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A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses

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Abstract

Interferon-alpha (IFN-α) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-α in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-α. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m2 per day) or high (5 MU/m2 per day) target dose of IFN-α. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-α actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) (p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-α because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-α are as effective as high doses in the treatment of CML.

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Contributions and acknowledgments

All the authors are members of the writing committee of this study. Besides, specific functions fulfilled were Steegmann, design of the study, final analysis, and coordination of the writing committee; Peñarrubia, validation of the data, statistical analysis, and final preparation of the manuscript; Lavilla, Casado, and Massagué, collection of data. We are indebted to the patient help of Dr. F. Rodriguez-Salvanés, statistician in the Epidemiology Unit of the Hospital de la Princesa. The comments of Dr. C. Burgaleta have been very helpful.

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Authors and Affiliations

  1. S. Hematología, Hospital del Río Hortega, Valladolid, Spain

    M. J. Peñarrubia

  2. S. Hematología, Hospital Ramón y Cajal, Madrid, Spain

    J. Odriozola

  3. S. Hematología, Hospital de la Arrixaca, Murcia, Spain

    C. González

  4. S. Hematología, Hospital Vall d¨Hebron, Barcelona, Spain

    I. Massagué

  5. S. Hematología, Hospital General Universitario, Valencia, Spain

    A. Miguel & J. D. González San Miguel

  6. S. Hematología, Hospital Insular, Las Palmas, Spain

    J. D. González San Miguel

  7. S. Hematología, Hospital Xeral de Galicia, Santiago de Compostela, Spain

    M. Pérez Encinas

  8. S. Hematología, Hospital Xeral Calde, Lugo, Spain

    E. Lavilla

  9. S. Hematología, Hospital Miguel Servet, Zaragoza, Spain

    M. P. Giraldo

  10. S. Hematología, Hospital Virgen de la Salud, Toledo, Spain

    L. F. Casado

  11. S. Hematología, Hospital Doctor Peset, Valencia, Spain

    S. Ferrer

  12. S. Hematología, Hospital de la Princesa, Diego de León 62, 28006, Madrid, Spain

    J. L. Steegmann

Authors
  1. M. J. Peñarrubia
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  2. J. Odriozola
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  3. C. González
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  4. I. Massagué
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  5. A. Miguel
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  6. J. D. González San Miguel
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  7. M. Pérez Encinas
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  8. E. Lavilla
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  9. M. P. Giraldo
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  10. L. F. Casado
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  11. S. Ferrer
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  12. J. L. Steegmann
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Consortia

Spanish Group on IFN and CML

Corresponding author

Correspondence to J. L. Steegmann.

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The authors listed about wrote this contribution on behalf of the Spanish Group on IFN and CML

Appendix

Appendix

Physicians and institutions participating in this study: Hospital de la Princesa (Madrid): J. L. Steegmann, E. Granados, M. J. Requena, F. Rodríguez-Salvanés, J. M. Fernández-Rañada. Hospital Ramón y Cajal (Madrid): J. Odriozola, J. García-Laraña, L. Escribano, J. López, J. Pérez-Oteyza, M. T. Ferro, L Villalón. H. U. de la Arrixaca (Murcia): C. González, M. Tamayo. H. Vall d¨Hebron (Barcelona): I Massagué, F. Zuazu. H.G.U. de Valencia (Valencia): A. Miguel, F. Carbonell. H. Insular (Las Palmas): J. D. González-San Miguel, J. M. Díaz Cremades. H.X. Galicia (Santiago de Compostela): M. Pérez-Encinas, M. J. Rabuñal, J. L. Bello. Hospital X. Calde (Lugo): E. Lavilla, M. A. González. Hospital Miguel Servet (Zaragoza): P. Giraldo, D. Rubio, M. Giralt. H. Virgen de la Salud (Toledo): L. F. Casado. Hospital Doctor Peset (Valencia): S. Ferrer, J. Rafecas. H. Puerta de Hierro: R. Forés. Hospital X. Cíes (Vigo): E. Benítez, C. Poderós. H. Río Hortega (Valladolid): M. J. Peñarrubia, L. J. García Frade. H. Dr. Negrín (Las Palmas): M. T. Gómez-Casares. H. Morales Messeguer (Murcia): C. Vallejo, J. Nieto. H. Montecelo (Pontevedra): L. Amador. H.U. de Getafe (Getafe): F. Oña, I. Delgado. H. Germans Trias i Pujol (Badalona): A. Flores. H. Central de Asturias (Oviedo): F. Jonte. H. Príncipe de Asturias (Alcalá de Henares): C. Burgaleta, J. García Suárez. H. Sta. Mª Madre (Orense): C. Hernández. H. Marina Alta (Denia): A. Abad, A. Aranda. H. Clínico (Elche): V. Conesa. H. NªSª del Rosell (Cartagena): A. Alix. H. Mutua de Terrassa: C. Estany.

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Peñarrubia, M.J., Odriozola, J., González, C. et al. A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses. Ann Hematol 82, 750–758 (2003). https://doi.org/10.1007/s00277-003-0724-z

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  • DOI: https://doi.org/10.1007/s00277-003-0724-z

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