Leukemia & Lymphoma
ISSN: 1042-8194 (Print) 1029-2403 (Online) Journal homepage: http://www.tandfonline.com/loi/ilal20
High Dose Chemotherapy with Autologous Marrow Transplantation in Follicular Lymphomas Ph. Colombat, C. Binet, C. Linassier, I. Desbois, J. P. Lamagnere, P. Biron & T. Philip To cite this article: Ph. Colombat, C. Binet, C. Linassier, I. Desbois, J. P. Lamagnere, P. Biron & T. Philip (1992) High Dose Chemotherapy with Autologous Marrow Transplantation in Follicular Lymphomas, Leukemia & Lymphoma, 7:sup1, 3-6, DOI: 10.3109/10428199209061555 To link to this article: http://dx.doi.org/10.3109/10428199209061555
Published online: 01 Jul 2009.
Submit your article to this journal
Article views: 7
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Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ilal20 Download by: [University of California, San Diego]
Date: 06 November 2015, At: 18:16
0 1992 Harwood Academic Publishers GmbH
Leukemia and Lymphoma, Vol. I , Supplement, pp. 3-6 Reprints available directly from the publisher Photocopying permitted by license only
Printed in the United Kingdom
High Dose Chemotherapy with Autologous Marrow Transplantation in Follicular Lymphomas .d
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
Ph. COLOMBAT, C. BINET, C. LINASSIER, I. DESBOIS, and J. P. LAMAGNERE Department of Haematology and Oncology-CHU, Tours, Cedex-France
P. BIRON and T. PHILIP Department of Bone Marrow Transplantation-CentreLeon Berard-28, Rue Laennec-69373, Lyon, Cedex
Twenty six adult patients with low grade nodular non Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation. Conditioning regimen was BEAM-BEAC in 15 patients and TBI + Cyclophosphamide in 11 patients. Twenty one patients were grafted with haematopoietic stem cells, 12 after bone marrow purging and five with peripheral blood stem cells (PBSC). Two patients were treated in CR1 of leukemic phase, six in PRl and eighteen in sensitive relapse. With a median follow-up of 30 months, the actuarial survival is 91% and actuarial event free survival 67%. These data confirm some interest of ABMT in the treatment of low grade follicular NHL. KEY WORDS:
Follicular lymphomas
autologous bone marrow transplantation.
PATIENTS AND METHODS
Low grade nodular non-Hodgkin's lymphomas (L-NHL) include follicular small cell (FSC) and follicular mixed small and large cell (FM) lymphoma. The optimal treatment of stage 1 1 1-1V of L-NHL has not yet been determined. Few data have been reported about efficacy of high dose conventional chemotherapy in L-NHL and in most cases, results are disappointing (1,4, 1 1 personnal communication). Few data exist about the value of ABMT in low grade non-Hodgkin's lymphomas2*'.' 3. We report the results of 26 follicular L-NHL who failed conventional therapy and subsequently received high dose therapy with a median follow-up of 30 months since ABMT.
Patients Twenty six unselected patients with low grade nodular NHL according to the working formulation" were included between July 1985 and December 1990, for the high dose therapy strategy. Inclusion criteria were first CR from leukemic phase at diagnosis, first partial remission or chemosensitive relapse. Eighteen patients had follicular mixed and eight follicular small cleaved cell lymphomas. There were 16 men and 10 women. Median age was 39 years (range 2658). For each patient staging was performed upon diagnosis, at relapse, before ABMT at 3,6, 12 and every 12 months after ABMT. Fifteen patients had bone marrow involvement at diagnosis, four with a leukemic phase and 3 others had bone marrow involvement at relapse. Six patients had constitutional symptons and 5 had bulky disease defined as tumor > 7 cm. All patients
Address for Correspondence: Doctor Ph. Colombat, Department of Haematology, CHU Bretonneau, 2 bis Boulevard Tonnelle, 37044 Tours Cedex, France. 3
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
4
PH.COLOMBAT er a/.
received conventional therapy as initial treatment with different protocols as described. All except three patients received an adriamycin containing regimen. At the time of ABMT, two patients were in first complete remission (CR l), one of leukemic disease, the other one after second line therapy (first line therapy obtained partial remission). Six patients were in first partial remission (PR l), two with minimal residual disease in nodes and four others with a minimal residual nodular involvement of bone marrow. Eighteen patients were grafted in chemosensitive relapse (eleven in CR2-second remission, four in PR2 second partial remission, two in CR3-third remission and one in PR3-third partial remission). The median period from diagnosis to transplantation was 26 months (range = 6-84 months).
