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774 Three Distinct Groups of Phenotype Severity in Beta-Thalassemia

Program: Oral and Poster Abstracts
Session: 112. Thalassemia and Globin Gene Regulation: Poster I
Hematology Disease Topics & Pathways:
Adult, survivorship, Diseases, thalassemia, Hemoglobinopathies, Young Adult, Study Population, Quality Improvement
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Aurelio Maggio, MD1, Angela Vitrano, PhD1*, Antonella Meloni, PhD2*, Walter Addario Pollina3*, Mehran Karimi, MD4, Amal El-Beshlawy, MD5, Mahmoud Hajipour6*, Vito Di Marco, MD7*, Saqib Hussain Ansari, MBBS, PhD8*, Aldo Filosa, MD9*, Paolo Ricchi, MD9*, Adriana Ceci, MD10*, Shahina Daar, MD11*, Sylvia Titi Singer, MD12, J F Borgio, MD13*, Alessia Pepe, MD2*, Salvatore Scondotto3*, Gabriella Dardanoni3*, Massimiliano Sacco, DR1*, Laura Pistoia, PhD2*, Rita Barone, MD1*, Fedele Bonifazi10*, Lorella Pitrolo, MD1* and Elliott P. Vichinsky, MD12

1Campus of Hematology Franco and Piera Cutino, AOOR Villa Sofia-V. Cervello, Palermo, Italy
2MRI Unit, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy
3Dipartimento Attività Sanitarie e Osservatorio Epidemiologico Assessorato Salute Regione Sicilia, Palermo, Italy
4Hematology Research Center, Nemazee Hospital, Shiraz University of Medical Science, Shiraz, Iran (Islamic Republic of)
5Pediatric Hospital, Cairo University, Mohandsein, Egypt
6Shiraz University of Medical Sciences, Shiraz, Iran (Islamic Republic of)
7Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy
8National Institute of Blood Disease and Bone Marrow Transplantation, KARACHI, OK, Pakistan
9Rare Blood Cell Disease Unit, AORN A. Cardarelli, Napoli, Italy
10Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus, Valenzano (BA), Italy
11Dept of Hematology, College of Medicine & Health Sciences, Sultan Qaboos University,, Muscat, Oman
12UCSF Benioff Children's Hospital Oakland, Oakland, CA
13Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia


Thalassemia Syndromes (TS) are commonly classified as transfusion-dependent-thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) at diagnosis on the basis of requirement for lifelong regular transfusion therapy for survival. However, data from observational studies and expert opinion suggest that these categories may reflect a wide spectrum rather than a dichotomy, and may actually be interchangeable at many parts of the disease journey. Thus, an evaluation of alternate clusters to classify TS patients remains of merit.


The aim of this study was to cluster TS patients on the basis of possible clinical indicators of phenotype severity (IPhS) using suitable algorithms and to determine whether these are able to detect cohorts with different clinical phenotypes.


Representatives from thirteen international centers from seven countries agreed on 19 IPhS to be collected for a retrospective study. Data from 7910 TS patients were collected. NbClust R Package was performed for exploring the existence of a substructure inside the studied TS population, determining the best number of clusters. Unsupervised Random Forest (RF) clustering and the Partitioning Around Medoids (PAM) algorithms were performed to define the clusters. The most important IPhS in defining clusters were selected according to the Gini index. Kaplan-Meier (K-M) survival curves of the identified clusters, defined by the selected IPhS, were used to represent the risk of death for these clusters.


NbClust method showed the existence of three possible clusters. The RF-PAM procedure defined three distinct clusters with a classification error rate of 4.3% (Fig 1). Moreover, the most important IPhS were patient age, mean serum ferritin level, age at diagnosis, age at first transfusion, age at first iron chelation, and number of complications. K-M curves showed statistically significant differences in survival among the three clusters (p<0.0001, Fig 2a) but not between the original classification of NTDT and TDT (p=0.0651, Fig 2b).


The observation of statistically significant differences in survival between the three newly identified clusters but not the original TDT-NTDT classification confirms that the latter classification is interchangeable, and a new triad classification system is required. These findings warrant further evaluation in prospective studies to determine specific thresholds for IPhs indicators that can aid physicians in assigning classes and tailoring care, in order to improve survival in TS patients.

Disclosures: Meloni: Chiesi Farmaceutici S.p.A.: Other: speakers’ honoraria. Pistoia: Chiesi Farmaceutici S.p.A.: Other: speakers’ honoraria. Vichinsky: Novartis: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; GBT: Consultancy, Research Funding.

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