Abstract
Chemosensitive response prior to transplantation has been shown to be most significant for survival post transplant. To estimate toxicity of a dose-intensive regimen that was to improve chemosensitive response rate, 15 patients with primary refractory lymphoma were enrolled in dose escalation of pre-transplant salvage chemotherapy. The first cycle had a fixed dose of ifosfamide 6 g/m2 and mitoxantrone 12 mg/m2, with arabinosyl cytosine (Ara-C) 2 g/m2, and methylprednisolone 2.0 g. Each cycle of the second and third had cisplatin 90 mg/m2, Ara-C 6 g/m2, methylprednisolone 2.0 g, and escalated doses of ifosfamide from 7.5 g/m2 to 15 g/m2 and mitoxantrone from 16 to 28 mg/m2. Blood stem cells were collected before the second cycle and ⩾3 × 106 CD34 cells/kg were infused 2 days after the second and third cycles, respectively. The maximum tolerated doses of ifosfamide and mitoxantrone were 11.25 g/m2 and 16 mg/m2, respectively. Acute renal failure and bacterial infection occurred as non-hematologic dose limiting toxicities. Eleven patients completed therapy. Five patients achieved complete remission and five had partial remission. Nine patients received autologous and four received allogeneic transplants. Currently, six are alive without evidence of disease, with a 3-year survival of 40%. Although preliminary, the regimen suggests acceptable toxicity and significant activity that warrants further study.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Philip T, Armitage JO, Spitzer G et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma New Engl J Med 1987 316: 1493 1498
Appelbaum FR, Sullivan KM, Buckner CD et al. Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation J Clin Oncol 1987 5: 1340 1347
Andre M, Henry-Amar M, Pico JL et al. Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study. Société Française de Greffe de Moelle J Clin Oncol 1999 17: 222 229
Burns LJ, Daniels KA, McGlave PB et al. Autologous stem cell transplantation for refractory and relapsed Hodgkin's disease: factors predictive of prolonged survival Bone Marrow Transplant 1995 16: 13 18
Crump M, Smith AM, Brandwein J et al. High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant J Clin Oncol 1993 11: 704 711
Moskowitz CH, Bertino JR, Glassman JR et al. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma J Clin Oncol 1999 17: 3776 3785
Kewalramani T, Zelenetz AD, Hedrick EE et al. High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis Blood 2000 96: 2399 2404
Brade WP, Herdrich K, Kachel-Fischer U et al. Dosing and side-effects of ifosfamide plus mesna J Cancer Res Clin Oncol 1991 117: (Suppl. 4) 164 186
Schiller JH, Storer B, Arzoomanian R et al. Phase I trial of mitoxantrone and granulocyte–macrophage colony-stimulating factor (GM-CSF) in patients with advanced solid malignancies Invest New Drugs 1993 11: 291 300
Tepler I, Cannistra SA, Frei E III et al. Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy J Clin Oncol 1993 11: 1583 1591
Bouabdallah R, Stoppa AM, Rossi JF et al. Intensive sequential chemotherapy (ISC 95) with growth factors and blood stem cell support in high-intermediate and high-risk (IPI 2 and IPI 3) aggressive non-Hodgkin's lymphoma: an oligocentric report on 42 patients Leukemia 1999 13: 950 956
Long GD, Negrin RS, Hoyle CF et al. Multiple cycles of high dose chemotherapy supported by hematopoietic progenitor cells as treatment for patients with advanced malignancies Cancer 1995 76: 860 868
Gingrich RD, Ginder GD, Burns LJ et al. BVAC ablative chemotherapy followed by autologous bone marrow transplantation for patients with advanced lymphoma Blood 1990 75: 2276 2281
Lee CK, Gingrich RD, deMagalhaes-Silverman M et al. Prophylactic reinfusion of T cells for T cell-depleted allogeneic bone marrow transplantation Biol Blood Marrow Transplant 1999 5: 15 27
Miller AB, Hoogstraten B, Staquet M et al. Reporting results of cancer treatment Cancer 1981 47: 207 214
Cheson BD, Horning SJ, Coiffier B et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group J Clin Oncol 1999 17: 1244 1253
Toma S, Palumbo R, Comandone A et al. Ambulatory 4-day continuous-infusion schedule of high-dose ifosfamide with mesna uroprotection and granulocyte colony-stimulating factor in advanced solid tumours: a phase I study Ann Oncol 1995 6: 193 196
Berns JS, Haghighat A, Staddon A et al. Irreversible renal failure after ifosfamide treatment. A clinicopathologic report of two patients Cancer 1995 76: 497 500
Nielsen OS, Judson I, van Hoesel Q et al. Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group Eur J Cancer 2000 36: 61 67
Weaver CH, Appelbaum FR, Petersen FB et al. High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy J Clin Oncol 1993 11: 1329 1335
Shankar G, Scott Bryson J, Darrell Jennings C et al. Idiopathic pneumonia syndrome after allogeneic bone marrow transplantation in mice. Role of pretransplant radiation conditioning Am J Respir Cell Mol Biol 1999 20: 1116 1124
Rodriguez MA, Cabanillas FC, Hagemeister FB et al. A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas Ann Oncol 1995 6: 609 611
Velasquez WS, McLaughlin P, Tucker S et al. ESHAP – an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4 year follow-up study J Clin Oncol 1994 12: 1169 1176
Rodriguez MA, Caballinas FC, Velasquez W et al. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP J Clin Oncol 1995 13: 1734 1741
Bonfante V, Viviani S, Devizzi L et al. High-dose ifosfamide and vinorelbine as salvage therapy for relapsed or refractory Hodgkin's disease Eur J Haematol 2001 64: (Suppl.) 51 55
Vose JM, Zhang MJ, Rowlings PA et al. Autologous Blood and Marrow Transplant Registry Lymphoma Working Committee. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry J Clin Oncol 2001 19: 406 413
Longo DL, Duffey PL, Young RC et al. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure J Clin Oncol 1992 10: 210 218
Bonfante V, Santoro A, Viviani S et al. Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD J Clin Oncol 1997 15: 528 534
Frei E III, Antman KH . Combination chemotherapy, dose and schedule In: Holland JF, Frei E III, Bast RC et al (eds) Cancer Medicine, 4th edn Williams & Wilkins: Philadelphia 1997 817 837
Frei E, Elias A, Wheeler C et al. The relationship between high-dose treatment and combination chemotherapy: the concept of summation dose intensity Clin Cancer Res 1998 4: 2027 2037
Meyer RM, Hryniuk WM, Goodyear MD . The role of dose intensity in determining outcome in intermediate-grade non-Hodgkin's lymphoma J Clin Oncol 1991 9: 339 347
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lee, CK., deMagalhaes-Silverman, M., Hayashi, M. et al. A dose escalation study for salvage chemotherapy in patients with refractory lymphoma prior to high-dose myeloablative therapy with stem cell transplantation. Bone Marrow Transplant 29, 647–652 (2002). https://doi.org/10.1038/sj.bmt.1703533
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703533