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05-12-2014 | Hematologic cancers | Book chapter | Article

10. Principles of Chemotherapy in Hodgkin Lymphoma

Authors: Peter Johnson, MD, FRCP, David Straus, MD

Publisher: Springer International Publishing

Abstract

Hodgkin lymphoma was the malignant disease for which the possibility of cure with combination chemotherapy in the majority of patients was first realized. As such it has provided a model upon which studies in many other types of malignancy have been based, and it is interesting to follow the trajectory of knowledge from early single-agent work through combinations, combined modalities, increasing complexity, and most recently selective de-escalation. Patients with advanced disease represent a minority of those affected by Hodgkin lymphoma. However, these patients represent the group in which the development and effects of chemotherapy are most readily appreciated, since the role of radiation therapy is markedly less than in those with localized disease.
Literature
1.
Wilkinson JF, Fletcher F (1947) Effect of beta-chloroethylamine hydrochlorides in leukaemia, Hodgkin’s disease, and polycythaemia vera; report on 18 cases. Lancet 2(6476):540–545PubMed
2.
Papac RJ (2001) Origins of cancer therapy. Yale J Biol Med 74(6):391–398PubMedCentralPubMed
3.
Zubrod CG (1979) Historic milestones in curative chemotherapy. Semin Oncol 6:490–505PubMed
4.
Gross R, Lambers K (1958) Erste erfarhungen in der Behandlung malignen tumoren mit einem neuen N-lost phosphamidester. Dtsch Med Wschr 83:458–462PubMed
5.
Rotolo V (1968) Vincaleukoblastine in the therapy of malignant neoplasms. Friuli Med 23(1):31–52PubMed
6.
Mathe G, Cattan A, Amiel JL, Schwarzenberg L, Schneider M (1969) Experimental therapeutic trials of leukemia and hematosarcomas: technologic and philosophic aspects. Ann NY Acad Sci 164(3):776–792PubMed
7.
Burchenal JH (1975) From wild fowl to stalking horses: alchemy in chemotherapy. Cancer 35:1121–1135PubMed
8.
Gilman A (1963) The initial clinical trial of nitrogen mustard. Am J Surg 105(574):578
9.
Wagener DJT (2009) The history of oncology. Springer, Berlin
10.
Mathe G, Schweisguth O, Schneider M, Amiel JL, Cattan A, Schwarzenberg L et al (1964) Value of vincaleukoblastine in the treatment of Hodgkin’s disease and other hematosarcomas and leukemias. Sem Ther 40(5):320–324PubMed
11.
Tubiana M, Henry-Amar M, Hayat M, Breur K, Werf-Messing B, Burgers M (1979) Long-term results of the E.O.R.T.C. randomized study of irradiation and vinblastine in clinical stages I and II of Hodgkin’s disease. Eur J Cancer 15(5):645–657PubMed
12.
Rosenberg SA, Kaplan HS (1966) Evidence for an orderly progression in the spread of Hodgkin’s disease. Cancer Res 26(6):1225–1231PubMed
13.
Tubiana M, Hayat M, Henry-Amar M, Breur K, van der Werf MB, Burgers M (1981) Five-year results of the E.O.R.T.C. randomized study of splenectomy and spleen irradiation in clinical stages I and II of Hodgkin’s disease. Eur J Cancer 17(3):355–363PubMed
14.
Bergsagel DE, Alison RE, Bean HA, Brown TC, Bush RS, Clark RM et al (1982) Results of treating Hodgkin’s disease without a policy of laparotomy staging. Cancer Treat Rep 66:717–731PubMed
15.
Selby P, McElwain TJ, Canellos G (1987) Chemotherapy for Hodgkin’s disease. Section I: MOPP and its variants. In: Selby P, McElwain TJ (eds) Hodgkin’s disease. Blackwell, Oxford
16.
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ et al (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30(18):2183–2189PubMedCentralPubMed
17.
Johnson PW, Federico M, Fossa A, Barrington SF, Kirkwood A, Roberts TH et al (2013) Response rates and toxicity of response-adapted therapy in advanced Hodgkin lymphoma: initial results. From the International RATHL Study. Hematological 98(s2):2
18.
DeVita VT, Simon RM, Hubbard SM, Young RC, Berard CW, Moxley JH et al (1980) Curability of advanced Hodgkin’s disease with chemotherapy. Ann Intern Med 92(5):587–595PubMed
19.
