Summary
Fifty-one consecutive patients with Hodgkin's disease (HD) have been treated with high-dose chemotherapy (HDT) and transplantation of autologous bone marrow (BM) (n=44), autologous BM plus peripheral blood stem cells (PBSC) (n=2), PBSC (n=1), syngeneic (n=1), or allogeneic BM (n=3). All patients had received standard salvage chemotherapy prior to HDT and were classified as sensitive (n=33) or resistant (n=17) to this treatment; one patient was in untreated relapse prior to BMT. The preparative regimens for patients receiving autologous BM and/or PBSC consisted of cyclophosphamide, VP 16, and BCNU (CVB) (n=44) or BCNU, etoposide, ara-C, and melphalan (BEAM) (n=3). The patients receiving allogeneic transplants were treated with the CVB regimen (n=2) or busulfan (16 mg/kg body wt.) and cyclophosphamide (200 mg/kg body wt.). With a median follow-up of 12 months, overall survival for 44 patients grafted with autologous BM is 61%±9%, progression-free survival for patients with sensitive disease is 44%±11%; no patient with resistant relapse survived beyond 1 year post transplant. Two of three patients grafted with allogeneic BM still survive 15 and 24 months after BMT with Karnofsky performance scores of 70% and 100%, respectively. The main toxicity encountered with the CVB regimen was interstitial pneumonia (IP), seen in four of 15 patients (27%) receiving ≥600 mg/m2 of BCNU. Three of these patients have died. The results show that HDT followed by hematopoietic stem cell rescue may effectively salvage an important fraction of patients with relapsed HD who respond to standard chemotherapy. The same approach is largely unsuccessful in patients with proven refractoriness to standard chemotherapy. Whether HDT followed by BMT or PBSC support is superior to intensive chemotherapy without stem cell support can be answered only by a prospectively randomized trial.
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Ahmed T, Ciavarella D, Feldman E, Ascensao J, Hussain F, Engelking C, Gingrich S, Mittelman A, Coleman M, Arlin ZA (1989) High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease. Leukemia 3: 19–22
Bierman P, Jagannath S, Armitage J, Spitzer G, Vose J, Cabanillas F, Kessinger A, Dicke K (1991) High-dose cyclophosphamide, carmustine, and etoposide in Hodgkin's disease: follow-up of 128 patients. In: Dicke KA, Armitage JO, Dicke-Evinger MJ (eds) Autologous Bone Marrow Transplantation. Proceedings of the Fifth International Symposium, August 22–25, 1990, The University of Nebraska Medical Center, Omaha, Nebraska 1990, pp 519–527
Budman DR, Anderson J, Obrecht JP, Canellos GP, Creaven P, Norton L, Gottlieb A (1985) Treatment of refractory Hodgkin's disease with teniposide, cisplatin, hexamethylmelamine, and prednisolone: Cancer and Leukemia Group B Trial 8171. Cancer Treat Rep 69: 719–720
Canellos GP (1992) The second chance for advanced Hodgkin's disease. J Clin Oncol 10: 175–177
Carella AM, Congui AM, Gaozza E, Mazza P, Ricci P, Visani G, Meloni G, Cimino G, Mangoni L, Coser P, Cetto GL, Cimino R, Alessandrino EP, Brusamolino E, Santini G, Tura S, Mandelli F, Rizzoli V, Bernasconi C, Marmont AM (1988) High-dose chemotherapy with autologous bone marrow transplantation in 50 advanced resistant Hodgkin's disease patients: a Italian Study Group Report. J Clin Oncol 6: 1411–1416
Chopra R, Linch DC, McMillan AK, Blair S, Patterson KG, Moir D, Richards JDM, Cervi P, Kinsey S, Goldstone AH (1992) Mini-BEAM followed by BEAM and ABMT for very poor risk Hodgkin's disease. Br J Haematol 81: 197–202
Gribben JG, Linch DC, Singer CRJ, McMillan AK, Jarrett M, Goldstone AH (1989) Successful treatment of refractory Hodgkin's disease by high-dose combination chemotherapy and autologous bone marrow transplantation. Blood 73: 340–344
Hagemeister FB, Tannir N, McLaughlin P, Salvador P, Riggs S, Velasquez WS, Cabanillas F (1987) MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease. J Clin Oncol 5: 556–561
Hiddemann W, Schmitz N, Pfreundschuh M, Pflüger K-H, Ollech-Chwoyka J, Tirier C, Maschmeyer G, Kirchner H, Wag-ner T, Koch P, Dahmen E, Fiedler W, Trümper L, Diehl V (1990) Treatment of refractory Hodgkin's disease with highdose cytosine arabinoside and mitoxantrone in combination. Results of a clinical phase-II study of the German Hodgkin Study Group. Cancer 66: 838–843
Hoppe RT (1991) Development of effective salvage treatment programs for Hodgkin's disease: an ongoing clinical challenge. Blood 77: 2093–2095
Jagannath S, Armitage JO, Dicke KA, Tucker SL, Velasquez WS, Smith K, Vaughan WP, Kessinger A, Horwitz LJ, Hagemeister FB, McLaughlin P, Cabanillas F, Spitzer G (1989) Prognostic factors for response and survival after high-dose cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 7: 179–185
Jones RJ, Piantadosi S, Mann RB, Ambinder RF, Seifter EJ, Vriesendorp HM, Abeloff MD, Burns WH, May WS, Rowley SD, Vogelsang GB, Wagner JE, Wiley JM, Wingard JR, Yeager AM, Saral R, Santos GW (1990) High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 8: 527–537
