Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes
David Bowen
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorDominic Culligan
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorSimon Jowitt
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorStephen Kelsey
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorGhulam Mufti
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorDavid Oscier
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorJane Parker
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorof the UK MDS Guidelines Group
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorDavid Bowen
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorDominic Culligan
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorSimon Jowitt
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorStephen Kelsey
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorGhulam Mufti
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorDavid Oscier
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorJane Parker
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this authorof the UK MDS Guidelines Group
1 Molecular and Cellular Pathology, Ninewells Hospital, Dundee, 2 Aberdeen Royal Infirmary, Aberdeen, 3 Stepping Hill Hospital, Stockport, 4 Department of Oncology, St. Bartholomews and Royal London MDS, London, 5 Department of Haematological Medicine, King's College of Medicine and Dentistry, London, and 6 Royal Bournemouth Hospital, Bournemouth, UK *Present address: Genetech, Inc., South San Francisco, CA, USA
Search for more papers by this author
References
- Ancliff, P.J. & Machin, S.J. (1998) Trigger factors for prophylactic platelet transfusion. Blood Reviews, 12, 234–238.
- Anderson, J.E., Appelbaum, F.R., Fisher, L.D., Schoch, G., Shulman, H., Anasetti, C., Bensinger, W.I., Bryant, E., Buckner, C.D., Doney, K., Martin, P.J., Sanders, J.E., Sullivan, K.M., Thomas, E.D., Witherspoon, R.P., Hansen, J.A. & Storb, R. (1993) Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood, 82, 677–681.
- Anderson, J.E., Appelbaum, F.R., Schoch, G., Gooley, T., Anasetti, C., Bensinger, W.I., Bryant, E., Buckner, C.D., Chauncey, T.R., Clift, R.A., Doney, K., Flowers, M., Hansen, J.A., Martin, P.J., Matthews, D.C., Sanders, J.E., Shulman, H., Sullivan, K.M., Witherspoon, R.P. & Storb, R. (1996) Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors. Blood, 87, 51–58.
- Anderson, J.E., Gooley, T.A., Schoch, G., Anasetti, C., Bensinger, W.I., Clift, R.A., Hansen, J.A., Sanders, J.E., Storb, R. & Appelbaum, F.R. (1997) Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy. Blood, 89, 2578–2585.
- Appelbaum, F.R. & Anderson, J. (1998) Allogeneic bone marrow transplantation for myelodysplastic syndrome: outcomes analysis according to IPSS score. Leukemia, 12, s25–s29.
- Aul, C., Gattermann, N. & Schneider, W. (1991) Treatment of advanced myelodysplastic syndromes with recombinant interferon-alpha 2b. European Journal of Haematology, 46, 11–16.
- Bain, B.J. (1996) The bone marrow aspirate of healthy subjects. British Journal of Haematology, 94, 206–209.
- Barrett, A.J., Molldrem, J.J., Saunthararajah, Y., Caples, M. & Young, N.S. (1998) Prolonged transfusion independence and disease stability in patients with myelodysplastic syndrome (MDS) responding to antithymocyte globulin (ATG). Blood, 92, 2932.
- Bennett, J.M., Catovsky, M.T., Daniel, G., Flandrin, D.A.G., Galton, H.R. & Sultan, C. (1982) Proposals for the classification of the myelodysplastic syndromes. British Journal of Haematology, 51, 189–199.
- Bourantas, K.L., Tsiara, S. & Christou, L. (1995) Treatment of 34 patients with myelodysplastic syndromes with 13-CIS retinoic acid. European Journal of Haematology, 55, 235–239.
- Bowen, D.T. & Hellstrom-Lindberg, E. (2001) Best supportive care for the anaemia of myelodysplasia: inclusion of recombinant erythropoietin therapy? Leukemia Research, 25, 19–21.
- Bowen, D.T., Denzlinger, C., Brugger, W., Culligan, D., Gelly, K., Adlakha, S., Groves, M., Hepburn, M. & Kanz, L. (1998) Poor response rate to a continuous schedule of Amifostine therapy for ‘low/intermediate risk’ myelodysplastic patients. British Journal of Haematology, 103, 785–787.
