Advanced search
Publication Cover
Expert Opinion on Biological Therapy Volume 16, 2016 - Issue 3
Submit an article Journal homepage
854
Views
4
CrossRef citations to date
0
Altmetric
Reviews

Salvage treatment for relapsed/refractory Hodgkin lymphoma: role of allografting, brentuximab vedotin and newer agents

Massimo MartinoHematology and Stem Cells Transplantation Unit, CTMO, Azienda Ospedaliera ‘BMM’, Reggio, ItalyCorrespondence[email protected]
,
Moreno FestucciaDivision of Hematology, A.O.U. Citta’ della Salute e della Scienza di Torino - Presidio Molinette, and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
,
Roberta FedeleHematology and Stem Cells Transplantation Unit, CTMO, Azienda Ospedaliera ‘BMM’, Reggio, Italy
,
Giuseppe ConsoleHematology and Stem Cells Transplantation Unit, CTMO, Azienda Ospedaliera ‘BMM’, Reggio, Italy
,
Michele CimminielloHematology and Stem Cell Transplant Unit, Azienda Ospedaliera San Carlo, Potenza, Italy
,
Paolo GavarottiDivision of Hematology, A.O.U. Citta’ della Salute e della Scienza di Torino - Presidio Molinette, and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
&
Benedetto BrunoDivision of Hematology, A.O.U. Citta’ della Salute e della Scienza di Torino - Presidio Molinette, and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
 show all
Pages 347-364 | Received 24 Aug 2015, Accepted 08 Dec 2015, Published online: 06 Feb 2016

References

  • Papers of special note have been highlighted as:
  • ● of interest (●)
  • ●● of considerable interest
  • Ansell SM. Hodgkin lymphoma: 2014 update on diagnosis, risk stratifıcation, and management. Am J Hematol. 2014;89:771–779.
  • SEER Stat Fact Sheets: Leukemia. NCI Surveillance, Epidemiology, and End Results Program. [ cited 2014 Aug 18]. Available from: http://seer.cancer.gov/statfacts/html/hodg.html.
  • Eichenauer DA, Engert A, André M, et al., ESMO Guidelines Working Group. Hodgkin’s lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [ abstract]. Ann Oncol. 2014;25:iii70–iii75.
  • Jagadeesh D, Diefenbach C, Evens AM. Hodgkin lymphoma in older patients: challenges and opportunities to improve outcomes. Hematol Oncol. 2013;31:69–75.
  • [Guideline] National Comprehensive Cancer Network. Hodgkin lymphoma. Version 2.2015. NCCN. [ cited 2015 Jun 30]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf.
  • Josting A, Rueffer U, Franklin J, et al. Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood. 2000;96:1280–1286.
  • Josting A, Franklin J, May M, et al. New prognostic score based on treatment outcome of patients with relapsed Hodgkin’s lymphoma registered in the database of the German Hodgkin’s lymphoma study group. J Clin Oncol. 2002;20:221–230.
  • Meyer RM, Gospodarowicz MK, Connors JM, et al.; Eastern Cooperative Oncology Group. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin’s lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23:4634–4642.
  • Meyer RM, Gospodarowicz MK, Connors JM, et al. NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med. 2012;366:399–408.