Longo DL, Young RC, Wesley M, Hubbard SM, Duffey PL, Jaffe ES et al (1986) Twenty years of MOPP therapy for Hodgkin’s disease. J Clin Oncol 4(9):1295–1306PubMed
20.
Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES et al (1992) Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327(21):1478–1484PubMed
21.
Carde P, MacKintosh FR, Rosenberg SA (1983) A dose and time response analysis of the treatment of Hodgkin’s disease with MOPP chemotherapy. J Clin Oncol 1(2):146–153PubMed
22.
Bonadonna G, Santoro A, Bonfante V, Valagussa P (1982) Cyclic delivery of MOPP and ABVD combinations in stage IV Hodgkin’s disease: rationale, background studies, and recent results. Cancer Treat Rep 66(4):881–887PubMed
23.
Ranson MR, Radford JA, Swindell R, Dikin DP, Wilkinson PM, Harris M et al (1991) An analysis of prognostic factors in stage III and IV Hodgkin’s disease treated at a single centre with MVPP. Ann Oncol 2(6):83–89
24.
Radford JA, Crowther D, Rohatiner AZ, Ryder WD, Gupta RK, Oza A et al (1995) Results of a randomized trial comparing MVPP chemotherapy with a hybrid regimen, ChlVPP/EVA, in the initial treatment of Hodgkin’s disease. J Clin Oncol 13(9):2379–2385PubMed
25.
Sutcliffe S, Wrigley PFM, Peto J, Lister TA, Stansfeld AG, Whitehouse JM et al (1978) MVPP chemotherapy regimen for advanced Hodgkin’s disease. Br Med J 6114:679–683
26.
Dady PJ, McElwain TJ, Austin DE, Barrett A, Peckham MJ (1982) Five years’ experience with ChlVPP: effective low-toxicity combination chemotherapy for Hodgkin’s disease chlvpp advanced HL. Br J Cancer 45:851–859PubMedCentralPubMed
27.
Selby P, Patel P, Milan S, Meldrum M, Mansi J, Mbidde E et al (1990) ChlVPP combination chemotherapy for Hodgkin’s disease: long-term results. Br J Cancer 62(2):279–285PubMedCentralPubMed
28.
Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM et al (2003) Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin’s disease: report of an intergroup trial. J Clin Oncol 21(4):607–614PubMed
29.
Johnson PWM, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS et al (2005) Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin’s lymphoma: results of the United Kingdom Lymphoma Group LY09 trial (ISRCTN97144519). J Clin Oncol 23(36):9208–9218PubMed
30.
Gobbi PG, Levis A, Chisesi T, Broglia C, Vitolo U, Stelitano C et al (2005) ABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin’s lymphoma: final results of a multicenter randomized trial by the intergruppo italiano linfomi. J Clin Oncol 23(36):9198–9207PubMed
31.
Hoskin PJ, Lowry L, Horwich A, Jack A, Mead B, Hancock BW et al (2009) Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin’s lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol 27(32):5390–5396PubMed
32.
Federico M, Luminari S, Iannitto E, Polimeno G, Marcheselli L, Montanini A et al (2009) ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin’s lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 27(5):805–811PubMed
33.
Gianni AM, Rambaldi A, Zinzani P, Levis A, Brusamolino E, Pulsoni A et al (2008) Comparable 3-year outcome following ABVD or BEACOPP first-line chemotherapy, plus pre-planned high-dose salvage, in advanced Hodgkin lymphoma (HL): a randomized trial of the Michelangelo, GITIL and IIL cooperative groups. ASCO Meeting Abstracts 05/20/;26(15_suppl):8506
34.
Santoro A, Bonadonna G, Bonfante V, Valagussa P (1982) Alternating drug combinations in the treatment of advanced Hodgkin’s disease. N Engl J Med 306(13):770–775PubMed
35.
Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L et al (1996) Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin’s disease: ten-year results. J Clin Oncol 14(5):1421–1430PubMed
36.
Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R et al (2004) Treatment of advanced Hodgkin’s disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin’s Lymphoma Study Group HD6 trial. Ann Oncol 15(2):276–282PubMed
37.
Engert A, Diehl V, Franklin J, Lohri A, Dorken B, Ludwig WD et al (2009) Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 27(27):4548–4554PubMed
38.
