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 Espanol de Linfomas/Trasplante de Medula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation

Abstract

BackgroundAlthough Hodgkin's lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting. Design and MethodsIn this phase II study 92 patients with relapsed Hodgkin's lymphoma and an HLA-identical sibling, a matched unrelated donor or a one antigen mismatched, unrelated donor were treated with salvage chemotherapy followed by reduced intensity allogeneic transplantation. Fourteen patients showed refractory disease and died from progressive lymphoma with a median overall survival after trial entry of 10 months (range, 6-17). Seventy-eight patients proceeded to allograft (unrelated donors, n=23). Fifty were allografted in complete or partial remission and 28 in stable disease. Fludarabine (150 mg/m 2 iv) and melphalan (140 mg/m 2 iv) were used as the conditioning regimen. Anti-thymocyte globulin was additionally used as graft-versus-host-disease prophylaxis for recipients of grafts from unrelated donors. ResultsThe non-relapse mortality rate was 8% at 100 days and 15% at 1 year. Relapse was the major cause of failure. The progression-free survival rate was 47% at 1 year and 18% at 4 years from trial entry. For the allografted population, the progression-free survival rate was 48% at 1 year and 24% at 4 years. Chronic graft-versus-host disease was associated with a lower incidence of relapse. Patients allografted in complete remission had a significantly better outcome. The overall survival rate was 71% at 1 year and 43% at 4 years. ConclusionsAllogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin's lymphoma. The reduced intensity conditioning approach significantly reduced non-relapse mortality; the high relapse rate represents the major remaining challenge in this setting. Blood and Marrow Transplantation. Haematologica 2012;97(2):310-317. doi:10.3324/haematol.2011 . 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

Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant

“…40,41 Importantly, several studies have shown that chemosensitivity at transplantation remains a major predictor of outcome of RIC allogeneic SCT (RIC-allo). 38,41,42 The expert panel acknowledges that RIC-allo may have a role in HL. For patients with primary refractory disease, and for those relapsing after first-line standard-dose chemotherapy, RIC-allo without previous ASCT is not recommended.…”

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

“…Unfortunately, approximately 50% 6 of these patients will relapse again, and at this point treatment options become limited to palliative chemotherapy, radiotherapy or experimental approaches, including new molecules and, in selected cases, allogeneic stem cell transplant (allotransplant). 7,8 Brentuximab vedotin (BV, previously known as SGN-35, Seattle Genetics, WA, USA) is a novel antibody-drug conjugate targeting CD30 linked to a payload comprising a potent tubulin toxin, monomethyl auristatin E. The cell surface antigen CD30 is ubiquitous across Hodgkin Reed-Sternberg 9 and ALCL 10 cells. Two pivotal studies have demonstrated its efficacy in relapsed/refractory Hodgkin lymphoma (HL) 11 and anaplastic large cell lymphoma (ALCL), 12 with overall response rates (ORR) of 75% and 86%, respectively, when administered as monotherapy.…”

High-dose melphalan with autologous stem cell support in refractory Hodgkin lymphoma patients as a bridge to second transplant

“…At our Institution, tandem HDC or tandem auto-allo-SCT are preferred therapeutic options in lymphoma patients not reaching CR after salvage chemotherapy, based on the poor outcome reported with the use of single HDC; [18][19][20] indeed, disease status before transplantation is a well-known, independent prognostic factor in lymphoma patients. 18,[21][22][23] From present results it emerges that HD-PAM as a bridge therapy may be a challenging option in this setting of poor-prognosis patients. Interestingly, in our hands HD-PAM converted 77% of refractory patients (17 out of 22 patient in SD or PD before HD-PAM) into PR, or even CR (Figure 1), thus enabling them to proceed to further therapy.…”