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Multicenter Study
. 2022 Dec 15;140(24):2556-2572.
doi: 10.1182/blood.2022015959.

KIR-favorable TCR-αβ/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial

Michael A Pulsipher  1   2 , Kwang W Ahn  3   4 , Nancy J Bunin  5 , Nahal Lalefar  6 , Eric Anderson  7 , Allyson Flower  8 , Mitchell S Cairo  8 , Julie-An Talano  9 , Sonali Chaudhury  10 , Carrie L Kitko  11 , Jamie L Duke  12 , Dimitrios Monos  12 , Wing Leung  13   14 , Christopher C Dvorak  15 , Hisham Abdel-Azim  2   16
Affiliations
Multicenter Study

KIR-favorable TCR-αβ/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial

Michael A Pulsipher et al. Blood. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: M.A.P. has served on advisory boards for Novartis, Mesoblast, Equillium, Medexus, and Vertex; has engaged in educational activities for Novartis; and has received study support from Miltenyi (not for this trial) and Adaptive. W.L. is an employee of Miltenyi. C.C.D. has been a consultant to and served on advisory boards of Jazz Pharmaceuticals, Alexion Inc, and Omeros Corporation. J.L.D. receives royalties from Omixon. D.M. is a consultant to, owns stock options in, and receives royalties from Omixon. S.C. has served on advisory boards of AbbVie, Viacord, and Alexion. H.A.-A. received study support from Adaptive. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Lymphocyte recovery over the first year after transplant for CD3, CD4, CD8, CD19, NK cells, CD45RA, and CD45RO. The y-axes are expressed in cells per microliter, and the x-axes are days after HCT infusion.
Figure 2.
Figure 2.
DFS and OS. Survival statistics by age (A-B), conditioning regimen (C-D), and MRD status (E-F).
Figure 3.
Figure 3.
Adjusted DFS and OS. Adjusted statistics of the full phase 2 cohort vs CIBMTR cohorts (A-B) and the flow MRD negative before HCT phase 2 vs CIBMTR cohorts (C-D).
Figure 4.
Figure 4.
Comparative adjusted statistics for the study cohorts. TRM (A), relapse (B), acute GVHD grades 2 to 4 (C), and chronic GVHD (D) for all phase 2 and CIBMTR comparator patients. Adjusted TRM (E), relapse (F), aGVHD grades 2 to 4 (G), and cGVHD (H) for all phase 2 and CIBMTR comparator patients who were MRD-negative at the time of HCT.
See this image and copyright information in PMC

Comment in

References

    1. Giebel S, Locatelli F, Lamparelli T, et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood. 2003;102(3):814–819. - PubMed
    1. Ruggeri L, Mancusi A, Capanni M, et al. Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood. 2007;110(1):433–440. - PMC - PubMed
    1. Velardi A, Ruggeri L, Mancusi A. Killer-cell immunoglobulin-like receptors reactivity and outcome of stem cell transplant. Curr Opin Hematol. 2012;19(4):319–323. - PubMed
    1. Weisdorf D, Cooley S, Devine S, et al. T cell-depleted partial matched unrelated donor transplant for advanced myeloid malignancy: KIR ligand mismatch and outcome. Biol Blood Marrow Transplant. 2012;18(6):937–943. - PMC - PubMed
    1. Verneris MR, Miller JS, Hsu KC, et al. Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia. Blood Adv. 2020;4(7):1350–1356. - PMC - PubMed

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