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734 Clonal Detection of Remission Kilobases // I I I I I I I I I 1 1 //—I D0 1 2 3 4 5 6 7 8 9 10 22 i â? H I (BamHI),——, (BamHI) Hpall sites Tis^i 67 8 9 ^ Probes,', Figure 2. 5'-half of the HPRT gene, this time showing Hpall cleavage sites. the active fragment no longer has homology to the probe and thus is no longer seen. Therefore, the use of two enzymes and two probes enables one to establish clonality in all polymorphic women. The following case illustrates the advantage of this methodology. A 21-year-old white woman presented to our institution in first hematologic remission of acute monocytic leukemia. Cytogenetic analysis revealed a normal female karyotype. Three months later, leukemic relapse occurred with 90% blasts in marrow and blood, and the patient underwent further chemotherapy. Allogeneic bone marrow transplantation from an HLAidentical brother was subsequently performed in second remission; engraftment was noted, and the donor male karyotype (46XY) was documented in 14 metaphases on day 19 posttransplant. <strong>Bone</strong> marrow aspirate on day 71 revealed leukemic relapse with 96% blast cells. Cytogenetics revealed a female karyotype with multiple abnormalities. The patient died on day 91 with resistant leukemia. DNA from the patient was analyzed during two relapse phases, one preceding bone marrow transplantation and one 71 days after transplantation. As shown in Figure 3, in each case digestion of the two BamHI alleles with either Hpall or Hhal produced little or no shift in fragment mobilities when probe 1 was used. The failure to detect hybridization in the 22-kb region with probe II in the BamHI, Hpall digests indicates that all active alleles were associated with the 22-kb fragment. The conclusion of leukemic monoclonality is thus supported by results with this probe. We are currently involved in examining two major groups of patients for clonality during remission. The first group comprises patients with acute myeloid leukemia in remission. We are monitoring 94 patients in complete remission at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston and are currently analyzing their granulocyte DNA for clonality. In the second group are patients with chronic myeloid leukemia, chronic phase, who are receiving interferon therapy. Many of these patients
Clonal Detection of Remission 3 735 0.65 - Probe I Probe II Figure 3. Two analyses of the DNA of a patient with acute monocytic leukemia. Changes evident in probe II prove monoclonality. are achieving hematologic remission and cytogenetic improvement (12). Our methodology permits us to evaluate the clonality of their granulocytes, which may increase our understanding of a Philadelphia chromosomenegative hematologic remission. REFERENCES 1. Keating MJ, McCredie KB, Freireich EJ. In Minimal Residual Disease in Acute Leukemia 1986, HagenbeekA, Lowenberg B, eds. Martinus Nijhoff, Boston, 1986:148. 2. Fearon ER, Burke PJ, Schiffer CA, Zehnbaver BA, Vogelstein B. N Engl J Med 1986;315:15.
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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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466 Treatment Strategies in Breast
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10 CO 0) I- m c o a. a. 3 W ? o k_
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476 Phase I and II Studies of Alkyl
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482 High-Dose Therapy and ABMT in B
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484 High-Dose Therapy and ABMT in B
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486 Immunodetection of Breast Carci
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ABMTfor Breast Cancer 491 only adju
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ABMT for Breast Cancer 493 Table 3.
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ABMTfor Breast Cancer 495 4. Eder J
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498 Occult Breast Cancer Cells in M
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504 Panel Discussion: Session IV DR
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506 Panel Discussion: Session IV a
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Detection of Bone Marrow Metastases
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Tumor Cell Detection 511 Two separa
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Tumor Cell Detection 513 immunofluo
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516 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
Page 707 and 708: Peripheral Stem Cell Transplants 68
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Page 712 and 713: 688 Peripheral Blood Stem Cell Tran
Page 718 and 719: 694 Bronchoscopy in Marrow Transpla
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Page 722 and 723: 698 T Lymphocyte CFU After ABMT cer
Page 724 and 725: 700 T Lymphocyte CFCI After ABMT RE
Page 726 and 727: 702 T Lymphocyte CFU After ABMT CMV
Page 729 and 730: Supportive Therapy H. Vriesendorp a
Page 731: X. Molecular Biology
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Page 742 and 743: 718 Electric Field-Mediated DMA Tra
Page 744 and 745: 720 Electric Field-Mediated DNA Tra
Page 747 and 748: Aberrant Gene Expression in Acute M
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Page 751 and 752: Aberrant Gene Expression in AML 727
Page 753: Aberrant Gene Expression in AML 729
Page 756 and 757: 732 Clonal Detection of Remission p
Page 760 and 761: 736 Clonal Detection of Remission 3
Page 763 and 764: Summary D. W. van Bekkum Attempts t
Page 765 and 766: Summary 741 T cell-depleted bone ma
Page 767 and 768: Summary 743 hybridization technique
Page 769: Summary 745 GENETIC THERAPY The las
Page 772 and 773: 748 Concluding Remarks time of the
Page 774 and 775: 750 Contributors and Participants F
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Page 780 and 781: 756 Contributors and Participants A
Page 782 and 783: 758 Contributors and Participants P
Page 786 and 787: 762 Contributors and Participants H
Page 788 and 789: 764 Contributors and Participants A
Page 790 and 791: 766 Contributors and Participants G
Page 794 and 795: 770 Contributors and Participants S
Page 796 and 797: 772 Contributors and Participants C
Page 800: 776 Contributors and Participants D
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