- Cheson, B.D., Bennett, J.M., Kantarjian, H., Pinto, A., Schiffer, C.A., Nimer, S.D., Lowenberg, B., Beran, M., De Witte, T.M., Stone, R.M., Mittelman, M., Sanz, G.F., Wijermans, P.W., Gore, S. & Greenberg, P.L. (2000) Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood, 96, 3671–3674.
- Clark, R.E., Jacobs, A., Lush, C.J. & Smith, S.A. (1987) Effect of 13-cis-retinoic acid on survival of patients with myelodysplastic syndrome. Lancet, 1, 763–765.
- Cotter, P.D., May, A., Fitzsimons, E.J., Houston, T., Woodcock, B.E., Al Sabah, A.I., Wong, L. & Bishop, D.F. (1995) Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. Journal of Clinical Investigations, 96, 2090–2096.
- Deeg, H.J., Shulman, H.M., Anderson, J.E., Bryant, E.M., Gooley, T.A., Slattery, J.T., Anasetti, C., Fefer, A., Storb, R. & Appelbaum, F.R. (2000) Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55–66 years of age. Blood, 95, 1188–1194.
- Demetri, G.D., Kris, M., Wade, J., Degos, L. & Cella, D. (1998) Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type: results from a prospective community oncology study. Journal of Clinical Oncology, 16, 3412–3425.
- Denzlinger, C., Bowen, D., Benz, D., Gelly, K., Brugger, W. & Kanz, L. (2000) Low-dose melphalan induces favourable responses in elderly patients with high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia. British Journal of Haematology, 108, 93–95.
- Di Raimondo, F., Longo, G., Cacciola, Jr, E., Milone, G., Palumbo, G.A., Cacciola, R.R., Alessi, M. & Giustolisi, R. (1996) A good response rate to recombinant erythropoietin alone may be expected in selected myelodysplastic patients. A preliminary clinical study. European Journal of Haematology, 56, 7–11.
- Dunn, D.E., Tanawattanacharoen, P., Boccuni, P., Nagakura, S., Green, S.W., Kirby, M.R., Kumar, M.S., Rosenfeld, S. & Young, N.S. (1999) Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Annals of Internal Medicine, 131, 401–408.
- Elias, L., Hoffman, R., Boswell, S., Tensen, L. & Bonnem, E.M. (1987) A trial of recombinant alpha 2 interferon in the myelodysplastic syndromes. I. Clinical results. Leukemia, 1, 105–110.
- Estey, E., Thall, P., Beran, M., Kantarjian, H., Pierce, S. & Keating, M. (1997) 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, 90, 2969–2977.
- Franchini, M., Gandini, G., De Gironcoli, M., Vassanelli, A., Borgna-Pignatti, C. & Aprili, G. (2000) Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood, 95, 2776–2779.
- Galvani, D.W., Nethersell, A.B. & Cawley, J.C. (1988) Alpha-interferon in myelodysplasia; clinical observations and effects on NK cells. Leukemia Research, 12, 257–262.
- Germing, U., Gattermann, N., Strupp, C., Aivado, M. & Aul, C. (2000a) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leukemia Research, 24, 983–992.
- Germing, U., Gattermann, N., Aivado, M., Hildebrandt, B. & Aul, C. (2000b) Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction. British Journal of Haematology, 108, 724–728.
- Gisslinger, H., Chott, A., Linkesch, W., Fritz, E. & Ludwig, H. (1990) Long-term alpha-interferon therapy in myelodysplastic syndromes. Leukemia, 4, 91–94.
- Glaspy, J., Bukowski, R., Steinberg, D., Taylor, C., Tchekmedyian, S. & Vadhanraj, S. (1997) Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Journal of Clinical Oncology, 15, 1218–1234.
- Greenberg, P., Cox, C., Lebeau, M.M., Fenaux, P., Morel, P., Sanz, G., Sanz, M., Vallespi, T., Hamblin, T., Oscier, D., Ohyashiki, K., Toyama, K., Aul, C., Mufti, G. & Bennett, J. (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes (Erratum in Blood 1998, 91, 1100).Blood 89, 2079–2088.
