jueves, 6 de junio de 2019

Childhood Hodgkin Lymphoma Treatment (PDQ®) 5/6 —Health Professional Version - National Cancer Institute

Childhood Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute
National Cancer Institute

Childhood Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version


Treatment of Primary Refractory or Recurrent Hodgkin Lymphoma in Children and Adolescents

The excellent response to frontline therapy among children and adolescents with Hodgkin lymphoma limits opportunities to evaluate second-line (salvage) therapy. Because of the small number of patients that fail primary therapy, no uniform second-line treatment strategy exists for this patient population.
Adverse prognostic factors after relapse include the following:[1][Level of evidence: 3iiA]
  • The presence of B symptoms (fever, weight loss, and night sweats) and extranodal disease.[2]
  • Early relapse (occurring 3–12 months from the end of therapy).[3,4]
  • Inadequate response to initial second-line therapy.[4]
Children with localized favorable (relapse ≥12 months after completing therapy) disease recurrences whose original therapy involved reduced cycles of risk-adapted therapy or with chemotherapy alone and/or low-dose involved-field radiation therapy (LD-IRFT) consolidation have a high likelihood of achieving long-term survival after treatment with more intensive conventional chemotherapy.[5,6]
Treatment options for children and adolescents with refractory or recurrent Hodgkin lymphoma include the following:

Chemotherapy and Targeted Therapy

Chemotherapy is the recommended second-line therapy, with the choice of specific agents, dose-intensity, and number of cycles determined by the initial therapy, disease characteristics at progression/relapse, and response to second-line therapy.
Agents used alone or in combination regimens in the treatment of refractory or recurrent pediatric Hodgkin lymphoma include the following:
  • ICE (ifosfamide, carboplatin, and etoposide).[7]
  • Ifosfamide and vinorelbine with or without bortezomib.[8][Level of evidence: 2Div]; [9][Level of evidence: 3iiiDiv]
  • Vinorelbine and gemcitabine.[10]
  • IEP/ABVD/COPP (ifosfamide, etoposide, prednisone/doxorubicin, bleomycin, vinblastine, dacarbazine/cyclophosphamide, vincristine, procarbazine, prednisone).[3]
  • EPIC (etoposide, prednisolone, ifosfamide, and cisplatin).[11]
  • APE (cytosine arabinoside, cisplatin, and etoposide).[12]
  • MIED (high-dose methotrexate, ifosfamide, etoposide, and dexamethasone).[13]
  • Rituximab (for patients with CD20-positive disease) alone or in combination with second-line chemotherapy.[14]
  • Brentuximab vedotin. Brentuximab vedotin has been evaluated in adults with Hodgkin lymphoma. (Refer to the Recurrent Adult Classic HL Treatment section in the PDQ summary on Adult Hodgkin Lymphoma Treatment for more information.) The U.S. Food and Drug Administration (FDA) indications for brentuximab vedotin in adult patients are as follows: (1) classical Hodgkin lymphoma after failure of autologous HCT or after failure of at least two previous multiagent chemotherapy regimens in patients who are not autologous HCT candidates, and (2) classical Hodgkin lymphoma at high risk of relapse or progression, as postautologous HCT consolidation therapy.
    1. A phase I study in adults with CD30-positive lymphomas identified a recommended phase II dose of 1.8 mg/kg on an every 3-week schedule and showed an objective response rate of 50% (6 of 12 patients) at the recommended phase II dose.[15][Level of evidence: 2Div]
    2. A phase II trial in adults with Hodgkin lymphoma (N = 102) who relapsed after autologous HCT showed the following:[16-19]
      • A complete remission rate of 34% and a partial remission rate of 40% was observed.[16-18]
      • Patients who achieved a complete remission (n = 34) had a 3-year progression-free survival (PFS) rate of 58% and a 3-year overall survival (OS) rate of 73%, with only 6 of 34 patients proceeding to allogeneic HCT while in remission.
      • Further follow-up demonstrated a 5-year OS rate of 41% and a PFS rate of 22%. However, patients who achieved a complete remission (38%) had a 5-year OS rate of 64% and a PFS rate of 52%.[19][Level of evidence: 2A]
    3. The number of pediatric patients treated with brentuximab vedotin is not sufficient to determine whether they respond differently than do adult patients. Clearance and volume of brentuximab vedotin significantly correlates with weight (P < .001), and its area under the curve and C max are lower in children than those reported in adult studies with weekly dosing.[20]
    4. The Children’s Oncology Group phase I/II study AHOD1221 (NCT01780662)investigated treatment with brentuximab vedotin and gemcitabine in 46 children and young adults with primary refractory Hodgkin Lymphoma or early relapse.[21]
      • The recommended phase II dose of brentuximab vedotin was 1.8 mg/kg.
      • Twenty-four of 42 patients (57%; 95% CI, 41%–72%) treated at this dose level experienced a complete response within the first four cycles. Four of 13 patients (31%) with partial response or stable disease had all target lesions with Deauville scores of 3 or less after cycle four. By modern response criteria, these are also complete responses, increasing the complete response rate to 28 of 42 patients (67%; 95% confidence interval [CI], 51%–80%).
      • Compared with alternate second-line regimens, brentuximab vedotin with gemcitabine offers the advantage of avoiding agents associated with late treatment-related sequelae, such as anthracyclines, alkylators, or epipodophyllotoxins.
    There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin with chemotherapy.

