Abstract
The purpose of this study was to determine the efficacy of and tolerance to antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndrome (MDS). Therapy consisted of ATG 40 mg/kg/day daily intravenously (i.v.) for 4 days; cyclosporine daily orally for 6 months with levels titrated between 200 and 400 mg/dl; and methylprednisone 1 mg/kg i.v. daily before each dose of ATG. Of 32 patients treated, 31 patients were evaluable. The median age was 59 years (range, 28–79 years). A total of 18 patients had refractory anemia (RA) or RA with ringed sideroblasts (RARS), 10 patients had RA with excess blasts (RAEB), two patients had RAEB in transformation, and one patient had chronic myelomonocytic leukemia. ATG, cyclosporine, and methylprednisone induced complete (N=4) or partial (N=1) remission in five patients (16% of total; RA, two patients; RARS, two patients; and RAEB, one patient). Durable complete remissions were observed in three of 18 patients (17%) with RA (N=1) or RARS (N=2) (12, 41+, and 60+ months). The most common adverse events were fever and allergic reactions. Hepatic and renal dysfunction, albeit consistently reversible, occurred in 19 and 13% of the patients, respectively. In conclusion, an ATG-based regimen can produce durable complete remissions in a subset of patients with MDS.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.
Abruzzese E, Buss D, Rainer R, Rao PN, Pettanati MJ . Study of clonality in myelodysplastic syndromes: detection of trisomy 8 in bone marrow cell smears by fluorescence in situ hybridization. Leukemia Res 1996; 20: 551–557.
Bernell P, Jacobsson B, Nordgren A, Hast R . Clonal cell lineage involvement in myelodysplastic syndromes studied by fluorescence in situ hybridization and morphology. Leukemia 1996; 10: 662–668.
Coiffier B, Adeleine P, Viala JJ, Bryon PA, Fiere D, Gentilhomme O et al . Dysmyelopoietic syndromes. A search for prognostic factors in 193 patients. Cancer 1983; 52: 83–90.
Foucar K, Langdon II RM, Armitage JO, Olson DB, Carroll Jr TJ . Myelodysplastic syndromes. A clinical and pathologic analysis of 109 cases. Cancer 1985; 56: 553–561.
Mufti GJ, Galton DA . Myelodysplastic syndromes: natural history and features of prognostic importance. Clin Haematol 1986; 15: 953–971.
Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S et al. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 1989; 74: 395–408.
Heaney ML, Golde DW . Myelodysplasia. N Engl J Med 1999; 340: 1649–1660.
Kurzrock R, Talpaz M, Estey E, O'Brien S, Estrov Z, Gutterman JU . Erythropoietin treatment in patients with myelodysplastic syndrome and anemia. Leukemia 1991; 5: 985–990.
Kurzrock R, Cortes J, Thomas DA, Jeha S, Pilat S, Talpaz M . Pilot study of low-dose interleukin-11 in patients with bone marrow failure. J Clin Oncol 2001; 19: 4165–4172.
Estey EH, Kurzrock R, Talpaz M, McCredie KB, O'Brien S, Kantarjian HM et al. Effects of low doses of recombinant human granulocyte–macrophage colony stimulating factor (GM-CSF) in patients with myelodysplastic syndromes. Br J Haematol 1991; 77: 291–295.
Negrin RS, Stein R, Vardiman J, Doherty K, Cornwell J, Krantz S et al. Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood 1993; 82: 737–743.
Ganser A, Volkers B, Greher J, Ottmann OG, Walther F, Becher R et al. Recombinant human granulocyte–macrophage colony-stimulating factor in patients with myelodysplastic syndromes – a phase I/II trial. Blood 1989; 73: 31–37.
Vadhan-Raj S, Keating M, LeMaistre A, Hittelman WN, McCredie K, Trujillo JM et al. Effects of recombinant human granulocyte–macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med 1987; 317: 1545–1552.
Negrin RS, Stein R, Doherty K, Cornwell J, Vardiman J, Krantz S et al. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 1996; 87: 4076–4081.
Hellstrom-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J et al. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol 1997; 99: 344–351.
Hellstrom-Lindberg E, Ahlgren T, Beguin Y, Carlsson M, Carneskog J, Dahl IM et al. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythro-poietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 1998; 92: 68–75.