doses of Asta Z (eight patients)' and immunological purging with two pan B monoclonal antibodies (four In 1990, five patients received peripheral blood stem cells collected in recovery phase of conventional chemotherapy with a Haemonetics Model V50 apheresis device (Haemonetics, Braintree, MA). The bone marrow was aspirated 1 to 24 months prior to transplantation. The bone marrow yield was a mean of 2.3 x lO'/kg nucleated cells per kilogram (range 0.4 to 4.0 x 10'/kg) and 8.6 x 104CFU-GM per kilogram (range 0.2 to 48 x 104/kg).
RESULTS Tumor response and survival
No toxic deaths occurred. Twenty of the twenty six patients are currently in complete remission after Three conditioning regimens were used in this transplantation with a median follow-up of 30 retrospective study. Chemotherapy alone was used in months. One patient died in CR ten months after 16 patients: fourteen patients received BEAM ABMT of encephalitis of unknown origin. Five consisting of Carmustine 300mg/m2 on day 1, patients relapsed 3, 11, 16, 16 and 36 months after Cytarabine 100 mg/m2 in a 30 minute infusion every graft; one of them died of progressive disease six 12 hours on days 2 to 5, Etoposide 100 mg/m2 as a 1 months after relapse. The actuarial event free survival hours infusion every 12 hours on days 2 to 5 and is 67% and overall survival 91%. The two patients grafted in first complete remission Melphalan 140 mg/m2 intravenously in 5 minutes on day 6. One patient received BEAC regimen which is with peripheral blood stem cells after TBI + Cysimilar to BEAM with Cyclophosphamide 35 mg/kg clophosamide regimen are well and alive at 6 and 16 as a 1 hour infusion on days 2 to 5 instead of months. Of the six patients grafted in first partial Melphalan. Eleven patients received fractionated TBI remission only one patient with initial leukemic on days -7, -6, - 5 and Cyclophosphamide disease relapsed 36 months after graft. Eighteen 60mg/kg on days -3 and -2. Total doses of patients received ABMT after relapse. Fifteen were in fractionated irradiation were 12 Gy with 18 Mev PR2 or CR2: two patients relapsed and one died in X-rays at a dose rate of 13 rads per minute. The lungs CR. Two of the three patients grafted in CR3 or PR3 were shielded at a dose of 8 Gy. Patients were relapsed. All the patients who relapsed in this group hydrated adequately and were given mesna (to received BEAM conditioning regimen and two were prevent cystitis), frusemide and antiemetics. transfused with monoclonal antibody purged marrow. Eight patients received involved field radiotherapy Of the three patients who did not receive an at 20 Gy in 10 fractions post BEAM and ABMT. adriamycin containing regimen as initial chemotherapy, one relapsed sixteen months after ABMT. Two out of four patients with monoclonal antibody purging, one of seven patients with chemical purging Hematopoietic stem cell procedures and two of none patients without purging have relapsed. At this time none of the five patients grafted Twenty one patients were engrafted with marrow with peripheral blood stem cells have relapsed (5 +, hematopoietic stem cells. In most cases, bone marrow 6 + , 16+, 22+, 25+).. was purged ex-vivo, if marrow involvement had been Only one patient have receiving irradiation post documented at any time before ABMT. Two ABMT relapsed. This relapse has occurred outside of techniques were used: chemical purging with adapted the involved irradiation field. Preparatory regimens
5
HIGH DOSE CHEMOTHERAPY
% SURVIVAL
I
100%
I
overall survival
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
1
0
12
24
36
I
.
E FS
48
60
72
D a t e of ABMT
Months from graft
Figure 1 Acturial event-free survival and overall survival of 26 patients in the study.
Engraftment
LATE TOXICITY
For all patients, the median period during which the leucocyte count was under 1 x 109/1 was 16 days (range 740). It was 15 days (range 10-38) for granulocytes less than 0.5 x 109/l. A 50 x 109/1 platelet count was achieved after a median period of 30 days (range 13-180). Bone marrow purging did not change the recovery periods for leucocytes and granulocytes, but we observed a slight albeit non significant lengthening of platelet recovery (p > 0.05). Few patients were grafted with peripheral blood stem cells, however all of these patients had a period of neutropenia of less than 16 days and a platelet recovery of more than 45 days.
