Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies

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Abstract

Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.

Original languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2017

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Hematologic Neoplasms
Bone Marrow Transplantation
Cyclophosphamide
Young Adult
Transplantation
Pediatrics
Graft vs Host Disease
Bone Marrow
Incidence
Mortality
Whole-Body Irradiation
National Institutes of Health (U.S.)
Tacrolimus
Immunosuppression
Disease-Free Survival
Comorbidity
Neutrophils
Blood Platelets
Recurrence

Keywords

  • Acute leukemia
  • Cyclophosphamide
  • HLA-haploidentical transplantation
  • Lymphoma
  • Myelodysplastic syndrome
  • Nonmyeloablative bone marrow transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{e8f8d2def77b4480a2e7889dcd7fda34,
title = "Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies",
abstract = "Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.",
keywords = "Acute leukemia, Cyclophosphamide, HLA-haploidentical transplantation, Lymphoma, Myelodysplastic syndrome, Nonmyeloablative bone marrow transplantation",
author = "Klein, {Orly R.} and Jessica Buddenbaum and Noah Tucker and Chen, {Allen R.} and Gamper, {Christopher J.} and David Loeb and Elias Zambidis and Llosa, {Nicolas J.} and Huo, {Jeffrey S.} and Nancy Robey and Holuba, {Mary Jo} and Kasamon, {Yvette L.} and McCurdy, {Shannon R.} and Richard Ambinder and Javier Bolaños-Meade and Leo Luznik and Fuchs, {Ephraim J.} and Jones, {Richard J.} and Cooke, {Kenneth R.} and Symons, {Heather J.}",
year = "2017",
month = "2",
doi = "10.1016/j.bbmt.2016.11.016",
volume = "23",
pages = "325--332",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "2",

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T1 - Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies

AU - Klein,Orly R.

AU - Buddenbaum,Jessica

AU - Tucker,Noah

AU - Chen,Allen R.

AU - Gamper,Christopher J.

AU - Loeb,David

AU - Zambidis,Elias

AU - Llosa,Nicolas J.

AU - Huo,Jeffrey S.

AU - Robey,Nancy

AU - Holuba,Mary Jo

AU - Kasamon,Yvette L.

AU - McCurdy,Shannon R.

AU - Ambinder,Richard

AU - Bolaños-Meade,Javier

AU - Luznik,Leo

AU - Fuchs,Ephraim J.

AU - Jones,Richard J.

AU - Cooke,Kenneth R.

AU - Symons,Heather J.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.

AB - Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.

KW - Acute leukemia

KW - Cyclophosphamide

KW - HLA-haploidentical transplantation

KW - Lymphoma

KW - Myelodysplastic syndrome

KW - Nonmyeloablative bone marrow transplantation

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U2 - 10.1016/j.bbmt.2016.11.016

DO - 10.1016/j.bbmt.2016.11.016

M3 - Article

VL - 23

SP - 325

EP - 332

JO - Biology of Blood and Marrow Transplantation

T2 - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

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