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culture, CFU-GM growth was significantly enhanced, thus allowing the growth of a sufficient number of CFU-GM to be analyzed at the cytogenetic level. On direct cytogenetic analysis, the overall mean (+SD) percentage of Phnegative metaphases was 7 + 20%. The mean (+SD) percentages of Ph-negative CFU-GM grown from untreated and mafosfamide-treated marrow samples were 19 + 29% and 31 + 37%, respectively. As compared to direct cytogenetic analysis, a statistically significant increase in the percentage of Ph-negative CFU- GM was observed both from untreated (P< 0.025) as well as mafosfamidetreated marrow samples (P< 0.025). Following stroma adherence (3 hrs.) and short-term suspension culture (3 days), four different CFU-GM populations, i.e., adherent CFU-GM, adherent mafosfamide-treated CFU-GM, non-adherent CFU-GM, and non-adherentmafosfamide-treated CFU-GM, were available for cytogenetic analysis. The mean (+SD) percentages of Ph-negative clones were 33 + 25% for adherent CFU- GM, 59 ± 40% for adherent mafosfamide-treated CFU-GM, 12 ± 16% for nonadherent CFU-GM, and 32 + 26% for non-adherent mafosfamide-treated CFU- GM. Overall, these data show an enrichment of Ph-negative clonogenic cells grown within the stroma adherent either untreated or mafosfamide-treated fractions, associated with an enrichment of Ph-positive CFU-GM within the stroma non-adherent fraction. If patients showing a percentage of Ph-negative clones < 20% were considered "unresponsive" to the treatment and excluded from this analysis then, the mean (+SD) percentages of Ph-negative clones were 47 + 19% for adherent CFU- GM, 81 + 21% for adherent mafosfamide-treated CFU-GM, 21 + 17% for nonadherent CFU-GM, and 39 + 23% for non-adherent mafosfamide-treated CFU- GM. DISCUSSION The aim of this report was to investigate, at the clonogenic cell level, the distribution of Ph-positive and Ph-negative CFU-GM between stroma adherent and stroma non-adherent CML marrow cells. It is demonstrated that: (a) a significant proportion of stroma adherent CFU- GM is Ph-negative; and (b) mafosfamide incubation significantly increases the percentage of Ph-negative CFU-GM within the stroma adherent fraction. Based on the results presented herein three major conclusions can be reached: (1) Ph-positive CML progenitor cells have a reduced binding capacity to normal marrow stroma; (2) mafosfamide has a selective effect on the Ph-positive clones and, at least in our experimental system, seems to spare Ph-negative clones with maintained stroma adherence activity; (3) the altered interactions of CML progenitors with marrow stroma might represent a new purging approach in view of autologous marrow transplantation. REFERENCES 1. Fialkow PJ, Gartler SM, and Yoshida A: Clonal origin of chronic myelocytic leukemia in man. Proc Natl Acad Sci USA 58:1468-1471,1987. 2. Kurzrock R, Gutterman JU, and Talpaz M: The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med 319:990-998,1988. 136 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION
3. Koeffler HP, and Golde DW: Chronic myelogenous leukemia. New concepts. N Engl J Med 304:1269-1274,1981. 4. Thomas DE, and Clift RA: Indications for marrow transplantation in chronic myelogenous leukemia. Blood 73:861-864,1989. 5. Eaves AC, Cashman JD, Gaboury LA et al: Unregulated proliferation of primitive chronic myeloid leukemia progenitors in the presence of normal marrow adherent cells. Proc Natl Acad Sei USA 83:5306-5310,1986. 6. Coulombel L, Kalousek DK, Eaves CJ, et al: Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. N Engl J Med 308:1493-1498, 1983. 7. Goto T, Nishikori M, Arlin Z, et al: Growth characteristics of leukemic and normal hematopoietic cells in Ph+ chronic myelogenous leukemia and effects of intensive treatment. Blood 59:793-808,1982. 8. Dube ID, Arlin ZA, Kalousek DK, et al: Nonclonal hemopoietic progenitor cells detected in long-term marrow cultures from a Turner syndrome mosaic with chronic myeloid leukemia. Blood 64:1284-1287,1984. 9. Hogge DE, Coulombel L, Kalousek DK, et al: Nonclonal hemopoietic progenitors in a G6PD heterozygote with chronic myelogenous leukemia revealed after long-term marrow culture. Am J Hematol 24:389-394,1987. 10. Goldman JM: Molecular biology and treatment of chronic myelogenous leukemia. Curr Opin Oncol 2:49-54,1990. 11. Barnett MJ, Eaves CJ, Phillips GL, et al: Successful autografting in chronic myeloid leukemia after maintenance of marrow in culture. Bone Marrow Transplant 4:345- 351,1989. 12. Carlo-Stella C, Mangoni L, Piovani G, et al: In vitro marrow purging in chronic myelogenous leukemia: effect of mafosfamide and recombinant granulocytemacrophage colony-stimulating factor. Bone Marrow Transplant 8:265-273,1991. 13. Gordon MY, Dowding CR, Riley GP, et al: Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia. Nature 328:342-344,1987. 14. Gordon MY, Atkinson J, Clarke D, et al: Deficiency of a phosphatidylinositolanchored cell adhesion molecule influences haemopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia. Leukemia 8:693-698,1991. 15. Gordon MY, Hibbin JA, Kearney LU, et al: Colony formation by primitive haemopoietic progenitors in cocultures of bone marrow cells and stromal cells. Br J Haematol 60:129-136,1985. 16. Carlo-Stella C, Cazzola M, Ganser A, et al: Synergistic antiproliferative effect of recombinant interferon-gamma with recombinant interferon-alpha on chronic myelogenous leukemia hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU- E, and CFU-GM). Blood 72:1293-1299,1988. 17. Yunis JJ: New chromosome techniques in the study of human neoplasia. Human Path 12:540-549,1981. 18. Dube ID, Eaves CJ, Kalousek DK, et al: A method for obtaining high quality chromosome preparations from single hemopoietic colonies on a routine basis. Cancer Gen Cytogen 4,157-168,1981. ACKNOWLEDGMENTS This work was supported in part by grants from Consiglio Nazionale delle Ricerche (PFO), Associazione Italiana per la Ricerca Sul Cancro (AIRC), MURST (40% - 60%, 1991), Regione Emilia-Romagna. SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 137
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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
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REFERENCES 1. Chopra R, Mc Millan A
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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 and 160: normal CD34+ progenitor cells
Page 161 and 162: sequence analysis of the human haem
Page 163: Bielefeld, FRG) or control medium w
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
Page 210 and 211: Table 6. Hematological Data of the
Page 212 and 213: 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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