Continuing Coverage of the IC-APL

Charlotte Niemeyer, MD, Chair of ASH’s International Members Committee (IMC) and Professor of Pediatrics at the University Children’s Hospital in Freiburg, Germany

Guillermo J. Ruiz-Arguelles, MD, FACP, FRCPA, Regional Coordinator of the IC-APL for Mexico, Clinica Ruiz de Puebla, Centro de Hematologia y Medicina Interna de Puebla in Puebla, Mexico

Lem Martinez, MD, Regional Coordinator of IC-APL in Montevideo, Uruguay

The IC-APL became successful because of the enormous effort and enthusiasm of national coordinators, local data managers, and laboratory scientists. However, not surprisingly, some funding from local and national sources of the participating countries had to be relocated to support the initiative. In Mexico, the Fundación Mexicana para la Salud (Mexican Foundation for Health), a non-government organization, supported the salary for data managers, while Roche Mexico ensured that molecular studies could be conducted in all the patients. Similarly, in Brazil a private organization made certain that there was no shortage of medications for IC-APL patients. In addition to local sponsorship, the IC-APL is grateful for a grant of €100,000 by the Umberto Veronesi Foundation in Milano, Italy. With this generous donation, the IC-APL was able to establish a network of well-trained data managers in all participating hospitals. This infrastructure will allow the participating countries to later undertake network-based clinical studies on patients with APL or other hematologic diseases. Last, but not least, it was the initiative by ASH which brought together international experts and physicians from Brazil, Mexico, and Uruguay to engage in this pioneer work. ASH continues to support IC-APL with two annual meetings, regular phone conferences, and staff resources. With this combined local, national, and international support, capacities for clinical studies can be established in countries with limited resources as demonstrated by the IC-APL.

Eduardo M. Rego, MD, Associate Professor, Division of Hematology, Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Brazil

Francesco Lo-Coco, MD, Professor of Hematology of the University Tor Vergata in Rome and Chairman of the Subcommitte on APL of the Italian Cooperative Group GIMEMA

Javier Garcés-Eisele, PhD, Consultant, Department of Molecular Biology, Laboratorios Clínicos de Puebla, Mexico

As an integrating and fundamental part of the project, laboratory investigators were involved since the beginning in the IC-APL group to standardize diagnostic and genetic studies for patients enrolled in the protocol. To this end, an ad-hoc subcommittee was created under the supervision of an investigator from each country and a few other external experts. The team has edited a manual containing guidelines for logistical issues (sample collection, shipment, storage, etc.) and for standardized RT-PCR, antibody-based and FISH methods for diagnosis, and specific recommendations for coagulation studies. The PG-M3 (anti-PML) antibody for rapid, specific, and low-cost identification of APL cells in diagnostic smears was distributed before the start of the protocol to central reference laboratories in the three participating countries. The group meets regularly using the virtual meeting facilities provided by the Cure4Kids Web site at St. Jude Hospital to discuss diagnostic tests for individual patients, including PCR and immunofluorescence images, which are uploaded and visualized for discussion during the meeting. Such activity has resulted in the availability of diagnostic confirmation and in patient-sample banking to be used for future research studies.

Raul Ribeiro, MD, Director of the International Outreach Program and Leukemia/Lymphoma Division at St. Jude Children’s Research Hospital

Rafael Jácomo, MD, Staff Physician at the University Hospital, Medical School of Ribeirão Preto, University of São Paulo

A critical component of the IC-APL project is to store and frequently analyze data generated by collaborating institutions. Systematic and constant monitoring is required to assure uniformity of protocol guidelines and detect possible inconsistencies among participants. Because the project is being simultaneously developed at multiple sites in different countries, a Web-based solution has been necessary. Cure4Kids, developed by the St. Jude International Outreach Program, supports free, secure online meetings for training, case-by-case review of patients, and discussion of protocol issues. The Pediatric Oncology Networked Database (POND) is a secure, multilingual online database customized to meet IC-APL protocol requirements. POND allows each institution to store its own data and generate site-specific reports. Selected and authorized data from the institutions can be automatically shared with the protocol coordinator in an anonymized way (using a unique study identification number) to facilitate coordination of the protocol and monitoring of eligibility and data quality. Minimal requirements include a computer with an Internet browser (any platform), speakers, a microphone, and a medium- or high-speed Internet connection. Data managers were trained through online classes and provided with a detailed manual for both POND and the IC-APL protocol. The data managers, participating physicians, and study coordinator meet online every two weeks to review the cases. Over a 10-month period, 40 patients with APL have been considered for enrollment on the IC-APL protocol. Three patients were ineligible because of a low-performance score or absence of the t(15;17) by RT-PCR. Three additional patients were excluded because of protocol violations. POND and online communication tools in Cure4Kids are reliable and easy to use. The initial findings underscore the need for close monitoring of treatment protocol guidelines.