  • Maucort-Boulch D, Djeridane M, Roy P, et al. Predictive and discriminating three-risk-group prognostic scoring system for staging Hodgkin lymphomas. Cancer. 2007;109:256–264.
  • Scott DW, Chan FC, Hong F, et al. Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical Hodgkin lymphoma. J Clin Oncol. 2013;31:692–700.
  • Bonadonna G, Bonfante V, Viviani S, et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin’s disease: long-term results. J Clin Oncol. 2004;22:2835–2841.
  • Bartlett NL, Rosenberg SA, Hoppe RT, et al. Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin’s disease: a preliminary report. J Clin Oncol. 1995;13:1080–1088.
  • Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med. 2003;348:2386–2395.
  • Duggan DB, Petroni GR, Johnson JL, et al. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin’s disease: report of an intergroup trial. J Clin Oncol. 2003;21:607–614.
  • Canellos G, Anderson J, Propert K, et al. Chemotherapy of Advanced Hodgkin’s Disease with MOPP, ABVD, or MOPP Alternating with ABVD. N Engl J Med. 1992;327:1478–1484.
  • Horning SJ, Hoppe RT, Breslin S, et al. Stanford V and radiotherapy for locally extensive and advanced Hodgkin’s disease: mature results of a prospective clinical trial. J Clin Oncol. 2002;20:630–637.
  • Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32:3048–3058.
  • McCarthy PL Jr, Hahn T, Hassebroek A, et al Trends in use of and survival after autologous hematopoietic cell transplantation in North America, 1995-2005: significant improvement in survival for lymphoma and myeloma during a period of increasing recipient age. Biol Blood Marrow Transplant. 2013;19:1116–1123.
  • Passweg JR, Baldomero H, Bader P, et al Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant. 2015;50:476–482.
  • Canellos GP, Rosenberg SA, Friedberg JW, et al. Treatment of Hodgkin lymphoma: a 50-year perspective. J Clin Oncol. 2014;32:163–168.
  • Perales MA, Ceberio I, Armand P, et al. Role of cytotoxic therapy with hematopoietic cell transplantation in the treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21:971–983.
  • Hoppe RT, Advani RH, Ai WZ, et al. Hodgkin lymphoma, version 2.2015. J Natl Compr Canc Netw. 2015;13:554–586.
  • Federico M, Bellei M, Brice P, et al. 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. 2003;21:2320–2325.
  • Arakelyan N, Berthou C, Desablens B, et al. Early versus late intensification for patients with high-risk Hodgkin lymphoma-3 cycles of intensive chemotherapy plus low-dose lymph node 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. 2008;113:3323–3330.
  • Carella AM, Bellei M, Brice P, et al. High-dose therapy and autologous stem cell transplantation versus conventional therapy for patients with advanced Hodgkin’s lymphoma responding to front-line therapy: long-term results. Haematologica. 2009;94:146–148.
  • Younes A, Bartlett NL, Leonard JP, et al. Brentuximab Vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812–1821.
  • Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of Brentuximab Vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30:2183–2189.

