Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438)

Thompson, John A.; Fisher, Richard I.; LeBlanc, Michael; Forman, Stephen J.; Press, Oliver W.; Unger, Joseph M.; Nademanee, Auayporn; Stiff, Patrick J.; Petersdorf, Stephen H.; Fefer, A

doi:10.1182/blood-2007-09-111708

Cited by 24 publications

(12 citation statements)

References 30 publications

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“…Interleukin-2 (IL-2) maintenance has been given in a variety of dosing schedules to up-regulate T cell immunity, but Phase III studies showed no effect on outcome after auto-HCT for NHL, AML or ALL. 58 Another approach was the induction of autologous GvHD using cyclosporine A (CSA) with interferon-γ (IFNγ) and IL-2. However, a randomized trial showed no benefit with this approach in patients with poor risk lymphoma.…”

Section: Preventing Relapse After Autologous Hematopoietic Cell Transmentioning

confidence: 99%

Back to the Future! The Evolving Role of Maintenance Therapy after Hematopoietic Stem Cell Transplantation

Hourigan

McCarthy

Lima

2014

Biology of Blood and Marrow Transplantation

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Relapse is a devastating event for patients with hematologic cancers treated with hematopoietic stem cell transplantation. In most situations, relapse treatment options are limited. Maintenance therapy offers the possibility of delaying or avoiding disease recurrence, but its role remains unclear in most conditions we transplant. Here, Dr. Hourigan presents an overview of minimal residual disease (MRD) measurement in hematologic malignancies and the applicability of MRD-based post-transplant interventions. Dr. McCarthy reviews current knowledge of maintenance therapy in the autologous transplant context, with emphasis on immunologic interventions and immune modulation strategies designed to prevent relapse. Dr. de Lima discusses current lines of investigation in disease recurrence prevention after allogeneic transplantation, focusing on AML and MDS.

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Section: Preventing Relapse After Autologous Hematopoietic Cell Transmentioning

confidence: 99%

Back to the Future! The Evolving Role of Maintenance Therapy after Hematopoietic Stem Cell Transplantation

Hourigan

McCarthy

Lima

2014

Biology of Blood and Marrow Transplantation

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“…The additional rationale for bringing IL-2 therapy into the posttransplant setting is its potential contribution to immunologic recovery and even the stimulation of a new, lesstolerized immune response to tumor antigens, analogous to the melanoma studies detailed earlier. Despite promising early pilot data [34][35][36][37], the randomized studies to evaluate the contribution of IL-2 following autologous transplant in leukemia and lymphoma failed to demonstrate a benefit [38,39]. Its potential role as an adjunct to post-transplant manipulations such as donor lymphocyte infusions following allogeneic transplant remains under evaluation ( Table 2).…”

Section: Il-2-based Therapy Of Hematologic Malignanciesmentioning

confidence: 98%

IL-2 in the therapy of melanoma and other malignancies

Margolin

2009

Med Oncol

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IL-2 as a single agent has been approved for use in both renal cancer and melanoma, and it has achieved widespread use in these malignancies for selected patients with metastatic disease. For these diseases, a role for IL-2-based therapy in the adjuvant setting has not been demonstrated, and current investigations involve the use of less toxic and less complex therapies. The activity of IL-2 has been studied extensively in other malignancies, particularly hematologic diseases such as leukemia and lymphoma. To date, IL-2 used either as a single agent or as a component of regimens containing one or more additional agents for diseases other than melanoma or renal cancer has shown promise, but the rapid emergence of safer agents for these and many other malignancies has tempered enthusiasm for IL-2-based regimens. Many investigations have been directed at enhancing the therapeutic ratio of IL-2, mostly by adding chemical modulators of downstream molecules associated with IL-2 toxicity. Other approaches, including variations on the chemical composition of IL-2 to alter its receptor-binding characteristics or its pharmacokinetic profile have been tried with limited success. The addition of targeting molecules co-administered with IL-2 or covalently bound to produce bispecific IL-2 containing molecules have shown promising activity and remain under investigation.

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“…A variety of immune-modulating agents have been used in small series and case reports, including cyclosporine, interferons, and interleukins (see comprehensive review by Kline et al [ 56 ]). Most recently, the Southwest Oncology Group published long-term data on a phase 3 randomized trial of ASCT for relapsed lymphoma patients with or without adjuvant interleukin-2 (IL-2) [ 57 ]. The researchers did not fi nd improvements in PFS or OS, and concluded that the dose and schedule of IL-2 administered did not benefi t patients.…”

Section: Posttransplant Therapies To Reduce Minimal Residual Diseasementioning

confidence: 98%

Management of relapsed diffuse large B-cell lymphoma

Kenkre¹,

Smith

2008

Curr Oncol Rep

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Despite more effective front-line regimens, a substantial portion of patients with diffuse large B-cell lymphoma relapse and require further therapy. Several trials have established the efficacy of autologous stem cell transplantation for relapsed diffuse large B-cell lymphomas, but the benefit has been largely restricted to patients with chemosensitive disease and low-risk features at the time of relapse. In an effort to improve outcomes following an autologous transplant, researchers are exploring several avenues, including improvement of salvage regimens, addition of radioimmunotherapy to preparative regimens, and application of posttransplant treatments to eliminate minimal residual disease. Allogeneic stem cell transplantation also appears promising, but there is much to learn about optimal patient selection and timing. This review outlines the current approach to the management of relapsed diffuse large B-cell lymphoma, with an emphasis on newer peritransplant therapies.

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Cited by 24 publications

References 30 publications

Back to the Future! The Evolving Role of Maintenance Therapy after Hematopoietic Stem Cell Transplantation

Back to the Future! The Evolving Role of Maintenance Therapy after Hematopoietic Stem Cell Transplantation

IL-2 in the therapy of melanoma and other malignancies

Management of relapsed diffuse large B-cell lymphoma

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