- Greenberg, P., Anderson, J.E., De Witte, T., Estey, E., Fenaux, P., Gupta, P., Hamblin, T., Hellstrom-Lindberg, E., List, A., Mufti, G., Neuwirtova, R., Ohyashiki, K., Sanz, G., Sanz, M., Oscier, D., Willman, C. & Members of the International MDS Study Group (2000) Problematic WHO reclassification of myelodysplastic syndromes. Journal of Clinical Oncology, 18, 3446–3452.
- Grossi, A., Fabbri, A., Santini, V., Leoni, F., Nozzoli, C., Longo, G., Pagliai, G., Ciolli, S. & Rossi, F.P. (2000) Amifostine in the treatment of low–risk myelodysplastic syndromes. Haematologica, 85, 367–371.
- Harris, N.L., Jaffe, E.S., Diebold, J., Flandrin, G., Muller-Hermelink, H.K., Vardiman, J., Lister, T.A. & Bloomfield, C.D. (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November 1997. Journal of Clinical Oncology, 17, 3835–3849.
- Hellstrom Lindberg, E. (1995) Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. British Journal of Haematology, 89, 67–71.
- Hellstrom Lindberg, E., Robert, K.H., Gahrton, G., Lindberg, G., Forsblom, A.M., Kock, Y. & Ost, A. (1992) A predictive model for the clinical response to low-dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia. British Journal of Haematology, 81, 503–511.
- Hellstrom Lindberg, E., Birgegard, G., Carlsson, M., Carneskog, J., Dahl, I.M., Dybedal, I., Grimfors, G., Merk, K., Tangen, J.M., Winqvist, I. & Ost, A. (1993) A combination of granulocyte colony-stimulating factor and erythropoietin may synergistically improve the anaemia in patients with myelodysplastic syndromes. Leukemia and Lymphoma, 11, 221–228.
- Hellstrom Lindberg, E., Negrin, R., Stein, R., Krantz, S., Lindberg, G., Vardiman, J., Ost, A. & Greenberg, P. (1997) Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. British Journal of Haematology, 99, 344–351.
- Hellstrom Lindberg, E., Ahlgren, T., Beguin, Y., Carlsson, M., Carneskog, J., Dahl, I.M., Dybedal, I., Grimfors, G., Kanter-Lewensohn, L., Linder, O., Luthman, M., Lofvenberg, E., Nilsson-Ehle, H., Samuelsson, J., Tangen, J.M., Winqvist, I., Oberg, G., Osterborg, A. & Ost, A. (1998) Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood, 92, 68–75.
- Hofmann, W.K., Kell, W.J., Fenaux, P., Castaigne, S., Ganser, A., Chomienne, C., Burnett, R., Kowal, C., Hoelzer, D. & Burnett, A.K. (2000) Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study. Leukemia, 14, 1583–1588.
- Imamura, M., Kobayashi, M., Kobayashi, S., Yoshida, K., Mikuni, C., Ishikawa, Y., Matsumoto, S., Sakamaki, S., Niitsu, Y., Hinoda, Y., Yachi, A., Kudoh, T., Chiba, S., Kasai, M., Oka, T., Okuno, A., Maekawa, I., Sakurada, K. & Miyazaki, T. (1994) Failure of combination therapy with recombinant granulocyte colony-stimulating factor and erythropoietin in myelodysplastic syndromes. Annals of Hematology, 68, 163–166.
- Italian Cooperative Study Group (1998) A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Italian Cooperative Study Group for rHuEpo in Myelodysplastic Syndromes. British Journal of Haematology, 103, 1070–1074.
- Jaffe, E.S., Harris, N.L., Stein, H. & Vardiman, J. (2001) Tumours of haematopoietic and lymphoid tissues. World Health Organisation classification of tumours. IARC Press, Lyon.
- Jonásova, A., Neuwirtová, R., Cermák, J., Vozobulová, V., Mociková, K., Sisková, M. & Hochová, I. (1998) Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. British Journal of Haematology, 100, 304–309.
- Kerndrup, G., Bendix-Hansen, K., Pedersen, B., Ellegaard, J. & Hokland, P. (1987) 13-cis retinoic acid treatment of myelodysplastic syndromes. Leukemia Research, 11, 7–16.
