Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States

Elliott Vichinsky; Alan Cohen; Alexis A. Thompson; Patricia J. Giardina; Ashutosh Lal; Carole Paley; Wendy Y. Cheng; Nora McCormick; Medha Sasane; Ying Qiu; Janet L. Kwiatkowski

doi:10.1002/pbc.27067

Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States

Elliott Vichinsky^*, Alan Cohen, Alexis A. Thompson, Patricia J. Giardina, Ashutosh Lal, Carole Paley, Wendy Y. Cheng, Nora McCormick, Medha Sasane, Ying Qiu, Janet L. Kwiatkowski

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Background: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group of thalassemia mutations and clinical phenotypes that do not require chronic transfusions. It is increasingly prevalent in the United States. Procedure: This study reviews the epidemiology and clinical characteristics of 138 patients with NTDT treated at four US thalassemia centers from 1997 to 2014. Data on laboratory results, transfusions, and clinical complications were collected from patient charts. Results: Overall, 84 patients with α-thalassemia (62 deletional hemoglobin H; 22 nondeletional hemoglobin H), 39 with β-thalassemia (26 with homozygous or double heterozygous β mutations; 13 with single β mutations with or without α triplication), and 15 with E/β-thalassemia (12 E/β ⁰ ; three E/β ⁺ ) were identified. At study entry, the median age for patients with α-thalassemia was 2.3 years; 9.2 years for patients with β-thalassemia and 2.2 years for patients with E/β-thalassemia. Most patients with α-thalassemia were Asian. Patients with β-thalassemia were predominantly Caucasian (46%) or of African descent (36%). Twenty percent of patients were born outside the United States and 5% were transfused before immigration. Complications varied by genotype and age. Individuals with nondeletional hemoglobin H were severely affected and, despite their young age, had many complications. Iron overload increased with age and was more common in patients who received transfusions. Conclusions: NTDT in the United States is a multi-ethnic disease with different genotypic mutations and phenotypic manifestations. A higher than expected proportion of patients was Black/African American. NTDT-related complications are common and increase with age, supporting a need for early diagnosis.

Original language	English (US)
Article number	e27067
Journal	Pediatric Blood and Cancer
Volume	65
Issue number	7
DOIs	https://doi.org/10.1002/pbc.27067
State	Published - Jul 2018

Funding

E.V. has received research funding from Novartis Pharmaceuticals Cor-porationandApoPharmaInc.J.L.K.servesasaconsultanttoIonisPhar-maceuticals, Agios Pharmaceuticals, and bluebird bio, and has received research funding as a co-investigator from Novartis Pharmaceuticals Corporation, Agios Pharmaceuticals, Apopharma, Inc., and bluebird bio. A.A.T. serves as a consultant to Novartis Pharmaceuticals Corporation, Celgene, and bluebird bio, and has received research funding from Novartis Pharmaceuticals Corporation, Baxalta, Amgen, Cel-gene, Mast Therapeutics Inc., and bluebird bio. P.J.G. has nothing to declare. C.P. and M.S. are employees of Novartis Pharmaceuticals Corporation. Y.Q. was an employee of Novartis Pharmaceuticals Corporation at the time of the study. W.Y.C. and N.M. are employees of Analysis Group, Inc., a consulting company that has received research grants from Novartis Pharmaceuticals Corporation. A.C. serves as a consultant to Novartis and Roche and serves on the DSMB for studies sponsored by ApoPharma. A.L. has nothing to declare.