Checkpoint Inhibitor Therapy

Treatments that block the interaction between programmed death-1 (PD-1) and its ligands have shown high levels of activity in adults with Hodgkin lymphoma. The anti–PD-1 antibody nivolumab induced objective responses in 20 of 23 adult patients (87%) with relapsed Hodgkin lymphoma.[22] Another anti–PD-1 antibody, pembrolizumab, produced an objective response rate of 65% in 31 heavily pretreated adult patients with Hodgkin lymphoma who relapsed after receiving brentuximab vedotin.[23] (Refer to the Recurrent Adult Classic HL Treatment section in the PDQ summary on Adult Hodgkin Lymphoma Treatment for more information.)
Evidence (pembrolizumab):
  1. Studies that used pembrolizumab to treat patients with relapsed Hodgkin lymphoma have reported the following:[23]; [24][Level of evidence: 3iiiDiv]
    • An overall response rate of 64% to 74%, with a complete response rate of 22.4% (95% CI, 6.9%–28.6%).
    • Pembrolizumab is well tolerated by patients and can be used to achieve a clinical complete remission before autologous or allogeneic HCT.
    • Pembrolizumab is FDA approved for use in cases of refractory disease or relapse after three or more lines of therapy.
Nivolumab is FDA approved in adult patients with classical Hodgkin lymphoma who have relapsed or progressed after autologous HCT and brentuximab vedotin or three or more lines of systemic therapy that included autologous HCT.[22,25]
There are ongoing trials to determine the toxicity and efficacy of combining brentuximab vedotin and nivolumab with chemotherapy in pediatric patients with Hodgkin lymphoma.

Chemotherapy Followed by Autologous Hematopoietic Cell Transplantation (HCT)

