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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02504

Haploidentical stem cell transplantation in children with hematological malignancies using + T-cell receptor and CD19+ cell depleted grafts: High CD56dim/CD56 bright NK cell ratio early following transplantation is associated with lower relapse incidence and better outcome.

 Miguel A. Diaz1*, Josune Zubicaray1, 2, Blanca Molina1, 2, Lorea Abad1, 2, Ana Castillo1, 2,  Elena Sebastian1, 2, Eva Galvez1, 2, Julia Ruiz1, 2, Jose L. Vicario3*, Manuel Ramirez1, 2, Julian Sevilla1, 2 and Marta Gonzalez-Vicent1, 2
  • 1Niño Jesús University Children's Hospital, Spain
  • 2Niño Jesús University Children's Hospital, Spain
  • 3Transfusion Center of the Community of Madrid, Spain

We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using T-cell receptor /CD19+ depleted grafts. Sixty-three
transplantations were performed in 60 patients. Twenty-eight patients were diagnosed of ALL, 27 patients of AML and in 8 other hematological malignancies. At time of transplantation 23 were in first CR, 20 in second CR, 20 beyond second CR. Four patients developed graft failure. Among engrafted patients, the median time to neutrophil and platelet recovery was 14 (range 9–25) and 10 days (range 7–30), respectively. The probability of non-relapse mortality by day +100 after transplantation was 10 ± 4%. With a median follow-up of 28 months, the probability of relapse was 32 ± 6% and disease-free survival was 52 ± 6%. Immune reconstitution was leaded by NK cells. As such, a high CD56 dim/ CD56bright NK cell ratio early after transplantation was associated with better DFS (≥3.5; 77±8% vs <3.5; 28±5%; p=0.001) due to lower relapse incidence (≥3.5; 15±7% vs <3.5; 37±9%; p=0.04). T-cell reconstitution was delayed and associated with severe infections after transplant. Viral reactivation/disease and presence of VOD/SOS in the non-caucasian population had a significant impact on non-relapse mortality. TCR+ and CD19+ cell-depleted haploidentical transplant is associated with encouraging results especially in patients in early phase of disease. A rapid expansion of “mature” natural killer cells early after transplantation resulted on lower probability of relapse, suggesting a graft versus leukemia effect independent from graft-versus-host reactions.

Keywords: T-cell depletion, NK cells, haploidentical transplantation, Immune reconstitution, Acute leukemia, Children

Received: 18 Jun 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Diaz, Zubicaray, Molina, Abad, Castillo, Sebastian, Galvez, Ruiz, Vicario, Ramirez, Sevilla and Gonzalez-Vicent. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD, PhD. Miguel A. Diaz, Niño Jesús University Children's Hospital, Madrid, Spain, mdiazperez@salud.madrid.org
PhD. Jose L. Vicario, Transfusion Center of the Community of Madrid, Madrid, Spain, jlvicario.trans@salud.madrid.org