Abstract
Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 μg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r2 = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.
| Original language | English |
|---|---|
| Pages (from-to) | 122-130 |
| Number of pages | 9 |
| Journal | British Journal of Haematology |
| Volume | 172 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2016 |
Keywords
- Iron overload
- MRI
- Sickle cell anaemia
- Sickle cell radiology
- Transfusions
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In: British Journal of Haematology, Vol. 172, No. 1, 01.01.2016, p. 122-130.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Organ iron accumulation in chronically transfused children with sickle cell anaemia
T2 - Baseline results from the TWiTCH trial
AU - Wood, John C.
AU - Cohen, Alan R.
AU - Pressel, Sara L.
AU - Aygun, Banu
AU - Imran, Hamayun
AU - Luchtman-Jones, Lori
AU - Thompson, Alexis A.
AU - Fuh, Beng
AU - Schultz, William H.
AU - Davis, Barry R.
AU - Ware, Russell E.
AU - George, Alex
AU - Mueller, Brigitta U.
AU - Heeney, Matthew M.
AU - Kalfa, Theodosia A.
AU - Nelson, Stephen
AU - Clark Brown, R.
AU - Gee, Beatrice
AU - Kwiatkowski, Janet L.
AU - Smith- Whitley, Kim
AU - Odame, Isaac
AU - Webb, Jennifer
AU - Yang, Elizabeth
AU - Lee, Margaret T.
AU - Piccone, Connie
AU - Jackson, Sherron M.
AU - Singh, Sharon
AU - Nottage, Kerri
AU - Hankins, Jane S.
AU - Miller, Scott T.
AU - Hilliard, Lee
AU - Alvarez, Ofelia
AU - Rhodes, Melissa
AU - Rogers, Zora R.
AU - Sarnaik, Sharada A.
AU - Owen, William C.
AU - Gauger, Cynthia
AU - Roberts, Carla
AU - Rothman, Jennifer A.
N1 - Funding Information: This work was supported by the National Heart Lung and Blood Institute (R01HL095647-05 and 5 R01 HL095511-05). We would like to credit all participating sites and investigators. The authors would also like to thank Resonance Health for their help setting up and interpreting the FerriScan analyses for this study. Participating sites and clinical investigators are listed as follows: Texas Children’s Hospital, Houston, Texas-Clinical Investigators: Alex George, MD, PhD, Brigitta U. Mueller, MD, MHCM; Study Coordinator: Bogdan R. Dinu, MD.; TCD Examiner: Leanne Gerhart. Boston Children’s Hospital, Boston, Massachusetts-Clinical Investigator: Matthew M. Heeney, MD; Study Coordinators: Latoya N. Lashley, MPH, Jesse K. McKenna, MPH, Kristen E. Sullivan, MA, Meredith L. Anderson, DO(c), BS; TCD Examiner: Carol E. Barnewolt, MD. Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio-Clinical Investigator: Theodosia A. Kalfa, MD, PhD; Study Coordinators: Adriane R. Hausfeld, RN, BSN, CCRP, Laurie A. Vanderah, RN, BSN; TCD Examiner: Janet M. Adams. Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota-Clinical Investigator: Stephen Nelson, MD; Study Coordinators: Ashley Kinsella, Nicole Hart, RN; TCD Examiner: Nancy Boettger. Emory/ CHOA, Atlanta, Georgia-Clinical Investigator: R. Clark Brown, MD PhD; Co-Investigator: Beatrice Gee, MD; Study Coordinators: Robin Pitts, FNP, MN, Mitchell Turner, Martha Ann Felder, Leann Schilling, MPH, Terrell Faircloth; TCD Examiners: Vivian Davis, Melissa Barber. Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania-Clinical Investigator: Janet L. Kwiatkowski, MD, MSCE; Co-Investigator: Kim Smith- Whitley, MD; Study Coordinators: John H. Hammond, Helen Stanley, Sage T Green, Hannah Ware; TCD Examiner: Brandi Kozak. The Hospital for Sick Children,Toronto, Ontario, Canada-Clinical Investigator: Isaac Odame, MB ChB, FRCPath, FRCPC; Study Coordinators: Rebecca Leroux, RN, BScN; TCD Examiner: Manuela Merelles-Pulcini RN, BScN, MSN. Children’s National Medical Center, Washington, DC-Clinical Investigator: Lori Luchtman-Jones MD; Jennifer Webb, MD; Co-Investigators: Brenda Martin, MSN CPNP, and Elizabeth Yang, MD PhD; Study Coordinator: Chantel Jenkins MSHS; TCD Examiner: Kadine L. Linden, BS, RT(R), RDMS. Columbia University-Clinical Investigator: Margaret T. Lee, MD; Study Coordinator: Susana Hernandez, RN; TCD Examiner: Samuel Trocio, Jr., MD, RVT. Rainbow Babies & Children’s Hospital, Case Western Reserve University, Cleveland, Ohio-Clinical Investigator: Connie Piccone, MD; Study Coordinator: Mary Debarr, RN, BSN; Additional: Anne Chapman, RN, BSN. University of South Alabama (USA), Mobile, Alabama-Clinical Investigator: Hamayun Imran, MD, MSc; Study Coordinators: Jennifer Williams, CRNP, Andretta McCovey, RN, BSN, CRA; TCD Examiner: Lee Vick. Medical University of South Carolina, Charleston, South Carolina-Clinical Investigator: Sherron M. Jackson, MD; Study Coordinator: Lisa Kuisel, RN, BSN; TCD Examiners: Toni Mullins, Shannon Harmon. Cohen Children’s Medical Center of New York, New Hyde Park, New York-Clinical Investigator: Banu Aygun, MD, Sharon Singh, MD; Study Coordinator: Antonella Farrell, BSN, RN; TCD Examiner: Albert Levy, RVT. St. Jude Children’s Research Hospital, Memphis, Tennessee-Clinical Investigator: Kerri Nottage, MD, MPH, Jane S. Hankins, MD, MS; Study Coordinators: Jennifer Larkin, and MS, CCRP, and Karen Wodowski, MSN, BC-PNP; TCD Examiner: Gail L. Fortner, BSN, RN. State University of New York- Downstate Medical Center, Brooklyn, New York-Clinical Investigator: Scott T. Miller, MD; Study Coordinator: Kathy Rey, PAC; TCD Examiner: Kathy Rey, PAC. University of Alabama at Birmingham (UAB) Birmingham, Alabama-Clinical Investigator: Lee Hilliard, MD; Study Coordinator: Jeanine Dumas, RN, MSN; TCD Examiner: Jeanine Dumas, RN, MSN. University of Miami Miller School of Medicine, Miami, Florida – Clinical Investigator: Ofelia Alvarez, MD; Study Coordinator: Tally Hustace, ARNP; TCD Examiner: Iszet-Campo Bustillo; Neurologist: Robert Lopez Alberola, Psychologist: Winsome Thompson, PhD. University of Mississippi Medical Center (UMMC), Jackson, Mississippi-Clinical Investigator: Melissa Rhodes, MD; Study Coordinator: Stephanie Pepper, RN; Glenda Thomas, RN; TCD Examiner: Desirae Flohr. University of Texas Southwestern, Dallas, Texas-Clinical Investigator: Zora R. Rogers, MD; Study Coordinator: Leah Adix, CCRP; TCD Examiner: Brad Cook, RN. Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan-Clinical Investigator: Sharada A. Sarnaik, MD; Study Coordinator: Theresa Spranger, MS; TCD Examiner: Sally Thompson- Reid, RD, MS; Study Nurse Coordinator: Mary Murphy, RN, MSN, PNP. Anna and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois-Clinical Investigator: Alexis A. Thompson, MD, MPH; Study Coordinator: Katherine Bianchi, MBA, CCRP; TCD Examiner: Katherine Bianchi. Children’s Hospital of The King’s Daughters, Norfolk, Virginia – Clinical Investigator: William C. Owen, MD; Study Coordinator: Sabrina Wigginton, BSN, RN, CPON; TCD Examiner: Anissa Lambert, BSN, RN; Additional: Lorrie Coggsdale, RN, CCRP, Annette S. Slade, MSN, PPCNP-BC. Nemours Children’s Clinic- Clinical Investigator: Cynthia Gauger, MD; Study Coordinators: Mary Lawlor. Funding Information: This work was supported by the National Heart Lung and Blood Institute (R01HL095647-05 and 5 R01 HL095511-05). We would like to credit all participating sites and investigators. The authors would also like to thank Resonance Health for their help setting up and interpreting the FerriScan analyses for this study. Participating sites and clinical investigators are listed as follows: Texas Children?s Hospital, Houston, Texas-Clinical Investigators: Alex George, MD, PhD, Brigitta U. Mueller, MD, MHCM; Study Coordinator: Bogdan R. Dinu, MD.; TCD Examiner: Leanne Gerhart. Boston Children?s Hospital, Boston, Massachusetts-Clinical Investigator: Matthew M. Heeney, MD; Study Coordinators: Latoya N. Lashley, MPH, Jesse K. McKenna, MPH, Kristen E. Sullivan, MA, Meredith L. Anderson, DO(c), BS; TCD Examiner: Carol E. Barnewolt, MD. Cincinnati Children?s Hospital Medical Center, Cincinnati, Ohio-Clinical Investigator: Theodosia A. Kalfa, MD, PhD; Study Coordinators: Adriane R. Hausfeld, RN, BSN, CCRP, Laurie A. Vanderah, RN, BSN; TCD Examiner: Janet M. Adams. Children?s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota-Clinical Investigator: Stephen Nelson, MD; Study Coordinators: Ashley Kinsella, Nicole Hart, RN; TCD Examiner: Nancy Boettger. Emory/ CHOA, Atlanta, Georgia-Clinical Investigator: R. Clark Brown, MD PhD; Co-Investigator: Beatrice Gee, MD; Study Coordinators: Robin Pitts, FNP, MN, Mitchell Turner, Martha Ann Felder, Leann Schilling, MPH, Terrell Faircloth; TCD Examiners: Vivian Davis, Melissa Barber. Children?s Hospital of Philadelphia, Philadelphia, Pennsylvania-Clinical Investigator: Janet L. Kwiatkowski, MD, MSCE; Co-Investigator: Kim Smith- Whitley, MD; Study Coordinators: John H. Hammond, Helen Stanley, Sage T Green, Hannah Ware; TCD Examiner: Brandi Kozak. The Hospital for Sick Children,Toronto, Ontario, Canada-Clinical Investigator: Isaac Odame, MB ChB, FRCPath, FRCPC; Study Coordinators: Rebecca Leroux, RN, BScN; TCD Examiner: Manuela Merelles-Pulcini RN, BScN, MSN. Children?s National Medical Center, Washington, DC-Clinical Investigator: Lori Luchtman-Jones MD; Jennifer Webb, MD; Co-Investigators: Brenda Martin, MSN CPNP, and Elizabeth Yang, MD PhD; Study Coordinator: Chantel Jenkins MSHS; TCD Examiner: Kadine L. Linden, BS, RT(R), RDMS. Columbia University-Clinical Investigator: Margaret T. Lee, MD; Study Coordinator: Susana Hernandez, RN; TCD Examiner: Samuel Trocio, Jr., MD, RVT. Rainbow Babies & Children?s Hospital, Case Western Reserve University, Cleveland, Ohio-Clinical Investigator: Connie Piccone, MD; Study Coordinator: Mary Debarr, RN, BSN; Additional: Anne Chapman, RN, BSN. University of South Alabama (USA), Mobile, Alabama-Clinical Investigator: Hamayun Imran, MD, MSc; Study Coordinators: Jennifer Williams, CRNP, Andretta McCovey, RN, BSN, CRA; TCD