One patient died of encephalitis of unknown origin ten months after ABMT while in CR. Conditioning regimen was TBI and cyclophosphamide and he did not receive other cranial irradiation. Cerebral scan was normal and electro-encephalogram was not in favour of viral origin.
Early toxicity Four gram positive cocci bacterial septicemias and four episodes of pneumonitis (one of pseudomonas aeroginosa origin) were observed in eight patients. Two patients had grade 3 hepatic toxicity according to the WHO ~ r i t e r i a ’ ~Nausea, . vomiting and mucositis were present in all patients, mostly of moderate intensity.
DISCUSSION Adequate treatment of disseminated low grade non-Hodgkin’s lymphoma is not yet Despite a high initial remission rate, there is a continuous relapse rate and no plateau in survival is obtained. Various approaches have been used from “watch and wait” strategy to high dose conventional chemotherapy. There is little data about the value of ABMT in L-NHL. Three important studies have been published. The first study from Nebraska Medical Centre’ included 19 heavily pre-treated patients; all but two were treated with active disease, at time of reporting 8-19 (42%) patients remain alive in continuous CR. The second study from London13 included 35 patients
’.
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
6
PH. COLOMBAT et a1
in second remission ( n = 24), third remission (n = 8) REFERENCES or beyond third remission ( n = 3). Twenty four 1. Anderson, K. C., Skarin, A. T., Rosenthal, D. S. et nl. (1984). patients were in CR and 13 with minimal residual Combination chemotherapy for advanced non-Hodgkin’s disease, 24 patients were alive in remission, four died lymphomas other than diffuse histiocytic and undifferenciated in remission and seven relapsed with a disease free histologies. Cancer Treat. Rep., 68, 1343-1 350. survival of 55%. The last study from Boston’ included 2. Bierman, P. J., Vose, J. M., Friedman, M. A,, et a/. (1989). High dose therapy with hematopoietic rescue for low grade 69 patients in sensitive relapse or incomplete non-Hodgkin’s lymphoma. Exp. Haematol., 17, 23 1 (a). remission. At ABMT, only 30 patients were in CCR, 3. Cheson, B. D., Wittes, R.E., Friedman, M. A. (1986). Low grade non-Hodgkin’s lymphomas revisited. Cancer Treat. Rep., 70, preparative regimen was TBI + Cyclophosphamide 1051-1054. and bone marrow was purged by anti B cell 4. Ezdinli E. Z., Anderson, J. R., Melvin, F. e t a l . (1985). Moderate monoclonal antibody. At the time of report one toxic versus agressive chemotherapy of nodular poorly differenciated and two late deaths were observed, 23 patients lymphoma. J. Clin. Oncol., 32, 769-775. relapsed with a short median follow-up of less than 5 . Favrot, M. C., Philip, I., Philip, T. et a/. (1986). Bone marrow purging procedure in Burkitt lymphoma with monoclonal 18 months. Expected disease free survival at 2 years antibodies and complement quantification by a liquid all is 53% for the 51 low grade patients and 88% for the culture monitoring system. Br. J. Haemat., 64, 161-168. transformed patients. Poor prognostic factors for 6. Favrot, M. C., Philip, I., Poncelet, P. et a/. Comparative efficiency of an immunomagnetic purging procedure and a DFS were status at ABMT (CR/PR). rabbit complement lysis to eliminate blast cells from the bone In our study overall event free survival is 67% and marrow. In “Proceedings of the third international workshop on autologous bone marrow transplantation, Dec. 86, overall survival 91%. Most of the patients of this Houston” Dickie, K. and Spitzer, G. editors 1987, 369-364. study had bad prognostic factors: initial leukemic 7. Freedman, A,, Ritz, J., Neuberg, D. et a/. (1991). Autologous bone marrow transplantation in 69 patients with a history of phase ( n = 4), bulky abdominal tumors ( n = 5), B low grade B-cell non-Hodgkin’s lymphoma. Blood, 77, symptoms (n = 6), PR after high dose conventional 2524-2529. first line therapy ( n = 6),first CR < 1 year ( n = 7). To 8. Gorin, N. C., Douay, L., Laporte, J. P. et al. (1986). Autologous