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

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PHASE III STUDIES There are a very limited number of Phase III prospectively randomized trials using dose-intensive therapy with marrow rescue for solid tumors. Currently, the ones with the highest profile are the high-risk stage II-III breast cancer studies that are being carried out collaboratively in the national cooperative groups. Two such trials are underway. There have been no interim analyses of survival or recurrence performed for these trials. Patient accrual is slow, but continues at a reasonable pace. The preliminary data on toxicity of the treatment (from the CALGB trial) has been acceptable. There is also a Phase III study for advanced breast cancer randomizing complete responders to conventional therapy to early verses late transplant. No results are available. At this point, Phase III trials need to be carefully designed with appropriate questions asked. Not all questions will need a Phase III trial; in some instances, it would be more appropriate to devote more time and attention to increasing the therapeutic index rather than asking inappropriate questions in a Phase III trial. THERAPEUTIC INDEX In order to increase the therapeutic index, one must decrease the toxicity and/or increase the efficacy of the treatment. Currently, efforts for decreasing toxicity have been aimed at supportive care issues, mediators of toxicity, and attenuation of dose. The proliferation of hematopoietic growth factors, both before and after the dose-intensive therapy, has made a small but significant impact on the infectious complications following the dose intensive therapy. Erythropoietin can reduce red blood cell transfusion requirements. As more growth factors develop, the beneficial effects on other lineages may be similarly shown. Other investigations have sought to block the mediators of toxicity, for example, by blocking tumor necrosis factor with pentoxifylline. Mixed results have been achieved with this approach, but the concept of blocking the mediators of toxicity is valid. Finally, efforts at optimizing the dosing schedule could decrease the toxicity. Attenuation of dose frequently reduces response, however, combining agents that are hopefully synergistic with sub-additive toxicity will result in lower toxicity and increased efficacy. Other ways at increasing efficacy could also include multiple courses of either single or multiple agents, better drugs, and obviously treating patients earlier in the course of their disease. The doseintensive approach should not be an alternative to Hospice. Patients that have a better performance status with less tumor bulk are likely to do better with a dose-intensive approach. OTHER ISSUES Ehxring the meeting, much had been discussed concerning the source of stem cells: bone marrow, peripheral blood, or both. The question should not be which is better, but rather how can we most effectively use this supportive care measure to provide the best effect. In future meetings, we may even want to change our title from autologous transplantation to something else because the stem cell support is really a supportive care issue, not a therapeutic one. As this treatment modality becomes used earlier, detection of minimal, residual disease will play an increasing role. It will also be an important way for negative selection of a stem cell product, i.e., to select cells that do not have tu- 252 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION
mor. The obverse of this coin is positive stem cell selection. <strong>Marrow</strong> and peripheral blood can be fractionated providing purer preparations of stem cells. Preliminary data was presented with the CD-34 positive selection of stem cells as an adjunct in treating women with breast cancer. Recovery of hematopoietic function was not impaired. These techniques also lead to the possibility of in vitro expansion of hematopoietic cells. Once peripheral blood or marrow have been harvested, small amounts could be expanded in the laboratory for subsequent use. Application of other areas of transplantation, especially in the area of gene therapy, would naturally follow. SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 253
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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
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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
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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 and 294: SUMMARY OF THE NON HODGKIN LYMPHOMA
Page 295: SUMMARY: AUTOLOGOUS MARROW TRANSPLA
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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