Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 9:8:282.
doi: 10.3389/fped.2020.00282. eCollection 2020.

T-Cell Replete Myeloablative Haploidentical Bone Marrow Transplantation Is an Effective Option for Pediatric and Young Adult Patients With High-Risk Hematologic Malignancies

Emmanuel Katsanis  1   2   3   4   5   6   7 , Lauren N Sapp  1   6 , Susie Cienfuegos Reid  1   6 , Naresh Reddivalla  1   7 , Baldassarre Stea  5   6   8
Affiliations

T-Cell Replete Myeloablative Haploidentical Bone Marrow Transplantation Is an Effective Option for Pediatric and Young Adult Patients With High-Risk Hematologic Malignancies

Emmanuel Katsanis et al. Front Pediatr. .

Abstract

Twenty-one pediatric and young adult patients (1.1-24.7 years) with hematologic malignancies underwent myeloablative T-cell replete haploidentical bone marrow transplant (haplo-BMT) between October 2015 to December 2019. Fifty-seven percent of the patients were ethnic or racial minorities. Thirteen patients had B-cell precursor acute lymphoblastic leukemia (B-ALL) with 10 receiving 1,200 cGy fractionated total body irradiation with fludarabine while the remaining 11 patients had targeted dose-busulfan, fludarabine, melphalan conditioning. Graft-vs.-host disease (GvHD) prophylaxis consisted of post-transplant cyclophosphamide (15 patients) or cyclophosphamide and bendamustine (six patients), with all patients receiving tacrolimus and mycophenolate mofetil. Twelve patients were in first or second remission at time of transplant with five in >2nd remission and four with measurable disease. Three patients had failed prior transplants and three CAR-T cell therapies. Only one patient developed primary graft failure but engrafted promptly after a second conditioned T-replete peripheral blood stem cell transplant from the same donor. An absolute neutrophil count of 0.5 × 109/L was achieved at a median time of 16 days post-BMT while platelet engraftment occurred at a median of 30 days. The cumulative incidence of grades III to IV acute GvHD and chronic GvHD was 15.2 and 18.1%, respectively. With a median follow-up of 25.1 months the relapse rate is 17.6% with an overall survival of 84.0% and a progression-free survival of 74.3%. The chronic graft-vs.-host-free relapse-free survival (CRFS) is 58.5% while acute and chronic graft-vs.-host-free relapse-free survival (GRFS) is 50.1%. Myeloablative conditioned T-replete haploidentical BMT is a viable alternative to matched unrelated transplantation for children and young adults with high-risk hematologic malignancies.

Keywords: GvHD; T-replete; haploidentical BMT; myeloablative; pediatric.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Engraftment of neutrophils and platelets and absolute lymphocyte count (ALC) over time. (A) Time to an ANC of 0.5 × 109/L. (B) Time to a platelet count of 20 × 109/L (C) ALC at 3, 6, and 12 months following haplo-BMT.
Figure 2
Figure 2
Kaplan-Meier estimates of acute and chronic- graft-vs.-host disease. (A) Cumulative incidence of grades II-IV and III-IV aGvHD. (B) Cumulative incidence of cGvHD.
Figure 3
Figure 3
CMV viremia. Cumulative incidence of CMV viremia.
Figure 4
Figure 4
Kaplan-Meier estimates of non-relapse mortality, relapse, and survival. (A) Cumulative incidence of non-relapse mortality (NRM) (B) Cumulative incidence of relapse. (C) Cumulative incidence of overall survival (OS), progression-free survival (PFS), chronic graft-vs.-host-free relapse-free survival (CRFS) and grade III-IV aGvHD-free, cGvHD-free, relapse-free survival (GRFS).
See this image and copyright information in PMC

References

    1. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. (2008) 14:641–50. 10.1016/j.bbmt.2008.03.005 - DOI - PMC - PubMed
    1. Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant. (2015) 50 (Suppl. 2):S37–9. 10.1038/bmt.2015.93 - DOI - PubMed
    1. Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. (2015) 126:1033–40. 10.1182/blood-2015-04-639831 - DOI - PMC - PubMed
    1. McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolanos-Meade J, Rosner GL, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. (2015) 125:3024–31. 10.1182/blood-2015-01-623991 - DOI - PMC - PubMed
    1. Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, et al. Comparison of outcomes of hematopoietic cell transplants from T-replete haploidentical donors using post-transplantation cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors and HLA-identical sibling donors: a multivariable analysis including disease risk index. Biol Blood Marrow Transplant. (2016) 22:125–33. 10.1016/j.bbmt.2015.09.002 - DOI - PubMed