bone marrow transplantation using marrow incubated with try to evaluate the efficacy of ABMT in the treatment ASTA 2 7557 n adult acute leukemia. Blood, 76, 1367-1376. of low grade non-Hodgkin’s lymphoma, we compared 9. Jones, S. E. (1986). Follicular lymphoma-Do no Harm-Cancer the length of CR post-ABMT with the length of first Treat, Rep., 70, 1055-1058. CR. At this time, 8 out of the 18 relapsing patients 10. National Cancer Institute-Sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a have a CR post-ABMT longer than the first CR. Two working formulation for clincical use. (1982). Cancer, 49, of the three patients in CR3 or PR3 have relapsed, we 21 12-2135. confirm the conclusions of Bierman et a1.’ that ABMT 11. Peterson, B. A,, Friuerra, G., Anderson, J. R. et al. (1985). Response of lowgrade lymphoma to Cyclophosphamide (CTX) should not to be performed too late in the natural or Cyclophosphamide, Adriamycin, Vincristine, Prednisone course of the disease. and Bleomycin (CAVP-B). Proc. ASCO, 4, C-822. In conclusion, this study confirms that ABMT has 12. Rosenberg, S. A. (1985). The low grade non-Hodgkin’s lymphomas: challenges and opportunities. J. Clin. Oncol., 2, some efficacy in the treatment of low grade follicular 299-3 10. non-Hodgkin’s lymphomas. In the context of the 13. Rohatiner, A. Z. S., Price, C. G . A., Dorey, E. et al. (1990). natural history of follicular lymphoma, longer Ablative therapy with autologous bone marrow transplantation as consilidation therapy for follicular lymphomas. Proceedings follow-up and carefully randomized studies will be of the Fourth International Conference on Malignant necessary to conclude the impact of this approach. Lymphoma. Lugano, 60, 83(a). Acknowledgement The excellent technical assistance of Jocelyne Pichery is deeply acknowledged.
14. W.H.0- Handbook for reporting of Cancer treatment. WHO effect publication, Geneva 1979: 48.
ISSN: 1042-8194 (Print) 1029-2403 (Online) Journal homepage: http://www.tandfonline.com/loi/ilal20
High Dose Chemotherapy with Autologous Marrow Transplantation in Follicular Lymphomas Ph. Colombat, C. Binet, C. Linassier, I. Desbois, J. P. Lamagnere, P. Biron & T. Philip To cite this article: Ph. Colombat, C. Binet, C. Linassier, I. Desbois, J. P. Lamagnere, P. Biron & T. Philip (1992) High Dose Chemotherapy with Autologous Marrow Transplantation in Follicular Lymphomas, Leukemia & Lymphoma, 7:sup1, 3-6, DOI: 10.3109/10428199209061555 To link to this article: http://dx.doi.org/10.3109/10428199209061555
Published online: 01 Jul 2009.
Submit your article to this journal
Article views: 7
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ilal20 Download by: [University of California, San Diego]
Date: 06 November 2015, At: 18:16
0 1992 Harwood Academic Publishers GmbH
Leukemia and Lymphoma, Vol. I , Supplement, pp. 3-6 Reprints available directly from the publisher Photocopying permitted by license only
Printed in the United Kingdom
High Dose Chemotherapy with Autologous Marrow Transplantation in Follicular Lymphomas .d
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
Ph. COLOMBAT, C. BINET, C. LINASSIER, I. DESBOIS, and J. P. LAMAGNERE Department of Haematology and Oncology-CHU, Tours, Cedex-France
P. BIRON and T. PHILIP Department of Bone Marrow Transplantation-CentreLeon Berard-28, Rue Laennec-69373, Lyon, Cedex
Twenty six adult patients with low grade nodular non Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation. Conditioning regimen was BEAM-BEAC in 15 patients and TBI + Cyclophosphamide in 11 patients. Twenty one patients were grafted with haematopoietic stem cells, 12 after bone marrow purging and five with peripheral blood stem cells (PBSC). Two patients were treated in CR1 of leukemic phase, six in PRl and eighteen in sensitive relapse. With a median follow-up of 30 months, the actuarial survival is 91% and actuarial event free survival 67%. These data confirm some interest of ABMT in the treatment of low grade follicular NHL. KEY WORDS:
Follicular lymphomas
autologous bone marrow transplantation.
