Blood Journal
Leading the way in experimental and clinical research in hematology

Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL

  1. Eduardo M. Rego1,*,
  2. Haesook T. Kim2,
  3. Guillermo J.. Ruiz-Argüelles3,
  4. Maria Soledad Undurraga4,
  5. Maria del Rosario Uriarte5,
  6. Rafael H. Jacomo1,
  7. Homero Gutiérrez-Aguirre6,
  8. Raul A. M. Melo7,
  9. Rosane Bittencourt8,
  10. Ricardo Pasquini9,
  11. Katia Pagnano10,
  12. Evandro M. Fagundes11,
  13. Maria de Lourdes Chauffaille12,
  14. Carlos S. Chiattone13,
  15. Lem Martinez5,
  16. Luis A. Meillón14,
  17. David Gómez-Almaguer6,
  18. Hau C. Kwaan15,
  19. Javier Garcés-Eisele3,
  20. Robert Gallagher16,
  21. Charlotte M. Niemeyer17,
  22. Stanley L. Schrier18,
  23. Martin Tallman19,
  24. David Grimwade20,
  25. Arnold Ganser21,
  26. Nancy Berliner22,
  27. Raul C. Ribeiro23,
  28. Francesco Lo-Coco24,
  29. Bob Löwenberg25, and
  30. Miguel A. Sanz26
  1. 1 Hematology/Oncology Division, Department of Internal Medicine, Medical School of Ribeirao Preto and Center for Cell Based Therapy, University of Sao Paulo, Ribeirao Preto, Brazil;
  2. 2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States;
  3. 3 Clinica Ruiz de Puebla, Puebla, Mexico;
  4. 4 Department of Hematology, Hospital del Salvador, Santiago, Chile;
  5. 5 Asociacion Espanola Primera de Socorros Mutuos, Montevideo, Uruguay;
  6. 6 Hematology Division, Hospital Universitario Dr Jose E. Gonzalez, Monterrey, Mexico;
  7. 7 Fundacao HEMOPE, Recife, Brazil;
  8. 8 Hematology Division, Federal University of Rio Grande do Sul, Porto Alegre, Brazil;
  9. 9 Hematology Division, Federal University of Parana, Curitiba, Brazil;
  10. 10 Hematology and Hemotherapy Center, University of Campinas UNICAMP, Campinas, Brazil;
  11. 11 Hematology Division, Federal University of Minas Gerais, Belo Horizonte, Brazil;
  12. 12 Hematology and Transfusion Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil;
  13. 13 Hematology Division, Santa Casa Medical School, Sao Paulo, Brazil;
  14. 14 Centro Medico Nacional Siglo XXI, Mexico City, Mexico;
  15. 15 Hematology/Oncology Division, Northwestern University Feinbeig School of Medicine, Chicago, IL, United States;
  16. 16 Medicine and Oncology, Albert Einstein Cancer Center, New York, NY, United States;
  17. 17 Department of Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany;
  18. 18 Department of Medicine, Stanford University, Stanford, CA, United States;
  19. 19 Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY, United States;
  20. 20 Department of Medical and Molecular Genetics, King's College London School of Medicine, London, United Kingdom;
  21. 21 Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
  22. 22 Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States;
  23. 23 Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, United States;
  24. 24 Department of Biopathology, University Tor Vergata, Rome, Italy;
  25. 25 Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands;
  26. 26 Department of Hematology, Hospital Universitario La Fe, Valencia Medical School, Valencia, Spain
  1. * Corresponding author; email: emrego{at}

Key points

  • Development of a network was able to reduce significantly the early mortality and to improve the OS of APL patients in developing countries


Modern treatment with all-trans retinoic acid (ATRA) and chemotherapy has converted acute promyelocytic leukemia (APL) into the most frequently curable leukemia. However, this progress has not yielded equivalent benefit to developing countries. The IC-APL was established to create a network in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment and supportive guidelines that were adapted to local circumstances. APL was elected as a model disease because of the potential impact of improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, laboratory and data management training programs, with regular virtual and face-to-face meetings. Complete hematological remission was achieved by 153/180 (85%) patients and 27 (15%) died during induction. After a median follow up of 28 months, the 2-year cumulative incidence of relapse (CIR), overall survival (OS) and disease-free survival (DFS) were 4.5%, 80% and 91%, respectively. The establishment of the IC-APL network resulted in a nearly 50% decrease in early mortality and a nearly 30% improvement in OS compared to historical controls, resulting in OS and DFS similar to those reported in developed countries.

  • Submitted August 23, 2012.
  • Accepted November 27, 2012.