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HIGH DOSE THERAPY WITH HEMATOPOIETIC STEM CELL RESCUE IN FOLLICULAR LYMPHOMA: A FRANCE AUTOGREFFE STUDY C. Linassier, D. Donadio, L. Fouillard, N. Milpied, H. Tilly, J. Pico, J.F. Abgrall, B. Coiffier, R. Herbrecht, T. Philip, Ph. Colombat TOURS, MONTPELLIER, Saint Antoine- PARIS, NANTES, ROUEN, Gustave Roussy-VILLEJUIF, BREST, LYON SUD, STRASBOURG, Leon Berard LYON ABSTRACT The value of high dose chemotherapy with haematological stem cell rescue is not yet determined in the treatment of low grade Non Hodgkin's lymphoma. We report herein, results of a "France Autogreffe" retrospective study about 42 patients grafted in first partial remission (n=13) or chemosensitive relapse (n=29) for follicular lymphoma before January 1990. The median age was 38 years (range 26-61). Preparative regimen was pure chemotherapy in 22 patients and TBI-containing regimen in 20 patients. Thirty-seven patients received marrow hematopoietic stem cells. Bone marrow purging was performed in 15 patients. Five patients received peripheral blood stem cells. Three patients died from transplantation toxicity and two others died in CR ten months after Autologous Bone Marrow Transplantation (ABMT). With a median follow up of 43 months, relapse free survival is 60 %, event free survival 58 % and overall survival 83 %. Follicular lymphoma is relatively common non Hodgkin's lymphoma. Median survival of advanced stage subgroup ranges from 5 to 10 years
ized in table 1. There were 21 males and 21 females with a median age 38 years (range 26-61 years). At diagnosis and at ABMT, ten patients had follicular small cleaved, 30 follicular mixed and 2 follicular large cell lymphoma. For each patient, staging including physical examination, thoracoabdominal CT scan and trephine biopsy was performed at diagnosis, at relapse, and after transplant at 3,6,12 months and subsequently every 12 months. Bone marrow involvement was detected only by trephine biopsy examination. Prognostic factors were determined at diagnosis: Ann Arbor stage, constitutional B-symptoms, bulky disease defined as peripheral lymph nodes > 5 cm or abdominal mass > 10 cm and number of extra nodal sites involved. All patients had previously received poly chemotherapy. At the time of ABMT, 13 patients were in first partial remission (PR1) and 29 in chemosensitive relapse (second complete remission (CR2) = 16, PR2 = 5; CR3 = 4; PR3 = 4). Preparative therapy was a combined chemotherapy in 22 patients and a TBI containing regimen in 20 patients. Chemotherapy regimens were BEAM in 17 patients (carmustine 300 mg/m 2 on day 1, cytosine arabinoside 200 mg/ m 2 / day on days 2 to 5, etoposide 200 mg/m 2 /day on days 2 to 5 and melphalan 140 mg/m 2 on day 6), BEAC (cyclophosphamide 35 mg/kg/day on days 2 to 5 instead of melphalan)in one patient, CBV (BCNU 300 mg/m 2 on day 1, cyclophosphamide 35 mg/kg/day on days 2 to 5 and etoposide 200 mg/m 2 /day on days 2 to 5) in 3 patients and TACC (CCNU 200 mg/m 2 on day 1, cytosine arabinoside 200 mg/m 2 /day and 6-thioguanine 200 mg/m 2 /day on days 2 to 5, cyclophosphamide 45 mg/kg/day on days 2 to 5) in one patient. Among these patients, 8 received radiotherapy in nodal involved sites after ABMT. Twenty patients were conditioned with TBI and cyclophosphamide (60 mg/kg/day) for two days; four patients received additive drugs: VP 16 (one patient), VP 16 and ARA C (two patients), BCNU and VP 16 (one patient). COLLECTION, PROCESSING AND INFUSION OF HEMATOPOIETIC STEM CELLS Thirty seven patients were grafted with marrow hematopoietic stem cells. In some institutions, if marrow involvement was documented at diagnosis or at relapse, bone marrow purging was performed. Two techniques were used: chemical purging with adapted doses of Asta Z (10 cases) and immunological purging with two pan B monoclonal antibodies (5 cases). No assessment of bone marrow purging efficiency was performed after purging. Five patients received peripheral blood stem cells. Peripheral Blood Stem Cell (PBSC) collection In all patients PBSC were collected with a Haemonetics Model V50 apheresis device (Haemonetics, Braintree, MA). Stem cells were collected during the recovery phase following aplasia induced by a conventional chemotherapy. PBSC were collected using the lymphosurge program of the Haemonetics V50 blood cell processor. Three or four cytapheresis were performed after each course of chemotherapy, as soon as leukocyte count had reached 1 x 10V1- Chemical Purging (n) Two weeks before harvesting an individual pre-test was performed to determine the dose of ASTA Z corresponding to 95 % destruction of CFU-GM (LD95). Purging was performed after adjustment to 20 x 1 (^nuclear cells par ml SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 63
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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
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 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 •
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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
Page 215:
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
Page 233:
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
Page 303 and 304:
Leonard Kalman, Hematology/Oncology
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D.R. Sutherland, Oncology Research,
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