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Kottaridis PD, Milligan DW, Chopra R, et al. In vivo CAMPATH-1H prevents qraft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96:2419-2425.
Hallemeier C, Girgis M, Blum W, et al. Outcomes of adults with acute myelogenous leukemia in remission given 550 cGy of single-exposure total body irradiation, cyclophosphamide, and unrelated donor bone marrow transplants. Biol Blood Marrow Transplant 2004; 10:310-319.
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.
Khouri IF, Keating M. Körbling 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.
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.
McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoiotic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97:3390-3400.
Childs R, Clave E, Contentin N, et al. Engraftment kinetics after non-myeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94:3234-3241
Sandmaier BM, Storb R. 2004. Nonmyeloablative therapy and hematopoietic cell transplantation for hematologic disorders. In: Blume KG, Forman SJ, Appelbaum FR, editors. Thomas' hematopoietic cell transplantation. 3rd ed. Oxford, UK: Blackwell Publishing Ltd.; pp. 1164-1176. This book chapter reviews the development of allogeneic HSCT after nonmyeloablative conditioning.
Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89:3048-3054.
Storb R, Yu C, Barnett T, et al. Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation. Blood 1999; 94:1131-1136.
Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300:1068-1073.
Kolb HJ, Schmidt C, Barrett AJ, et al. Graft-versus-leukemia reactions in allogeneic chimeras. Blood 2004; 103:767-776. This paper contains an update of a large European study evaluating the efficacy of DLI as treatment of relapse after allogeneic HSCT, and nicely reviews mechanisms of graft-versus-tumor effects.
Baron F, Maris MB, Sandmaier BM, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol 2005; 23:1993-2003. This large study showed that both grade I acute GVHD and extensive chronic GVHD were associated with decreased risk of relapse/progression and better PFS after allogeneic HSCT with nonmyeloablative conditioning. Conversely, grade II-IV acute GVHD was not associated with decreased risk of relapse but. rather. caused nonrelapse mortality and, therefore, was associated with decreased PFS.
Giralt S, Thal PF, Khouri I, et al. Mclphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97:631-637
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. This large multicenter study showed encouraging current PFS and low nonrelapse mortality in patients given related or unrelated grafts after alemtuzumab-containing reduced-intensity conditioning. The reduced incidence of acute GVHD and its associated nonrelapse mortality due to alemtuzumab use seemed to balance the increased infectious complications and relapse rates.
Or R, Shapira MY, Resnick I, et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase (comment in: Blood 2003; 101:5084; author reply 5084-5085; PMID: 12788790). Blood 2003; 101:441-445.
Girgis M, Hallemeier C, Blum W, et al. Chimerism and clinical outcomes of 110 unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide. Blood 2005; 105:3035-3041.
Khoun 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,
Niederwieser D, Maris M, Shizuru JA, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101:1620-1629.
Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102:2021-2030.
Sandmaier BM, Maris M, Maloney DG, et al. Low-dose total body irradiation (TBI) conditioning for hematopoietic cell transplants (HCT) from HLA-matched related (MRD) and unrelated (URD) donors for patients with hematologic malignancies: a five-year experience [abstract #264]. Blood 2003: 102:78-79.
Weiden PL, Sullivan KM, Flournoy N, et al. Antileukemic effect of chronic graft-versus-host disease. Contribution to improved survival after allogeneic marrow transplantation. N Engl J Mod 1981; 304:1529-1533.
Horowitz MM, Gale RP, Sondei PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75:555-562,
Gratwohl A, Hermans J, Apperley J, et al. Acute graft-versus-host disease: grade- and outcome in patients with chronic myelogenous leukemia [review]. Blood 1995; 86:813-818
Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 1995: 86:2041-2050.
Collins RH Jr. Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15:433-444.
