 CD
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ABMT Timing in Lymphoma 289 Median
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ABMT Timing in Lymphoma 291 in a mi
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ABMT Timing in Lymphoma 293 Develop
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ABMT Timing in Lymphoma 295 53. Sto
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298 Treatment Strategies for NHL PA
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300 Treatment Strategies for NHL 10
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302 Treatment Strategies for NHL 2)
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304 Treatment Strategies for NHL al
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306 Treatment Strategies for NHL 31
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308 Panel Discussion: Session IIB m
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IIC. International Randomized Study
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314 Proposed International Adult Ly
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International Randomized Trial in N
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International NHL Trial 337 dispari
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International NHL Trial 339 cannot
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International NHL Trial 341 ORGANIZ
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Lymphoma T. Philip and G. Spitzer,
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IID. Purging and Detection
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348 Chemoimmunoseparation of T Lymp
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350 Chemoimmunoseparation of T Lymp
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352 Burkitt's Lymphoma Purging Assa
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354 Burkitts Lymphoma Purging Assay
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356 Burkitt's Lymphoma Purging Assa
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358 Burkitts Lymphoma Purging Assay
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360 Purging Methods in Burkitt's Ly
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366 Leukemia Cell Sensitivity to Im
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368 Leukemia Cell Sensitivity to Im
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370 Leukemia Cell Sensitiuity to Im
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372 Panel Discussion: Session IID D
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ABMTfor Neuroblastoma 377 sedimenta
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ABMT for Neuroblastoma 379 EX VIVO
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ABMTfor Neuroblastoma 381 PATIENTS
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Repeated High-Dose Chemotherapy Fol
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ABMT in Metastatic Neuroblastoma 38
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ABMT in Metastatic neuroblastoma 39
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394 Clnpurged ABMTfor Neuroblastoma
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396 Unpurged ABMTfor Neuroblastoma
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398 Unpurged ABMTfor Neuroblastoma
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ENSG 1—Randomized Study of High-D
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High-Dose Melphalan in Neuroblastom
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High-Dose Melphalan in Neuroblastom
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408 ABMTin 65 Patients With Neurobl
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410 ABMT in 65 Patients With. Neuro
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416 ABMTin 65 Patients With neurobl
Page 443 and 444: A Single Institution's Experience o
Page 445 and 446: ABMT in Neuroblastoma 421 procedure
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Page 461 and 462: Digital Image Analysis System 437 c
Page 463 and 464: Digital Image Analysis System 439 C
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Page 468 and 469: 444 Immune-magnetic Purging ofBurki
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Page 479 and 480: High-Dose Chemotherapy Intensificat
Page 481 and 482: High-Dose Chemotherapy and ABMT in
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Page 490 and 491: 466 Treatment Strategies in Breast
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Page 513 and 514: Autologous Bone Marrow Transplantat
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Page 517 and 518: ABMT for Breast Cancer 493 Table 3.
