Opinion statement
Nonmyeloablative stem cell transplantation, also referred to as minitransplantation or reduced-intensity transplantation, is a novel approach to lymphoma treatment offering the lure of harnessing graft-versus-lymphoma (GVL) effects while decreasing regimen-related toxicity. The general concept is to provide a sufficiently immunosuppressive and moderately myelosuppressive treatment regimen to allow donor and host hematopoietic coexistence or chimerism. The most popular regimens incorporate a purine analog (eg, fludarabine) and an alkylating agent (eg, cyclophosphamide or melphalan). Newer regimens include the monoclonal antibody alemtuzumab, which may reduce the incidence of acute graft-versus-host disease (GVHD). Early reports demonstrate a GVL effect; however, the underlying lymphoma subtype and pace of disease often dictate which patients can capitalize on GVL benefits. Clinical reports show mixed results, which may reflect variations in patient selection. Although most patients successfully engraft, the effect on lymphoma control and GVHD must be evaluated carefully. Future investigations continue to delineate the optimal timing of nonmyeloablative transplantation, the optimal patient population, the optimal preparative regimen, and the optimal GVHD prophylaxis. Supportive care remains a critical component of management because the reduced-intensity regimens do not abrogate the risk of serious infection and many do not appear to decrease the incidence of chronic GVHD. Nonmyeloablative hematopoietic stem cell transplantation may broaden the applicability of allogeneic transplantation in malignant lymphomas, especially for indolent subtypes.
Similar content being viewed by others
References and Recommended Reading
Ratanatharathorn V, Uberti J, Karanes C, et al.: Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin’s lymphoma. Blood 1994, 84:1050–1055. One of the only prospective randomized trials comparing autologous and standard allogeneic stem cell transplantation for lymphoid malignancies. The authors demonstrate a significantly higher probability of disease progression in the autologous group, thus supporting the existence of GVL benefit with allogeneic transplantation.
van Besien K, Thall P, Korbling M, et al.: Allogeneic transplantation for recurrent or refractory non-Hodgkin’s lymphoma with poor prognostic features after conditioning with thiotepa, busulfan, and cyclophosphamide: experience in 44 consecutive patients. Biol Blood Marrow Transplant 1997, 3:150–156.
van Besien KW, de Lima M, Giralt SA, et al.: Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect. Bone Marrow Transplant 1997, 19:977–982.
Khouri IF, Lee MS, Romaguera J, et al.: Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graftversus-malignancy. Ann Oncol 1999, 10:1293–1299.
van Besien KW, Mehra RC, Giralt SA, et al.: Allogeneic bone marrow transplantation for poor-prognosis lymphoma: response, toxicity and survival depend on disease histology. Am J Med 1996, 100:299–307. The optimal patient population that is likely to benefit from allogeneic transplantation strategies is still evolving. However, this article, among others, suggests that low-grade lymphomas are more likely to manifest a GVL effect after allogeneic transplantation, compared to more aggressive subtypes.
Khouri IF, Saliba RM, Giralt SA, et al.: Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 2001, 98:3595–3599.
Kyriakou CA, Milligan D, Chopra R, et al.: Outcome of non-myeloablative stem cell transplantation for NHL is dependent on histology: good for patients with low grade disease and poor for those with high grade lymphoma. [abstract]. Blood 2001, 98(Suppl 1):1737.
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.
Spitzer TR, McAfee S, Sackstein R, et al.: Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol Blood Marrow Transplant 2000, 6:309–320.
Khouri IF, Keating M, Korbling M, et al.: Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998, 16:2817–2824. One of the first reports of nonmyeloablative stem cell transplantation in lymphomas. The authors elegantly summarize the concept of radioimmunotherapy regimens and apply it to a population of patients with refractory lymphomas.
Bertz H, Illerhaus G, Veelken H, Finke J: Allogeneic hematopoietic stem cell transplantation for patients with relapsed or refractory lymphomas: comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens. Ann Oncol 2002, 13:135–139.
Kottaridis PD, Milligan DW, Chopra R, et al.: In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000, 96:2419–2425. Alemtuzumab is an important addition to reduced-intensity regimens that may decrease the incidence of acute GVHD. However, its impact on disease control, chronic GVHD, and profound immunosuppression with CMV reactivation must be carefully addressed in future studies.
Branson K, Chopra R, Kottaridis PD, et al.: Role of nonmyeloablative allogeneic stem cell transplantation after failure of autologous transplantation in patients with lymphoproliferative malignancies. J Clin Oncol 2002, 20:4022–4031.
Chakrabarti S, Mackinnon S, Chopra R, et al.: High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 2002, 99:4357–4363.
Perez-Simon JA, Kottaridis PD, Martino R, et al.: Nonmyeloablative transplantation with or without alemtuzumab: comparison between two prospective studies in patients with lymphoproliferative disorders. Blood 2002, 100:3121–3127.
Chakraverty R, Peggs K, Chopra R, et al.: Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 2002, 99:1071–1078.
Confer DL, Stroncek DF: Bone marrow and peripheral blood stem cell donors. In Hematopoietic Cell Transplantation. Edited by Thomas ED, Blume KG, Forman SJ. Malden: Blackwell Science, Inc.; 1999:421–430.
Heldal D, Brinch L, Tjonnfjord G, et al.: Donation of stem cells from blood or bone marrow: results of a randomised study of safety and complaints. Bone Marrow Transplant 2002, 29:479–486.
The University of Chicago Hospitals: In Formulary of Accepted Drugs. Canada: Lexi-Comp, Inc.; 2001.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Smith, S.M. Nonmyeloablative transplantation for lymphoma. Curr. Treat. Options in Oncol. 4, 261–268 (2003). https://doi.org/10.1007/s11864-003-0001-3
Issue Date:
DOI: https://doi.org/10.1007/s11864-003-0001-3