Klimo P, Connors JM (1985) MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin’s disease. J Clin Oncol 3(9):1174–1182PubMed
39.
Aleman BM, Raemaekers JM, Tirelli U, Bortolus R, t Veer MB, Lybeert ML et al (2003) Involved-field radiotherapy for advanced Hodgkin’s lymphoma. N Engl J Med 348(24):2396–2406PubMed
40.
Horning SJ, Williams J, Bartlett NL, Bennett JM, Hoppe RT, Neuberg D et al (2000) Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin’s disease: eastern cooperative oncology group pilot study E1492. J Clin Oncol 18(5):972PubMed
41.
Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA (2002) Stanford V and radiotherapy for locally extensive and advanced Hodgkin’s disease: mature results of a prospective clinical trial. J Clin Oncol 20(3):630–637PubMed
42.
Radford JA, Rohatiner AZS, Ryder WDJ, Deakin DP, Barbui T, Lucie NP et al (2002) ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin’s disease. J Clin Oncol 20(13):2988–2994PubMed
43.
DeVita VT Jr, DeVita VT Jr, Hellman S, Rosenberg SA (1989) Principles of chemotherapy. Cancer: principles and practice of oncology. J.B. Lippincott Company, Philadelphia, pp 276–300
44.
Skipper HE, Schabel FM, Wilcox WS (1964) Experimental evaluation of potential anti-cancer agents. XII. On the criteria and kinetics associated with “curability” of experimental leukemia. Cancer Chemother Rep 35:1–111PubMed
45.
Bonadonna G, Monfardini S, Oldini C (1969) Comparative effects of vinblastine and procarbazine in advanced Hodgkin’s disease. Eur J Cancer (1965) 5(4):393–402
46.
Coltman CA (1980) Chemotherapy of advanced Hodgkin’s disease. Semin Oncol 7:155–173PubMed
47.
Bernard J (1966) Current general principles of the treatment of Hodgkin’s disease, lymphosarcoma and reticulosarcoma. Rev Prat 16(7):871–879PubMed
48.
Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M et al (2007) Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin’s lymphoma. Haematologica 92(1):35–41 [Clinical Trial]PubMed
49.
DeVita VT Jr, Carbone PP (1967) Treatment of Hodgkin’s disease. Med Ann Distrib C 36(4):232–234
50.
DeVita VT, Serpick AA, Carbone PP (1970) Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann Intern Med 73(6):881–895PubMed
51.
Frei E III, Luce JK, Gamble JF, Coltman CA Jr, Constanzi JJ, Talley RW et al (1973) Combination chemotherapy in advanced Hodgkin’s disease: induction and maintenance of remission. Ann Intern Med 79(3):376–382PubMed
52.
Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A et al (1994) A randomized study in stage IIIB and IV Hodgkin’s disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol 12(2):279–287PubMed
53.
Carde P, Hayat M, Cosset JM, Somers R, Burgers JM, Sizoo W et al (1988) Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin’s disease: experience of the European Organization for Research and Treatment of Cancer. NCI Monogr 6:303–310PubMed
54.
Young RC, Chabner BA, Canellos GP, Schein PS, DeVita VT (1973) Maintenance chemotherapy for advanced Hodgkin’s disease in remission. Lancet 301(7816):1339–1343
55.
Lowenbraun STAN, DeVita VT, Serpick AA (1970) Combination chemotherapy with nitrogen mustard, vincristine, procarbazine and prednisone in previously treated patients with Hodgkin’s disease. Blood 36(6):704–717PubMed
56.
Fisher RI, DeVita VT, Hubbard SP, Simon R, Young RC (1979) Prolonged disease-free survival in Hodgkin’s disease with MOPP reinduction after first relapse. Ann Intern Med 90(5):761–763PubMed
57.
Arseneau JC, Sponzo RW, Levin DL, Schnipper LE, Bonner H, Young RC et al (1972) Non lymphomatous malignant tumors complicating Hodgkin’s disease: possible association with intensive therapy. N Engl J Med 287(22):1119–1122PubMed
58.
Weiden PL, Lerner KG, Gerdes A, Heywood JD, Fefer A, Thomas ED (1973) Pancytopenia and leukemia in Hodgkin’s disease: report of three cases. Blood 42(4):571–577PubMed
59.
