The International Consortium on Acute Leukemia (ICAL), a network strongly supported by ASH, brings together clinical investigators from Europe, North America, and South America to collaborate on treatment protocols and strategies. Lorena Lobo de Figueiredo-Pontes, MD, PhD, a member of the consortium, writes about her experience. She is an associate professor at Ribeirão Preto Medical School at the University of São Paulo in Brazil.
As a member of the hematology staff at the coordinating center (Ribeirão Preto Medical School) in Brazil, I am active in the work of ICAL. In Brazil, the ICAL studies, which were initiated under the leadership of Eduardo Rego, MD, professor of hematology/oncology at the University of São Paulo Medical School, included patients from 11 centers in the southern regions of the country.
Our initial effort involved the clinical study of acute promyelocytic leukemia, resulting in significant clinical and laboratory achievements. (Details of the long-term and continuous improvements have recently been published.) With all the hospitals involved in the study following the same clinical protocol, overall survival of more than 800 patients was shown to parallel the survival rates of patients in high-income countries, and death rates diminished over time as compared to the pre-ICAL period.1
Since 2020, I have had the privilege of serving as the national coordinator of the second major ICAL study, ICAML2015, which aims to reach the unmet clinical and laboratory needs of patients with low- and intermediate-risk acute myeloid leukemia (AML) who are eligible for intensive chemotherapy. To date, the study has screened 801 individuals with AML and included 428 patients from 11 centers in Brazil. Clinical data and outcome analysis have revealed that although survival has improved since the beginning of the study, early death is still a major challenge.
One of the most notable achievements of the study was the implementation of an eight-gene next-generation sequencing (NGS) panel designed by Peter J.M. Valk, PhD, associate professor and head of the Hemato-oncology Laboratory at the Department of Hematology at the Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. NGS data were combined with conventional cytogenetics and reverse transcription polymerase chain reaction for specific mutations to optimize the genetic analysis at diagnosis. These achievements made it possible to significantly improve risk stratification and reclassify patients to lower- or higher-risk groups,2 potentially influencing treatment decisions for consolidation. In countries where bone marrow transplantation beds are not readily available, this progress is of the utmost importance.
I am very proud to lead the ICAL flow cytometry studies in Brazil. Under the supervision of Sylvie Freeman, DPhil, MBChB, professor of immunohematology at the University of Birmingham’s Institute of Immunology and Immunotherapy in Birmingham, UK, we developed an eight-color flow cytometry panel for measurable residual disease (MRD) assessment after treatment. This protocol was feasible and applicable to virtually all cases, with MRD detection after the end of induction influencing both overall and event-free survival, as well as the incidence of relapse for intermediate-risk patients. (A manuscript on the protocol feasibility and clinical implications is currently being prepared).
In summary, through teamwork, dedication, and the efforts of the involved centers and members of the international committee, the ICAL network has brought significant advancements to the knowledge and management of AML in participating Latin American countries. Continuous support from ASH and local resources has made this possible. Independent of its broader global implications, the consortium has influenced my professional career as a hematologist, namely my growing experience with AML clinical management and research skills.
In San Diego, our ICAL plenum and laboratory subcommittees met to hear progress reports from the national coordinators of each country. Our discussions focused on the clinical impact of the molecular and flow cytometry methods that have been implemented. We also covered new aims for the ICAL protocol, with an eye toward decision-making strategies regarding the improvement of care for patients with AML in developing countries.
References
- Koury LCA, Kim HT, Undurraga MS, et al. Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia. Blood. 2024;144(12):1257-1270.
- Traina F, Figueiredo-Pontes LL, Ayrosa MI, et al. Feasibility and relevance of incorporating genetic testing by next-generation sequencing for acute myeloid leukemia patients treated in low- and middle-income countries. Blood. 2023, 142 (Suppl 1):2929.