PATIENTS AND METHODS
Low grade nodular non-Hodgkin's lymphomas (L-NHL) include follicular small cell (FSC) and follicular mixed small and large cell (FM) lymphoma. The optimal treatment of stage 1 1 1-1V of L-NHL has not yet been determined. Few data have been reported about efficacy of high dose conventional chemotherapy in L-NHL and in most cases, results are disappointing (1,4, 1 1 personnal communication). Few data exist about the value of ABMT in low grade non-Hodgkin's lymphomas2*'.' 3. We report the results of 26 follicular L-NHL who failed conventional therapy and subsequently received high dose therapy with a median follow-up of 30 months since ABMT.
Patients Twenty six unselected patients with low grade nodular NHL according to the working formulation" were included between July 1985 and December 1990, for the high dose therapy strategy. Inclusion criteria were first CR from leukemic phase at diagnosis, first partial remission or chemosensitive relapse. Eighteen patients had follicular mixed and eight follicular small cleaved cell lymphomas. There were 16 men and 10 women. Median age was 39 years (range 2658). For each patient staging was performed upon diagnosis, at relapse, before ABMT at 3,6, 12 and every 12 months after ABMT. Fifteen patients had bone marrow involvement at diagnosis, four with a leukemic phase and 3 others had bone marrow involvement at relapse. Six patients had constitutional symptons and 5 had bulky disease defined as tumor > 7 cm. All patients
Address for Correspondence: Doctor Ph. Colombat, Department of Haematology, CHU Bretonneau, 2 bis Boulevard Tonnelle, 37044 Tours Cedex, France. 3
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
4
PH.COLOMBAT er a/.
received conventional therapy as initial treatment with different protocols as described. All except three patients received an adriamycin containing regimen. At the time of ABMT, two patients were in first complete remission (CR l), one of leukemic disease, the other one after second line therapy (first line therapy obtained partial remission). Six patients were in first partial remission (PR l), two with minimal residual disease in nodes and four others with a minimal residual nodular involvement of bone marrow. Eighteen patients were grafted in chemosensitive relapse (eleven in CR2-second remission, four in PR2 second partial remission, two in CR3-third remission and one in PR3-third partial remission). The median period from diagnosis to transplantation was 26 months (range = 6-84 months).
doses of Asta Z (eight patients)' and immunological purging with two pan B monoclonal antibodies (four In 1990, five patients received peripheral blood stem cells collected in recovery phase of conventional chemotherapy with a Haemonetics Model V50 apheresis device (Haemonetics, Braintree, MA). The bone marrow was aspirated 1 to 24 months prior to transplantation. The bone marrow yield was a mean of 2.3 x lO'/kg nucleated cells per kilogram (range 0.4 to 4.0 x 10'/kg) and 8.6 x 104CFU-GM per kilogram (range 0.2 to 48 x 104/kg).
RESULTS Tumor response and survival
No toxic deaths occurred. Twenty of the twenty six patients are currently in complete remission after Three conditioning regimens were used in this transplantation with a median follow-up of 30 retrospective study. Chemotherapy alone was used in months. One patient died in CR ten months after 16 patients: fourteen patients received BEAM ABMT of encephalitis of unknown origin. Five consisting of Carmustine 300mg/m2 on day 1, patients relapsed 3, 11, 16, 16 and 36 months after Cytarabine 100 mg/m2 in a 30 minute infusion every graft; one of them died of progressive disease six 12 hours on days 2 to 5, Etoposide 100 mg/m2 as a 1 months after relapse. The actuarial event free survival hours infusion every 12 hours on days 2 to 5 and is 67% and overall survival 91%. The two patients grafted in first complete remission Melphalan 140 mg/m2 intravenously in 5 minutes on day 6. One patient received BEAC regimen which is with peripheral blood stem cells after TBI + Cysimilar to BEAM with Cyclophosphamide 35 