VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

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glycoprotein half-life, etc) of the CD34 polypeptide may be important modulators of this structure's functional capabilities. TRANSPLANTATION. Several studies of autologous BM transplantation using autografts purged of malignant cells are suggestive of clinical benefit. Such trials have employed 'purging' to eliminate neoplastic cells from the autografts of patients with hematologic malignancies. As indicated earlier, 'positive selection' of hematopoietic stem/progenitor cells represents an alternative strategy for 'processing' BM cells prior to transplantation. We have recently described a simple, rapid and flexible method to isolate primitive hematopoietic progenitor cells from normal BM. The CD34+ cells were selected using the high-affinity, 'class II' antibody QBEND10 (see epitope mapping studies), and immunomagnetic beads. Prior depletion of naturally adherent cells was not required. After magnetic selection of CD34+ cells/magnetic beads, the cells were detached from the beads by incubation with the Pasteurella haemolytica glycoprotease which selectively cleaves glycoproteins rich in O-linked glycans, like CD34 (5) . The purity of the released cells was assessed by immuno-fluorescence using either of the class III CD34 antibodies, TUK3 or 115.2, whose epitopes are not removed by the glycoprotease. The purity (up to 95%) and yield (up to 80%) of the enzyme-released cells was high. The purified cells, which generated normal numbers of hematopoietic colonies in semi-solid media, were enriched 81-fold for multi-lineage progenitors and reconstituted hematopoiesis in long-term culture, indicating that the functional competence of CD34+ progenitor cells in vitro, was unaffected by glycoprotease treatment
sequence analysis of the human haemopoietic progenitor cell antigen CD34. Leukemia 2:793803,1988. Simmons DL, Satterthwaite AB, Teñen DG et al: Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic stem cells. J Immunol 148: 267-271,1992. Marsh JCW, Sutherland DR, Davidson Jet al: Retention of progenitor cell function in CD34+ cells purified using a novel O-sialo-glycoprotease. Leukemia, 926-9334,1992. Verfaille CM, Miller WJ, Boylan K, et al: Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression. Blood 79:1003-1010,1992 Mr= 110 kD Mr(-SA) = 150 kD Mr (-CHO) = 40 kD N - LINKED CHO O-LINKED CHO CD34 ANTIGEN ,NH, >— WW WW Am Am COOH 36% Ser/Thr (300 A) extended? globular? ACTIVATED PROTEIN KINASE C + OTHER KINASES? Schematic representation of the structural characteristics of the human CD34 antigen. The number and approximate location of the cysteine residues and N-linked glycosylation sites are based upon the full-length cDNA clones (7). Though the presence of multiple, negatively charged (heavily sialylated), Olinked glycans is well documented (6), the precise number, location (-) and complexity of them is not known. The precise locations of the serine residues phosphorylated by activated protein kinases C or other kinases (refs in 2) are not currently known. The estimate of the length of the extended NH2-terminal domain of about 300 Angstroms is based upon observations of the extended extracellular domain of the similarly heavily O-glycosylated CD43 molecule (see 2). SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 133
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Autologous Bone Marrow Transplantat
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CONTENTS nviAum TMLHTA'I OTT! 7 A l
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AUTOLOGOUS BONE MARROW TRANSPLANTAT
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TREATMENT OF NONSMALL CELL LUNG CAN
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SUMMARY OF THE NON HODGKIN LYMPHOMA
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Session I: Leukemia
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TRIAL PROGRESS The trial opened in
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Table 1. Achievement of Second Remi
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ALLOGENEIC VERSUS AUTOLOGOUS BONE M
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pts). The other 56 pts are too earl
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Figure 1 EORTC-GIMEMA AML 8 A EORTC
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PATIENTS AND METHODS Patients The B
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Thus, as the results of some ongoin
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COMPARISON OF INTENSIVE CONSOLIDATI
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over, 13 pts who had received ICC1
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Session II: Future Directions
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in a previous report 3 . Analysis a
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Engraftment of granulocyte, monocyt
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0.2 - 0.1 - ABMT with mAb purging f
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ENHANCED REGENERATION OF NATURAL KI
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RESULTS The in vivo immune effects
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16. Rizzoli V, Mangoni L, Carlo-Ste
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hydroperoxycyclophosphamide (4HC)-t
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survival in patients undergoing ABM
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IMMUNOTHERAPY OF AML AFTER ABMT - S
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Otherwise toxicity was mild to mode
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Therapy. Amsterdam Elsevier 1987;89
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200 IL6 in serum 44 SIXTH INTERNATI
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sodes), fewer days of i.v. antibiot
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Session III: Myeloma
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trary, in case of adequate collecti
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tion is considered, and all the mor
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Table 3: Cost effectiveness of high
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Session W: Lymphoma
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METHODS Selection of patients and t
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marrow treatment. Am J Med 85:829,1
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HIGH DOSE THERAPY WITH HEMATOPOIETI
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in TC 19 medium (Flobio), with an h
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progression for a long time after A
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Table 2. STATUS AT GRAFT Remission
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IL Figura 3 70 SIXTH INTERNATIONAL