●● Brentuximab Vedotin (BV) was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT).

  • Rothe A, Sasse S, Goergen H, et al. Brentuximab Vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012;120:1470–1472.
  • Zinzani PL, Viviani S, Anastasia A, et al. Brentuximab Vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials. Haematologica. 2013;98:1232–1236.
  • Zinzani PL, Corradini P, Gianni AM, et al. Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position Paper. Clin Lymphoma Myeloma Leuk. 2015;15:507–513. DOI:10.1016/j.clml.2015.06.008.
  • Aparicio J, Segura A, Garcerá S, et al. ESHAP is an active regimen for relapsing Hodgkin’s disease. Ann Oncol. 1999;10:593–595.
  • Josting A, Rudolph C, Reiser M, et al. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol. 2002;13:1628–1635.
  • Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin’s lymphoma. Haematologica. 2007;92:35–41.
  • Schmitz N, Pfistner B, Sextro M, et al Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet. 2002;359:2065–2071.
  • Vigouroux S, Milpied N, Andrieu JM, et al. Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin’s disease: comparison with combined-modality therapy. Bone Marrow Transplant. 2002;29:833–842.
  • Fermé C, Mounier N, Diviné M, et al. 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. 2002;20:467–475.
  • Stiff PJ, Unger JM, Forman SJ, et al.; Southwest Oncology Group. The value of augmented preparative regimens combined with an autologous bone marrow transplant for the management of relapsed or refractory Hodgkin disease: a Southwest Oncology Group phase II trial. Biol Blood Marrow Transplant. 2003;9:529–539.
  • Tarella C, Cuttica A, Vitolo U, et al. High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence. Cancer. 2003;97:2748–2759.
  • Popat U, Hosing C, Saliba RM, et al. Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin’s lymphoma. Bone Marrow Transplant. 2004;33:1015–1023.
  • Lavoie JC, Connors JM, Phillips GL, et al. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100patients treated in Vancouver. Blood. 2005;106:1473–1478.
  • Morabito F, Stelitano C, Luminari S, et al. The role of high-dose therapyand autologous stem cell transplantation in patients with primaryrefractory Hodgkin’s lymphoma: a report from the Gruppo Italiano per lo Studio dei Linfomi (GISL). Bone Marrow Transplant. 2006;37:283–288.
  • Czyz J, Dziadziuszko R, Knopinska-Postuszuy W, et al. Outcome and prognostic factors in advanced Hodgkin’s disease treated with high dose chemotherapy and autologous stem cell transplantation: astudy of 341 patients. Ann Oncol. 2004;15:1222–1230.
  • Schellong G, Dorffel W, Claviez A, et al. Salvage therapy of progressive and recurrent Hodgkin’s disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group. J Clin Oncol. 2005;23:6181–6189.
  • Sieniawski M, Franklin J, Nogova L, et al. Outcome of patients experiencing progression or relapse after primary treatment with two cycles of chemotherapy and radiotherapy for early-stage favorable Hodgkin’s lymphoma. J Clin Oncol. 2007;25:2000–2005.
  • Viviani S, Di Nicola M, Bonfante V, et al. Long-term results of high dose chemotherapy with autologous bone marrow or peripheralstem cell transplant as first salvage treatment for relapsed or refractory Hodgkin lymphoma: a single institution experience. Leuk Lymph. 2010;51:1251–1259. DOI:10.3109/10428194.2010.486090.
  • Garfin PM, Link MP, Donaldson SS, et al. Improved outcomes after autologous bone marrow transplantation for children with relapsed or refractory Hodgkin lymphoma: twenty years experience at a single institution. Biol Blood Marrow Transplant. 2015;21:326–334.
  • Nieto Y, Popat U, Anderlini P, et al. Autologous stem cell transplantation for refractory or poor-risk relapsed Hodgkin’s lymphoma:effect of the specific high-dose chemotherapy regimen on outcome. Biol Blood Marrow Transplant. 2013;19:410–417.
