Prognostic Role of Minimal Disseminated Disease and <i>NOTCH1/FBXW7</i> Mutational Status in Children with Lymphoblastic Lymphoma: The AIEOP Experience
Federica Lovisa,
Ilaria Gallingani,
Elena Varotto,
Cristiano Pasin,
Elisa Carraro,
Barbara Michielotto,
Anna Garbin,
Carlotta Caterina Damanti,
Marco Pizzi,
Emanuele S. G. d’Amore,
Matilde Piglione,
Paola Muggeo,
Salvatore Buffardi,
Luciana Vinti,
Veronica Maria Folsi,
Daniela Onofrillo,
Alessandra Biffi,
Barbara Buldini,
Marta Pillon,
Lara Mussolin
Affiliations
Federica Lovisa
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Ilaria Gallingani
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Elena Varotto
Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy
Cristiano Pasin
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Elisa Carraro
Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, Italy
Barbara Michielotto
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Anna Garbin
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Carlotta Caterina Damanti
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Marco Pizzi
General Pathology and Cytopathology Unit, Department of Medicine-DMED, University of Padova, 35121 Padova, Italy
Emanuele S. G. d’Amore
Department of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy
Matilde Piglione
Paediatric Haematology, Department of Paediatrics, University Hospital Città della Salute e della Scienza di Torino, 10126 Torino, Italy
Paola Muggeo
Pediatric Oncology and Hematology Unit, University Hospital of Policlinico, 70120 Bari, Italy
Salvatore Buffardi
Department of Paediatric Haemato-Oncology, Santobono-Pausilipon Children’s Hospital, 80123 Napoli, Italy
Luciana Vinti
Department of Pediatric Hemato-Oncology, Ospedale Bambino Gesù, 00165 Rome, Italy
Veronica Maria Folsi
Department of Pediatrics, Pediatrics Clinic, Spedali Civili of Brescia, 25123 Brescia, Italy
Daniela Onofrillo
Paediatric Haemato-Oncology Unit, Hematology Department, Hospital of Pescara, 65124 Pescara, Italy
Alessandra Biffi
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Barbara Buldini
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
Marta Pillon
Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, Italy
Lara Mussolin
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
NOTCH1/FBXW7 (N/F) mutational status at diagnosis is employed for T-cell lymphoblastic lymphoma (T-LBL) patients’ stratification in the international protocol LBL 2018. Our aim was to validate the prognostic role of Minimal Disseminated Disease (MDD) alone and in combination with N/F mutational status in a large retrospective series of LBL pediatric patients. MDD was analyzed in 132 bone marrow and/or peripheral blood samples by flow cytometry. Mutations in N/F genes were analyzed on 58 T-LBL tumor biopsies. Using the previously established cut-off of 3%, the four-year progression-free survival (PFS) was 57% for stage I–III patients with MDD ≥ 3% versus 80% for patients with MDD inferior to cut-off (p = 0.068). We found a significant worsening in the four-year PFS for nonmutated (51 ± 12%) compared to mutated patients (100%, p = 0.0013). Combining MDD and N/F mutational status in a subgroup of available cases, we found a statistically significant difference in the four-year PFS for different risk groups (p = 0.0012). Overall, our results demonstrate that N/F mutational status has a more relevant prognostic value than MDD at diagnosis. However, the combination of N/F mutations with MDD analysis could identify patients with very aggressive disease, which might benefit from a more intensive treatment.
