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Reduced-intensity transplantation for lymphoma

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Opinion statement

Non-myeloablative stem cell transplantation was clinically introduced nearly a decade ago to circumvent the need for intensive preparative transplant regimens and instead rely on graft-versus-malignancy effects to eradicate disease. The general concept is to provide a sufficiently immunosuppressive and moderately myelosuppressive treatment regimen to allow donor and host hematopoietic coexistence, or chimerism. Because not all regimens are truly “non-myeloablative,” a more appropriate term is reduced-intensity transplantation (RIT), which is used throughout this review. The most popular regimens incorporate a purine analog (such as fludarabine) and an alkylating agent (such as cyclophosphamide or melphalan), with or without low-dose total body irradiation. The addition of T-cell-depleting monoclonal antibodies, such as alemtuzumab, appears to reduce the incidence of acute graft-versus-host disease. For non-Hodgkin's lymphomas, the precise role of RIT continues to be defined. There are many questions regarding the optimal population and the timing of the modality. There is ample support that graft-versuslymphoma (GVL) is a true phenomenon, but the specific contribution of GVL to outcomes after RIT is still in question, and some subtypes appear more susceptible to GVL than others. Clearly, the procurement of an uncontaminated graft plays a role. Supportive care remains a critical component of management because the reducedintensity regimens do not completely abrogate the risk of serious infection and many do not appear to decrease the incidence of chronic graft-versus-host disease. Thus, transplant-related morbidity and mortality and graft-versus-host disease remain major obstacles, and future efforts should focus on minimizing risks and more clearly identifying patient-specific and disease-specific predictors of outcome.

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References and Recommended Reading

  1. 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.

    PubMed  CAS  Google Scholar 

  2. 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.

    PubMed  Google Scholar 

  3. 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.

    Article  PubMed  Google Scholar 

  4. Mandigers CM, Verdonck LF, Meijerink JP, et al.: Graftversus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation. Bone Marrow Transplant 2003, 32:1159–1163.

    Article  PubMed  CAS  Google Scholar 

  5. van Besien K, Smith S, Anastasi J, et al.: Irreversible myelosuppression after fludarabine-melphalan conditioning: observations in patients with graft rejection. Blood 2004, 102:4373–4374.

    Article  Google Scholar 

  6. van Besien K, Carreras J, Zhang MJ, et al.: Reduced intensity vs. myeloablative conditioning for HLA matched sibling transplantation in follicular lymphoma (oral presentation, American Society of Hematology). Blood 2005, 106.

  7. Ershler WB, Artz AS, Keller ET: Issues of aging and geriatric medicine: relevance to cancer treatment and hematopoietic reconstitution. Biol Blood Marrow Transplant 2006, 12:100–106.

    Article  PubMed  Google Scholar 

  8. Corradini P, Dodero A, Bregni M, et al.: Reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas: impact of pre-transplantation factors on long-term outcome [abstract]. Blood 2005, 106:1129.

    Google Scholar 

  9. Sorror ML, Maris MB, Storer B, et al.: Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004, 104:961–968. Improved risk stratification in terms of comorbidities will be important for future identification of patients appropriate for RIT. This paper proposes a modification of a wellknown geriatric assessment tool and adapts it to the transplant population.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. Dean RM, Fowler DH, Wilson WH, et al.: Efficacy of reduced-intensity allogeneic stem cell transplantation in chemotherapy-refractory non-Hodgkin lymphoma. Biol Blood Marrow Transplant 2005, 11:593–599.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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).

  14. Khouri IF, Keating M, Korbling M, et al.: Transplant-lite: induction of graft-versus-malignancy using fludarabinebased nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998, 16:2817–2824. One of the first papers to discuss the rationale for RIT for lymphoid malignancies.

    PubMed  CAS  Google Scholar 

  15. Bertz H, Illerhaus G, Veelken H, Finke J: Allogeneic hematopoetic 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.

    Article  PubMed  CAS  Google Scholar 

  16. van Besien K, Loberiza FR Jr, Bajorunaite R, et al.: Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 2003, 102:3521–3529.

    Article  PubMed  CAS  Google Scholar 

  17. Khouri I, Saliba RM, Lee MS, et al.: Longer follow-up confirms a low relapse rate after non-myeloablative transplantation (NMT) for non-Hodgkin's lymphoma (NHL), including patients with pet or gallium-avid disease [abstract]. Blood 2005, 106:44.

    Google Scholar 

  18. Maris MB, Sandmaier BM, Storer BE, et al.: Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for relapsed or refractory follicular lymphoma [abstract]. Blood 2005, 106:1130.