- Killick, S.B., Marsh, J.C., Cavenagh, J.D., Mijovic, A., Mufti, G., Gordonsmith, E.C. & Bowen, D.T. (1999) Antithymocyte globulin for the treatment of patients with ‘low risk’ myelodysplastic syndromes. Blood, 94, 1371a.
- Koeffler, H.P., Hirji, K. & Itri, L. (1985) 1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells. Cancer Treatment Report, 69, 1399–1407.
- Koeffler, H.P., Heitjan, D., Mertelsmann, R., Kolitz, J.E., Schulman, P., Itri, L., Gunter, P. & Besa, E. (1988) Randomized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders. Blood, 71, 703–708.
- Kouides, P.A. & Bennett, J.M. (1996) Morphology and classification of the myelodysplastic syndromes and their pathologic variants. Seminars in Hematology, 33, 95–110.
- Kuriyama, K., Tomonaga, M., Matsuo, T., Ginnai, I. & Ichimaru, M. (1986) Diagnostic significance of detecting pseudo-Pelger–Huet anomalies and micro-megakaryocytes in myelodysplastic syndrome. British Journal of Haematology, 63, 665–669.
- List, A.F., Brasfield, F., Heaton, R., Glinsmann Gibson, B., Crook, L., Taetle, R. & Capizzi, R. (1997) Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome. Blood, 90, 3364–3369.
- Mantovani, L., Lentini, G., Hentschel, B., Wickramanayake, P.D., Loeffler, M., Diehl, V. & Tesch, H. (2000) Treatment of anaemia in myelodysplastic syndromes with prolonged administration of recombinant human granulocyte colony-stimulating factor and erythropoietin. British Journal of Haematology, 109, 367–375.
- Mellibovsky, L., Diez, A., Perez-Vila, E., Serrano, S., Nacher, M., Aubia, J., Supervia, A. & Recker, R.R. (1998) Vitamin D treatment in myelodysplastic syndromes. British Journal of Haematology, 100, 516–520.
- Mijovic, A. & Mufti, G.J. (1998) The myelodysplastic syndromes: towards a functional classification. Blood Review, 12, 73–83.
- Miller, K.B., Kim, K., Morrison, F.S., Winter, J.N., Bennett, J.M., Neiman, R.S., Head, D.R., Cassileth, P.A., O'Connell, M.J. & Kyungmann, K. (1992) The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study[published erratum appears in Annals of Hematology 1993; 66, 164]. Annals of Hematology, 65, 162–168.
- Molldrem, J.J., Caples, M., Mavroudis, D., Plante, M., Young, N.S. & Barrett, A.J. (1997) Antithymocyte globulin for patients with myelodysplastic syndrome. British Journal of Haematology, 99, 699–705.
- Morel, P., Hebbar, M., Lai, J.L., Duhamel, A., Preudhomme, C., Wattel, E., Bauters, F. & Fenaux, P. (1993) Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia, 7, 1315–1323.
- Morel, P., Declercq, C., Hebbar, M., Bauters, F. & Fenaux, P. (1996) Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques. British Journal of Haematology, 94, 116–119.
- Mufti, G.J., Stevens, J.R., Oscier, D.G., Hamblin, T.J. & Machin, D. (1985) Myelodysplastic syndromes: a scoring system with prognostic significance. British Journal of Haematology, 59, 425–433.
- Murphy, M.F., Wallington, T.B., Kelsey, P., Boulton, F., Bruce, M., Cohen, H., Duguid, J., Knowles, S.M., Poole, G. & Williamson, L.M. (2001) Guidelines for the clinical use of red cell transfusions. British Journal of Haematology, 113, 24–31.
- Nand, S., Ellis, T., Messmore, H., Fisher, S.G., Gaynor, E. & Fisher, R.I. (1992) Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. Leukemia, 6, 220–223.
- Negrin, R.S., Stein, R., Vardiman, J., Doherty, K., Cornwell, J., Krantz, S. & Greenberg, P.L. (1993) Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood, 82, 737–743.
- Negrin, R.S., Stein, R., Doherty, K., Cornwell, J., Vardiman, J., Krantz, S. & Greenberg, P.L. (1996) Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood, 87, 4076–4081.