  • Rancea M, Monsef I, Von Tresckow B, et al. High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database System Rev. 2013;6:CD009411. DOI:10.1002/14651858.CD009411.pub2.
  • Brice P, Bouabdallah R, Moreau P, et al. Prognostic factors for survival after high-dose therapy and autologous stem cell transplantation for patients with relapsing Hodgkin’s disease: analysis of 280 patients from the French registry. Société Française de Greffe de Moëlle. Bone Marrow Transplant. 1997;20:21–26.
  • Moskowitz CH, Nimer SD, Zelenetz AD, et al. 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. 2001;97:616–623.
  • Jabbour E, Hosing C, Ayers G, et al. Pretransplant positive positron emission tomography/gallium scans predict poor outcome in patients with recurrent/refractory Hodgkin lymphoma. Cancer. 2007;109:2481–2489.
  • Moskowitz AJ, Yahalom J, Kewalramani T, et al. Pretransplantation functional imaging predicts outcome following autologous stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Blood. 2010;116:4934–4937.
  • Colwill R, Crump M, Couture F, et al. Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin’s disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol. 1995;13:396–402.
  • Villa D, Seshadri T, Puig N, et al. Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin’s lymphoma resistant to platinum-containing first-line salvage chemotherapy. Haematologica. 2012;97:751–757.
  • Majhail NS, Weisdorf DJ, Defor TE, et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2006;12:1065–1072.
  • Ansell S. Novel agents in the therapy of Hodgkin lymphoma. Am Soc Clin Oncol Educ Book. 2015;35:e479–82. DOI:10.14694/EdBook_AM.2015.35.e479.
  • Montes-Moreno S. Hodgkin’s Lymphomas: a Tumor recognized by its microenvironment. Adv Hematol. 2011;2011:142395. DOI:10.1155/2011/142395.
  • Durkop H, Latza U, Hummel M, et al. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin’s disease. Cell. 1992;68:421–427.
  • Smith CA, Gruss HJ, Davis T, et al. CD30 antigen, a marker for Hodgkin’s lymphoma, is a receptor whose ligand defınes an emerging family of cytokines with homology to TNF. Cell. 1993;73:1349–1360.
  • Dubowchik GM, Mosure K, Knipe JO, et al. Cathepsin B-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (Taxol®), mitomycin C and doxorubicin. Bioorg Med Chem Lett. 1998;8:3347–3352. DOI:10.1016/S0960-894X(98)00610-6.
  • Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102:1458–1465. DOI:10.1182/blood-2003-01-0039.
  • Sanderson RJ, Hering MA, James SF, et al. In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res. 2005;11:843–852.
  • Okeley NM, Miyamoto JB, Zhang X, et al. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res. 2010;16:888–897.
  • ADCETRIS (Brentuximab Vedotin) for injection [package insert] [Internet]. Bothell (WA): Seattle Genetics, Inc; 2012 [cited 2013 Jul 30]. Available from: http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf
  • De Claro RA, McGinn K, Kwitkowski V, et al. U.S. Food and Drug Administration approval summary: Brentuximab Vedotin for the treatment of relapsed Hodgkin lymphoma or relapsed systemic anaplastic large-cell lymphoma. Clin Cancer Res. 2012;18:5845–5849.
  • Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–586.
  • Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase 2 study of Brentuximab Vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125:1236–1243.
  • Chen RW, Palmer J, Martin P, et al. Results of a phase II trial of Brentuximab Vedotin as first line salvage therapy in relapsed/refractory HL prior to AHCT. Blood. 2014;124:501.
  • Younes A, Connors JM, Park SI, et al. Brentuximab Vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013;14:1348–1356.
  • Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab Vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853–1862.