Sherins RJ, DeVita VT Jr (1973) Effect of drug treatment for lymphoma on male reproductive capacity. Studies of men in remission after therapy. Ann Intern Med 79(2):216–220PubMed
60.
Corder MP, Young RC, Brown RS, Devita VT (1972) Phytohemagglutinin-induced lymphocyte transformation: the relationship to prognosis of Hodgkin’s disease. Blood 39(5):595–601PubMed
61.
Crowther D, Wagstaff J, Deakin D, Todd I, Wilkinson P, Anderson H et al (1984) A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin’s disease. J Clin Oncol 2(8):892–897PubMed
62.
Nicholson WM, Beard ME, Crowther D, Stansfeld AG, Vartan CP, Malpas JS et al (1970) Combination chemotherapy in generalized Hodgkin’s disease. Br Med J 3(713):7–10PubMedCentralPubMed
63.
McElwain TJ, Toy J, Smith E, Peckham MJ, Austin DE (1977) A combination of chlorambucil, vinblastine, procarbazine and prednisolone for treatment of Hodgkin’s disease. Br J Cancer 36(276):280
64.
Luce JK, Gamble JF, Wilson HE, Monto RW, Isaacs BL, Palmer RL et al (1971) Combined cyclophosphamide vincristine, and prednisone therapy of malignant lymphoma. Cancer 28(2):306–317PubMed
65.
Bonadonna G, Monfardini S (1969) Cardiac toxicity of daunorubicin. Lancet 1(7599):837PubMed
66.
Frei E, Luce JK, Talley RW, Veitkvicius VK, Wilson HE (1972) 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) in the treatment of lymphoma. Cancer Treat Rep 56(5):667–670
67.
O’Bryan RM, Luce JK, Tailey RW, Gottlieb JA, Baker LH, Bonadonna G (1973) Phase II evaluation of adriamycin in human neoplasia. Cancer 32(1):1–8PubMed
68.
Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C (1975) Combination chemotherapy of Hodgkin’s disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer 36(1):252–259PubMed
69.
Boleti E, Mead GM (2007) ABVD for Hodgkin’s lymphoma: full-dose chemotherapy without dose reductions or growth factors. Ann Oncol 18(2):376–380PubMed
70.
Martin WG, Ristow KM, Habermann TM, Colgan JP, Witzig TE, Ansell SM (2005) Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin’s lymphoma. J Clin Oncol 23(30):7614–7620PubMed
71.
Straus DJ, Portlock CS, Qin J, Myers J, Zelenetz AD, Moskowitz C et al (2004) Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood 104(12):3483–3489PubMed
72.
Canellos GP, Duggan D, Johnson J, Niedzwiecki D (2004) How important is bleomycin in the adriamycin + bleomycin + vinblastine + dacarbazine regimen? J Clin Oncol 22(8):1532–1533PubMed
73.
Skoetz N, Trelle S, Rancea M, Haverkamp H, Diehl V, Engert A et al (2013) Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin’s lymphoma: a systematic review and network meta-analysis. Lancet Oncol 14(10):943–952 [Meta-Analysis Review]PubMed
74.
Goldie JH, Coldman AJ (1979) A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 63(11–12):1727–1733PubMed
75.
Goldie JH, Coldman AJ (1986) Analyzing the patterns of treatment failure. J Clin Oncol 4(6):825–826PubMed
76.
Straus DJ, Myers J, Passe S, Young CW, Nisce LZ, Lee BJ et al (1980) The eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin’s disease: a follow-up report. Cancer 46(2):233–240PubMed
77.
Young CW, Straus DJ, Myers J, Passe S, Nisce LZ, Lee BJ et al (1982) Multidisciplinary treatment of advanced Hodgkin’s disease by an alternating chemotherapeutic regimen of MOPP/ABDV and low-dose radiation therapy restricted to originally bulky disease. Cancer Treat Rep 66(4):907–914PubMed
78.
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A et al (2012) Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet 379(9828):1791–1799 [Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]PubMed
79.
Canellos GP, Niedzwiecki D (2002) Long-term follow-up of Hodgkin’s disease trial. N Engl J Med 346(18):1417–1418PubMed
80.
Norton L, Simon R (1977) Tumor size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep 61:1307–1317PubMed
81.
Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D et al (2003) Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 348(24):2386–2395PubMed
82.
Linch DC, Winfield D, Goldstone AH, Moir D, Hancock B, McMillan A et al (1993) Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet 341(8852):1051–1054PubMed
83.
Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M et al (2002) Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 359(9323):2065–2071PubMed
84.
Hasenclever D, Brosteanu O, Gerike T, Loeffler M (2001) Modelling of chemotherapy: the effective dose approach. Ann Hematol 80(Suppl 3):B89–B94PubMed
85.
Hasenclever D, Loeffler M, Diehl V (1996) Rationale for dose escalation of first line conventional chemotherapy in advanced Hodgkin’s disease. German Hodgkin’s Lymphoma Study Group. Ann Oncol 7(Suppl 4):95–98PubMed
86.
Owadally WS, Sydes MR, Radford JA, Hancock BW, Cullen MH, Stenning SP et al (2010) Initial dose intensity has limited impact on the outcome of ABVD chemotherapy for advanced Hodgkin lymphoma (HL): data from UKLG LY09 (ISRCTN97144519). Ann Oncol 21:568–573PubMed
87.
Brosteanu O, Hasenclever D, Loeffler M, Diehl V, German Hodgkin’s Lymphoma Study Group (2004) Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin’s disease. Ann Hematol 83(3):176–182PubMed
88.
Ribrag V, Koscielny S, Casasnovas O, Cazeneuve C, Brice P, Morschhauser F et al (2009) Pharmacogenetic study in Hodgkin lymphomas reveals the impact of UGT1A1 polymorphisms on patient prognosis. Blood 113(14):3307–3313PubMed
89.
Henry-Amar M, Hayat M, Meerwaldt JH, Burgers M, Carde P, Somers R et al (1990) Causes of death after therapy for early stage Hodgkin’s disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group. Int J Radiat Oncol Biol Phys 19(5):1155–1157PubMed
90.
Van Leeuwen FE, Klokman WJ, Hagenbeek A, Noyon R, Van den Beltdusebout AW, Van Kerkhoff EHM et al (1994) 2nd cancer risk following Hodgkins-disease – a 20-year follow-up-study. J Clin Oncol 12(2):312–325PubMed
91.
Bartlett NL, Rosenberg SA, Hoppe RT, Hancock SL, Horning SJ (1995) Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin’s disease: a preliminary report. J Clin Oncol 13(5):1080–1088PubMed
92.
Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD et al (2013) Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol 31(6):684–691PubMedCentralPubMed
93.
Green JA, Dawson AA, Fell LF, Murray S (1980) Measurement of drug dosage intensity in MVPP therapy in Hodgkin’s disease. Br J Clin Pharmaco 9:511–514
94.
Diehl V, Sieber M, Ruffer U, Lathan B, Hasenclever D, Pfreundschuh M et al (1997) BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin’s disease. The German Hodgkin’s Lymphoma Study Group. Ann Oncol 8(2):143–148PubMed
95.
Diehl V, Haverkamp H, Mueller R, Mueller-Hermelink H, Cerny T, Markova J et al (2009) Eight cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): final analysis of the HD12 trial of the German Hodgkin Study Group (GHSG). ASCO Meeting Abstracts 05/20/;27(15S):8544
96.
Engert A, Franklin J, Mueller RP, Eich HT, Gossmann A, Mueller-Hermelink HK et al (2006) HD12 randomised trial comparing 8 dose-escalated cycles of BEACOPP with 4 escalated and 4 baseline cycles in patients with advanced stage Hodgkin Lymphoma (HL): an analysis of the German Hodgkin Lymphoma Study Group (GHSG), University of Cologne, D-50924 Cologne, Germany. ASH Annual Meeting Abstracts 11/16/;108(11):99
97.
Kobe C, Dietlein M, Franklin J, Markova J, Lohri A, Amthauer H et al (2008) Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma. Blood 112(10):3989–3994PubMedCentralPubMed
98.
Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V et al (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365(3):203–212PubMed
99.
Carde P, Karrasch M, Fortpied C, Brice P, Khaled HM, Caillot D et al (2012) ABVD (8 cycles) versus BEACOPP (4 escalated cycles => 4 baseline) in stage III-IV high-risk Hodgkin Lymphoma (HL): first results of EORTC 20012 Intergroup randomized phase III clinical trial. J Clin Oncol 30(Suppl): abstract 8002
100.
von Tresckow B, Haverkamp H, Boll B, Eichenauer DA, Sasse S, Fuchs M et al (2013) Impact of dose reduction of bleomycin and vincristine in patients with advanced Hodgkin lymphoma treated with BEACOPP: a comprehensive analysis of the German Hodgkin Study Group (GHSG) HD12 and HD15 trials. Blood 122(21): abstract 637
101.