Keywords

United States
clinical iron overload
epidemiology
nontransfusion-dependent thalassemia
thalassemia trait

ASJC Scopus subject areas

Hematology
Oncology
Pediatrics, Perinatology, and Child Health

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@article{066aa45feeb14910bb37418442d79fb7,

title = "Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States",

abstract = " Background: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group of thalassemia mutations and clinical phenotypes that do not require chronic transfusions. It is increasingly prevalent in the United States. Procedure: This study reviews the epidemiology and clinical characteristics of 138 patients with NTDT treated at four US thalassemia centers from 1997 to 2014. Data on laboratory results, transfusions, and clinical complications were collected from patient charts. Results: Overall, 84 patients with α-thalassemia (62 deletional hemoglobin H; 22 nondeletional hemoglobin H), 39 with β-thalassemia (26 with homozygous or double heterozygous β mutations; 13 with single β mutations with or without α triplication), and 15 with E/β-thalassemia (12 E/β 0 ; three E/β + ) were identified. At study entry, the median age for patients with α-thalassemia was 2.3 years; 9.2 years for patients with β-thalassemia and 2.2 years for patients with E/β-thalassemia. Most patients with α-thalassemia were Asian. Patients with β-thalassemia were predominantly Caucasian (46%) or of African descent (36%). Twenty percent of patients were born outside the United States and 5% were transfused before immigration. Complications varied by genotype and age. Individuals with nondeletional hemoglobin H were severely affected and, despite their young age, had many complications. Iron overload increased with age and was more common in patients who received transfusions. Conclusions: NTDT in the United States is a multi-ethnic disease with different genotypic mutations and phenotypic manifestations. A higher than expected proportion of patients was Black/African American. NTDT-related complications are common and increase with age, supporting a need for early diagnosis.",

keywords = "United States, clinical iron overload, epidemiology, nontransfusion-dependent thalassemia, thalassemia trait",

author = "Elliott Vichinsky and Alan Cohen and Thompson, {Alexis A.} and Giardina, {Patricia J.} and Ashutosh Lal and Carole Paley and Cheng, {Wendy Y.} and Nora McCormick and Medha Sasane and Ying Qiu and Kwiatkowski, {Janet L.}",

note = "Funding Information: E.V. has received research funding from Novartis Pharmaceuticals Cor-porationandApoPharmaInc.J.L.K.servesasaconsultanttoIonisPhar-maceuticals, Agios Pharmaceuticals, and bluebird bio, and has received research funding as a co-investigator from Novartis Pharmaceuticals Corporation, Agios Pharmaceuticals, Apopharma, Inc., and bluebird bio. A.A.T. serves as a consultant to Novartis Pharmaceuticals Corporation, Celgene, and bluebird bio, and has received research funding from Novartis Pharmaceuticals Corporation, Baxalta, Amgen, Cel-gene, Mast Therapeutics Inc., and bluebird bio. P.J.G. has nothing to declare. C.P. and M.S. are employees of Novartis Pharmaceuticals Corporation. Y.Q. was an employee of Novartis Pharmaceuticals Corporation at the time of the study. W.Y.C. and N.M. are employees of Analysis Group, Inc., a consulting company that has received research grants from Novartis Pharmaceuticals Corporation. A.C. serves as a consultant to Novartis and Roche and serves on the DSMB for studies sponsored by ApoPharma. A.L. has nothing to declare. Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",

year = "2018",

month = jul,

doi = "10.1002/pbc.27067",

language = "English (US)",

volume = "65",

journal = "Pediatric Blood and Cancer",

issn = "1545-5009",

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number = "7",

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TY - JOUR

T1 - Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States

AU - Vichinsky, Elliott

AU - Cohen, Alan

AU - Thompson, Alexis A.

AU - Giardina, Patricia J.

AU - Lal, Ashutosh

AU - Paley, Carole

AU - Cheng, Wendy Y.

AU - McCormick, Nora

AU - Sasane, Medha

AU - Qiu, Ying

AU - Kwiatkowski, Janet L.