●● Early consolidation with BV after ASCT improved progression-free survival (PFS).

  • Moskowitz AJ, Schöder H, Yahalom J, et al. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin’s lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol. 2015;16:284–292.
  • Bonthapally V, Wu E, Macalalad A, et al. Brentuximab Vedotin in relapsed/refractory Hodgkin lymphoma post-autologous transplant: meta-analysis versus historical data. Curr Med Res Opin. 2015; 16 March 2015. [ published online]. DOI:10.1185/03007995.2015.1030378.
  • Bonthapally V, Yang H, Ayyagari R, et al. Brentuximab Vedotin compared with other therapies in relapsed/refractory Hodgkin lymphoma post autologous stem cell transplant: median overall survival meta-analysis. Curr Med Res Opin. 2015;31:1377–1389.
  • LaCasce A, Bociek RG, Matous J, et al. Brentuximab Vedotin in combination with bendamustine for patients with Hodgkin lymphoma who are relapsed or refractory after frontline therapy. Blood. 2014;124:293.
  • Von Tresckow B, Diehl V. An update on emerging drugs for Hodgkin lymphoma. Expert Opin Emerg Drugs. 2014;19:215–224.
  • Bagcchi S. Nivolumab shows clinical activity in Hodgkin’s lymphoma. Lancet Oncol. 2015;16:e108. DOI:10.1016/S1470-2045(15)70024-0.
  • Ansell SM. Targeting immune checkpoints in lymphoma. Curr Opin Hematol. 2015;22:337–342.
  • Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–319.
  • Moskowitz CH, Ribrag V, Michot JM, et al. PD-1 blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical Hodgkin lymphoma after Brentuximab Vedotin failure: preliminary results from a phase 1b study (KEYNOTE-013). Blood. 2014;124:290.
  • Sureda A, Schmitz N. Role of allogeneic stem cell transplantation in relapsed or refractory Hodgkin’s disease. Ann Oncol. 2002;13:128–132.
  • Moscato T, Fedele R, Messina G, et al. Hematopoietic progenitor cells transplantation for recurrent or refractory Hodgkin’s lymphoma. Expert Opin Biol Ther. 2013;13:1013–1027.
  • Castagna L, Carlo-Stella C, Mazza R, et al. Current role of autologous and allogeneic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2015;7:e2015015. DOI:10.4084/mjhid.2015.015.
  • Gajewski JL, Phillips GL, Sobocinski KA, et al Bone marrow transplants from HLA identical siblings in advanced Hodgkin’s disease. J Clin Oncol. 1996;14:572–578.
  • Alvarez I, Sureda A, Caballero MD, et al. Non myeloablative stem cell transplantation is an effective therapy for refractory or relapsed Hodgkin lymphoma: results of a spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006;12:172–183.
  • Anderlini P, Saliba R, Acholonu S, et al. Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s disease: low transplant- related mortality and impact of intensity of conditioning regimen. Bone Marrow Transplant. 2005;35:943–951.
  • Anderlini P, Saliba R, Acholonu S, et al. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008;93:257–264.
  • Burroughs LM, O’Donnell PV, Sandmaier BM, et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following non- myeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:1279–1287.
  • Corradini P, Dodero A, Farina L, et al. Allogeneic stem cell transplantation following reduced intensity conditioning can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome. Leukemia. 2007;21:2316–2323.
  • Horstmann K, Boumendil A, Finke J, et al. Second allo-SCT in patients with lymphoma relapse after a first allogeneic transplantation. A retrospective study of the EBMT Lymphoma Working Party. Bone Marrow Transplant. 2015;50:790–794.
  • Devetten MP, Hari PN, Carreras J, et al. Unrelated donor reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2009;15:109–117.
  • Majhail NS, Weisdorf DJ, Wagner JE, et al. Comparable results of umbilical cord blood a HLA-matched sibling donor hematopoietic stem cell transplantation after reduced-intensity preparative regimen for advanced Hodgkin lymphoma. Blood. 2006;107:3804–3807.
  • Marcais A, Porcher R, Robin M, et al. Impact of disease status and stem cell source on the results of reduced intensity conditioning transplant for Hodgkin’s lymphoma: a retrospective study from the French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Haematologica. 2013;98:1467–1475.
  • Milpied N, Fielding AK, Pearce RM, et al Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin’s disease. J Clin Oncol. 1996;14:1291–1296.
  • Peggs KS, Hunter A, Chopra R, et al. Clinical evidence of a graft-versus-Hodgkin’s-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet. 2005;365:1934–1941.
  • Peggs KS, Sureda A, Qian W, et al. Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusionson long-term outcomes. Br J Haematol. 2007;139:70–80.

●● Disease status at stem cell transplantation (SCT) significantly impacted overall survival and PFS.

  • Claviez A, Canals C, Dierickx D, et al. Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation. Blood. 2009;114:2060–2067.
  • Raiola A, Dominietto A, Varaldo R, et al. Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma. Bone Marrow Transplant. 2014;49:190–194.
  • Robinson SP, Goldstone AH, Mackinnon S, et al. Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood. 2002;100:4310–4316.
  • Robinson SP, Sureda A, Canals C, et al. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome. Haematologica. 2009;94:230–238.
  • Sarina B, Castagna L, Farina L, et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010;115:3671–3677.
  • Sureda A, Robinson S, Canals C, et al. Reduced- intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26:455–462.

●● The use of reduced intensity conditioning (RIC) protocols significantly reduced allogeneic-SCT (ALLO-SCT) transplant-related mortality in relapsed HL patients.

