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

More documents

Recommendations

Info

LONG TERM FOLLOW UP OF POOR PROGNOSIS STAGE IV BREAST CANCER PATIENTS TREATED WITH TWO COURSES OF HIGH-DOSE CHEMOTHERAPY AND BONE MARROW SUPPORT Frank Dunphy, Gary Spitzer, Jonathan Yau, Susan Huan, Jorge Spinolo, Sundar Jagannath, Ralph Wallerstein, Karel Dicke, Aman Buzdar, Gabriel Hortobagyi From the Division of Bone Marrow Transplantation, Medical Oncology,and Hematology (FD, GS), Department of Internal Medicine, Saint Louis University Medical Center, St. Louis, MO 63110-0250; and the Department of Hematology (JY, SH, JS, SJ, RW, KD) and Breast Medical Oncology (AB, GH), The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030. Address reprint requests to: Frank Dunphy, ME) Saint Louis University Medical Center Division of Bone Marrow Transplantation, Medical Oncology, and Hematology 3635 Vista Ave. at Grand Blvd. P.O. Box 15250 St. Louis, MO 63110-0250 INTRODUCTION Stage IV breast cancer patients who are estrogen receptor-negative (ER-) or estrogen receptor-positive (ER+) "refractory" to hormonal manipulation represent a poor prognosis subgroup which behaves in an aggressive manner with a short survival and few protracted disease-free survivors. With conventional chemotherapy the median survival of this subgroup is 15-18 months, with a 10% three-year progression-free and overall survival. 0 "*' We describe long term follow up data in this poor-risk subgroup of breast cancer patients. They were initially treated with conventional induction chemotherapy followed by intensificationwith two courses of high-dose cyclophosphamide 4.5-6g/m 2 /course; etoposide 750-1500mg/m 2 /course; cisplatin 120- 180mg/m 2 /course. We include data of response rates, duration of response, survival, and toxicity. Patient Population and Treatment Plan Eighty stage IV ER- or ER+ "primary hormonal refractory" breast cancer patients were treated between May, 1985 and August, 1990. All patients were in first relapse. Patients were initially treated for stage IV disease with conventional combination chemotherapy (Induction Phase) to the point of maximal response. Patients with stable or responding disease then received high-dose therapy (Intensive Phase)(Fig.l). Forty-four patients were randomized to receive marrow infusion. Thirty-six were randomized to the no-marrow arm. 118 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION
Intensive hydration to maintain high urine output was started 24 hours prior to intensification chemotherapy and continued for one week. Cyclophosphamide was infused intravenously over one hour on days 1,2, and 3. Etoposide was infused over four hours every 12 hours on days 1,2, and 3. Cisplatinwas administered over 2 hours on days 1,2, and 3. RESULTS Response Seventy-seven patients had measurable or assessable disease at the time of intensification. Three patients had no evidence of disease (NED) after surgical resection, these were not assessable for response to induction. Seventy-nine patients were treated with median 4 cycles of induction chemotherapy (77 patients with measurable disease and two NED patients). Seventy-nine percent (79%) received Adriamycin-based induction chemotherapy. Twenty-one percent (21%) were treated with Methotrexate chemotherapy combinations. Seven patients suffering early death during the intensive phase were considered treatment failures and scored as treatment related early deaths. Median duration of follow-up for the entire group of 80 patients is 83+ weeks (range, 13- 283+). Median duration of follow-up for the 24 surviving patients is 172+ weeks(range 74+-283+). Response to induction chemotherapy was 77%. Thirty-one percent (31%) were complete responders and 46% were partial responders. Twenty-three percent (23%) had nonresponsive stable disease. The "overall response" was defined as response in those patients with measurable disease who completed both induction and intensive phases. The three NED patients were censored from response evaluation. The "overall response" was 79%. Complete remission in 55% and partial response in 25%. Thirty-seven percent 37% of partial responders and 33% of stable disease patients to induction chemotherapy were converted to complete remission after the intensive phase. Median progression-free survival measured from beginning induction therapy is 50 weeks (95% confidence interval, 44 to 61 weeks)(Fig. 2). Median survival is 83 weeks (95% confidence interval, 68 to 110 weeks) (Fig. 3). Patients followed long term show that the