mg/kg clophosamide regimen are well and alive at 6 and 16 as a 1 hour infusion on days 2 to 5 instead of months. Of the six patients grafted in first partial Melphalan. Eleven patients received fractionated TBI remission only one patient with initial leukemic on days -7, -6, - 5 and Cyclophosphamide disease relapsed 36 months after graft. Eighteen 60mg/kg on days -3 and -2. Total doses of patients received ABMT after relapse. Fifteen were in fractionated irradiation were 12 Gy with 18 Mev PR2 or CR2: two patients relapsed and one died in X-rays at a dose rate of 13 rads per minute. The lungs CR. Two of the three patients grafted in CR3 or PR3 were shielded at a dose of 8 Gy. Patients were relapsed. All the patients who relapsed in this group hydrated adequately and were given mesna (to received BEAM conditioning regimen and two were prevent cystitis), frusemide and antiemetics. transfused with monoclonal antibody purged marrow. Eight patients received involved field radiotherapy Of the three patients who did not receive an at 20 Gy in 10 fractions post BEAM and ABMT. adriamycin containing regimen as initial chemotherapy, one relapsed sixteen months after ABMT. Two out of four patients with monoclonal antibody purging, one of seven patients with chemical purging Hematopoietic stem cell procedures and two of none patients without purging have relapsed. At this time none of the five patients grafted Twenty one patients were engrafted with marrow with peripheral blood stem cells have relapsed (5 +, hematopoietic stem cells. In most cases, bone marrow 6 + , 16+, 22+, 25+).. was purged ex-vivo, if marrow involvement had been Only one patient have receiving irradiation post documented at any time before ABMT. Two ABMT relapsed. This relapse has occurred outside of techniques were used: chemical purging with adapted the involved irradiation field. Preparatory regimens
5
HIGH DOSE CHEMOTHERAPY
% SURVIVAL
I
100%
I
overall survival
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
1
0
12
24
36
I
.
E FS
48
60
72
D a t e of ABMT
Months from graft
Figure 1 Acturial event-free survival and overall survival of 26 patients in the study.
Engraftment
LATE TOXICITY
For all patients, the median period during which the leucocyte count was under 1 x 109/1 was 16 days (range 740). It was 15 days (range 10-38) for granulocytes less than 0.5 x 109/l. A 50 x 109/1 platelet count was achieved after a median period of 30 days (range 13-180). Bone marrow purging did not change the recovery periods for leucocytes and granulocytes, but we observed a slight albeit non significant lengthening of platelet recovery (p > 0.05). Few patients were grafted with peripheral blood stem cells, however all of these patients had a period of neutropenia of less than 16 days and a platelet recovery of more than 45 days.
One patient died of encephalitis of unknown origin ten months after ABMT while in CR. Conditioning regimen was TBI and cyclophosphamide and he did not receive other cranial irradiation. Cerebral scan was normal and electro-encephalogram was not in favour of viral origin.
Early toxicity Four gram positive cocci bacterial septicemias and four episodes of pneumonitis (one of pseudomonas aeroginosa origin) were observed in eight patients. Two patients had grade 3 hepatic toxicity according to the WHO ~ r i t e r i a ’ ~Nausea, . vomiting and mucositis were present in all patients, mostly of moderate intensity.
DISCUSSION Adequate treatment of disseminated low grade non-Hodgkin’s lymphoma is not yet Despite a high initial remission rate, there is a continuous relapse rate and no plateau in survival is obtained. Various approaches have been used from “watch and wait” strategy to high dose conventional chemotherapy. There is little data about the value of ABMT in L-NHL. Three important studies have been published. The first study from Nebraska Medical Centre’ included 19 heavily pre-treated patients; all but two were treated with active disease, at time of reporting 8-19 (42%) patients remain alive in continuous CR. The second study from London13 included 35 patients
’.
