Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders

Orly R. Klein, Allen R. Chen, Christopher Gamper, David M. Loeb, Elias Zambidis, Nicolas Llosa, Jeffrey Huo, Amy E. Dezern, Diana Steppan, Nancy Robey, Mary Jo Holuba, Kenneth R. Cooke, Heather J. Symons

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted.

Original languageEnglish (US)
Pages (from-to)895-901
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

Fingerprint

Hematopoietic Stem Cell Transplantation
Cyclophosphamide
Transplantation
Tissue Donors
Graft vs Host Disease
Transplants
Hemoglobinopathies
Pediatrics
Mortality
Mycophenolic Acid
Tacrolimus
Hematologic Neoplasms
Clinical Trials

Keywords

  • Bone marrow failure syndromes
  • Cyclophosphamide
  • HLA-haploidentical
  • Immunodeficiency
  • Reduced-intensity conditioning

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders. / Klein, Orly R.; Chen, Allen R.; Gamper, Christopher; Loeb, David M.; Zambidis, Elias; Llosa, Nicolas; Huo, Jeffrey; Dezern, Amy E.; Steppan, Diana; Robey, Nancy; Holuba, Mary Jo; Cooke, Kenneth R.; Symons, Heather J.

In: Biology of Blood and Marrow Transplantation, Vol. 22, No. 5, 01.05.2016, p. 895-901.

Research output: Contribution to journalArticle

Klein, OR, Chen, AR, Gamper, C, Loeb, DM, Zambidis, E, Llosa, N, Huo, J, Dezern, AE, Steppan, D, Robey, N, Holuba, MJ, Cooke, KR & Symons, HJ 2016, 'Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders', Biology of Blood and Marrow Transplantation, vol. 22, no. 5, pp. 895-901. https://doi.org/10.1016/j.bbmt.2016.02.001
Klein, Orly R. ; Chen, Allen R. ; Gamper, Christopher ; Loeb, David M. ; Zambidis, Elias ; Llosa, Nicolas ; Huo, Jeffrey ; Dezern, Amy E. ; Steppan, Diana ; Robey, Nancy ; Holuba, Mary Jo ; Cooke, Kenneth R. ; Symons, Heather J. / Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders. In: Biology of Blood and Marrow Transplantation. 2016 ; Vol. 22, No. 5. pp. 895-901.
@article{d5cce3b4626d4bc1a699aba1592f9b44,
title = "Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders",
abstract = "Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted.",
keywords = "Bone marrow failure syndromes, Cyclophosphamide, HLA-haploidentical, Immunodeficiency, Reduced-intensity conditioning",
author = "Klein, {Orly R.} and Chen, {Allen R.} and Christopher Gamper and Loeb, {David M.} and Elias Zambidis and Nicolas Llosa and Jeffrey Huo and Dezern, {Amy E.} and Diana Steppan and Nancy Robey and Holuba, {Mary Jo} and Cooke, {Kenneth R.} and Symons, {Heather J.}",
year = "2016",
month = "5",
day = "1",
doi = "10.1016/j.bbmt.2016.02.001",
language = "English (US)",
volume = "22",
pages = "895--901",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders

AU - Klein, Orly R.

AU - Chen, Allen R.

AU - Gamper, Christopher

AU - Loeb, David M.

AU - Zambidis, Elias

AU - Llosa, Nicolas

AU - Huo, Jeffrey

AU - Dezern, Amy E.

AU - Steppan, Diana

AU - Robey, Nancy

AU - Holuba, Mary Jo

AU - Cooke, Kenneth R.

AU - Symons, Heather J.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted.

AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted.

KW - Bone marrow failure syndromes

KW - Cyclophosphamide

KW - HLA-haploidentical

KW - Immunodeficiency

KW - Reduced-intensity conditioning

UR - http://www.scopus.com/inward/record.url?scp=84963673066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963673066&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2016.02.001

DO - 10.1016/j.bbmt.2016.02.001

M3 - Article

VL - 22

SP - 895

EP - 901

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 5

ER -