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

Orly R. Klein, Jessica Buddenbaum, Noah Tucker, Allen R. Chen, Christopher J. Gamper, David Loeb, Elias Zambidis, Nicolas J. Llosa, Jeffrey S. Huo, Nancy Robey, Mary Jo Holuba, Yvette L. Kasamon, Shannon R. McCurdy, Richard Ambinder, Javier Bolaños-Meade, Leo Luznik, Ephraim J. Fuchs, Richard J. Jones, Kenneth R. Cooke, Heather J. Symons

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages325-332
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

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

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 Bola{\~n}os-Meade and Leo Luznik and Fuchs, {Ephraim J.} and Jones, {Richard J.} and Cooke, {Kenneth R.} and Symons, {Heather J.}",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.bbmt.2016.11.016",
language = "English (US)",
volume = "23",
pages = "325--332",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
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TY - JOUR

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

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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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ER -