Examiner: Lee Vick. Medical University of South Carolina, Charleston, South Carolina-Clinical Investigator: Sherron M. Jackson, MD; Study Coordinator: Lisa Kuisel, RN, BSN; TCD Examiners: Toni Mullins, Shannon Harmon. Cohen Children?s Medical Center of New York, New Hyde Park, New York-Clinical Investigator: Banu Aygun, MD, Sharon Singh, MD; Study Coordinator: Antonella Farrell, BSN, RN; TCD Examiner: Albert Levy, RVT. St. Jude Children?s Research Hospital, Memphis, Tennessee-Clinical Investigator: Kerri Nottage, MD, MPH, Jane S. Hankins, MD, MS; Study Coordinators: Jennifer Larkin, and MS, CCRP, and Karen Wodowski, MSN, BC-PNP; TCD Examiner: Gail L. Fortner, BSN, RN. State University of New York- Downstate Medical Center, Brooklyn, New York-Clinical Investigator: Scott T. Miller, MD; Study Coordinator: Kathy Rey, PAC; TCD Examiner: Kathy Rey, PAC. University of Alabama at Birmingham (UAB) Birmingham, Alabama-Clinical Investigator: Lee Hilliard, MD; Study Coordinator: Jeanine Dumas, RN, MSN; TCD Examiner: Jeanine Dumas, RN, MSN. University of Miami Miller School of Medicine, Miami, Florida ? Clinical Investigator: Ofelia Alvarez, MD; Study Coordinator: Tally Hustace, ARNP; TCD Examiner: Iszet-Campo Bustillo; Neurologist: Robert Lopez Alberola, Psychologist: Winsome Thompson, PhD. University of Mississippi Medical Center (UMMC), Jackson, Mississippi-Clinical Investigator: Melissa Rhodes, MD; Study Coordinator: Stephanie Pepper, RN; Glenda Thomas, RN; TCD Examiner: Desirae Flohr. University of Texas Southwestern, Dallas, Texas-Clinical Investigator: Zora R. Rogers, MD; Study Coordinator: Leah Adix, CCRP; TCD Examiner: Brad Cook, RN. Children?s Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan-Clinical Investigator: Sharada A. Sarnaik, MD; Study Coordinator: Theresa Spranger, MS; TCD Examiner: Sally Thompson- Reid, RD, MS; Study Nurse Coordinator: Mary Murphy, RN, MSN, PNP. Anna and Robert H. Lurie Children?s Hospital of Chicago, Chicago, Illinois-Clinical Investigator: Alexis A. Thompson, MD, MPH; Study Coordinator: Katherine Bianchi, MBA, CCRP; TCD Examiner: Katherine Bianchi. Children?s Hospital of The King?s Daughters, Norfolk, Virginia ? Clinical Investigator: William C. Owen, MD; Study Coordinator: Sabrina Wigginton, BSN, RN, CPON; TCD Examiner: Anissa Lambert, BSN, RN; Additional: Lorrie Coggsdale, RN, CCRP, Annette S. Slade, MSN, PPCNP-BC. Nemours Children?s Clinic- Clinical Investigator: Cynthia Gauger, MD; Study Coordinators: Mary Lawlor. Publisher Copyright: © 2016 John Wiley & Sons Ltd.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 μg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r2 = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.
AB - Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 μg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r2 = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.
KW - Iron overload
KW - MRI
KW - Sickle cell anaemia
KW - Sickle cell radiology
KW - Transfusions
UR - http://www.scopus.com/inward/record.url?scp=84955710899&partnerID=8YFLogxK
U2 - 10.1111/bjh.13791
DO - 10.1111/bjh.13791
M3 - Article
C2 - 26523836
AN - SCOPUS:84955710899
SN - 0007-1048
VL - 172
SP - 122
EP - 130
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 1
ER -