Improving the treatment outcome of acute promyelocytic leukemia in developing countries through an international network

In developed countries, the standard treatment for acute promyelocytic leukemia (APL), as recommended by evidence-based guidelines such as those of the EuropeanLeukemiaNET, is a combination of all-trans retinoic acid, a derivative of Vitamin A, and an anthracycline-based chemotherapy; this results in a five-year overall survival rate of approximately 90 percent. The morbidity and mortality of APL in patients in developing countries is significantly higher. Researchers from the International Consortium on Acute Promyelocytic Leukemia (IC-APL), an initiative of the American Society of Hematology, aimed to reduce this difference in survival. They have made progress through the IC-APL’s international network of clinicians and researchers dedicated to accelerating patient diagnosis and delivering prompt treatment through the implementation of evidence-based guidelines in developing countries.

In this study, any patient suspected of having APL was immediately started on all-trans retinoic acid, while bone marrow samples were sent to a central laboratory in order to confirm the diagnosis quickly. A total of 102 patients (70 in Brazil, 25 in Mexico, and seven in Uruguay) were enrolled and received treatment identical to the LPA 2005 protocol set forth by the PETHEMA working group of the Spanish Association of Hematology and Hemotherapy, which consisted of all-trans retinoic acid, idarubicin, mitoxantrone, and cytosine arabinoside combination therapy. In this study, however, patients received daunorubicin instead of idaribicin, which is a more affordable version of anthracycline. Patient cases were discussed online among local hematologists every other week, and international experts participated as needed.

The study found that participation in the IC-APL resulted in an approximately 40 percent decrease in early mortality and a marked improvement in the long-term outcome of patients with APL to levels similar to those reported in developed countries. A total of 77 patients (79 percent) achieved a complete remission, and one-year overall and disease-free survival from the date of complete response was 95 percent.

“It is unfortunate that even with the availability of effective treatment options, in developing countries such as Brazil, Mexico, and Uruguay, patients with acute promyelocyctic leukemia are not receiving prompt treatment and thus face higher mortality rates than those in developed countries,” said lead study author Eduardo M. Rego, MD, PhD, Professor of the Medical School of Ribeirão Preto at the University of São Paulo in Ribeirão Preto, Brazil. “The IC-APL protocol is an affordable program that has radically changed the fate of these patients through the implementation of simple measures and international collaboration between doctors.”