Lucia Dora Notarangelo1, Annalisa Agostini2, Maddalena Casale3, Piera Samperi4, Francesco Arcioni5, Paolo Gorello6, Silverio Perrotta3, Nicoletta Masera7, Angelica Barone8, Elisa Bertoni1, Elisa Bonetti9, Roberta Burnelli10, Tommaso Casini11, Giovanni Carlo Del Vecchio12, Beatrice Filippini13, Fiorina Giona14, Paola Giordano12, Chiara Gorio1, Eleonora Marchina15, Margherita Nardi16, Angela Petrone17, Raffaella Colombatti18, Laura Sainati18, Giovanna Russo4. 1. Hematology Oncology Unit, Children's Hospital, ASST Spedali Civili, Brescia, Italy. 2. Pediatrics Clinic, University of Brescia, Spedali Civili di Brescia, Brescia, Italy. 3. Department of Woman, Child and General and Specialist Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy. 4. Unit of Pediatric Hematology and Oncology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. 5. Pediatric Hematology and Oncology with Bone Marrow Transplation, Azienda Ospedaliera di Perugia, Perugia, Italy. 6. Department of Medicine, University of Perugia, CREO, Hematology, Perugia, Italy. 7. Department of Pediatrics, Università di Milano Bicocca, Fondazione MBBM, Monza, Italy. 8. Department of Pediatric Onco-Hematology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 9. Department of Pediatric Onco-Hematology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 10. Pediatric Oncology University Hospital, Sant'Anna Hospital, Ferrara, Italy. 11. Pediatric Hematology-Oncology, IRCCS Meyer Children's Hospital, Florence, Italy. 12. Pediatric Unit "F. Vecchio", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 13. Department of Pediatrics, Infermi Hospital Rimini, Rimini, Italy. 14. Department of Cellular Biotechnologies and Hematology, Policlinico Umberto I, Sapienza University, Hematology, Rome, Italy. 15. Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 16. Onco-Hematologic Pediatric Center, University Hospital of Pisa, Pisa, Italy. 17. Department of Pediatrics, Rovereto Hospital, Rovereto, Italy. 18. Clinic of Pediatric Hematology Oncology, Department of Woman's and Child Health, Azienda Ospedaliera-Università di Padova, Padova, Italy.
Abstract
OBJECTIVES: HbS/β+ patients' presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/β+ patients, with genotype-phenotype correlation, in order to offer guidance for clinical management of such patients. METHODS: Retrospective cohort study of HbS/β+ patients among 15 AIEOP Centres. RESULTS: A total of 41 molecularly confirmed S/β+ patients were enrolled (1-55 years, median 10.9) and classified on β+ mutation: IVS-I-110, IVS-I-6, promoter, and "others." Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS-I-110 group presented the lowest median age at first SCD-related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS-I-6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers. CONCLUSIONS: HbS/β+ is not always a mild disease. Patients with IVS-I-110 mutation could benefit from a standard of care like SS and S/β° patients. Standardization of treatment is needed.
OBJECTIVES:HbS/β+ patients' presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/β+ patients, with genotype-phenotype correlation, in order to offer guidance for clinical management of such patients. METHODS: Retrospective cohort study of HbS/β+ patients among 15 AIEOP Centres. RESULTS: A total of 41 molecularly confirmed S/β+ patients were enrolled (1-55 years, median 10.9) and classified on β+ mutation: IVS-I-110, IVS-I-6, promoter, and "others." Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS-I-110 group presented the lowest median age at first SCD-related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS-I-6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers. CONCLUSIONS:HbS/β+ is not always a mild disease. Patients with IVS-I-110 mutation could benefit from a standard of care like SS and S/β° patients. Standardization of treatment is needed.