Jones RJ, Ambinder RF, Piantadosi St, Santos GW (1991) Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood 77: 649–653
Kessinger A, Bierman PJ, Vose JM, Armitage JO (1991) Highdose cyclophosphamide, carmustine, and etoposide followed by autologous peripheral stem cell transplantation for patients with relapsed Hodgkin's disease. Blood 77: 2322–2325
Körbling M, Holle R, Haas R, Knauf W, Dörken B, Ho AD, Kuse R, Pralle H, Fliedner TM, Hunstein W (1990) Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site. J Clin Oncol 8: 978–985
Longo DL, Duffey PL, Young RC, Hubbard SM, Ihde DC, Glatstein E, Phares JC, Jaffe ES, Urba WJ, DeVita VT (1992) Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure. J Clin Oncol 10: 210–218
Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50: 163–170
Perren TJ, Selby PJ, Milan S, Meldrum M, McElwain TJ (1990) Etoposide-and adriamycin-containing combination chemotherapy (HOPE-Bleo) for relapsed Hodgkin's disease. Br J Cancer 61: 919–923
Pfreundschuh MG, Schoppe WD, Fuchs R, Pflüger KH, Loeffler M, Diehl V (1987) Lomustine, etoposide, vindesine, and dexamethasone (CEVD) in Hodgkin's lymphoma refractory to cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) and doxorubicin, bleomycin, vinblastine, and darcabazine (ABVD): a multicenter trial of the German Hodgkin Study Group. Cancer Treat Rep 71: 1203–1207
Pfreundschuh M, Koch P, Kuse R, Lathan B, Rüffer U, Schmitz N, Diehl V, German Hodgkin Study Group (1991) DEXABEAM as salvage therapy for COPP + ABVD refractory Hodgkin's disease: a phase-II study of the German Hodgkin Study Group. Eur J Cancer [Suppl] 2: S 237
Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat Ph, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi M, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K (1987) 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. N Engl J Med 316: 1493–1498
Phillips GL, Wolff SN, Herzig RH, Lazarus HM, Fay JW, Lin H-S, Shina DC, Glasgow GP, Griffith RC, Lamb CW, Herzig GP (1989) Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation. Blood 73: 2086–2092
Reece DE, Barnett MJ, Connors JM, Fairey RN, Greer JP, Herzig GP, Herzig RH, Klingemann HG, O'Reilly SE, Shepherd JD, Spinelli JJ, Voss NJ, Wolff SN, Phillips GL (1991) Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 9: 1871–1879
Santoro A, Viviani S, Bonfante V, Valagussa P, Bonadonna G (1987) CEP in Hodgkin's disease (HD) resistant to MOPP and ABVD. Proc Am Soc Clin Oncol 6: 199
Schmitz N, Dreger P, Zander A, Peters S, Ehninger G, Wandt H, Kolb HJ, Hecht T (1992) Recombinant human granulocyte colony-stimulating factor (Filgrastim) after autologous bone marrow transplantation for lymphoma: an open-label randomized trial in Germany. Blood 80 [Suppl 1]: 292a
Schulman P, McCarroll K, Cooper MR, Norton L, Barcos M, Gottlieb AJ (1990) Phase-II study of MOPLACE chemotherapy for patients with previously treated Hodgkin's disease: a CALGB study. Med Pediatr Oncol 18: 482–486
Sheridan WP, Begley CG, Juttner AA, Szer J, To LB, Maher D, McGrath KM, Morstyn G, Fox RM (1992) Effect of peripheral-blood progenitor cells mobilized by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet 339: 640–644
Straus DJ, Myers J, Koziner B, Lee BJ, Clarkson BD (1983) Combination chemotherapy for the treatment of Hodgkin's disease in relapse. Results with lomustine (CCNU), melphalan (Alkeran), and vindesine (DVA) alone (CAD) and in alternation with MOPP and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV). Cancer Chemother Pharmacol 11: 80–85
Tourani J-M, Levy R, Colonna P, Desablens B, Leprise P-Y, Guilhot F, Brahimi S, Belhani M, Ifrah N, Sensebe L, Lemevel A, Lotz J-P, Le Maignan Ch, Andrieu J-M (1992) High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease. J Clin Oncol 10: 1086–1094
Tseng A jr, Jacobs C, Coleman CN, Horning SJ, Lewis BJ, Rosenberg SA (1987) Third-line chemotherapy for resistant Hodgkin's disease with lomustine, etoposide, and methotrexate. Cancer Treat Rep 71: 475–478
Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B (1988) Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood 71: 117–122
Wheeler C, Antin JH, Churchill WH, Come SE, Smith BR, Bubley GJ, Rosenthal DS, Rappaport JM, Ault KA, Schnipper LE, Eder JP (1990) Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dosefinding study. J Clin Oncol 8: 648–656
Zulian GB, Selby P, Milan S, Nandi A, Gore M, Forgeson G, Perren TJ, McElwain TJ (1989) High-dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease. Br J Cancer 59: 631–635
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Schmitz, N., Glass, B., Dreger, P. et al. High-dose chemotherapy and hematopoietic stem cell rescue in patients with relapsed Hodgkin's disease. Ann Hematol 66, 251–256 (1993). https://doi.org/10.1007/BF01738475
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DOI: https://doi.org/10.1007/BF01738475