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Multicenter Study
. 2023 Sep 26;7(18):5639-5648.
doi: 10.1182/bloodadvances.2023010281.

Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias

Juan C Fierro-Pineda  1   2 , Hua-Ling Tsai  1 , Amanda Blackford  1 , Andrew Cluster  3 , Emi Caywood  4 , Jignesh Dalal  5 , Jeffrey Davis  6 , Maarten Egeler  7 , Jeffrey Huo  8 , Michelle Hudspeth  9 , Amy Keating  10 , Susan S Kelly  11 , Joerg Krueger  12 , Dean Lee  13 , Leslie Lehmann  14 , Lisa Madden  15 , Benjamin Oshrine  16 , Michael A Pulsipher  17 , Terry Fry  10 , Heather J Symons  1
Affiliations
Multicenter Study

Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias

Juan C Fierro-Pineda et al. Blood Adv. .

Abstract

Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with posttransplant cyclophosphamide (PTCy). To our knowledge, we report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the Pediatric Transplantation and Cellular Therapy Consortium. Nine centers performed transplants in 32 patients having acute leukemias or MDS, with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median patient age was 12 years. Diagnoses included AML (15), ALL (11), mixed-lineage leukemia (1), and MDS (5). Transplant-related mortality (TRM) at 180 days was 0%. The cumulative incidence (CuI) of grade 2 acute graft-versus-host disease (aGVHD) on day 100 was 13%. No patients developed grades 3-4 aGVHD. The CuI of moderate-to-severe chronic GVHD (cGVHD) at 1 year was 4%. Donor engraftment occurred in 27 patients (84%). Primary graft failures included 3 patients who received suboptimal bone marrow grafts; all successfully engrafted after second transplants. The CuI of relapse at 1 year was 32%, with more relapse among patients MRD positive pre-BMT vs MRD negative. Overall survival rates at 1 and 2 years were 77% and 73%, and event-free survival rate at 1 and 2 years were 68% and 64%. There was no TRM or severe aGVHD, low cGVHD, and favorable relapse and survival rates. This successful pilot trial has led to a phase 3 trial comparing MAC haploBMT vs HLA-matched unrelated donor BMT in the Children's Oncology Group. This trial was registered at www.clinicaltrials.gov as #NCT02120157.

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Conflict of interest statement

Conflict-of-interest disclosure: M.H. reports advisory board activities for Novartis, Mesoblast, Jazz Pharmaceuticals, and Kadmon Pharmaceuticals. D.L. reports research funding, consulting, and licensing fees from Kiadis Pharma. B.O. is a full-time employee of ImmunoGen Inc. M.A.P. reports advisory board activities for Novartis, Gentibio, bluebird bio, Vertex, Medexus, and Equillium; educational honoraria from Novartis; and study support from Miltenyi and Adaptive. H.J.S. reports speaker bureau activity for Jazz Pharmaceuticals. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Conditioning regimens. (A) Chemotherapy-based; (B) TBI-based.
Figure 2.
Figure 2.
CuI of GVHD.
Figure 3.
Figure 3.
Relapse. (A) CuI of relapse; (B) CuI of relapse based on the MRD results; (C) CuI of relapse based on the DRI; and (D) CuI of based on the by disease type.
Figure 4.
Figure 4.
Probabilities of OS, EFS, and GRFS.
See this image and copyright information in PMC

Comment in

  • Haplo ever after: haplo PTCy for children.
    Talano JA, Broglie L. Talano JA, et al. Blood Adv. 2023 Sep 26;7(18):5637-5638. doi: 10.1182/bloodadvances.2023010755. Blood Adv. 2023. PMID: 37756536 Free PMC article. No abstract available.

References

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