Truitt RL. The Mortimer M. Bortin Lecture: to destroy by the reaction of immunity: the search for separation of graft-versus-leukemia and graft-versus-host. Biol Blood Marrow Transplant 2004; 10:505-523. This paper nicely reviews efforts to manipulate the graft-versus-tumor effects and separate it from the potentially fatal complications of GVHD in animal models and in humans.
Burroughs L, Storb R. Low-intensity allogeneic hematopoietic stem cell transplantation for myeloid malignancies: separating graft-versus-leukemia effects from graft-versus-host disease. Curr Opin Hematol 2005; 12:45-54.
Sayer HG, Kröger M, Beyer J, et al. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant 2003; 31:1089-1095.
de Lima M, Anagnostopoulos A, Munsell M, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104:865-872. This study retrospectively compared outcomes of patients with acute myeloid leukemia or myelodysplastic syndrome given HSCT after nonmyeloablative or reduced-intensity conditioning. The 3-year overall survival was comparable between the two groups.
Michallet AS, Furst S, Le QH, et al. Impact of chimaerism analysis and kinetics on allogeneic haematopoietic stem cell transplantation outcome after conventional and reduced-intensity conditioning regimens. Br J Haematol 2005; 128:676-689.
Perez-Simon JA, Diez-Campelo M, Martino R, et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood 2003; 102:1108-1113.
Kroger N, Perez-Simon JA, Myint H, et al. Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma. Biol Blood Marrow Transplant 2004; 10:698-708.
Cao TM, Shizuru JA, Wong RM, et al. Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose. Blood 2005; 105:2300-2306.
Crawley C, Lalancette M, Szydlo R, et al. Outcomes for reduced intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the chronic leukemia working party of the EBMT. Blood 2005; 105:4532-4539. Large retrospective study showing that chemoresistance, and the use of alemtuzumab in the conditioning regimen, adversely affected PFS in patients given non-myeloablative HSCT as treatment for multiple myeloma. Conversely, chronic GVHD was associated with better PFS. This study suggests that heavily pretreated patients with multiple myeloma, and those with refractory disease, do not benefit from this approach.
Baron F, Baker JE, Storb R, et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004; 104:2254-2262. This paper showed that assessing donor chimerism levels among T-cells and NK cells early after HSCT might help identify patients at risk for graft rejection, acute GVHD and relapse, and thereby allow early interventions with DLI or immunosuppressive drugs.
Baron F, Storb R, Gooley T, et al. Assessing donor chimerism level among CD3 T, CD4 T, CD8 T, and NK cells predicts subsequent graft rejection, GVHD, and relapse after allogeneic HCT with nonmyeloablative conditioning [abstract 31]. Biol Blood Marrow Transplant 2005; 11(Suppl):11.
Mohty M, Bagattini S, Chabannon C, et al. CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Exp Hematol 2004; 32:1097-1102.
Panse JP, Heimfeld S, Guthrie KA, et al. Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after nonmyeloablative conditioning. Br J Haematol 2005; 128:659-667.
Baron F, Maris MB, Storer BE, et al. High doses of transplanted CD34 + cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia 2005; 19:822-828.
Peggs KS, Sureda A, Hunter A, et al. Impact of in vivo T-cell depletion on outcome following reduced intensity transplantation for Hodgkin lymphoma: comparison between 2 prospective studies [abstract 807]. Blood 2004; 104:230.
Peggs KS, Mackinnon S, Williams CD, et al. Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. Biol Blood Marrow Transplant 2003; 9:257-265.
Peggs KS, Mackinnon S, Linch DC. The role of allogeneic transplantation in non-Hodgkin's lymphoma. Br J Haematol 2005; 128:153-168.
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.
Peggs KS, Thomson K, Hart H, et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism and disease responses. Blood 2004; 103:1548-1556, These two papers [48,49] report the efficacy of DLI as treatment for relapse after HSCT reduced-intensity or non-myeloablative conditioning.
