Abstract
The aim of this pilot study was to exploit the graft-versus-tumor potential of allogeneic transplants while improving safety of the procedure. Twelve patients with advanced hematological malignancies and solid tumors underwent a low intensity conditioning regimen (fludarabine and cyclophosphamide) followed by an allogeneic peripheral blood stem cell transplantation. The median time to achieve an absolute neutrophil count of more than 0.5 × 109/l and an untransfused platelet count of more than 20 × 109/l was 15 and 14 days, respectively. The main extra-hematological toxicities were mucositis and infections. Acute graft-versus-host (GVHD) disease was experienced by 62% of evaluable patients (grade II/B or III/C 80%) responsive to steroids. Extensive chronic GVHD was observed in 62% of patients. Non-relapse transplant-related mortality by day +30 was observed in three patients (25%). Eight out of 12 patients were full donor chimeric by day +100. One patient showed a mixed chimerism at day +37 when he died from progressive disease. One patient was in complete remission (CR) before allogeneic transplantation, and after transplantation four patients achieved CR and four experienced progressive disease. Our study confirms that a low intensity conditioning regimen for allogeneic stem cell transplantation is feasible and effective in heavily pretreated patients.
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References
Childs R, Chernoff A, Contentin N et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation New Engl J Med 2000 343: 750 758
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
Ueno NT, Rondon G, Mirza NQ et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer J Clin Oncol 1998 16: 986 993
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
Steis RG, Urba WJ, Kopp WC . Kinetics of recovery of CD4+ T cells in peripheral blood of deoxycoformycin-treated patients J Natl Cancer Inst 1991 83: 1678 1679
Dreger P, Haferlach T, Eckstein V et al. G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation: safety, kinetics of mobilization, and composition of the graft Br J Haematol 1994 87: 609 613
Arpinati M, Green CL, Haimfeld S et al. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells Blood 2000 95: 2484 2490
Pan L, Delmonte J Jr, Jalonen CK, Ferrara JL . Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease Blood 1995 86: 4422 4429
Mielcarek M, Graf L, Johnson G, Torok-Storb B . Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation Blood 1998 92: 215 221
Blaise D, Kuentz M, Fortanier C et al. Randomized trial of bone marrow versus lenogastrim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societe Française de greffe de moelle J Clin Oncol 2000 18: 537 546
Powels R, Mehta J, Kulkarni S et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial Lancet 2000 335: 1231 1237
Schmitz N, Bacigalupo A, Hasenclever D et al. Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation Bone Marrow Transplant 1998 21: 995 1003
Bensinger WI, Martin PJ, Storer B et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers New Engl J Med 2001 344: 175 181
Ottinger HD, Beelen DW, Scheulen B et al. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow Blood 1996 88: 2775 2779
Rachamim N, Gan J, Segall H et al. Tolerance induction by ‘megadose’ hematopoietic transplants: donor-type human CD34 stem cells induce potent specific reduction of host anti-donor cytotoxic T lymphocyte precursors in mixed lymphocyte culture Transplantation 1998 65: 1386 1393
Petz LD, Yam P, Wallace RB et al. Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies Blood 1987 70: 1331 1337
Hill RS, Petersen FB, Storb R et al. Mixed hematologic chimerism after allogeneic marrow transplantation for severe aplastic anemia is associated with a higher risk of graft rejection and a lessened incidence of acute graft-versus-host disease Blood 1986 67: 811 816
Mattsson J, Uzunel M, Remberger M, Ringden O . T cell mixed chimerism is significantly correlated to a decreased risk of acute graft-versus-host disease after allogeneic stem cell transplantation Transplantation 2001 71: 433 439
McSweeney PA, Storb R . Mixed chimerism: preclinical studies and clinical applications Biol Blood Marrow Transplant 1999 5: 192 203
Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplantation 1974 18: 295 304
Rowlings PA, Przepiorka D, Klein JP et al. IBMTR severity index for grading acute graft-versus-host disease : retrospective comparision with Glucksberg grade Br J Haematol 1997 97: 855 864
Hughes WT, Armstrong D, Bodey GP et al. Guidelines for the use of antimicrobial infectious agents in neutropenic patients with unexplained fever Clin Infect Dis 1997 25: 551 573
Feinstein L, Storb R . Nonmyeloablative hemopoietic cell transplantation Curr Op Oncol 2001 13: 95 100
Barrett J, Childs R . Non-myeloablative stem cell transplants Br J Haematol 2000 111: 6 17
Champlin R ., Khouri I., Shimoni A. et al. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy Br J Haematol 2000 111: 18 29
Bornhauser M, Thiede C, Schuler U et al. Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin Bone Marrow Transplant 2000 26: 119 125
Nagler A, Slavin S, Varadi G et al. Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma Bone Marrow Transplant 2000 25: 1021 1028
Anderlini P, Giralt S, Andersson B et al. Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease Bone Marrow Transplant 2000 26: 615 620
Garban F, Attal M, Rossi JF et al Intergroupe Francophone du Myelome. Immunotherapy by non-myeloablative allogeneic stem cell transplantation in multiple myeloma: results of a pilot study as salvage therapy after autologous transplantation Leukemia 2001 15: 642 646
Badros A, Barlogie B, Morris C et al. High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions Blood 2001 97: 2574 2579
Eibl B, Schwaighofer H, Nachbaur D et al. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer Blood 1996 88: 1501 1508
Carella AM, Cavaliere M, Lerma E et al. Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hemopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma J Clin Oncol 2000 23: 3918 3924
Martino R, Caballero MD, Canals C et al. Reduced-intensity conditioning reduces the risk of sever infections after allogeneic peripheral blood stem cell transplantation Bone Marrow Transplant 2001 28: 341 347
Giralt S, Thall PF, Khouri I et al. : Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation Blood 2001 97: 631 637
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Castagna, L., Bertuzzi, A., Nozza, A. et al. Reduced intensity conditioning regimen followed by glycosylated G-CSF mobilized PBSCT in patients with solid tumors and malignant lymphomas. Bone Marrow Transplant 30, 207–214 (2002). https://doi.org/10.1038/sj.bmt.1703626
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DOI: https://doi.org/10.1038/sj.bmt.1703626