Myeloablative chemotherapy with autologous HCT is the recommended approach for patients who develop refractory disease during therapy or relapsed disease within 1 year after completing therapy.[7,26-33]; [34][Level of evidence: 3iiA]; [35][Level of evidence: 3iiiA] In addition, this approach is also recommended for those who recur with extensive disease after the first year of completing therapy or for those who recur after initial therapy that included intensive (alkylating agents and anthracyclines) multiagent chemotherapy and radiation therapy.
  • Autologous HCT has been preferred for patients with relapsed Hodgkin lymphoma because of the historically high transplant-related mortality (TRM) associated with allogeneic transplantation.[36] After autologous HCT, the projected survival rate is 45% to 70% and PFS is 30% to 89%.[18,34,37,38]; [39][Level of evidence: 3iiiA]
  • Brentuximab vedotin as maintenance therapy given for 1 year after autologous HCT in adult patients with high risk of relapse or progression was demonstrated to improve PFS in a randomized, placebo-controlled, phase III trial.[40]
  • A multicenter, open-label, dose-escalation, phase I/II study evaluated the safety, maximum tolerated dose, and pharmacokinetics of brentuximab vedotin and identified a recommended phase II dose in 36 pediatric patients with relapsed or refractory classical Hodgkin lymphoma (n = 19) and anaplastic large cell lymphoma (n = 17). Toxicity was manageable (33% of patients had transient, limited-severity peripheral neuropathy), the maximum tolerated dose was not reached, and pediatric pharmacokinetics were similar to that of adults. The recommended phase II dose of brentuximab vedotin was 1.8 mg/m2 and it was administered for up to 16 cycles (median, 10 cycles) on the phase II arm. Among Hodgkin lymphoma participants on the phase II arm, 47% of patients achieved an overall response (33% complete response, 13% partial response), which provided a bridge to HCT for some patients.[41][Level of evidence: 3iii]
  • The most commonly utilized preparative regimen for peripheral blood stem cell transplant is the BEAM regimen (carmustine [BCNU], etoposide, cytarabine, melphalan) or CBV regimen (cyclophosphamide, carmustine, etoposide).[32,37-39]; [34][Level of evidence: 3iiA]; [35][Level of evidence:3iiiA] Carmustine may produce significant pulmonary toxicity.[39]
  • Other noncarmustine-containing preparative regimens have been utilized, including high-dose busulfan, etoposide, and cyclophosphamide [42] and lomustine, cytarabine, cyclophosphamide, and etoposide (LACE).[43][Level of evidence: 3iii]
Adverse prognostic features for outcome after autologous HCT include extranodal disease at relapse, bulky mediastinal mass at time of transplant, advanced stage at relapse, primary refractory disease, poor response to chemotherapy, and a positive positron emission tomography scan before autologous HCT.[1,37-39,44,45]
(Refer to the Autologous HCT section in the PDQ summary on Childhood Hematopoietic Cell Transplantation for more information about transplantation.)

Chemotherapy Followed by Allogeneic HCT

For patients who fail after autologous HCT or for patients with chemoresistant disease, allogeneic HCT has been used with encouraging results.[11,36,46-48] Investigations of reduced-intensity allogeneic transplantation that typically use fludarabine or low-dose total body irradiation to provide a nontoxic immunosuppression have demonstrated acceptable rates of TRM.[49-53]
(Refer to the Allogeneic HCT section in the PDQ summary on Childhood Hematopoietic Cell Transplantation for more information about transplantation.)

Involved-site Radiation Therapy (ISRT)

ISRT to sites of recurrent disease may enhance local control if these sites have not been previously irradiated. ISRT is generally administered after high-dose chemotherapy and stem cell rescue.[54] For patients who are not responsive to salvage therapy, ISRT may be an appropriate consideration before HCT.[55]

Response Rates for Primary Refractory Hodgkin Lymphoma

Salvage rates for patients with primary refractory Hodgkin lymphoma are poor even with autologous HCT and radiation. However, intensification of therapy followed by HCT consolidation has been reported to achieve long-term survival in some studies.
Evidence (response to treatment of primary refractory Hodgkin lymphoma):
  1. In one large series, 5-year OS after primary refractory Hodgkin lymphoma was attained with aggressive second-line therapy (high-dose chemoradiation therapy) and autologous HCT in 49% of patients.[56]
  2. In a Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) study, patients with primary refractory Hodgkin lymphoma (progressive disease on therapy or relapse within 3 months from the end of therapy) had 10-year event-free survival (EFS) and OS rates of 41% and 51%, respectively.[3]
  3. A study of 53 adolescent patients of the same types as those who participated in the GPOH study had similar results for EFS and OS.[57] Chemosensitivity to standard-dose second-line chemotherapy predicted a better survival (66% OS), and tumors that remained refractory to chemotherapy did poorly (17% OS).[58]
  4. Another group has reported the PFS post-HCT for chemosensitive patients as 80%, compared with 0% for those with chemoresistant disease.[34]

