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Evidence for Three Distinct Classes of Phenotype Severity in Beta-Thalassaemia

18 Pages Posted: 20 Feb 2019

See all articles by Aurelio Maggio

Aurelio Maggio

Campus of Hematology Franco and Piera Cutino

Angela Vitrano

Campus of Hematology Franco and Piera Cutino

Antonella Meloni

Fondazione Toscana Gabriele Monasterio

Walter Addario Pollina

Regione Siciliana

Mehran Karimi

Shiraz University of Medical Sciences

Amal El-Beshlawy

Cairo University

Mahmoud Hajipour

Shiraz University of Medical Sciences

Vito Di Marco

University of Palermo - Section of Gastroenterology and Hepatology

Saqib Hussain Ansari

National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)

Aldo Filosa

Cardarelli Hospital

Paolo Ricchi

Cardarelli Hospital

Adriana Ceci

Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus

Shahina Daar

Sultan Qaboos University

Sylvia Titi Singer

University of California, San Francisco (UCSF) - Division of Hematology/Oncology

Zaki A. Naserullah

Dammam Maternity and Child Hospital

Alessia Pepe

Fondazione Toscana Gabriele Monasterio

Salvatore Scondotto

Regione Siciliana

Kunle Adekile

Kuwait University

Marie Charlotte Bouesseau

Department of Ethics, Equity, Trade & Human Rights

Soteroula Christou

University of Nicosia

Gabriella Dardanoni

Regione Siciliana

Jianpei Fang

Sun Yat-Sen University (SYSU) - Sun Yat-sen Memorial Hospital

Suthat Fucharoen

Khon Kaen University

Olivier Hermine

Hôpital Necker-Enfants Malades

Ibrahim Hishamshah

General Hospital Kuala Lumpur

Paolo Moi

Universita di Cagliari

Sana Al-Jarrash

Dammam Maternity and Child Hospital

Laura Pistoia

Fondazione Toscana Gabriele Monasterio

Lorella Pitrolo

Campus of Hematology Franco and Piera Cutino

Paolo Rigano

Campus of Hematology Franco and Piera Cutino

Massimiliano Sacco

Campus of Hematology Franco and Piera Cutino

Farrukh Shah

Whittington Hospital

Alok Srivastava

Christian Medical College

Vip Viprakasit

Mahidol University

Mahmoud Yassin

Hamad Medical Corporation

Elliott Vichinsky

University of California, San Francisco (UCSF) - Division of Hematology/Oncology

More...

Abstract

Background: Classification of phenotype severity in patients with beta-thalassaemia has so far relied mainly on expert opinion using parameters of genotype, clinical features at diagnosis, and transfusion requirement. The aim of this study was to use a large dataset of patients with beta-thalassaemia and evaluate a classification system based on onset variables agreed on by an international expert group, including age at diagnosis, at first transfusion, and at first iron chelation.

Methods: A retrospective dataset of 7910 patients with homozygous or compound heterozygous beta-thalassaemia was used and subjected to cluster and classification analysis starting with the onset variables.    

Results: Cluster analysis suggested that three clusters with minimal overlapping exist. Three phenotype severity classes (mild, moderate, severe) were accordingly assigned which showed statistically significant descending variation of age at diagnosis and start of transfusion and iron chelation. The estimated classification error rate was only 3.07% with an accuracy of 96.93%. It was evident that severe patients had higher blood requirement and iron overload levels and showed a younger age for mortality especially from heart disease. Although mild and moderate patients showed the opposite in gradual severity, they still showed evidence of high morbidity rate for complications that require longer time to manifest (eg liver damage and hepatocellular carcinoma).    

Conclusion: Age of diagnosis and start of transfusion and iron chelation distinguish three classes of phenotype severity in beta-thalassaemia that carry unique clinical profiles.  Further prospective studies are recommended to validate these findings.

Funding Statement: The authors state: "None"

Declaration of Interests: The authors state: " None to disclose."

Ethics Approval Statement: An International Health Repository (IHR) protocol, approved on May 25th, 2017 by the Italian Ethical Committee (EudraCT and Sponsor's Protocol Code Numbers were 2017-004457-17 and 143AOR2017) was established to allow collection of relevant data.   