    Article  CAS  Google Scholar 

  19. Morris E, Thomson K, Craddock C, et al.: Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 2004, 104:3865–3871.

    Article  PubMed  CAS  Google Scholar 

  20. Faulkner RD, Craddock C, Byrne JL, et al.: BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. Blood 2004, 103:428–434.

    Article  PubMed  CAS  Google Scholar 

  21. Russell NH, Byrne JL, Faulkner RD, et al.: Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation. Bone Marrow Transplant 2005, 36:437–441.

    Article  PubMed  CAS  Google Scholar 

  22. Khouri IF, Lee MS, Romaguera J, et al.: Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versusmalignancy. Ann Oncol 1999, 10:1293–1299.

    Article  PubMed  CAS  Google Scholar 

  23. Corradini P, Tarella C, Olivieri A, et al.: Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 2002, 99:75–82.

    Article  PubMed  CAS  Google Scholar 

  24. Khouri IF, Lee MS, Saliba RM, et al.: Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003, 21:4407–4412.

    Article  PubMed  CAS  Google Scholar 

  25. Maris MB, Sandmaier BM, Storer BE, et al.: Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. Blood 2004, 104:3535–3542.

    Article  PubMed  CAS  Google Scholar 

  26. Coiffier B, Brousse N, Peuchmaur M, et al.: Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d'Etude des Lymphomes Agressives). Ann Oncol 1990, 1:45–50.

    PubMed  CAS  Google Scholar 

  27. Gisselbrecht C, Gaulard P, Lepage E, et al.: Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Blood 1998, 92:76–82.

    PubMed  CAS  Google Scholar 

  28. Melnyk A, Rodriguez A, Pugh WC, Cabannillas F: Evaluation of the Revised European-American Lymphoma Classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin's lymphoma. Blood 1997, 89:4514–4520.

    PubMed  CAS  Google Scholar 

  29. Corradini P, Dodero A, Zallio F, et al.: Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol 2004, 22:2172–2176. This report on peripheral T-NHL convincingly demonstrates the presence of a GVL effect in T-NHL.

    Article  PubMed  Google Scholar 

  30. Molina A, Zain J, Arber DA, et al.: Durable clinical, cytogenetic, and molecular remissions after allogeneic hematopoietic cell transplantation for refractory Sezary syndrome and mycosis fungoides. J Clin Oncol 2005, 23:6163–6171. This report on cutaneous T-NHL convincingly demonstrates the presence of a GVL effect in T-NHL.

    Article  PubMed  Google Scholar 

  31. Mansour MR, Dogan A, Morris EC, et al.: Allogeneic transplantation for hepatosplenic alphabeta T-cell lymphoma. Bone Marrow Transplant 2005, 35:931–934.

    Article  PubMed  CAS  Google Scholar 

  32. Aoyama Y, Yamane T, Hino M, et al.: Nodal gamma/delta T cell lymphoma in complete remission following allogeneic bone marrow transplantation from an HLA-matched unrelated donor. Acta Haematol 2001, 105:49–52.

    Article  PubMed  CAS  Google Scholar 

  33. Rodriguez J, Munsell M, Yazji S, et al.: Impact of highdose chemotherapy on peripheral T-cell lymphomas. J Clin Oncol 2001, 19:3766–3770.

    PubMed  CAS  Google Scholar 

  34. Corradini P, Dodero A, Zallio F, et al.: Nonmyeloablative conditioning followed by allogeneic transplantation has a better outcome than high-dose chemotherapy plus autografting in non-Hodgkin's lymphomas with T-cell histology [abstract]. Blood 2002, 100:1654.

    Google Scholar 

  35. Kline J, Pollyea DA, Stock W, et al.: Pre-transplant ganciclovir and post transplant high-dose valacyclovir reduce CMV infections after alemtuzumab-based conditioning. Bone Marrow Transplant 2006, 37:307–310.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    PubMed  CAS  Google Scholar 

  37. 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.

    Article  PubMed  Google Scholar 

  38. Perez-Simon JA, Kottaridis PD, Martino R, et al.: Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood 2002, 100:3121–3127.

    Article  PubMed  CAS  Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

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  1. Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC2115, 60637, Chicago, IL, USA

    Sonali M. Smith MD

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Smith, S.M. Reduced-intensity transplantation for lymphoma. Curr. Treat. Options in Oncol. 7, 295–305 (2006). https://doi.org/10.1007/s11864-006-0039-0

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