Second Relapse After Initial Treatment With Autologous HCT

In a phase II study, patients (median age, 26.5 years) who had relapsed or refractory disease after autologous HCT received brentuximab vedotin, with an objective response rate of 73% and a complete remission rate of 34%. Patients who achieved a complete remission (n = 34) had a 3-year PFS rate of 58% and a 3-year OS rate of 73%, with only 6 of 34 patients proceeding to allogeneic SCT while in remission.[18][Level of evidence: 2A]

Treatment Options Under Clinical Evaluation

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
  1. Anti–PD-1 antibodies being studied in children with Hodgkin lymphoma include nivolumab (ADVL1412 [NCT02304458]) and pembrolizumab (NCT02332668). The anti–PD-L1 antibody atezolizumab is also being studied in children with Hodgkin lymphoma (NCT02541604). Nivolumab in combination with brentuximab vedotin is being studied in an international phase II trial in children with Hodgkin lymphoma (CheckMate 755 [NCT02927769]).

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Metzger ML, Hudson MM, Krasin MJ, et al.: Initial response to salvage therapy determines prognosis in relapsed pediatric Hodgkin lymphoma patients. Cancer 116 (18): 4376-84, 2010. [PUBMED Abstract]
  2. 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 97 (3): 616-23, 2001. [PUBMED Abstract]
  3. Schellong G, Dörffel 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 23 (25): 6181-9, 2005. [PUBMED Abstract]
  4. Gorde-Grosjean S, Oberlin O, Leblanc T, et al.: Outcome of children and adolescents with recurrent/refractory classical Hodgkin lymphoma, a study from the Société Française de Lutte contre le Cancer des Enfants et des Adolescents (SFCE). Br J Haematol 158 (5): 649-56, 2012. [PUBMED Abstract]
  5. Nachman JB, Sposto R, Herzog P, et al.: Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol 20 (18): 3765-71, 2002. [PUBMED Abstract]
  6. Rühl U, Albrecht M, Dieckmann K, et al.: Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial. Int J Radiat Oncol Biol Phys 51 (5): 1209-18, 2001. [PUBMED Abstract]
  7. Cairo MS, Shen V, Krailo MD, et al.: Prospective randomized trial between two doses of granulocyte colony-stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent or refractory solid tumors: a children's cancer group report. J Pediatr Hematol Oncol 23 (1): 30-8, 2001. [PUBMED Abstract]
  8. Horton TM, Drachtman RA, Chen L, et al.: A phase 2 study of bortezomib in combination with ifosfamide/vinorelbine in paediatric patients and young adults with refractory/recurrent Hodgkin lymphoma: a Children's Oncology Group study. Br J Haematol 170 (1): 118-22, 2015. [PUBMED Abstract]
  9. Trippett TM, Schwartz CL, Guillerman RP, et al.: Ifosfamide and vinorelbine is an effective reinduction regimen in children with refractory/relapsed Hodgkin lymphoma, AHOD00P1: a children's oncology group report. Pediatr Blood Cancer 62 (1): 60-4, 2015. [PUBMED Abstract]
  10. Cole PD, Schwartz CL, Drachtman RA, et al.: Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin's disease: a children's oncology group report. J Clin Oncol 27 (9): 1456-61, 2009. [PUBMED Abstract]
  11. Shankar A, Hayward J, Kirkwood A, et al.: Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma--results of the UK HD3 relapse treatment strategy. Br J Haematol 165 (4): 534-44, 2014. [PUBMED Abstract]
  12. Wimmer RS, Chauvenet AR, London WB, et al.: APE chemotherapy for children with relapsed Hodgkin disease: a Pediatric Oncology Group trial. Pediatr Blood Cancer 46 (3): 320-4, 2006. [PUBMED Abstract]
  13. Sandlund JT, Pui CH, Mahmoud H, et al.: Efficacy of high-dose methotrexate, ifosfamide, etoposide and dexamethasone salvage therapy for recurrent or refractory childhood malignant lymphoma. Ann Oncol 22 (2): 468-71, 2011. [PUBMED Abstract]
  14. Schulz H, Rehwald U, Morschhauser F, et al.: Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood 111 (1): 109-11, 2008. [PUBMED Abstract]
