Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts
Sabina Chiaretti,
Antonella Vitale,
Gianni Cazzaniga,
Sonia Maria Orlando,
Daniela Silvestri,
Paola Fazi,
Maria Grazia Valsecchi,
Loredana Elia,
Anna Maria Testi,
Francesca Mancini,
Valentino Conter,
Geertruy te Kronnie,
Felicetto Ferrara,
Francesco Di Raimondo,
Alessandra Tedeschi,
Giuseppe Fioritoni,
Francesco Fabbiano,
Giovanna Meloni,
Giorgina Specchia,
Giovanni Pizzolo,
Franco Mandelli,
Anna Guarini,
Giuseppe Basso,
Andrea Biondi,
Robin Foà
Affiliations
Sabina Chiaretti
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Antonella Vitale
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Gianni Cazzaniga
Tettamanti Research Center, Pediatric Clinic, University of Milano-Bicocca, Milan, Italy
Sonia Maria Orlando
GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
Daniela Silvestri
Medical Statistics Unit, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy
Paola Fazi
GIMEMA Data Center, GIMEMA Foundation, Rome, Italy
Maria Grazia Valsecchi
Medical Statistics Unit, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy
Loredana Elia
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Anna Maria Testi
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Francesca Mancini
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Valentino Conter
Department of Pediatrics, Ospedali Riuniti di Bergamo, Bergamo, Italy
Geertruy te Kronnie
Pediatric Onco-hematology Clinic, University of Padua, Azienda Ospedaleria Universitaria, Padova, Italy
Felicetto Ferrara
Division of Haematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy
Francesco Di Raimondo
Department of Clinical and Molecular Bio-Medicine, Section of Hematology, Oncology and Clinical Pathology, University of Catania, Italy
Alessandra Tedeschi
Department of Transfusion Medicine and Division of Hematology, Niguarda Ca’ Granda Hospital, Milan, Italy
Giuseppe Fioritoni
Department of Hematology, Civic Hospital, Pescara, Italy
Francesco Fabbiano
Institute of Hematology, Ospedali Riuniti Villa Sofia-Cervello Hospital, Palermo, Italy
Giovanna Meloni
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Giorgina Specchia
Hematology Section, Department of Pathological Anatomy, University of Bari, Italy
Giovanni Pizzolo
Department of Medicine, Haematology Section, University Hospital of Verona, Italy
Franco Mandelli
GIMEMA, GIMEMA Foundation, Rome, Italy
Anna Guarini
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
Giuseppe Basso
Pediatric Onco-hematology Clinic, University of Padua, Azienda Ospedaleria Universitaria, Padova, Italy
Andrea Biondi
Tettamanti Research Center, Pediatric Clinic, University of Milano-Bicocca, Milan, Italy;Medical Statistics Unit, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy
Robin Foà
Division of Hematology, Department of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, Italy
The outcome of children and adults with acute lymphoblastic leukemia is markedly different. Since there is limited information on the distribution of clinico-biological variables in different age cohorts, we analyzed 5202 patients with acute lymphoblastic leukemia enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in nine age cohorts. The highest prevalence of acute lymphoblastic leukemia was observed in children, although a second peak was recorded from the 4th decade onwards. Interestingly, the lowest incidence was found in females between 14–40 years. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated with MLL/AF4 positivity, was more frequent in patients between 10–50 years. T-lineage leukemia (14.2%) was rare among small children and increased in patients aged 10–40 years. The prevalence of the BCR/ABL1 rearrangement increased progressively with age starting from the cohort of patients 10–14 years old and was present in 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5th decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that acute lymphoblastic leukemia in adolescents and young adults is characterized by a male prevalence, higher percentage of T-lineage cases, an increase of poor prognostic molecular markers with aging compared to cases in children, and conclusively quantified the progressive increase of BCR/ABL+ cases with age, which are potentially manageable by targeted therapies.