Proctor SJ, Mackie M, Dawson A, Prescott B, Lucraft HL, Angus B et al (2002) A population-based study of intensive multi-agent chemotherapy with or without autotransplant for the highest risk Hodgkin’s disease patients identified by the Scotland and Newcastle Lymphoma Group (SNLG) prognostic index: a Scotland and Newcastle Lymphoma Group study (SNLG HD III). Eur J Cancer 38(6):795–806PubMed
102.
Federico M, Bellei M, Brice P, Brugiatelli M, Nagler A, Gisselbrecht C et al (2003) High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin’s lymphoma responding to front-line therapy. J Clin Oncol 21(12):2320–2325PubMed
103.
Arakelyan N, Berthou C, Desablens B, De Guibert S, Delwail V, Moles MP et al (2008) Radiation therapy versus 4 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine plus myeloablative chemotherapy with autologous stem cell transplantation five-year results of a randomized trial on behalf of the GOELAMS group. Cancer 113(12):3323–3330PubMed
104.
Aleman BM, van den Belt-Dusebout AW, Klokman WJ, Van’t Veer MB, Bartelink H, van Leeuwen FE (2003) Long-term cause-specific mortality of patients treated for Hodgkin’s disease. J Clin Oncol 21(18):3431–3439PubMed
105.
Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT et al (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355(15):1572–1582PubMed
106.
Matasar MJ, McCallen LN, Reidel ER, Ford JS, Oeffinger KC, Straus DJ (2009) Late mortality and morbidity of patients with Hodgkin lymphoma treated in adulthood. J Clin Oncol 27(15s Suppl): abstract 8547
107.
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN et al (2012) ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 366(5):399–408PubMedCentralPubMed
108.
Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P (2004) ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin’s disease: long-term results. J Clin Oncol 22(14):2835–2841PubMed
109.
Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C et al (2007) Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin’s lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25(23):3495–3502PubMed
110.
Engert A, Plutschow A, Eich HT, Lohri A, Dorken B, Borchmann P et al (2010) Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363(7):640–652PubMed
111.
Eich HT, Diehl V, Gorgen H, Pabst T, Markova J, Debus J et al (2010) Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol 28(27):4199–4206PubMed
112.
Advani R, Hoppe R, Rosenberg SA, Horning S (2007) Stage I/II Hodgkin’s Disease (HD) with bulky mediastinal disease or other Risk Factors (RF); the Stanford V experience. Haematologica 92(s5):27
113.
Advani R, Maeda L, Lavori P, Quon A, Hoppe R, Breslin S et al (2007) Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin’s disease. J Clin Oncol 25(25):3902–3907PubMed
114.
Advani RH, Horning SJ (1999) Treatment of early-stage Hodgkin’s disease. Semin Hematol 36(3):270–281PubMed
115.
Young RC, Canellos GP, Chabner BA et al (1978) Patterns of relapse in advanced Hodgkin’s disease treated with combination chemotherapy. Cancer 42:1001–1007PubMed
116.
Loeffler M, Brosteanu O, Hasenclever D, Sextro M, Assouline D, Bartolucci AA et al (1998) Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin’s disease. International Database on Hodgkin’s Disease Overview Study Group. J Clin Oncol 16(3):818–829PubMed
117.
Johnson PWM, Sydes MR, Hancock BW, Cullen MH, Radford JA, Stenning SP (2010) Consolidation radiotherapy in patients with advanced Hodgkin lymphoma: survival data from the UKLG LY09 randomised controlled trial (ISRCTN97144519). J Clin Oncol 28:3352–3359PubMed
118.
Diehl V, Loeffler M, Pfreundschuh M, Ruehl U, Hasenclever D, Nisters-Backes H et al (1995) Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin’s disease. German Hodgkins’ Study Group (GHSG). Ann Oncol 6(9):901–910PubMed
119.
Ferme C, Sebban C, Hennequin C, Divine M, Lederlin P, Gabarre J et al (2000) Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin’s disease: results of the Groupe d’etudes des Lymphomes de l’Adulte H89 trial. Blood 95(7):2246–2252PubMed
120.
