TY - JOUR
T1 - Stable to improved cardiac and pulmonary function in children with high-risk sickle cell disease following haploidentical stem cell transplantation
AU - Friedman, Deborah
AU - Dozor, Allen J.
AU - Milner, Jordan
AU - D’Souza, Marise
AU - Talano, Julie An
AU - Moore, Theodore B.
AU - Shenoy, Shalini
AU - Shi, Qiuhu
AU - Walters, Mark C.
AU - Vichinsky, Elliott
AU - Parsons, Susan K.
AU - Braniecki, Suzanne
AU - Moorthy, Chitti R.
AU - Ayello, Janet
AU - Flower, Allyson
AU - Morris, Erin
AU - Mahanti, Harshini
AU - Fabricatore, Sandra
AU - Klejmont, Liana
AU - van de Ven, Carmella
AU - Baxter-Lowe, Lee Ann
AU - Cairo, Mitchell S.
N1 - Funding Information:
Funding This study was supported in large part by FDA R01FD004090 held by MSC and in small part by the Pediatric Cancer Research Foundation, held by MSC.
Funding Information:
Conflict of interest MSC has received funding from the FDA (R01FD004090), the Pediatric Cancer Research Foundation (PCRF), Otsuka and Miltenyi. Although not related to this study, MCW is a consultant for Bluebird Bio, Inc., Bioverativ, Sangamo, Veevo, Editas Medicine and is medical director for AllCells, Inc. Biosciences. SKP is a consultant to Seattle Genetics, also unrelated to this study. EV is a consultant for ApoPharma, on the advisory committee for Global Blood Therapeutics and receives royalties from UptoDate. All other authors declare no conflicts of interest.
Funding Information:
Acknowledgements This study was supported in large part by FDA R01FD004090 held by Dr. Cairo and in small part by the Pediatric Cancer Research Foundation, held by Dr. Cairo. We would like to thank Virginia Davenport, RN for her superb editorial assistance. We would also like to thank the patients and families who participated in this clinical trial and all the members of the external data safety monitoring committee and external advisory committee (Supplementary Fig. 3).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/9
Y1 - 2021/9
N2 - Children with sickle cell disease (SCD) are at high-risk of progressive, chronic pulmonary and cardiac dysfunction. In this prospective multicenter Phase II trial of myeloimmunoablative conditioning followed by haploidentical stem cell transplantation in children with high-risk SCD, 19 patients, 2.0–21.0 years of age, were enrolled with one or more of the following: history of (1) overt stroke; (2) silent stroke; (3) elevated transcranial Doppler velocity; (4) multiple vaso-occlusive crises; and/or (5) two or more acute chest syndromes and received haploidentical transplants from 18 parental donors. Cardiac and pulmonary centralized cores were established. Pulmonary function results were expressed as percent of the median of healthy reference cohorts, matched for age, sex, height and race. At 2 years, pulmonary functions including forced expiratory volume (FEV), FEV1/ forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity of lung for carbon monoxide (DLCO) were stable to improved compared to baseline values. Importantly, specific airway conductance was significantly improved at 2 years (p < 0.004). Left ventricular systolic function (fractional shortening) and tricuspid regurgitant velocity were stable at 2 years. These results demonstrate that haploidentical stem cell transplantation can stabilize or improve cardiopulmonary function in patients with SCD.
AB - Children with sickle cell disease (SCD) are at high-risk of progressive, chronic pulmonary and cardiac dysfunction. In this prospective multicenter Phase II trial of myeloimmunoablative conditioning followed by haploidentical stem cell transplantation in children with high-risk SCD, 19 patients, 2.0–21.0 years of age, were enrolled with one or more of the following: history of (1) overt stroke; (2) silent stroke; (3) elevated transcranial Doppler velocity; (4) multiple vaso-occlusive crises; and/or (5) two or more acute chest syndromes and received haploidentical transplants from 18 parental donors. Cardiac and pulmonary centralized cores were established. Pulmonary function results were expressed as percent of the median of healthy reference cohorts, matched for age, sex, height and race. At 2 years, pulmonary functions including forced expiratory volume (FEV), FEV1/ forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity of lung for carbon monoxide (DLCO) were stable to improved compared to baseline values. Importantly, specific airway conductance was significantly improved at 2 years (p < 0.004). Left ventricular systolic function (fractional shortening) and tricuspid regurgitant velocity were stable at 2 years. These results demonstrate that haploidentical stem cell transplantation can stabilize or improve cardiopulmonary function in patients with SCD.
UR - http://www.scopus.com/inward/record.url?scp=85111544082&partnerID=8YFLogxK
U2 - 10.1038/s41409-021-01298-7
DO - 10.1038/s41409-021-01298-7
M3 - Article
C2 - 33958740
AN - SCOPUS:85111544082
VL - 56
SP - 2221
EP - 2230
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 9
ER -