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- as far as relapses are concerned: resistant relapses are still a bad indication for marrow transplantation and sensitive relapses are probably the best candidate for this modality of therapy. Sensitive relapses are patients where 1st CR is absolutely demonstrated and include only CR and PR after two courses of rescue conventional chemotherapy. In this setting the results are now between 40 and 60% long term survival at 5 years and the current PARMA randomized study is trying to demonstrate definitive interest of this modality of therapy. I want to stress again that it is somewhat unethical not to put patients in the PARMA protocol because we are not able yet to demonstrate the utility of this therapy. Some insurance did not reimburse in the States this modality, which is probably the best one, and we need very few patients now to complete the PARMA study with a definitive conclusion. - last point: primary refractory patients are still very bad candidates for marrow transplantation. In this field, allegeneic and autologous bone marrow transplantation are equivalent despite two reports that allegeneic decreases the number of relapses. A lot of published papers (especially from the Nebraska team) show that peripheral blood stem cell is also equivalent to autologous marrow transplantation in this setting. CONCLUSION: Non-Hodgkin's lymphoma is still one of the major fields for bone marrow transplantation and we all hope that in the near future several randomized studies will definitively establish this therapy in the field. 250 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION
SUMMARY: AUTOLOGOUS MARROW TRANSPLANTATION FOR SOLID TUMORS Roger H. Herzig, M.D. PHASE I STUDIES Nearly twenty years ago, the Phase I single agent dose escalation studies began. Alkylating agents were chosen because of their properties of little nonmyeloid toxicity, a log-linear dose response relationship could be demonstrated in vitro cell lines and in conventional dose clinical studies, and they are generally non-cross resistant. These sequential, single agent studies defined the toxicity and feasibility of dose-intensive therapy with marrow support. While novel and unusual non-myeloid toxicity was discovered, more importantly, a further dose-response for most agents was demonstrated. The Phase I studies left questions of scheduling open, but it did lead to other trials using multiple agents and/or multiple courses. What still remains is how to increase the therapeutic index of increasing the efficacy while decreasing the toxicity of these dose-intensive regimens. PHASE II STUDIES The Phase II studies of dose-intensive therapy demonstrated efficacy in a number of tumors. These studies were generally conducted in patients with advanced, refractory disease. Overall, a high response rate was seen, usually in excess of 60% to 70%, of which 20-40% of the responses were complete. Of note, about 10-15% of the patients achieved significant disease-free survival of more than a year. The promising results in these trials led to the use of dose-intensive therapy earlier in the course of the disease. The solid tumors that fall into this category, in which the dose-intensive therapy is probably effective, include breast, ovary, melanoma, testicular cancer, Ewing's sarcoma, and neuroblastoma. A second group of tumor types in which the dose-intensive therapy is possibly effective include colon, lung, glioblastoma, and metastatic carcinoma adenocarcinoma of unknown primary. The results in these patients showed high response rates but fewer patients with complete responses or with long-term, disease-free survival. It would also probably be beneficial to use a dose-intensive approach in these patients earlier in their treatment. There are some tumor types in which the Phase II trials provided either insufficient data or the tumors were unresponsive to high-dose therapy. Few patients with Wilm's tumor have been treated, however, dramatic responses in some of these patients have been documented. There has been a renewed interest in the non-Ewing's sarcomas, especially in the European community, and again responses are seen even after conventional therapy has failed. In the category of tumors that are unresponsive include patients with renal cell carcinoma. None of the patients in several series with this diagnosis responded to high-dose therapy. SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 251
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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
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1992;10:175-7. 3. McMillan A, Golds
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B. DAILY DAY AGENT DOSE -7 -6 -5 -4
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cohort with HR treated with BEC-2 i
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p R 0 P O R T I 0 N 1 0.9 0.8 0.7 0
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TABLE 3. TOXICITY BEC TAVe TMJ as 2
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ies. 10 Longer blood half-lives hav