Rodriguez J, Rodriguez MA, Fayad L, McLaughlin P, Swan F, Sarris A et al (1999) ASHAP: a regimen for cytoreduction of refractory or recurrent Hodgkin’s disease. Blood 93(11):3632–3636PubMed
121.
Aparicio J, Segura A, Garcera S, Oltra A, Santaballa A, Yuste A et al (1999) ESHAP is an active regimen for relapsing Hodgkin’s disease. Ann Oncol 10(5):593–595PubMed
122.
Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA et al (2001) A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood 97(3):616–623PubMed
123.
Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH et al (2002) Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol 13(10):1628–1635PubMed
124.
Baetz T, Belch A, Couban S, Imrie K, Yau J, Myers R et al (2003) Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol 14(12):1762–1767PubMed
125.
Plunkett W, Huang P, Searcy CE, Gandhi V (1996) Gemcitabine: preclinical pharmacology and mechanisms of action. Semin Oncol 23(5 Suppl 10):3–15PubMed
126.
Friedberg JW, Neuberg D, Kim H, Miyata S, McCauley M, Fisher DC et al (2003) Gemcitabine added to doxorubicin, bleomycin, and vinblastine for the treatment of de novo Hodgkin disease: unacceptable acute pulmonary toxicity. Cancer 98(5):978–982PubMed
127.
Bierman PJ, Bagin RG, Jagannath S, Vose JM, Spitzer G, Kessinger A et al (1993) High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin’s disease: long-term follow-up in 128 patients. Ann Oncol 4(9):767–773PubMed
128.
Brice P, Marolleau JP, Pautier P, Makke J, Cazals D, Dombret H et al (1996) Hematologic recovery and survival of lymphoma patients after autologous stem-cell transplantation: comparison of bone marrow and peripheral blood progenitor cells. Leuk Lymphoma 22(5–6):449–456PubMed
129.
Sweetenham JW, Taghipour G, Milligan D, Blystad AK, Caballero D, Fassas A et al (1997) High-dose therapy and autologous stem cell rescue for patients with Hodgkin’s disease in first relapse after chemotherapy: results from the EBMT. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 20(9):745–752PubMed
130.
Sweetenham JW, Carella AM, Taghipour G, Cunningham D, Marcus R, Della Volpe A et al (1999) High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin’s disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party. J Clin Oncol 17(10):3101–3109PubMed
131.
Andre M, Henry-Amar M, Pico JL, Brice P, Blaise D, Kuentz M et al (1999) Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin’s disease induction failure: a case-control study. Societe Francaise de Greffe de Moelle. J Clin Oncol 17(1):222–229PubMed
132.
Ferme C, Mounier N, Divine M, Brice P, Stamatoullas A, Reman O et al (2002) Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d’Etudes des Lymphomes de l’Adulte H89 Trial. J Clin Oncol 20(2):467–475PubMed
133.
Perz JB, Giles C, Szydlo R, O’Shea D, Sanz J, Chaidos A et al (2007) LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin’s lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre. Bone Marrow Transplant 39(1):41–47PubMed
134.
Moskowitz CH, Yahalom J, Zelenetz AD, Zhang Z, Filippa D, Teruya-Feldstein J et al (2010) High-dose chemo-radiotherapy for relapsed or refractory hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol 148(6):890–897PubMedCentralPubMed
135.
Ansell SM, Horwitz SM, Engert A, Khan KD, Lin T, Strair R et al (2007) Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin’s lymphoma and anaplastic large-cell lymphoma. J Clin Oncol 25(19):2764–2769PubMed
136.
Younes A, Romaguera J, Hagemeister F, McLaughlin P, Rodriguez MA, Fiumara P et al (2003) A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer 98(2):310–314PubMed
137.
Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT et al (2003) Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood 101(11):4285–4289PubMed
138.
Mendler JH, Kelly J, Voci S, Marquis D, Rich L, Rossi RM et al (2008) Bortezomib and gemcitabine in relapsed or refractory Hodgkin’s lymphoma. Ann Oncol 19(10):1759–1764PubMedCentralPubMed
139.
Younes A, Pro B, Fanale M, McLaughlin P, Neelapu S, Fayad L et al (2007) Isotype-selective HDAC inhibitor MGCD0103 decreases serum TARC concentrations and produces clinical responses in heavily pretreated patients with relapsed classical Hodgkin lymphoma. Blood 110(11):2566