  • Sureda A, Canals C, Arranz R, et al. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin’s lymphoma. Results of the HDR-ALLO study – a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012;97:310–317.
  • Raiola AM, Van Lint MT, Valbonesi M, et al. Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: A study on 593 infusions. Bone Marrow Transplant. 2003;31:687–693. DOI:10.1038/sj.bmt.1703883.
  • Champlin R, Khouri I, Komblau S, et al. Reinventing bone marrow transplantation. Nonmyeloablative preparative regimens and induction of graft-vs-malignancy effect. Oncology (Williston Park). 1999;13:621–628.
  • Woolfrey A, Pulsipher MA, Storb R. Nonmyeloablative hematopoietic cell transplant for treatment of immune deficiency. Curr Opin Pediatr. 2001;13:539–545. DOI:10.1097/00008480-200112000-00008.
  • Satwani P, Cooper N, Rao K, et al Reduced intensity conditioning and allogeneic stem cell transplantation in childhood malignant and nonmalignant diseases. Bone Marrow Transplant. 2008;41:173–182. DOI:10.1038/sj.bmt.1705923.
  • Spitzer TR. Haploidentical stem cell transplantation: the always present but overlooked donor. Hematology Am Soc Hematol Educ Program. 2005;2005:390–395. DOI:10.1182/asheducation-2005.1.390.
  • Aversa F, Tabilio A, Velardi A, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339:1186–1193. DOI:10.1056/NEJM199810223391702.
  • Mehta J, Singhal S, Gee AP, et al. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients. Bone Marrow Transplant. 2004;33:389–396. DOI:10.1038/sj.bmt.1704391.
  • Luznik L, O’Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–650.

● Post-SCT cyclophosphamide is effective as graft-versus-host disease (GVHD) prophylaxis after HAPLO-SCT.

  • Thomson KJ, Peggs KS, Smith P, et al. Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin’s lymphoma following autologous stem cell transplantation. Bone Marrow Transplant. 2008;41:765–770.
  • Guglielmi C, Arcese W, Dazzi F, et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: Prognostic relevance of the initial cell dose. Blood. 2002;100:397–405.
  • Peggs KS, Kayani I, Edwards N, et al. Donor lymphocyte infusions modulate relapse risk in mixed chimeras and induce durable salvage in relapsed patients after T-cell-depleted allogeneic transplantation for Hodgkin’s lymphoma. J Clin Oncol. 2011;29:971–978.
  • Ram R, Gooley TA, Maloney DG, et al. Histology and time to progression predict survival for lymphoma recurring after reduced intensity conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17:1537–1545.
  • Akpek G, Ambinder RF, Piantadosi S, et al. Long-term results of blood and marrow transplantation for Hodgkin’s lymphoma. J Clin Oncol. 2001;19:4314–4321.
  • Peniket AJ, Ruiz De Elvira MC, Taghipour G, et al An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant. 2003;31:667–678.
  • Freytes CO, Loberiza FR, Rizzo JD, et al. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry. Blood. 2004;104:3797–3803.
  • Kewalramani T, Nimer SD, Zelenetz AD, et al. Progressive disease following autologous transplantation in patients with chemosensitive relapsed or primary refractory Hodgkin’s disease or aggressive non Hodgkin’s lymphoma. Bone Marrow Transplant. 2003;32:673–679.
  • Smith SM, Van Besien K, Carreras J, et al. Second autologous stem cell transplantation for relapsed lymphoma after a prior autologous transplant. Biol Blood Marrow Transplant. 2008;14:904–912.
  • Castagna L, Sarina B, Todisco E, et al. Allogeneic stem cell transplantation compared with chemotherapy for poor-risk Hodgkin lymphoma. Biol Blood Marrow Transplant. 2009;15:432–438.
  • Crocchiolo R, Castagna L, Garciaz S, et al. Tandem autologous-allogeneic stem cell transplantation as a feasible and effective procedure in high-risk lymphoma patients. Haematologica. 2015;100:e423-e427. DOI:10.3324/haematol.2015.129452.

● Tandem AUTO/ALLO-SCT is feasible and effective in patients with high-risk HD.

  • Thomson KJ, Kayani I, Ardeshna K, et al. A response-adjusted PET-based transplantation strategy in primary resistant and relapsed Hodgkin Lymphoma. Leukemia. 2013;27(6):1419–1422.

●● The study indicates the prognostic value of functional imaging in predicting outcomes of patients with R/R HL.

  • Gibb A, Jones C, Bloor A, et al. Brentuximab Vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013;98:611–614.
  • Chen R, Palmer JM, Thomas SH, et al. Brentuximab Vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2012;119:6379–6381.

●● BV before RIC ALLO-SCT does not appear to adversely affect engraftment, GVHD or survival and may provide sufficient disease control to enable RIC ALLO-SCT.