Economopoulos T, Stathakis N, Foudoulakis A, Papadoulis N, Dervenoulas J, Papageorgiou E et al. Myelodysplastic syndromes: analysis of 131 cases according to the FAB classification. Eur J Haematol 1987; 38: 338–344.
de Witte T, Suciu S, Peetermans M, Fenaux P, Strijckmans P, Hayat M et al. Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG). Leukemia 1995; 9: 1805–1811.
Talpaz M, Zhang F, Kurzrock R . Myelodysplastic syndromes. Hemato–Oncol Clin Manage Modules 2001; 5: 1–27.
Estey E, Thall P, Beran M, Kantarjian H, Pierce S, Keating M . Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia (AML)) on outcome of AML-type chemotherapy. Blood 1997; 90: 2969–2977.
Kurzrock R . Myelodysplastic syndrome overview. Semin Hematol 2002; 39: 18–25.
Luger S, Sacks N . Bone marrow transplantation for myelodysplastic syndrome – who? when? and which? Bone Marrow Transplant 2002; 30: 199–206.
Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002; 20: 2429–2440.
Frickhofen N, Kaltwasser JP, Schrezenmeier H, Raghavachar A, Vogt HG, Herrmann F et al. Treatment of aplastic anemia with antithymocyte globulin and methylprednisolone with or without cyclosporine. N Engl J Med 1991; 324: 1297–1304.
Rosenfeld SJ, Kimball J, Vining D, Young NS . Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. Blood 1995; 85: 3058–3065.
Young N, Griffith P, Brittain E, Elfenbein G, Gardner F, Huang A et al. A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. Blood 1988; 72: 1861–1869.
Barrett J, Saunthararajah S, Molldrem J . Myelodysplastic syndrome and aplastic anemia: Distinct entities or diseases linked by a common pathophysiology? Semin Hematol 2000; 37: 15–29.
Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000; 96: 3671–3674.
Young NS, Maciejewski J . The pathophysiology of acquired aplastic anemia. N Engl J Med 1997; 1336: 1365–1372.
Molldrem JJ, Jiang YZ, Stetler-Stevenson M, Mavroudis D, Hensel N, Barrett AJ . Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br J Haematol 1998; 102: 1314–1322.
Dhodapkar MV, Li CY, Lust JA, Tefferi A, Phyliky RL . Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood 1994; 84: 1620–1627.
Biesma DH, van den Tweel JG, Verdonck LF . Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer 1997; 79: 1548–1551.
Sugawara T, Endo K, Shishido T, Sato A, Kameoka J, Fukuhara O et al. T cell-mediated inhibition of erythropoiesis in myelodysplastic syndromes. Am J Hematol 1992; 41: 304–305.
Smith MA, Smith JG . The occurrence subtype and significance of haemopoietic inhibitory T cells (HIT cells) in myelodysplasia: an in vitro study. Leukemkia Res 1991; 15: 597–601.
Saunthararajah Y, Molldrem JL, Rivera M, Williams A, Stetler-Stevenson M, Sorbara L et al. Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features. Br J Haematol 2001; 112: 195–200.
Tichelli A, Gratwohl A, Wuersch A, Nissen C, Speck B . Antilymphocyte globulin for myelodysplastic syndrome. Br J Haematol 1988; 68: 139–140.
Molldrem JJ, Caples M, Mavroudis D, Plante M, Young NS, Barrett AJ . Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 1997; 99: 699–705.
Jonasova A, Neuwirtova R, Cermak J, Vozobulova V, Mocikova K, Siskova M et al. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol 1998; 100: 304–309.
Maciejewski JP, Risitano A, Sloand EM, Nunez O, Young NS . Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Blood 2002; 99: 3129–3133.
Raghavachar A, Janssen JW, Schrezenmeier H, Wagner B, Bartram CR, Schulz AS et al. Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia. Blood 1995; 86: 2938–2947.
Mortazavi Y, Chopra R, Gordon-Smith EC, Rutherford TR . Clonal patterns of X-chromosome inactivation in female patients with aplastic anaemia studies using a novel reverse transcription polymerase chain reaction method. Eur J Haematol 2000; 64: 385–395.