Bethge WA, Hegenbart U, Stuart MJ, et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood 2004; 103:790-795. See [48].
Sandmaier BM, Maloney DG, Maris MB, et al. Conversion of low donor chimerism following nonmyeloablative conditioning for hematopoietic cell transplantation (HCT) using pentostatin and donor lymphocyte infusion (DLI) [abstract 186]. Blood 2004; 104:57.
Baron F, Maris MB, Storer BE, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia. Biol Blood Marrow Transplant 2005; 11:272-279.
Kroger N, Shimoni A, Zagrivnaja M, et al. Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma. Blood 2004; 104:3361-3363. This report showed promising efficacy of a combination of low-dose thalidomide and DLI as treatment for patients with relapse of multiple myeloma after HSCT.
Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem cell transplantation for chronic lymphocytic leukemia: impact of rituximab on immunomodulation and survival. Exp Hematol 2004; 32:28-35. This study suggested that combining rituximab with nomyeloablative conditioning or with DLI might increase the GVT effects.
Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102:756-762.
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 pretransplant comorbidities. Blood 2004; 104:961-968. A retrospective study comparing morbidity and mortality after nonmyeloablative versus myeloablative unrelated HSCT. This study demonstrated lower morbidity and lower nonrelapse mortality in nonmyeloablative recipients. In addition, the incidence of grades III-IV acute GVHD was significantly lower in nonmyeloablative recipients. Furthermore, comorbidities at HSCT efficiently predicted posttransplant toxicity and nonrelapse mortality.
Diaconescu R, Flowers CR, Storer B, et al. Morbidity and mortality with nonmyeloablative compared to myeloablative conditioning before hematopoietic cell transplantation from HLA matched related donors. Blood 2004; 104:1550-1558. A retrospective study comparing morbidity and mortality after nonmyeloablative versus myeloablative related HSCT. This study demonstrated lower morbidity and comparable non-relapse mortality in nonmyeloablative recipients. High pretransplantation comorbidity scores predicted higher nonrelapse mortality.
Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood 2005; 105:1810-1814. This retrospective study compared outcomes of patients over age 50 given allogeneic HSCT after myeloablative or nonmyeloablative conditioning. Nonmyeloablative recipients had at least as good 2-year survival.
Ho AYL, Pagliuca A, Kenyon M, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan and alemtuzumab (FBC) conditioning. Blood 2004; 104:1616-1623.
Kerbauy FR, Storb R, Hegenbart U, et al. Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML. Leukemia 2005; 19:990-997. This study demonstrated that BCR/ABL negativity could be achieved in a majority of patients given related PBSC after nonmyeloablative conditioning combining 2 Gy TBI and fludarabine.
Sorror ML, Maris MB, Sandmaier BM, et al. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 2005; 23:3819-3829.
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. This large multicenter study showed promising results of allogeneic HSCT after nonmyeloablative conditioning as treatment for patients with mantle cell lymphoma.
Sorror ML, Maris MB, Storb RF, et al. Hematopoietic cell transplantation (HCT)-specific-comorbidity index: a new tool for risk assessment before allogeneic HCT [abstract 67]. Biol Blood Marrow Transplant 2005; 11 (Suppl 1):23-24.
Molldrem JJ, Komanduri K, Wieder E. Overexpressed differentiation antigens as targets of graft-versus-leukemia reactions [review]. Curr Opin Hematol 2002; 9:503-508.
Kloosterboer FM, van Luxemburg-Hejis SAP, van Soest RA, et al. Direct cloning of leukemia-reactive T cells from patients treated with donor lymphocyte infusion shows a relative dominance of hematopoiesis-restricted minor histocompatibility antigen HA-1 and HA-2 specific T cells. Leukemia 2004; 18:798-808.
Bethge WA, Sandmaier BM. Targeted cancer therapy and immunosuppression using radiolabeled monoclonal antibodies. Semin Oncol 2004; 31:68-82.