Page 519: ABMTfor Breast Cancer 495 4. Eder J
Page 522 and 523: 498 Occult Breast Cancer Cells in M
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Page 530 and 531: 506 Panel Discussion: Session IV a
Page 533 and 534: Detection of Bone Marrow Metastases
Page 535 and 536: Tumor Cell Detection 511 Two separa
Page 537: Tumor Cell Detection 513 immunofluo
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520 Etoposide and Cisplatin for Lun
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Lung Cancer G. Spitzer and H. Lazar
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Panel Discussion: Session V 525 com
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Panel Discussion: Session V 527 col
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Treatment of Advanced Melanoma With
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ABMT in Melanoma 533 Table 1. Three
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ABMT in Melanoma 535 mg/m 2 ). The
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Melanoma/ Sarcoma/ Carcinoma R. Ben
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Panel Discussion: Session VI 539 re
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VII. Brain Cancer
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544 Carmustine and ABMT for Maligna
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546 Carmustine and ABMTfor Malignan
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Pilot Study of High-Dose Carmustine
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High-Dose Carmustine and Transplant
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High-Dose Chemotherapy With Autolog
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High-Dose Therapy of CNS Gliomas Ta
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High-Dose Therapy of CHS Gliomas 56
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High-Dose Therapy of CHS Gliomas 56
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566 Panel Discussion: Session VII A
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VIII. New Regimens
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572 Clinical Intensification Regime
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574 Clinical Intensification Regime
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Clinical Intensification Regimens f
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Clinical Intensification Regimens f
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High-Dose Busulfan and Cyclophospha
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Busulfan + Cyclophosphamide in Chil
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The Intensive Use of Carmustine Wit
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Intensive Use ofCarmustine 591 6. P
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594 BEAM: Cytoreductive Regimen for
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596 BEAM: Cytoreductiue Regimen for
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602 Total Body Irradiation, Cytarab
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604 Total Body Irradiation, Cytarab
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606 Panel Discussion: Session VIII
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Herpesvirus Infections After Autolo
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Herpesvirus Infections 611 Table 2.
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Herpesvirus Infections 613 contrast
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616 Peripheral Stem Cell Transplant
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CO ^ CO COi-t'ycOi-T-CO O E « to T
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fc CD rr ^ O < c E + o — ce S O O
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o E ra o CD .Q Û ra co CL o E o 15
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634 Toxic Deaths in ABMT PATIENTS A
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636 Toxic Deaths in ABMT Table 2. D
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638 Toxic Deaths in ABMT defined an
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640 Infectious Complications ofABMT
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Infectious Complications of Autolog
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Infections in ABMT 649 Table 1. ABM
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Infections in ABMT 651 herpes simpl
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Newer Antibiotic Regimens in Cancer
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Antibiotics in Cancer Patients 655
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Antibiotics in Cancer Patients 657
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660 Amphotericin B for Neutropenic
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662 Amphotericin B for Neutropenie
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664 Amphotericin B for Neutropenie
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666 IVIg in ABMT in autologous tran
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668 IVlg in ABMT 25. Neiman PE, Ree
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670 Natural Killer Cells and Transp
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672 Natural Killer Cells and Transp
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Autologous Transplantation of Circu
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678 Transplantation of Circulating
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Restoration of Hematopoietic Functi
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Peripheral Stem Cell Transplants 68
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Peripheral Stem Cell Transplants 68
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688 Peripheral Blood Stem Cell Tran
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694 Bronchoscopy in Marrow Transpla
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696 Bronchoscopy in Marrow Transpla
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698 T Lymphocyte CFU After ABMT cer
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700 T Lymphocyte CFCI After ABMT RE
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702 T Lymphocyte CFU After ABMT CMV
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Supportive Therapy H. Vriesendorp a
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X. Molecular Biology
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770 Human ADA in Monkeys years in a
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7/2 Human ADA in Monkeys supernatan
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714 Human ADA in Monkeys Number of
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776 Human ADA in Monkeys primate ma
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718 Electric Field-Mediated DMA Tra
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720 Electric Field-Mediated DNA Tra
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Aberrant Gene Expression in Acute M
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+ z + + + les •ras a z E i ü (0
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Aberrant Gene Expression in AML 727
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Aberrant Gene Expression in AML 729
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732 Clonal Detection of Remission p
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734 Clonal Detection of Remission K
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736 Clonal Detection of Remission 3
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Summary D. W. van Bekkum Attempts t
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Summary 741 T cell-depleted bone ma
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Summary 743 hybridization technique
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Summary 745 GENETIC THERAPY The las
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748 Concluding Remarks time of the
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750 Contributors and Participants F
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754 Contributors and Participants P
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756 Contributors and Participants A
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758 Contributors and Participants P
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762 Contributors and Participants H
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764 Contributors and Participants A
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766 Contributors and Participants G
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770 Contributors and Participants S
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772 Contributors and Participants C
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776 Contributors and Participants D
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