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agents have been developed cautious
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Table 1. Radioisotopes for RIT. Pur
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The treatment criterion in this stu
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more than 80% of the cases. Patient
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Disease Free Survival 800 Time •
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Session VI: Breast Cancer
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achieved a complete remission survi
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acil, vincristine, prednisone (CMFV
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t: 3 en a in S « J •S •> c ai
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LONG TERM FOLLOW UP OF POOR PROGNOS
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tors both for progression-free surv
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222 INDUCTION PHASE ESTROGEN RECEPT
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THE PHARMACOLOGY OF INTENSIVE CYCLO
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PK VARIABILITY OF CPA/CDDP/BCNU Whe
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5. Groshow LB, Piantadosi S, Santos
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- Tn'üTiifi'.m'jii.'yjKJiHtyiwiT T
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normal CD34+ progenitor cells
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sequence analysis of the human haem
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Bielefeld, FRG) or control medium w
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3. Koeffler HP, and Golde DW: Chron
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ply infected with supernatants from
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controls must be carefully matched
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Fig. IB: GPI isozyme analysis of 2
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PROCESSING OF STEM CELLS FOR TRANSP
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in progress using marker genes to l
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Table 1. Factors Affecting Quality
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Figure 2 .2 A Refractory/Relapsed L
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HIGH DOSE CHEMOTHERAPY IN GERM CELL
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carboplatin and etoposide with auto
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HIGH DOSE THERAPY IN GERM CELL TUMO
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Confusing data come out from early
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Session Mill: Lung Cancer
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Of the 14 limited stage patients in
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esponses with persistent nodular di
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hanced, detection of initial failur
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Cellules. Bull Cancer 1987;74:587-5
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30 36 42 48 54 60 66 72 78 84 12 18
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Table 2: Toxicity of CBP Regimen fo
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TREATMENT OF NONSMALL CELL LUNG CAN
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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
Page 243 and 244: CHRONIC MYELOGENOUS LEUKEMIA WITH B
Page 245 and 246: DISCUSSION In this study, the use o
Page 247 and 248: AUTOGRAFTING IN CHRONIC MYELOID LEU
Page 249 and 250: Table 1 Remission Deaths Graft Hema
Page 251 and 252: 16 (800 mg/m2 per day for two conse
Page 253: Session XII: CNS
Page 256 and 257: 1.2 Description of the study The tr
Page 258 and 259: 3. Conclusion In conclusion, treatm
Page 260 and 261: 3. Conclusion Hematological toxicit
Page 263: Session XIII: Peripheral Stem Cells
Page 266 and 267: Crouse, 1992). In the present repor
Page 268 and 269: with no evidence of systemic diseas
Page 270 and 271: Administration of rhSCF at doses of
Page 272 and 273: In summary, the ligand for c-kit ha
Page 274 and 275: AUTOGRAFTING WITH G-CSF-MOBILIZED B
Page 276 and 277: cells and CD34+ cells observed in t
Page 278 and 279: 6. Brugger W, Bross K, Frisch J, et
Page 280 and 281: 100 -l Collection Efficiency Figure
Page 282 and 283: MATERIALS AND METHODS PATIENTS. Pat
Page 284 and 285: None of the patients included in ar
Page 286 and 287: 9. Aurer I, Ribas A, Gale RP. What
Page 288 and 289: 246 o 0.6 b 0.1 B1 Figure 2 p = 0.0
Page 291 and 292: AUTOLOGOUS BONE MARROW TRANSPLANTAT
Page 293: SUMMARY OF THE NON HODGKIN LYMPHOMA
Page 297 and 298: mor. The obverse of this coin is po
Page 299 and 300: treated at Memorial Hospital in New
Page 301 and 302: Contributors and Participants Tause
Page 303 and 304: Leonard Kalman, Hematology/Oncology
Page 305: D.R. Sutherland, Oncology Research,
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