Downloaded by [University of California, San Diego] at 18:16 06 November 2015
6
PH. COLOMBAT et a1
in second remission ( n = 24), third remission (n = 8) REFERENCES or beyond third remission ( n = 3). Twenty four 1. Anderson, K. C., Skarin, A. T., Rosenthal, D. S. et nl. (1984). patients were in CR and 13 with minimal residual Combination chemotherapy for advanced non-Hodgkin’s disease, 24 patients were alive in remission, four died lymphomas other than diffuse histiocytic and undifferenciated in remission and seven relapsed with a disease free histologies. Cancer Treat. Rep., 68, 1343-1 350. survival of 55%. The last study from Boston’ included 2. Bierman, P. J., Vose, J. M., Friedman, M. A,, et a/. (1989). High dose therapy with hematopoietic rescue for low grade 69 patients in sensitive relapse or incomplete non-Hodgkin’s lymphoma. Exp. Haematol., 17, 23 1 (a). remission. At ABMT, only 30 patients were in CCR, 3. Cheson, B. D., Wittes, R.E., Friedman, M. A. (1986). Low grade non-Hodgkin’s lymphomas revisited. Cancer Treat. Rep., 70, preparative regimen was TBI + Cyclophosphamide 1051-1054. and bone marrow was purged by anti B cell 4. Ezdinli E. Z., Anderson, J. R., Melvin, F. e t a l . (1985). Moderate monoclonal antibody. At the time of report one toxic versus agressive chemotherapy of nodular poorly differenciated and two late deaths were observed, 23 patients lymphoma. J. Clin. Oncol., 32, 769-775. relapsed with a short median follow-up of less than 5 . Favrot, M. C., Philip, I., Philip, T. et a/. (1986). Bone marrow purging procedure in Burkitt lymphoma with monoclonal 18 months. Expected disease free survival at 2 years antibodies and complement quantification by a liquid all is 53% for the 51 low grade patients and 88% for the culture monitoring system. Br. J. Haemat., 64, 161-168. transformed patients. Poor prognostic factors for 6. Favrot, M. C., Philip, I., Poncelet, P. et a/. Comparative efficiency of an immunomagnetic purging procedure and a DFS were status at ABMT (CR/PR). rabbit complement lysis to eliminate blast cells from the bone In our study overall event free survival is 67% and marrow. In “Proceedings of the third international workshop on autologous bone marrow transplantation, Dec. 86, overall survival 91%. Most of the patients of this Houston” Dickie, K. and Spitzer, G. editors 1987, 369-364. study had bad prognostic factors: initial leukemic 7. Freedman, A,, Ritz, J., Neuberg, D. et a/. (1991). Autologous bone marrow transplantation in 69 patients with a history of phase ( n = 4), bulky abdominal tumors ( n = 5), B low grade B-cell non-Hodgkin’s lymphoma. Blood, 77, symptoms (n = 6), PR after high dose conventional 2524-2529. first line therapy ( n = 6),first CR < 1 year ( n = 7). To 8. Gorin, N. C., Douay, L., Laporte, J. P. et al. (1986). Autologous bone marrow transplantation using marrow incubated with try to evaluate the efficacy of ABMT in the treatment ASTA 2 7557 n adult acute leukemia. Blood, 76, 1367-1376. of low grade non-Hodgkin’s lymphoma, we compared 9. Jones, S. E. (1986). Follicular lymphoma-Do no Harm-Cancer the length of CR post-ABMT with the length of first Treat, Rep., 70, 1055-1058. CR. At this time, 8 out of the 18 relapsing patients 10. National Cancer Institute-Sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a have a CR post-ABMT longer than the first CR. Two working formulation for clincical use. (1982). Cancer, 49, of the three patients in CR3 or PR3 have relapsed, we 21 12-2135. confirm the conclusions of Bierman et a1.’ that ABMT 11. Peterson, B. A,, Friuerra, G., Anderson, J. R. et al. (1985). Response of lowgrade lymphoma to Cyclophosphamide (CTX) should not to be performed too late in the natural or Cyclophosphamide, Adriamycin, Vincristine, Prednisone course of the disease. and Bleomycin (CAVP-B). Proc. ASCO, 4, C-822. In conclusion, this study confirms that ABMT has 12. Rosenberg, S. A. (1985). The low grade non-Hodgkin’s lymphomas: challenges and opportunities. J. Clin. Oncol., 2, some efficacy in the treatment of low grade follicular 299-3 10. non-Hodgkin’s lymphomas. In the context of the 13. Rohatiner, A. Z. S., Price, C. G . A., Dorey, E. et al. (1990). natural history of follicular lymphoma, longer Ablative therapy with autologous bone marrow transplantation as consilidation therapy for follicular lymphomas. Proceedings follow-up and carefully randomized studies will be of the Fourth International Conference on Malignant necessary to conclude the impact of this approach. Lymphoma. Lugano, 60, 83(a). Acknowledgement The excellent technical assistance of Jocelyne Pichery is deeply acknowledged.
14. W.H.0- Handbook for reporting of Cancer treatment. WHO effect publication, Geneva 1979: 48.