  • Chen R, Palmer JM, Tsai NC, et al. Brentuximab Vedotin is associated with improved progression-free survival after allogeneic transplantation for Hodgkin lymphoma. Biol Blood Marrow Transplant. 2014;20:1864–1868.
  • Garciaz S, Coso D, Peyrade F, et al. Brentuximab Vedotin followed by allogeneic transplantation as salvage regimen in patients with relapsed and/or refractory Hodgkin’s lymphoma. Hematol Oncol. 2014;32:187–191.
  • Zallio F, Pini M, Busca A, et al. Safety and efficacy of Brentuximab Vedotin (SGN-35) in Hodgkin Lymphoma patients undergoing reduced intensity allogeneic stem cell transplant following a relapse after autologous transplant. Haematologica. 2014;99(s1):431.
  • Michallet AS, Guillermin Y, Deau B, et al. Sequential combination of gemcitabine, vinorelbine, pegylated liposomal doxorubicin and Brentuximab as a bridge regimen to transplant in relapsed or refractory Hodgkin lymphoma. Haematologica. 2015;100:e269–71. DOI:10.3324/haematol.2015.124784.
  • Illidge T, Bouabdallah R, Chen R, et al. Allogeneic transplant following Brentuximab Vedotin in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Leuk Lymphoma. 2015;56:703–710.
  • Steinberg A, Renteria AS, Scigliano E, et al. Bendamustine-brentuximab: bridging to transplant. 2015 BMT Tandem United States; February 11–15; San Diego. BBMT. 2015;21(2):S312–S313. DOI:10.1016/j.bbmt.2014.11.498.
  • Stathis A, Younes A. The new therapeutical scenario of Hodgkin lymphoma. Ann Oncol. 2015 Jun 2;26:2026–2033. DOI:10.1093/annonc/mdv256.
  • Gopal AK, Ramchandren R, O’Connor OA, et al. Safety and efficacy of Brentuximab Vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012;120:560–568.
  • Carlo-Stella C, Ricci F, Dalto S, et al. Brentuximab Vedotin in patients with Hodgkin lymphoma and a failed allogeneic stem cell transplantation: results from a named patient program at four Italian centers. Oncologist. 2015;20:323–328.
  • Theurich S, Malcher J, Wennhold K, et al. Brentuximab Vedotin combined with donor lymphocyte infusions for early relapse of Hodgkin lymphoma after allogeneic stem-cell transplantation induces tumor-specific immunity and sustained clinical remission. J Clin Oncol. 2013;31:e59–e63.
  • Chen YB, McDonough S, Hasserjian R, et al. Expression of CD30 in patients with acute graft-versus-host disease. Blood. 2012;120:691–696.
  • Amedei A, Pimpinelli N, Grassi A, et al. Skin CD30(+) T cells and circulating levels of soluble CD30 are increased in patients with graft versus host disease. Auto Immun Highlights. 2013;5:21–26.
  • Kuruvilla J, Nagy T, Pintilie M, et al. Similar response rates and superior early progression-free survival with gemcitabine, dexamethasone, and cisplatin salvage therapy compared with carmustine, etoposide, cytarabine, and melphalan salvage therapy prior to autologous stem cell transplantation for recurrent or refractory Hodgkin lymphoma. Cancer. 2006;106:353–360.
  • Muenst S, Soysal SD, Tzankov A, et al. The PD-1/PD-L1 pathway: biological background and clinical relevance of an emerging treatment target in immunotherapy. Expert Opin Ther Targets. 2015;19(2):201–211.
  • Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci. 2011;1217:45–59.
  • Schmid-Bindert G, Jiang T. First-line nivolumab (anti-PD-1) monotherapy in advanced NSCLC: the story of immune checkpoint inhibitors and “the sorcerers apprentice”. Transl Lung Cancer Res. 2015;4(3):215–216.
  • Albiges L, Fay AP, Xie W, et al. Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma. Eur J Cancer. 2015;51:2580–2586. DOI:10.1016/j.ejca.2015.08.017.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.