N1 - Funding Information: E.V. has received research funding from Novartis Pharmaceuticals Cor-porationandApoPharmaInc.J.L.K.servesasaconsultanttoIonisPhar-maceuticals, Agios Pharmaceuticals, and bluebird bio, and has received research funding as a co-investigator from Novartis Pharmaceuticals Corporation, Agios Pharmaceuticals, Apopharma, Inc., and bluebird bio. A.A.T. serves as a consultant to Novartis Pharmaceuticals Corporation, Celgene, and bluebird bio, and has received research funding from Novartis Pharmaceuticals Corporation, Baxalta, Amgen, Cel-gene, Mast Therapeutics Inc., and bluebird bio. P.J.G. has nothing to declare. C.P. and M.S. are employees of Novartis Pharmaceuticals Corporation. Y.Q. was an employee of Novartis Pharmaceuticals Corporation at the time of the study. W.Y.C. and N.M. are employees of Analysis Group, Inc., a consulting company that has received research grants from Novartis Pharmaceuticals Corporation. A.C. serves as a consultant to Novartis and Roche and serves on the DSMB for studies sponsored by ApoPharma. A.L. has nothing to declare. Publisher Copyright: © 2018 Wiley Periodicals, Inc.

PY - 2018/7

Y1 - 2018/7

N2 - Background: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group of thalassemia mutations and clinical phenotypes that do not require chronic transfusions. It is increasingly prevalent in the United States. Procedure: This study reviews the epidemiology and clinical characteristics of 138 patients with NTDT treated at four US thalassemia centers from 1997 to 2014. Data on laboratory results, transfusions, and clinical complications were collected from patient charts. Results: Overall, 84 patients with α-thalassemia (62 deletional hemoglobin H; 22 nondeletional hemoglobin H), 39 with β-thalassemia (26 with homozygous or double heterozygous β mutations; 13 with single β mutations with or without α triplication), and 15 with E/β-thalassemia (12 E/β 0 ; three E/β + ) were identified. At study entry, the median age for patients with α-thalassemia was 2.3 years; 9.2 years for patients with β-thalassemia and 2.2 years for patients with E/β-thalassemia. Most patients with α-thalassemia were Asian. Patients with β-thalassemia were predominantly Caucasian (46%) or of African descent (36%). Twenty percent of patients were born outside the United States and 5% were transfused before immigration. Complications varied by genotype and age. Individuals with nondeletional hemoglobin H were severely affected and, despite their young age, had many complications. Iron overload increased with age and was more common in patients who received transfusions. Conclusions: NTDT in the United States is a multi-ethnic disease with different genotypic mutations and phenotypic manifestations. A higher than expected proportion of patients was Black/African American. NTDT-related complications are common and increase with age, supporting a need for early diagnosis.

AB - Background: Nontransfusion-dependent thalassemia (NTDT) refers to a diverse group of thalassemia mutations and clinical phenotypes that do not require chronic transfusions. It is increasingly prevalent in the United States. Procedure: This study reviews the epidemiology and clinical characteristics of 138 patients with NTDT treated at four US thalassemia centers from 1997 to 2014. Data on laboratory results, transfusions, and clinical complications were collected from patient charts. Results: Overall, 84 patients with α-thalassemia (62 deletional hemoglobin H; 22 nondeletional hemoglobin H), 39 with β-thalassemia (26 with homozygous or double heterozygous β mutations; 13 with single β mutations with or without α triplication), and 15 with E/β-thalassemia (12 E/β 0 ; three E/β + ) were identified. At study entry, the median age for patients with α-thalassemia was 2.3 years; 9.2 years for patients with β-thalassemia and 2.2 years for patients with E/β-thalassemia. Most patients with α-thalassemia were Asian. Patients with β-thalassemia were predominantly Caucasian (46%) or of African descent (36%). Twenty percent of patients were born outside the United States and 5% were transfused before immigration. Complications varied by genotype and age. Individuals with nondeletional hemoglobin H were severely affected and, despite their young age, had many complications. Iron overload increased with age and was more common in patients who received transfusions. Conclusions: NTDT in the United States is a multi-ethnic disease with different genotypic mutations and phenotypic manifestations. A higher than expected proportion of patients was Black/African American. NTDT-related complications are common and increase with age, supporting a need for early diagnosis.

KW - United States

KW - clinical iron overload

KW - epidemiology

KW - nontransfusion-dependent thalassemia

KW - thalassemia trait

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JO - Pediatric Blood and Cancer

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ER -

Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States

Abstract

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