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512 Tumor Cell Detection Table 3. Incidence of Tumor Cells Detected in the Marrow by Immunofluorescence as a Function of Disease Extension Tumor Cells in the Marrow Detected by Immunofluorescence Clinical Stage Present Absent Total Limited disease 7 (29%) 17 24 Extensive disease 9 (60%) 6 15 Total 16 (41%) 23 39 or LCA3 were found in 7 out of 24 patients with limited disease and in 9 out of 15 patients with extensive disease. A remarkable heterogeneity in the tumor recognition was noted. Anti- LCA1 recognized tumor cells in 11 (68%) of 16 of the 16 marrows studied, and anti-LCA2 and LCA3 each recognized 7 (43%) out of the 16. DISCUSSION The goal of the present study was to investigate the human tumor stem cell assay and indirect immunofluorescence with anti-LCAl, LCA2, and LCA3 in the detection of SCLC metastases in the bone marrow. In this study, we have not found a good correlation between morphological evidence of marrow involvement by SCLC and growth of tumor colonies in soft agar; the sensitivity ([true positives]/[true positives plus false negatives]) being 0.2. Nevertheless, there were seven samples of histologically negative marrow in which the tumor stem cell assay grew colonies. Even if this system has a low sensitivity, probably because of the low plating efficiency of the tumor cells, it has the advantage of documenting the presence of viable clonogenic cells in the bone marrow. All patients with morphological evidence of marrow involvement had SCLC cells identified by anti-LCAl, LCA2, or LCA3 antibodies, the sensitivity of the indirect immunofluorescence being 1. Anti-LCAl, LCA2, and LCA3 were unreactive with 15 normal bone marrow samples but did react with 11 bone marrow samples negative by conventional morphological methods. The antigenic heterogeneity found on the cell surface using anti-LCAl, LCA2, and LCA3 highlights the advantage in using a panel of MAbs with different specificities. Bone marrow involvement was found in 24% of 24 patients who had otherwise limited disease. A positive pretreatment bone marrow is an unfavorable prognostic indicator both for survival and for duration of remission (1). The prognostic significance of bone marrow micrometastases detected by indirect immunofluorescence in patients with limited disease and morphologically negative bone marrow is not yet known. A prospective trial might address this question. This experiment using human tumor stem cell assay and indirect
Tumor Cell Detection 513 immunofluorescence indicates that detection of SCLC metastases unperceived by conventional methods can be achieved. In future studies, these methodologies will be applied to monitor autologous bone marrow grafts and efficacy of purging procedures. REFERENCES 1. Hirsch FR, Hansen HH. Cancer 1980:46:204. 2. Anner RM, Drewinko B. Cancer 1977;39:1337. 3. Bagley CM, Rath GJ. Proc Am Assoc Cancer Res 1976;17:198. 4. Choi CH, Carey RW. Cancer 1976:37:2651. 5. Hirsch F, Hansen HH, Dombernowsky P, Mainau B. Cancer 1977;39:2563. 6. Holoye PY, Samuels ML, Lanzotti VJ, Smith T, Barkley HT, Jr. JAMA 1977:237:1221. 7. Ihde DC, Simms EB, Mathews MJ, Cohen MH, Bunn PA, Minna JD. Blood 1979;53:677. 8. Hamburger A, Salmon SE. Science 1977;197:461. 9. Pollard EB, Tia F, Myers JW, Clark G, Coltman CA, van Hoff DD. Cancer Res 1981 ;41:1015. 10. Humblet Y, Canon JL, Sekhavot M, Seyens AM, Manouvriez P, Lebacq-Verheyden AM, Bazin H, Prignot J, Symann M. Pathol Biol (in press). 11. Humblet Y, Sekhavot M, Seyens AM, Symann M. Lung Cancer (in press).
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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
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A Single Institution's Experience o
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ABMT in Neuroblastoma 421 procedure
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ABMT in Neuroblastoma 423 therapies
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426 Purged Marrow Engraftment in Ne
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Digital Image Analysis System for D
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Digital Image Analysis System 435 d
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Digital Image Analysis System 437 c
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Digital Image Analysis System 439 C
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Digital Image Analysis System 441 1
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444 Immune-magnetic Purging ofBurki
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450 Panel Discussion: Session III W
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452 Panel Discussion: Session III e
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High-Dose Chemotherapy Intensificat
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High-Dose Chemotherapy and ABMT in
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High-Dose Chemotherapy and ABMT in
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Page 533 and 534: Detection of Bone Marrow Metastases
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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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