- Nemunaitis, J., Rosenfeld, C., Getty, L., Boegel, F., Meyer, W., Jennings, L.W., Zeigler, Z. & Shadduck, R. (1995) Pentoxifylline and ciprofloxacin in patients with myelodysplastic syndrome. A phase II trial. American Journal of Clinical Oncology, 18, 189–193.
- Nevill, T.J., Fung, H.C., Shepherd, J.D., Horsman, D.E., Nantel, S.H., Klingemann, H.G., Forrest, D.L., Toze, C.L., Sutherland, H.J., Hogge, D.E., Naiman, S.C., Le, A., Brockington, D.A. & Barnett, M.J. (1998) Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation. Blood, 92, 1910–1917.
- Nosslinger, T., Reisner, R., Koller, E., Gruner, H., Tuchler, H., Nowotny, H., Pittermann, E. & Pfeilstocker, M. (2001) Myelodysplastic syndromes, from French–American–British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution. Blood, 98, 2935–2941.
- Novitzky, N., Mohamed, R., Finlayson, J. & Du, T.C. (2000) Increased apoptosis of bone marrow cells and preserved proliferative capacity of selected progenitors predict for clinical response to anti-inflammatory therapy in myelodysplastic syndromes. Experimental Hematology, 28, 941–949.
- Omoto, E., Deguchi, S., Takaba, S., Kojima, K., Yano, T., Katayama, Y., Sunami, K., Takeuchi, M., Kimura, F., Harada, M. & Kimura, I. (1996) Low-dose melphalan for treatment of high-risk myelodysplastic syndromes. Leukemia, 10, 609–614.
- Petti, M.C., Latagliata, R., Avvisati, G., Spiriti, M.A., Montefusco, E., Spadea, A. & Mandelli, F. (1996) Treatment of high-risk myelodysplastic syndromes with lymphoblastoid alpha interferon. British Journal of Haematology, 95, 364–367.
- Picozzi, Jr, V.J., Swanson, G.F., Morgan, R., Hecht, F. & Greenberg, P.L. (1986) 13-cis retinoic acid treatment for myelodysplastic syndromes. Journal of Clinical Oncology, 4, 589–595.
- Pippard, M.J. & Weatherall, D.J. (2000) Oral iron chelation therapy for thalassaemia: an uncertain scene. British Journal of Haematology, 111, 2–5.
- Ramos, F., Fernandez-Ferrero, S., Suarez, D., Barbon, M., Rodriguez, J.A., Gil, S., Megido, M., Ciudad, J., Lopez, N., Del Canizo, C. & Orfao, A. (1999) Myelodysplastic syndrome: a search for minimal diagnostic criteria. Leukemia Research, 23, 283–290.
- Raza, A., Qawi, H., Lisak, L., Andric, T., Dar, S., Andrews, C., Venugopal, P., Gezer, S., Gregory, S., Loew, J., Robin, E., Rifkin, S., Hsu, W.T. & Huang, R.W. (2000) Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. Blood, 95, 1580–1587.
- Remacha, A.F., Arrizabalaga, B., Villegas, A., Manteiga, R., Calvo, T., Julia, A., Fernandez, F.I., Gonzalez, F.A., Font, L., Junca, J., Del Arco, A., Malcorra, J.J., Equiza, E.P., De Mendiguren, B.P. & Romero, M. (1999) Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group. Haematologica, 84, 1058–1064.
- Rodriguez, J.N., Dieguez, J.C., Muniz, R., Martino, M.L., Fernandez-Jurado, A., Amian, A., Canavate, M. & Prados, D. (1994) Human recombinant erythropoietin in the treatment of myelodysplastic syndromes anemia. Meta-analytic study. Sangre (Barcelona), 39, 435–439.
- Rose, E.H., Abels, R.I., Nelson, R.A., Mccullough, D.M. & Lessin, L. (1995) The use of rHuEpo in the treatment of anemia related to myelodysplasia (MDS). British Journal of Haematology, 89, 831–837.
- Santini, V. & Ferrini, P.R. (1998) Differentiation therapy of myelodysplastic syndromes: fact or fiction? British Journal of Haematology, 102, 1124–1138.
- Sanz, G.F., Sanz, M.A., Vallespí, T., Cañizo, M.C., Torrabadella, M., García, S., Irriguible, D. & San Miguel, J.F. (1989) 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, 74, 395–408.
