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Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants.
Biol Blood Marrow Transplant. 2020 Jun 11 [Online ahead of print]BB

Abstract

Allogeneic hematopoietic cell transplantation (HCT) for children with nonmalignant disorders is challenged by potential drug-related toxicities and poor engraftment. This retrospective analysis expands on our single pediatric medical center experience with targeted busulfan, fludarabine, and intravenous (IV) alemtuzumab as a low-toxicity regimen to achieve sustained donor engraftment. Sixty-two patients received this regimen for their first HCT for a nonmalignant disorder between 2004 and 2018. Donors were matched sibling in 27%, 8/8 HLA allele-matched unrelated in 50%, and 7/8 HLA allele-mismatched in 23% (some of whom received additional immunoablation with thiotepa or clofarabine). Five patients experienced graft failure for a cumulative incidence of 8.4% (95% CI, 1 to 16%). In engrafted patients, the median donor chimerism in whole blood and CD3, CD14/15, and CD19 subsets at 1-year were 96%, 90%, 99%, and 99%, respectively. Only one patient received donor lymphocyte infusions (DLIs) for poor chimerism. Two patients died following disease progression despite 100% donor chimerism. The 3-year cumulative incidence of treatment-related mortality was 10% (95% CI, 2 to 17%). Overall survival and event-free-survival at 3-years were 87% (95% CI, 78 to 95%) and 80% (95% CI, 70 to 90%), respectively. The 6-month cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 7% (95% CI, 3 to 13%), while the 3-year cumulative incidence of chronic GVHD was 5% (95% CI, 0 to 11%). These results suggest that use of targeted busulfan, fludarabine and IV alemtuzumab offers a well-tolerated option for children with nonmalignant disorders to achieve sustained engraftment with a low incidence of GVHD.

Authors+Show Affiliations

Indiana University School of Medicine, Indianapolis, Indiana.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California; Department of Clinical Pharmacy, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California; Division of Pediatric Hematology and Oncology, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California; Division of Pediatric Hematology and Oncology, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California.Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, California. Electronic address: christopher.dvorak@ucsf.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32534101

Citation

Contreras, Cristina F., et al. "Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 2020.
Contreras CF, Long-Boyle JR, Shimano KA, et al. Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants. Biol Blood Marrow Transplant. 2020.
Contreras, C. F., Long-Boyle, J. R., Shimano, K. A., Melton, A., Kharbanda, S., Dara, J., Higham, C., Huang, J. N., Cowan, M. J., & Dvorak, C. C. (2020). Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2020.06.004
Contreras CF, et al. Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants. Biol Blood Marrow Transplant. 2020 Jun 11; PubMed PMID: 32534101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants. AU - Contreras,Cristina F, AU - Long-Boyle,Janel R, AU - Shimano,Kristin A, AU - Melton,Alexis, AU - Kharbanda,Sandhya, AU - Dara,Jasmeen, AU - Higham,Christine, AU - Huang,James N, AU - Cowan,Morton J, AU - Dvorak,Christopher C, Y1 - 2020/06/11/ PY - 2020/03/27/received PY - 2020/05/29/revised PY - 2020/06/02/accepted PY - 2020/6/14/pubmed PY - 2020/6/14/medline PY - 2020/6/14/entrez KW - Alemtuzumab KW - Busulfan KW - Fludarabine KW - Nonmalignant JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. N2 - Allogeneic hematopoietic cell transplantation (HCT) for children with nonmalignant disorders is challenged by potential drug-related toxicities and poor engraftment. This retrospective analysis expands on our single pediatric medical center experience with targeted busulfan, fludarabine, and intravenous (IV) alemtuzumab as a low-toxicity regimen to achieve sustained donor engraftment. Sixty-two patients received this regimen for their first HCT for a nonmalignant disorder between 2004 and 2018. Donors were matched sibling in 27%, 8/8 HLA allele-matched unrelated in 50%, and 7/8 HLA allele-mismatched in 23% (some of whom received additional immunoablation with thiotepa or clofarabine). Five patients experienced graft failure for a cumulative incidence of 8.4% (95% CI, 1 to 16%). In engrafted patients, the median donor chimerism in whole blood and CD3, CD14/15, and CD19 subsets at 1-year were 96%, 90%, 99%, and 99%, respectively. Only one patient received donor lymphocyte infusions (DLIs) for poor chimerism. Two patients died following disease progression despite 100% donor chimerism. The 3-year cumulative incidence of treatment-related mortality was 10% (95% CI, 2 to 17%). Overall survival and event-free-survival at 3-years were 87% (95% CI, 78 to 95%) and 80% (95% CI, 70 to 90%), respectively. The 6-month cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 7% (95% CI, 3 to 13%), while the 3-year cumulative incidence of chronic GVHD was 5% (95% CI, 0 to 11%). These results suggest that use of targeted busulfan, fludarabine and IV alemtuzumab offers a well-tolerated option for children with nonmalignant disorders to achieve sustained engraftment with a low incidence of GVHD. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/32534101/Reduced_Toxicity_Conditioning_for_Non-Malignant_Hematopoietic_Cell_Transplants L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(20)30351-7 DB - PRIME DP - Unbound Medicine ER -
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