HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with fanconi anemia

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Abstract

We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given Tcell-depleted, CD34+ positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of Tcell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.

Original languageEnglish
Pages (from-to)571-576
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number4
DOIs
Publication statusPublished - 2014

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Fanconi Anemia
Hematopoietic Stem Cell Transplantation
Confidence Intervals
T-Lymphocytes
Disease-Free Survival
Incidence
Tissue Donors
Unrelated Donors
Survival
Graft Rejection
Graft vs Host Disease
Siblings
Stem Cells
Pediatrics
Transplants
Mortality

Keywords

  • Fanconi anemia
  • Haploidentical stem cell transplantation
  • Reduced-intensity conditioning
  • Tcell depletion

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{0f52d95eaa474eedb85d3f4a90aad859,
title = "HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with fanconi anemia",
abstract = "We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given Tcell-depleted, CD34+ positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75{\%}), and the cumulative incidence of graft rejection was 17{\%} (95{\%} confidence interval [CI], 5{\%} to 59{\%}). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17{\%} (95{\%} CI, 5{\%} to 59{\%}) and 35{\%} (95{\%} CI, 14{\%} to 89{\%}), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17{\%} (95{\%} CI, 5{\%} to 59{\%}). The 5-year overall survival, event-free survival, and disease-free survival were 83{\%} (95{\%} CI, 62{\%} to 100{\%}), 67{\%} (95{\%} CI, 40{\%} to 93{\%}), and 83{\%} (95{\%} CI, 62{\%} to 100{\%}), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of Tcell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.",
keywords = "Fanconi anemia, Haploidentical stem cell transplantation, Reduced-intensity conditioning, Tcell depletion",
author = "Marco Zecca and Luisa Strocchio and Daria Pagliara and Patrizia Comoli and Alice Bertaina and Giovanna Giorgiani and Cesare Perotti and Franco Corbella and Letizia Brescia and Franco Locatelli",
year = "2014",
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language = "English",
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pages = "571--576",
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TY - JOUR

T1 - HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with fanconi anemia

AU - Zecca, Marco

AU - Strocchio, Luisa

AU - Pagliara, Daria

AU - Comoli, Patrizia

AU - Bertaina, Alice

AU - Giorgiani, Giovanna

AU - Perotti, Cesare

AU - Corbella, Franco

AU - Brescia, Letizia

AU - Locatelli, Franco

PY - 2014

Y1 - 2014

N2 - We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given Tcell-depleted, CD34+ positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of Tcell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.

AB - We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given Tcell-depleted, CD34+ positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of Tcell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.

KW - Fanconi anemia

KW - Haploidentical stem cell transplantation

KW - Reduced-intensity conditioning

KW - Tcell depletion

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DO - 10.1016/j.bbmt.2014.01.015

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JO - Biology of Blood and Marrow Transplantation

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