- Slavin, S., Nagler, A., Naparstek, E., Kapelushnik, Y., Aker, M., Cividalli, G., Varadi, G., Kirschbaum, M., Ackerstein, A., Samuel, S., Amar, A., Brautbar, C., Ben Tal, O., Eldor, A. & Or, R. (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood, 91, 756–763.
- Stasi, R., Brunetti, M., Bussa, S., Conforti, M., Digiulio, C., Crescenzi, A., Terzoli, E., Vecchione, A. & Pagano, A. (1997a) Response to recombinant human erythropoietin in patients with myelodysplastic syndromes. Clinical Cancer Research, 3, 733–739.
- Stasi, R., Brunetti, M., Bussa, S., Conforti, M., Martin, L.S., La Presa, M., Bianchi, M., Parma, A. & Pagano, A. (1997b) Serum levels of tumour necrosis factor-alpha predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome. Clinical Laboratory Haematology, 19, 197–201.
- Stone, R.M., Spriggs, D.R., Arthur, K.A., Mayer, R.J., Griffin, J. & Kufe, D.W. (1993) Recombinant human gamma interferon administered by continuous intravenous infusion in acute myelogenous leukemia and myelodysplastic syndromes. American Journal of Clinical Oncology, 16, 159–163.
- Sutton, L., Chastang, C., Ribaud, P., Jouet, J.P., Kuentz, M., Attal, M., Reiffers, J., Tigaud, J.M., Rio, B., Dauriac, C., Legros, M., Dreyfus, F., Lioure, B., Troussard, X., Milpied, N., Witz, F., Oriol, P., Cahn, J.Y., Michallet, M., Gluckman, E., Ifrah, N., Pico, J.L., Vilmer, E. & Leblond, V. (1996) Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Societe Francaise de Greffe de Moelle. Blood, 88, 358–365.
- Tricot, G., Wolf-Peeters, C., Vlietinck, R. & Verwilghen, R.L. (1984) Bone marrow histology in myelodysplastic syndromes. II. Prognostic value of abnormal localization of immature precursors in MDS. British Journal of Haematology, 58, 217–225.
- Tuzuner, N., Cox, C., Rowe, J.M. & Bennett, J.M. (1994) Bone marrow cellularity in myeloid stem-cell disorders: impact of age correction. Leukemia Research, 18, 559–564.
- Tuzuner, N., Cox, C., Rowe, J.M., Watrous, D. & Bennett, J.M. (1995) Hypocellular myelodysplastic syndromes (MDS): new proposals. British Journal of Haematology, 91, 612–617.
- Visani, G., Tosi, P., Manfroi, S., Ottaviani, E., Finelli, C., Cenacchi, A., Bendandi, M. & Tura, S. (1995) All-trans retinoic acid in the treatment of myelodysplastic syndromes. Leukemia and Lymphoma, 19, 277–280.
- Wattel, E., Guerci, A., Hecquet, B., Economopoulos, T., Copplestone, A., Mahe, B., Couteaux, M.E., Resegotti, L., Voglova, V., Foussard, C., Pegourie, B., Michaux, J.J., Deconinck, E., Stoppa, A.M., Mufti, G., Oscier, D. & Fenaux, P. (1996) A randomized trial of hydroxyurea versus vp16 in adult chronic myelomonocytic leukemia. Blood, 88, 2480–2487.
- Wattel, E., Debotton, S., Lai, J.L., Preudhomme, C., Lepelley, P., Bauters, F. & Fenaux, P. (1997) Long-term follow-up of de novo myelodysplastic syndromes treated with intensive chemotherapy: incidence of long-term survivors and outcome of partial responders. British Journal of Haematology, 98, 983–991.
- Wijermans, P., Lubbert, M., Verhoef, G., Bosly, A., Ravoet, C., Andre, M. & Ferrant, A. (2000) Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. Journal of Clinical Oncology, 18, 956–962.
- De Witte, T., Van Biezen, A., Hermans, J., Labopin, M., Runde, V., Or, R., Meloni, G., Mauri, S.B., Carella, A., Apperley, J., Gratwohl, A. & Laporte, J.P. (1997) Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS. Chronic and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation. Blood, 90, 3853–3857.