KIR-favorable TCR-αβ/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial. Blood 2022 Dec 15;140(24):2556-2572
Date
07/02/2022Pubmed ID
35776909Pubmed Central ID
PMC9918850DOI
10.1182/blood.2022015959Scopus ID
2-s2.0-85144585749 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
We performed a prospective multicenter study of T-cell receptor αβ (TCR-αβ)/CD19-depleted haploidentical hematopoietic cell transplantation (HCT) in children with acute leukemia and myelodysplastic syndrome (MDS), to determine 1-year disease-free survival (DFS) and compare 2-year outcomes with recipients of other donor cell sources. Fifty-one patients aged 0.7 to 21 years were enrolled; donors were killer immunoglobulin-like receptor (KIR) favorable based on ligand mismatch and/or high B content. The 1-year DFS was 78%. Superior 2-year DFS and overall survival (OS) were noted in patients <10 years of age, those treated with reduced toxicity conditioning (RTC) rather than myeloablative conditioning, and children with minimal residual disease <0.01% before HCT. Multivariate analysis comparing the KIR-favorable haploidentical cohort with controls showed similar DFS and OS compared with other donor cell sources. Multivariate analysis also showed a marked decrease in the risk of grades 2 to 4 and 3 to 4 acute graft versus host disease (aGVHD), chronic GVHD, and transplant-related mortality vs other donor cell sources. Ethnic and racial minorities accounted for 53% of enrolled patients, and data from a large cohort of recipients/donors screened for KIR showed that >80% of recipients had a KIR-favorable donor by our definition, demonstrating that this approach is broadly applicable to groups often unable to find donors. This prospective, multicenter study showed improved outcomes using TCR-αβ/CD19-depleted haploidentical donors using RTC for children with acute leukemia and MDS. Randomized trials comparing this approach with matched unrelated donors are warranted. This trial was registered at https://clinicaltrials.gov as #NCT02646839.
Author List
Pulsipher MA, Ahn KW, Bunin NJ, Lalefar N, Anderson E, Flower A, Cairo MS, Talano JA, Chaudhury S, Kitko CL, Duke JL, Monos D, Leung W, Dvorak CC, Abdel-Azim HAuthors
Kwang Woo Ahn PhD Director, Professor in the Data Science Institute department at Medical College of WisconsinJulie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antigens, CD19Child
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Prospective Studies
Receptors, Antigen, T-Cell, alpha-beta
Receptors, KIR
Transplantation Conditioning