  15. Younes A, Bartlett NL, Leonard JP, et al.: Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363 (19): 1812-21, 2010. [PUBMED Abstract]
  16. Sea: ADCETRIS (Brentuximab Vedotin): Prescribing Information. Bothell, Wa: Seattle Genetics, 2012. Available online. Last accessed April 12, 2019.
  17. 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 30 (18): 2183-9, 2012. [PUBMED Abstract]
  18. 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 125 (8): 1236-43, 2015. [PUBMED Abstract]
  19. Chen R, Gopal AK, Smith SE, et al.: Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 128 (12): 1562-6, 2016. [PUBMED Abstract]
  20. Flerlage JE, Metzger ML, Wu J, et al.: Pharmacokinetics, immunogenicity, and safety of weekly dosing of brentuximab vedotin in pediatric patients with Hodgkin lymphoma. Cancer Chemother Pharmacol 78 (6): 1217-1223, 2016. [PUBMED Abstract]
  21. Cole PD, McCarten KM, Pei Q, et al.: Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1-2 trial. Lancet Oncol 19 (9): 1229-1238, 2018. [PUBMED Abstract]
  22. Ansell SM, Lesokhin AM, Borrello I, et al.: PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 372 (4): 311-9, 2015. [PUBMED Abstract]
  23. Armand P, Shipp MA, Ribrag V, et al.: Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol 34 (31): 3733-3739, 2016. [PUBMED Abstract]
  24. Chen R, Zinzani PL, Fanale MA, et al.: Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol 35 (19): 2125-2132, 2017. [PUBMED Abstract]
  25. Younes A, Santoro A, Shipp M, et al.: Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17 (9): 1283-94, 2016. [PUBMED Abstract]
  26. 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 Syst Rev 6: CD009411, 2013. [PUBMED Abstract]
  27. Aparicio J, Segura A, Garcerá S, et al.: ESHAP is an active regimen for relapsing Hodgkin's disease. Ann Oncol 10 (5): 593-5, 1999. [PUBMED Abstract]
  28. Kobrinsky NL, Sposto R, Shah NR, et al.: Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. J Clin Oncol 19 (9): 2390-6, 2001. [PUBMED Abstract]
  29. Bonfante V, Viviani S, Santoro A, et al.: Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease. Br J Haematol 103 (2): 533-5, 1998. [PUBMED Abstract]
  30. Zinzani PL, Bendandi M, Stefoni V, et al.: Value of gemcitabine treatment in heavily pretreated Hodgkin's disease patients. Haematologica 85 (9): 926-9, 2000. [PUBMED Abstract]
  31. Santoro A, Bredenfeld H, Devizzi L, et al.: Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. J Clin Oncol 18 (13): 2615-9, 2000. [PUBMED Abstract]
  32. Baker KS, Gordon BG, Gross TG, et al.: Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin's disease in children and adolescents. J Clin Oncol 17 (3): 825-31, 1999. [PUBMED Abstract]
  33. Akhtar S, Rauf SM, Elhassan TA, et al.: Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma. Ann Hematol 95 (9): 1521-35, 2016. [PUBMED Abstract]
  34. Shafer JA, Heslop HE, Brenner MK, et al.: Outcome of hematopoietic stem cell transplant as salvage therapy for Hodgkin's lymphoma in adolescents and young adults at a single institution. Leuk Lymphoma 51 (4): 664-70, 2010. [PUBMED Abstract]
  35. Claviez A, Sureda A, Schmitz N: Haematopoietic SCT for children and adolescents with relapsed and refractory Hodgkin's lymphoma. Bone Marrow Transplant 42 (Suppl 2): S16-24, 2008. [PUBMED Abstract]
  36. 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 31 (8): 667-78, 2003. [PUBMED Abstract]
  37. Lieskovsky YE, Donaldson SS, Torres MA, et al.: High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin's disease: results and prognostic indices. J Clin Oncol 22 (22): 4532-40, 2004. [PUBMED Abstract]
  38. Akhtar S, Abdelsalam M, El Weshi A, et al.: High-dose chemotherapy and autologous stem cell transplantation for Hodgkin's lymphoma in the kingdom of Saudi Arabia: King Faisal specialist hospital and research center experience. Bone Marrow Transplant 42 (Suppl 1): S37-S40, 2008. [PUBMED Abstract]