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( 5 ) lowed by ABMT than refractory
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74 Figure 4 Low grade lymphoma - pr
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(range 15-55); 68 males and 32 fema
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our experience, this has a seven-ye
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30. Colombat P, Gorin NC, Lemonnier
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82 OVERALL SURUIWL from ABUT (accor
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PROGNOSTIC FACTORS IN ADVANCED STAG
Page 109 and 110: REFERENCES 1. Chopra R, Mc Millan A
Page 111 and 112: lished data to attempt to assess th
Page 113 and 114: 1992;10:175-7. 3. McMillan A, Golds
Page 115 and 116: B. DAILY DAY AGENT DOSE -7 -6 -5 -4
Page 117 and 118: cohort with HR treated with BEC-2 i
Page 119 and 120: p R 0 P O R T I 0 N 1 0.9 0.8 0.7 0
Page 121 and 122: TABLE 3. TOXICITY BEC TAVe TMJ as 2
Page 123 and 124: ies. 10 Longer blood half-lives hav
Page 125 and 126: agents have been developed cautious
Page 127 and 128: Table 1. Radioisotopes for RIT. Pur
Page 129 and 130: The treatment criterion in this stu
Page 131 and 132: more than 80% of the cases. Patient
Page 133 and 134: Disease Free Survival 800 Time •
Page 135: Session VI: Breast Cancer
Page 138 and 139: achieved a complete remission survi
Page 140 and 141: acil, vincristine, prednisone (CMFV
Page 142 and 143: t: 3 en a in S « J •S •> c ai
Page 144 and 145: LONG TERM FOLLOW UP OF POOR PROGNOS
Page 146 and 147: tors both for progression-free surv
Page 148 and 149: 222 INDUCTION PHASE ESTROGEN RECEPT
Page 150 and 151: THE PHARMACOLOGY OF INTENSIVE CYCLO
Page 152 and 153: PK VARIABILITY OF CPA/CDDP/BCNU Whe
Page 154 and 155: 5. Groshow LB, Piantadosi S, Santos
Page 157 and 158: - Tn'üTiifi'.m'jii.'yjKJiHtyiwiT T
Page 159: normal CD34+ progenitor cells
Page 163 and 164: Bielefeld, FRG) or control medium w
Page 165 and 166: 3. Koeffler HP, and Golde DW: Chron
Page 167 and 168: ply infected with supernatants from
Page 169 and 170: controls must be carefully matched
Page 171 and 172: Fig. IB: GPI isozyme analysis of 2
Page 173 and 174: PROCESSING OF STEM CELLS FOR TRANSP
Page 175 and 176: in progress using marker genes to l
Page 177 and 178: Table 1. Factors Affecting Quality
Page 179: Figure 2 .2 A Refractory/Relapsed L
Page 183 and 184: HIGH DOSE CHEMOTHERAPY IN GERM CELL
Page 185 and 186: carboplatin and etoposide with auto
Page 187 and 188: HIGH DOSE THERAPY IN GERM CELL TUMO
Page 189 and 190: Confusing data come out from early
Page 191: Session Mill: Lung Cancer
Page 194 and 195: Of the 14 limited stage patients in
Page 196 and 197: esponses with persistent nodular di
Page 198 and 199: hanced, detection of initial failur
Page 200 and 201: Cellules. Bull Cancer 1987;74:587-5
Page 202 and 203: 30 36 42 48 54 60 66 72 78 84 12 18
Page 204 and 205: Table 2: Toxicity of CBP Regimen fo
Page 206 and 207: TREATMENT OF NONSMALL CELL LUNG CAN
Page 208 and 209: Table 1. Combination Chemotherapy R
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Table 6. Hematological Data of the
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ence in survival among the three hi
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Session IX: Ovarian Cancer
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lymph node involvement or parenchym
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higher frequencies of neurotoxicity
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12. Ovarian Cancer Meta-Analysis Pr
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Table 2. Randomized Trials Employin
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BONE MARROW TRANSPLANTATION FOR OVA
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1). Data from the survey was combin
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carboplatinum and ifosfamide. The s
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Session X: Sarcoma
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ated doses in a recent Pediatric On
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cytokines to reduce hospitalization
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TABLE 2 Dose Escalation Schedule Do
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CHRONIC MYELOGENOUS LEUKEMIA WITH B
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DISCUSSION In this study, the use o
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AUTOGRAFTING IN CHRONIC MYELOID LEU
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Table 1 Remission Deaths Graft Hema
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16 (800 mg/m2 per day for two conse
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Session XII: CNS
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1.2 Description of the study The tr
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3. Conclusion In conclusion, treatm
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3. Conclusion Hematological toxicit
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Session XIII: Peripheral Stem Cells
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Crouse, 1992). In the present repor
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with no evidence of systemic diseas
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Administration of rhSCF at doses of
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In summary, the ligand for c-kit ha
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AUTOGRAFTING WITH G-CSF-MOBILIZED B
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cells and CD34+ cells observed in t
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6. Brugger W, Bross K, Frisch J, et
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100 -l Collection Efficiency Figure
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MATERIALS AND METHODS PATIENTS. Pat
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None of the patients included in ar
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9. Aurer I, Ribas A, Gale RP. What
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246 o 0.6 b 0.1 B1 Figure 2 p = 0.0
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AUTOLOGOUS BONE MARROW TRANSPLANTAT
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SUMMARY OF THE NON HODGKIN LYMPHOMA
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SUMMARY: AUTOLOGOUS MARROW TRANSPLA
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mor. The obverse of this coin is po
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treated at Memorial Hospital in New
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Contributors and Participants Tause
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Leonard Kalman, Hematology/Oncology
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D.R. Sutherland, Oncology Research,
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