Autologous and allogeneic transplant for Hodgkin’s – pro

Some 20-30 % of patients with Hodgkin’s lymphoma achieve a remission and then relapse. In general, the longer the initial complete remission, the better the outlook with any form of salvage therapy.
A variety of treatment regimens have been used for patients with relapsed Hodgkin’s disease. In addition to MOPP or ABVD in patients who received the opposite regimen initially, a number of other treatments have been used. Unfortunately, the number of patients achieving extended survival free of Hodgkin’s disease is quite poor, although patients with no adverse risk characteristics (see above) have been reported to have 5-year failure-free survivals as high as 50%. For this reason a variety of high dose stem cell approaches approaches have been studied. Autologous bone marrow transplantation can cure patients with multiply relapsed Hodgkin’s disease. Because of the superior results in patients treated early in the course of the disease, most advocates of bone marrow transplantation would prefer to use it as part of the treatment of the initial relapse following any effective initial chemotherapy regimen. In this setting, patients who receive an alternate standard chemotherapy regimen and achieve at least a partial remission then undergo autologous transplantation. Refractory patients also benefit from ASCT. The results in this setting have yielded durable remissions in 47% to 85% of patients. In a randomized trial conducted in Europe, patients with relapsed, chemosensitive Hodgkin’s disease had a significantly better failure-free survival with transplantation rather than continuing standard dose chemotherapy.

In some patients in whom HDC fails, allogeneic HSC transplantation may be a viable option. In this method, myeloablative therapy (chemotherapy and sometimes RT) is followed by the infusion of HSCs from a genetically matched donor. This offers the potential for an immunological antitumor effect from T-cells provided by the HSC donor, which may improve the chances for cure of the disease. Historically, allogeneic transplantation for Hodgkin disease has been considered too high risk for most patients due a high transplant-related mortality. However, evolution of transplant protocols to include less toxic conditioning regimens will likely expand the utility of this option for patients with refractory Hodgkin disease. Allogeneic transplantation for Hodgkin disease should ideally be performed in the context of a clinical trial but is considered standard of care already at this time.

In a review, Mink and Armitage (2001) stated that autologous stem cell transplantation has proven to be beneficial in selected patients with HD. Transplantation appeared to increase event-free survival in patients who failed to enter complete remission with initial therapy. When a patient relapses after a complete remission, transplantation is probably the best option and particularly so if the remission lasted less than 1 year. Transplantation as part of primary therapy for very high-risk patients may be beneficial, and is standard therapy at this time. Lazarus et al (2001) reviewed data from the Autologous Blood and Marrow Transplant Registry (n = 414) to determine relapse, disease-free survival, overall survival, and prognostic factors in patients with relapsed HD. They concluded that autologous hematopoietic stem cell transplantation (autotransplantation) should be considered for patients with HD in first relapse or second remission. This is also the 2011 NCCN recommendation (Hodg-6) as category 3.

NCCN says that allogeneic stem cell transplantation can be used in selected patients; it is a category 3 recommendation (HODG-15).

Mink SA, Armitage JO. High-dose therapy in lymphomas: A review of the current status of allogeneic and autologous stem cell transplantation in Hodgkin’s disease and non-Hodgkin’s lymphoma. Oncologist. 2001;6(3):247-256.

Lazarus HM, Loberiza FR Jr, Zhang MJ, et al. Autotransplants for Hodgkin’s disease in first relapse or second remission: A report from the autologous blood and marrow transplant registry (ABMTR). Bone Marrow Transplant. 2001;27(4):387-396.

Reece DE. Hematopoietic stem cell transplantation in Hodgkin disease. Curr Opin Oncol. 2002;14(2):165-170.

A. Engert et al, Hodgkin’s lymphoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up, On behalf of the ESMO Guidelines Working Ann Oncol (2009) 20 (suppl 4): iv108-iv109.

Ercole Brusamolino, Andrea Bacigalupo, Giovanni Barosi, Giampaolo Biti, Paolo G. Gobbi, Alessandro Levis, Monia Marchetti, Armando Santoro, Pier Luigi Zinzani, and Sante Tura

Classical Hodgkin’s lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up Haematologica 2009 94: 550-565

Balsalobre P, Díez-Martín JL, Re A, Michieli M, Ribera JM, Canals C, Rosselet A, Conde E, Varela R, Cwynarski K, Gabriel I, Genet P, Guillerm G, Allione B, Ferrant A, Biron P, Espigado I, Serrano D, Sureda A. Autologous stem-cell transplantation in patients with HIV-related lymphoma. Clin Oncol. 2009 May 1;27(13):2192-8.

Canellos GP, Mauch PM. Hematopoietic cell transplantation in classical Hodgkin lymphoma. In: UpToDate, Basow, DS (Ed), UpToDate,Waltham,MA, 2013. Literature review current through March 2013.

Moskowitz AJ, Perales MA, Kewalramani T, et al. Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J Haematol 2009; 146:158.

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.

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

Corradini P, Sarina B, Farina L. Allogeneic transplantation for Hodgkin’s lymphoma. Br J Haematol 2011; 152:261

John Kuruvilla et al, How I treat relapsed and refractory Hodgkin lymphoma. Blood April 21, 2011 vol. 117 no. 16 4208-4217

 

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