Keywords: classification; indexes of phenotype severity; random forest clustering; clinical severity

Suggested Citation

Maggio, Aurelio and Vitrano, Angela and Meloni, Antonella and Pollina, Walter Addario and Karimi, Mehran and El-Beshlawy, Amal and Hajipour, Mahmoud and Di Marco, Vito and Ansari, Saqib Hussain and Filosa, Aldo and Ricchi, Paolo and Ceci, Adriana and Daar, Shahina and Singer, Sylvia Titi and Naserullah, Zaki A. and Pepe, Alessia and Scondotto, Salvatore and Adekile, Kunle and Bouesseau, Marie Charlotte and Christou, Soteroula and Dardanoni, Gabriella and Fang, Jianpei and Fucharoen, Suthat and Hermine, Olivier and Hishamshah, Ibrahim and Moi, Paolo and Al-Jarrash, Sana and Pistoia, Laura and Pitrolo, Lorella and Rigano, Paolo and Sacco, Massimiliano and Shah, Farrukh and Srivastava, Alok and Viprakasit, Vip and Yassin, Mahmoud and Vichinsky, Elliott, Evidence for Three Distinct Classes of Phenotype Severity in Beta-Thalassaemia (February 15, 2019). Available at SSRN: https://ssrn.com/abstract=3335042 or http://dx.doi.org/10.2139/ssrn.3335042

Aurelio Maggio (Contact Author)

Campus of Hematology Franco and Piera Cutino ( email )

AOOR Villa Sofia-V. Cervello
Palermo
Italy

Angela Vitrano

Campus of Hematology Franco and Piera Cutino

AOOR Villa Sofia-V. Cervello
Palermo
Italy

Antonella Meloni

Fondazione Toscana Gabriele Monasterio

Pisa
Italy

Walter Addario Pollina

Regione Siciliana

Palermo
Italy

Mehran Karimi

Shiraz University of Medical Sciences

Zand Ave
Shiraz, Fars
Iran

Amal El-Beshlawy

Cairo University

Orman
Giza, 12613
Egypt

Mahmoud Hajipour

Shiraz University of Medical Sciences

Zand Ave
Shiraz, Fars
Iran

Vito Di Marco

University of Palermo - Section of Gastroenterology and Hepatology

Palermo
Italy

Saqib Hussain Ansari

National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD)

Karachi
Pakistan

Aldo Filosa

Cardarelli Hospital

Naples
Italy

Paolo Ricchi

Cardarelli Hospital

Naples
Italy

Adriana Ceci

Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus

Valenzano
Italy

Shahina Daar

Sultan Qaboos University

PO Box 20
Al-khod SQU 123
Muscat
Oman

Sylvia Titi Singer

University of California, San Francisco (UCSF) - Division of Hematology/Oncology

San Francisco, CA 94143
United States

Zaki A. Naserullah

Dammam Maternity and Child Hospital

Dammam
Saudi Arabia

Alessia Pepe

Fondazione Toscana Gabriele Monasterio

Pisa
Italy

Salvatore Scondotto

Regione Siciliana

Palermo
Italy

Kunle Adekile

Kuwait University

Safat, 13060
Kuwait

Marie Charlotte Bouesseau

Department of Ethics, Equity, Trade & Human Rights ( email )

20 Avenue Appia
Geneva 27, CH-1211
Switzerland

Soteroula Christou

University of Nicosia

46 Makedonitissas Avenue
Nicosia, Nicosia 24005
Cyprus

Gabriella Dardanoni

Regione Siciliana

Palermo
Italy

Jianpei Fang

Sun Yat-Sen University (SYSU) - Sun Yat-sen Memorial Hospital

107 Yanjiang W Rd
Guangzhou
China

Suthat Fucharoen

Khon Kaen University

23 Moo 16 Mittapap Rd
Nai-Muang, Muang District 40002
Thailand

Olivier Hermine

Hôpital Necker-Enfants Malades

Paris
France

Ibrahim Hishamshah

General Hospital Kuala Lumpur

Jalan Pahang
Malaysia

Paolo Moi

Universita di Cagliari

Cagliari, 09124
Italy

Sana Al-Jarrash

Dammam Maternity and Child Hospital

Dammam
Saudi Arabia

Laura Pistoia

Fondazione Toscana Gabriele Monasterio ( email )

Pisa
Italy

Lorella Pitrolo

Campus of Hematology Franco and Piera Cutino

AOOR Villa Sofia-V. Cervello
Palermo
Italy

Paolo Rigano

Campus of Hematology Franco and Piera Cutino

AOOR Villa Sofia-V. Cervello
Palermo
Italy

Massimiliano Sacco

Campus of Hematology Franco and Piera Cutino

AOOR Villa Sofia-V. Cervello
Palermo
Italy

Farrukh Shah

Whittington Hospital

London
United Kingdom

Alok Srivastava

Christian Medical College

Vellore, Tamil Nadu
India

Vip Viprakasit

Mahidol University

69 Vipawadee Rangsit Road
Phayatai, Bangkok, Nakhonpathom 10400
Thailand

Mahmoud Yassin

Hamad Medical Corporation

Doha
Qatar

Elliott Vichinsky

University of California, San Francisco (UCSF) - Division of Hematology/Oncology

San Francisco, CA 94143
United States

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