progression-free interval and overall survival curves have reached a plateau after 142 weeks (2.7 years) and 180 weeks (3.5 years) respectively, persisting at greater than 5 year follow-up. Characteristics of patients constituting the tail of the progression-free interval and survival curves reveal predominately one or two sites of parenchymal lung or regional nodal relapse at the time they started induction chemotherapy. Using univariate analysis, four features predicted for improved progression-free survival or overall survival. These include: (1) disease site distributed to lung or regional lymph nodes (P=.093 and .007); (2) one disease site (P=.030 and .006); (3) disease-free interval (DFI) from diagnosis to detection of metastasis of greater or equal to 1 year (P=.038 and .042); (4) response to induction chemotherapy with complete response or no evidence of disease (P=.011 and .037). By multivariate analysis five variables were significant "negative" predic- Sixm INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 119
Page 1:
Autologous Bone Marrow Transplantat
Page 5 and 6:
CONTENTS nviAum TMLHTA'I OTT! 7 A l
Page 7 and 8:
AUTOLOGOUS BONE MARROW TRANSPLANTAT
Page 9 and 10:
TREATMENT OF NONSMALL CELL LUNG CAN
Page 11:
SUMMARY OF THE NON HODGKIN LYMPHOMA
Page 15:
Session I: Leukemia
Page 18 and 19:
TRIAL PROGRESS The trial opened in
Page 20 and 21:
Table 1. Achievement of Second Remi
Page 22 and 23:
ALLOGENEIC VERSUS AUTOLOGOUS BONE M
Page 24 and 25:
pts). The other 56 pts are too earl
Page 26 and 27:
Figure 1 EORTC-GIMEMA AML 8 A EORTC
Page 28 and 29:
PATIENTS AND METHODS Patients The B
Page 30 and 31:
Thus, as the results of some ongoin
Page 32 and 33:
COMPARISON OF INTENSIVE CONSOLIDATI
Page 34 and 35:
over, 13 pts who had received ICC1
Page 37:
Session II: Future Directions
Page 40 and 41:
in a previous report 3 . Analysis a
Page 42 and 43:
Engraftment of granulocyte, monocyt
Page 44 and 45:
0.2 - 0.1 - ABMT with mAb purging f
Page 46 and 47:
ENHANCED REGENERATION OF NATURAL KI
Page 48 and 49:
RESULTS The in vivo immune effects
Page 50 and 51:
16. Rizzoli V, Mangoni L, Carlo-Ste
Page 52 and 53:
hydroperoxycyclophosphamide (4HC)-t
Page 54 and 55:
survival in patients undergoing ABM
Page 56 and 57:
IMMUNOTHERAPY OF AML AFTER ABMT - S
Page 58 and 59:
Otherwise toxicity was mild to mode
Page 60 and 61:
Therapy. Amsterdam Elsevier 1987;89
Page 62 and 63:
200 IL6 in serum 44 SIXTH INTERNATI
Page 64 and 65:
sodes), fewer days of i.v. antibiot
Page 67:
Session III: Myeloma
Page 70 and 71:
trary, in case of adequate collecti
Page 72 and 73:
tion is considered, and all the mor
Page 74 and 75:
Table 3: Cost effectiveness of high
Page 77:
Session W: Lymphoma
Page 80 and 81:
METHODS Selection of patients and t
Page 82 and 83:
marrow treatment. Am J Med 85:829,1
Page 84 and 85:
HIGH DOSE THERAPY WITH HEMATOPOIETI
Page 86 and 87:
in TC 19 medium (Flobio), with an h
Page 88 and 89:
progression for a long time after A
Page 90 and 91:
Table 2. STATUS AT GRAFT Remission
Page 92 and 93:
IL Figura 3 70 SIXTH INTERNATIONAL
Page 94 and 95: ( 5 ) lowed by ABMT than refractory
Page 96 and 97: 74 Figure 4 Low grade lymphoma - pr
Page 98 and 99: (range 15-55); 68 males and 32 fema
Page 100 and 101: our experience, this has a seven-ye
Page 102 and 103: 30. Colombat P, Gorin NC, Lemonnier
Page 104 and 105: 82 OVERALL SURUIWL from ABUT (accor
Page 107 and 108: 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 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 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
Page 210 and 211:
Table 6. Hematological Data of the
Page 212 and 213:
ence in survival among the three hi
Page 215:
Session IX: Ovarian Cancer
Page 218 and 219:
lymph node involvement or parenchym
Page 220 and 221:
higher frequencies of neurotoxicity
Page 222 and 223:
12. Ovarian Cancer Meta-Analysis Pr
Page 224 and 225:
Table 2. Randomized Trials Employin
Page 226 and 227:
BONE MARROW TRANSPLANTATION FOR OVA
Page 228 and 229:
1). Data from the survey was combin
Page 230 and 231:
carboplatinum and ifosfamide. The s
Page 233:
Session X: Sarcoma
Page 236 and 237:
ated doses in a recent Pediatric On
Page 238 and 239:
cytokines to reduce hospitalization
Page 240 and 241:
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 and 294:
SUMMARY OF THE NON HODGKIN LYMPHOMA
Page 295 and 296:
SUMMARY: AUTOLOGOUS MARROW TRANSPLA
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,
show all

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

Create successful ePaper yourself

Delete template?

Save as template?