Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients

Nicolas Llosa, Kenneth R Cooke, Allen R Chen, Christopher Gamper, Orly Klein, Elias Zambidis, Brandon Luber, Gary Rosner, Nicholas Siegel, Mary Jo Holuba, Nancy Robey, Masanori Hayashi, Richard J Jones, Ephraim J Fuchs, Matthias Holdhoff, David M. Loeb, Heather Symons

Research output: Contribution to journalArticle

Abstract

High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7%) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88%, 56%, and 21% at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - 2017

Fingerprint

Bone Marrow Transplantation
Cyclophosphamide
Young Adult
Pediatrics
Transplants
Neoplasms
Disease-Free Survival
Transplantation
Tissue Donors
Mycophenolic Acid
Melphalan
Survival
Whole-Body Irradiation
Graft vs Host Disease
Sirolimus
Neutrophils
Blood Platelets
Bone Marrow
Recurrence
Mortality

Keywords

  • Adolescent and young adult
  • Cyclophosphamide
  • Haploidentical bone marrow transplantation
  • High-risk solid tumors
  • Pediatric
  • Reduced-intensity conditioning
  • Sirolimus

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{393d347fb22d47e689e42270782823c6,
title = "Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients",
abstract = "High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7{\%}) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88{\%}, 56{\%}, and 21{\%} at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.",
keywords = "Adolescent and young adult, Cyclophosphamide, Haploidentical bone marrow transplantation, High-risk solid tumors, Pediatric, Reduced-intensity conditioning, Sirolimus",
author = "Nicolas Llosa and Cooke, {Kenneth R} and Chen, {Allen R} and Christopher Gamper and Orly Klein and Elias Zambidis and Brandon Luber and Gary Rosner and Nicholas Siegel and Holuba, {Mary Jo} and Nancy Robey and Masanori Hayashi and Jones, {Richard J} and Fuchs, {Ephraim J} and Matthias Holdhoff and Loeb, {David M.} and Heather Symons",
year = "2017",
doi = "10.1016/j.bbmt.2017.08.012",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients

AU - Llosa, Nicolas

AU - Cooke, Kenneth R

AU - Chen, Allen R

AU - Gamper, Christopher

AU - Klein, Orly

AU - Zambidis, Elias

AU - Luber, Brandon

AU - Rosner, Gary

AU - Siegel, Nicholas

AU - Holuba, Mary Jo

AU - Robey, Nancy

AU - Hayashi, Masanori

AU - Jones, Richard J

AU - Fuchs, Ephraim J

AU - Holdhoff, Matthias

AU - Loeb, David M.

AU - Symons, Heather

PY - 2017

Y1 - 2017

N2 - High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7%) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88%, 56%, and 21% at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.

AB - High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus. All assessable patients were full donor chimeras on day 30 with a median neutrophil recovery of 19 days and platelet recovery of 21 days. One patient (7%) exhibited secondary graft failure associated with concomitant infection. The median follow-up time was 15 months. Overall survival was 88%, 56%, and 21% at 6, 12, and 24 months, respectively. Median survival from transplant date was 14 months with a median progression-free survival 7 months. We observed limited graft-versus-host disease in 3 patients and nonrelapse mortality in 1 patient. We demonstrated that RIC haploBMT with PTCy is feasible and has acceptable toxicities in patients with incurable pediatric and AYA solid tumors; thus, this approach serves as a platform for post-transplant strategies to prevent relapse and optimize progression-free survival.

KW - Adolescent and young adult

KW - Cyclophosphamide

KW - Haploidentical bone marrow transplantation

KW - High-risk solid tumors

KW - Pediatric

KW - Reduced-intensity conditioning

KW - Sirolimus

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U2 - 10.1016/j.bbmt.2017.08.012

DO - 10.1016/j.bbmt.2017.08.012

M3 - Article

C2 - 28807769

AN - SCOPUS:85029460424

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

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