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Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome

We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ(+) T-cell receptor/CD19(+) depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were...

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Autores principales: Diaz, Miguel A., Zubicaray, Josune, Molina, Blanca, Abad, Lorea, Castillo, Ana, Sebastian, Elena, Galvez, Eva, Ruiz, Julia, Vicario, Jose Luis, Ramirez, Manuel, Sevilla, Julian, González-Vicent, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831520/
https://www.ncbi.nlm.nih.gov/pubmed/31736949
http://dx.doi.org/10.3389/fimmu.2019.02504
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author Diaz, Miguel A.
Zubicaray, Josune
Molina, Blanca
Abad, Lorea
Castillo, Ana
Sebastian, Elena
Galvez, Eva
Ruiz, Julia
Vicario, Jose Luis
Ramirez, Manuel
Sevilla, Julian
González-Vicent, Marta
author_facet Diaz, Miguel A.
Zubicaray, Josune
Molina, Blanca
Abad, Lorea
Castillo, Ana
Sebastian, Elena
Galvez, Eva
Ruiz, Julia
Vicario, Jose Luis
Ramirez, Manuel
Sevilla, Julian
González-Vicent, Marta
author_sort Diaz, Miguel A.
collection PubMed
description We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ(+) T-cell receptor/CD19(+) depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed. Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR. Four patients developed graft failure. 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 (NRM) 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/)CD56(bright) NK cell ratio early after transplantation was associated with better disease-free survival (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 venooclusive disease of liver in the non-caucasian population had a significant impact on NRM. αβ(+) T-cell receptor/CD19(+) cell-depleted haploidentical transplant is associated with good outcomes 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 vs. leukemia effect independent from graft-vs.-host reactions.
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spelling pubmed-68315202019-11-15 Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome Diaz, Miguel A. Zubicaray, Josune Molina, Blanca Abad, Lorea Castillo, Ana Sebastian, Elena Galvez, Eva Ruiz, Julia Vicario, Jose Luis Ramirez, Manuel Sevilla, Julian González-Vicent, Marta Front Immunol Immunology We prospectively analyzed outcomes of haploidentical hematopoietic stem cell transplantation using αβ(+) T-cell receptor/CD19(+) depleted grafts. Sixty-three transplantations were performed in 60 patients. Twenty-eight patients were diagnosed with acute lymphoblastic leukemia (ALL), 27 patients were diagnosed with acute myelogenous leukemia, and in eight other hematological malignancies were diagnosed. Twenty-three were in first complete remission (CR), 20 in second CR, 20 beyond second CR. Four patients developed graft failure. 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 (NRM) 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/)CD56(bright) NK cell ratio early after transplantation was associated with better disease-free survival (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 venooclusive disease of liver in the non-caucasian population had a significant impact on NRM. αβ(+) T-cell receptor/CD19(+) cell-depleted haploidentical transplant is associated with good outcomes 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 vs. leukemia effect independent from graft-vs.-host reactions. Frontiers Media S.A. 2019-10-30 /pmc/articles/PMC6831520/ /pubmed/31736949 http://dx.doi.org/10.3389/fimmu.2019.02504 Text en Copyright © 2019 Diaz, Zubicaray, Molina, Abad, Castillo, Sebastian, Galvez, Ruiz, Vicario, Ramirez, Sevilla and González-Vicent. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Immunology
Diaz, Miguel A.
Zubicaray, Josune
Molina, Blanca
Abad, Lorea
Castillo, Ana
Sebastian, Elena
Galvez, Eva
Ruiz, Julia
Vicario, Jose Luis
Ramirez, Manuel
Sevilla, Julian
González-Vicent, Marta
Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome
title Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome
title_full Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome
title_fullStr Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome
title_full_unstemmed Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome
title_short Haploidentical Stem Cell Transplantation in Children With Hematological Malignancies Using αβ(+) T-Cell Receptor and CD19(+) Cell Depleted Grafts: High CD56(dim)/CD56(bright) NK Cell Ratio Early Following Transplantation Is Associated With Lower Relapse Incidence and Better Outcome
title_sort haploidentical stem cell transplantation in children with hematological malignancies using αβ(+) t-cell receptor and cd19(+) cell depleted grafts: high cd56(dim)/cd56(bright) nk cell ratio early following transplantation is associated with lower relapse incidence and better outcome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831520/
https://www.ncbi.nlm.nih.gov/pubmed/31736949
http://dx.doi.org/10.3389/fimmu.2019.02504
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