Socie G . Could aplastic anaemia be considered a pre-pre-leukaemic disorder? Eur J Haematol Suppl 1996; 60: 60–63.
Sole F, Espinet B, Sanz GF, Cervera J, Calasanz MJ, Luno E et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J Haematol 2000; 108: 346–356.
de Souza Fernandez T, Ornellas MH, Otero de Carvalho L, Tabak D, Abdelhay E . Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia. Leukemia Res 2000; 24: 839–848.
Bernasconi P, Alessandrino EP, Boni M, Bonfichi M, Morra E, Lazzarino M et al. Karyotype in myelodysplastic syndromes: relations to morphology, clinical evolution, and survival. Am J Hematol 1994; 46: 270–277.
Vila L, Charrin C, Archimbaud E, Treille-Ritouet D, Fraisse J, Felman P et al. Correlations between cytogenetics and morphology in myelodysplastic syndromes. Blut 1990; 60: 223–227.
Maciejewski JP, Follmann D, Nakamura R, Saunthararajah Y, Rivera CE, Simonis T et al. Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Blood 2001; 98: 3513–3519.
Young NS, Barrett AJ . The treatment of severe acquired aplastic anemia. Blood 1995; 85: 3367–3377.
Hunter RF, Mold NG, Mitchell RB, Huang AT . Differentiation of normal marrow and HL60 cells induced by antithymocyte globulin. Proc Natl Acad Sci USA 1985; 82: 4823–4827.
Huang AT, Mold NG . The role of CD45RO in antithymocyte globulin's stimulation of primitive haemopoietic cells. Br J Haematol 1994; 88: 643–646.
Killick SB, Marsh JC, Gordon-Smith EC, Sorlin L, Gibson FM . Effects of antithymocyte globulin on bone marrow CD34+ cells in aplastic anaemia and myelodysplasia. Br J Haematol 2000; 108: 582–591.
Gluckman E, Esperou-Bourdeau H, Baruchel A, Boogaerts M, Briere J, Donadio D et al. Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. Blood 1992; 79: 2540–2546.
Marsh J, Schrezenmeier H, Marin P, Ilhan O, Ljungman P, McCann S et al. Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party. Blood 1999; 93: 2191–2195.
Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C et al. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med 2002; 137: 156–163.
Mineishi S, Filippa D, Childs B, Castro-Malaspina H . Hypoplastic myelodysplastic syndrome (MDS): clinical, hematologic, and pathologic observations in 36 cases. Blood 1994; 84: 315a.
List AF, Glinsmann-Gibson B, Spier C, Taetle R In vitro and in vivo response to cyclosporin-A in myelodysplastic syndromes (MDS): identification of a hypocellular subset responsive to immune suppression. Blood 1992; 80: 28a.
Killick SB, Mufti G, Cavenagh JD, Mijovic A, Peacock JL, Gordon-Smith JC, Taetle R . A pilot study of antithymocyte globulin (ATG) in the treatment of patients with ‘low-risk’ myelodysplasia. Br J Haematol 2003; 120: 679–684.
Bielory L, Gascon P, Lawley TJ, Young NS, Frank MM . Human serum sickness: a prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone marrow failure. Medicine 1988; 67: 40–57.
Doney K, Pepe M, Storb R, Bryant E, Anasetti C, Appelbaum FR et al. Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone. Blood 1992; 79: 2566–2571.
Author information
Authors and Affiliations
Additional information
There was no research support for this study
Rights and permissions
About this article
Cite this article
Yazji, S., Giles, F., Tsimberidou, AM. et al. Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes. Leukemia 17, 2101–2106 (2003). https://doi.org/10.1038/sj.leu.2403124
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2403124
Keywords
This article is cited by
-
Management of anemia in low-risk myelodysplastic syndromes treated with erythropoiesis-stimulating agents newer and older agents
Medical Oncology (2018)
-
T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS
Blood Cancer Journal (2014)
-
Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes
International Journal of Hematology (2013)
-
Immunosuppressive therapy for myelodysplastic syndromes: Refining the indications
Current Hematologic Malignancy Reports (2008)
-
Levels of soluble HLA-I and β2M in patients with acute myeloid leukemia and advanced myelodysplastic syndrome: association with clinical behavior and outcome of induction therapy
Leukemia (2007)