Summary:
We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation. Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics. Since August 1998, 60 patients (30 on each arm) have completed the study. There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study. Significantly, the duration of grade I–IV mucositis was decreased in the group that received amifostine (P=0.02). Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine. However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity. There were also no differences in early mortality, relapse and long-term survival. We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.
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References
Davidson DE, Grenan MM, Sweeney TR . Biological characteristics of some improved radioprotectors. In: Brady LW (ed.). Radiation Sensitizers. Masson: New York, 1980; pp 309–320.
Wasserman TH, Phillips TL, Ross G et al. Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by WR-2721. Cancer Clin Trials 1981; 4: 3–6.
Yuhas JM, Spellman JM, Culo F . The role of WR-2721 in radiotherapy and/or chemotherapy. Cancer Clin Trials 1980; 3: 211–216.
Douay L, Hu C, Giarratana MC, Gorin NC . Amifostine (WR-2721) protects normal haematopoietic stem cells against cyclophosphamide derivatives' toxicity without compromising their antileukaemic effects. Eur J Cancer 1995; 31A (Suppl. 1): S14–S16.
Calabro-Jones PM, Fahey RC, Smoluk GD et al. Alkaline phosphatase promotes radioprotection and accumulation of WR-1065 in V79-171 cells incubated in medium containing WR-2721. Int J Radiat Biol 1985; 47: 23–27.
Yang JL, Fernandes DJ, Speicher L et al. Biochemical determinants of the cytoprotective effect of amifostine. Proc Am Assoc Cancer Res 1996; 36: 290 (abstr 1725).
Douay L, Hu C, Giarratana MC, Gorin NC . Comparative effects of amifostine (Ethyol) on normal hematopoietic stem cells vs human leukemic cells during ex vivo purging in autologous bone marrow transplants. Semin Oncol 1994; 21 (Suppl. 11): 16–20.
Cronin S, Uberti JP, Ayash LJ et al. Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2000; 26: 1247–1249.
Chauncey TR, Gooley TA, Lloid ME et al. Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Am J Clin Oncol 2000; 23: 406–411.
Miller AB, Hoogstraten B, Staquet M, Winkler A . Reporting results of cancer treatment. Cancer 1981; 47: 207–214.
NCI/NIH Common Toxicity Criteria v2.0 (CTC) 1998.
Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Mantel N . Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50: 163–170.
Storb R, Deeg HJ, Whitehead J et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 31: 729–735.
Lorusso D, Ferrandina G, Greggi S et al. Multicenter Italian Trials in Ovarian Cancer investigators. Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients. Ann Oncol 2003; 14: 1086–1093.
Athanassiou H, Antonadou D, Coliarakis N et al. Oncology Hellenic Group. Protective effect of amifostine during fractionated radiotherapy in patients with pelvic carcinomas: results of a randomized trial. Int J Radiat Oncol Biol Phys 2003; 56: 1154–1160.
Werner-Wasik M, Scott C, Movsas B et al. Amifostine as mucosal protectant in patients with locally advanced non-small cell lung cancer (NSCLC) receiving intensive chemotherapy and thoracic radiotherapy (RT): results of the radiation therapy oncology group (RTOG) 98-01 study. Int J Radiat Oncol Biol Phys 2003; 57 (Suppl.): S216.
Brizel DM, Overgaard J . Does amifostine have a role in chemoradiation treatment? Lancet Oncol 2003; 4: 378–381.
Giatromanolaki A, Sivridis E, Maltezos E, Koukourakis ML . Down-regulation of intestinal-type alkaline phosphatase in the tumor vasculature and stroma provides a strong basis for explaining amifostine selectivity. Semin Oncol 2002; 29 (Suppl. 19): 14–21.
Thieblemont C, Dumontet C, Saad H et al. Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma. Bone Marrow Transplant 2002; 30: 769–775.
Hartmann JT, von Vangerow A, Fels LM et al. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. Br J Cancer 2001; 84: 313–320.
Phillips II GL . The potential of amifostine in high-dose chemotherapy and autologous hematopoietic stem cell transplantation. Semin Oncol 2002: (Suppl. 19): 53–56.
Poloni A, Leoni P, Curzi L et al. Ex vivo pharmacological purging of leukapheresis collections with nitrogen mustard: amifostine pretreatment improves both early and late peripheral blood progenitor cell recovery. Exp Hematol 1999; 27: 1548–1556.
Emmanouilides C, Territo M, Andrey J, Mason J . A randomized phase II study of amifostine used as stem cell protectant in non-Hodgkin lymphoma patients receiving cisplatin-based salvage chemotherapy prior to stem cell transplant. J Hematother Stem Cell Res 2001; 10: 887–893.
Rick O, Beyer J, Schwella N, Siegert W . Influence of amifostine on reconstitution of lymphocyte subpopulations after conventional- and high-dose chemotherapy in patients with germ cell tumor. Ann Hematol 2002; 81: 717–722.
Shaw LM, Glover DJ, Turrisi A et al. Pharmocokinetics of WR-2721. Pharmacol Ther 1988; 39: 195–201.
Heimdahl A . Prevention and management of oral infections in cancer patients. Support Care Cancer 1999; 7: 224–228.
Edmiston Jr CE, Condon RE . Bacterial translocation. Surg Gynecol Obstet 1991; 173: 73–83.
Acknowledgements
We thank the nursing staff in the Department of Haematology, Singapore General Hospital for excellent nursing care and Schering-Plough Singapore for sponsoring this clinical trial.
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Hwang, W., Koh, LP., Ng, H. et al. A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 34, 51–56 (2004). https://doi.org/10.1038/sj.bmt.1704521
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DOI: https://doi.org/10.1038/sj.bmt.1704521
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