  39. Harris RE, Termuhlen AM, Smith LM, et al.: Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children's Oncology Group study A5962. Biol Blood Marrow Transplant 17 (2): 249-58, 2011. [PUBMED Abstract]
  40. 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 randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 385 (9980): 1853-62, 2015. [PUBMED Abstract]
  41. Locatelli F, Mauz-Koerholz C, Neville K, et al.: Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. Lancet Haematol 5 (10): e450-e461, 2018. [PUBMED Abstract]
  42. Wadehra N, Farag S, Bolwell B, et al.: Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation. Biol Blood Marrow Transplant 12 (12): 1343-9, 2006. [PUBMED Abstract]
  43. Gupta A, Gokarn A, Rajamanickam D, et al.: Lomustine, cytarabine, cyclophosphamide, etoposide - An effective conditioning regimen in autologous hematopoietic stem cell transplant for primary refractory or relapsed lymphoma: Analysis of toxicity, long-term outcome, and prognostic factors. J Cancer Res Ther 14 (5): 926-933, 2018 Jul-Sep. [PUBMED Abstract]
  44. 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 109 (12): 2481-9, 2007. [PUBMED Abstract]
  45. Satwani P, Ahn KW, Carreras J, et al.: A prognostic model predicting autologous transplantation outcomes in children, adolescents and young adults with Hodgkin lymphoma. Bone Marrow Transplant 50 (11): 1416-23, 2015. [PUBMED Abstract]
  46. Cooney JP, Stiff PJ, Toor AA, et al.: BEAM allogeneic transplantation for patients with Hodgkin's disease who relapse after autologous transplantation is safe and effective. Biol Blood Marrow Transplant 9 (3): 177-82, 2003. [PUBMED Abstract]
  47. Claviez A, Klingebiel T, Beyer J, et al.: Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin's disease. Ann Hematol 83 (4): 237-41, 2004. [PUBMED Abstract]
  48. Sureda A, Schmitz N: Role of allogeneic stem cell transplantation in relapsed or refractory Hodgkin's disease. Ann Oncol 13 (Suppl 1): 128-32, 2002. [PUBMED Abstract]
  49. Carella AM, Cavaliere M, Lerma E, et al.: Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma. J Clin Oncol 18 (23): 3918-24, 2000. [PUBMED Abstract]
  50. 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 100 (13): 4310-6, 2002. [PUBMED Abstract]
  51. 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 15 (1): 109-17, 2009. [PUBMED Abstract]
  52. 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 94 (2): 230-8, 2009. [PUBMED Abstract]
  53. Rauf MS, Maghfoor I, Elhassan TA, et al.: High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy. Med Oncol 32 (1): 388, 2015. [PUBMED Abstract]
  54. Wadhwa P, Shina DC, Schenkein D, et al.: Should involved-field radiation therapy be used as an adjunct to lymphoma autotransplantation? Bone Marrow Transplant 29 (3): 183-9, 2002. [PUBMED Abstract]
  55. Constine LS, Yahalom J, Ng AK, et al.: The Role of Radiation Therapy in Patients With Relapsed or Refractory Hodgkin Lymphoma: Guidelines From the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 100 (5): 1100-1118, 2018. [PUBMED Abstract]
  56. Morabito F, Stelitano C, Luminari S, et al.: The role of high-dose therapy and autologous stem cell transplantation in patients with primary refractory Hodgkin's lymphoma: a report from the Gruppo Italiano per lo Studio dei Linfomi (GISL). Bone Marrow Transplant 37 (3): 283-8, 2006. [PUBMED Abstract]
  57. Akhtar S, El Weshi A, Rahal M, et al.: High-dose chemotherapy and autologous stem cell transplant in adolescent patients with relapsed or refractory Hodgkin's lymphoma. Bone Marrow Transplant 45 (3): 476-82, 2010. [PUBMED Abstract]
  58. Moskowitz CH, Kewalramani T, Nimer SD, et al.: Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease. Br J Haematol 124 (5): 645-52, 2004. [PUBMED Abstract]

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