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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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)
Pages (from-to)2127-2136
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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

Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients. / Llosa, Nicolas J.; Cooke, Kenneth R.; Chen, Allen R.; Gamper, Christopher J.; Klein, Orly R.; Zambidis, Elias T.; Luber, Brandon; Rosner, Gary; Siegel, Nicholas; Holuba, Mary Jo; Robey, Nancy; Hayashi, Masanori; Jones, Richard J.; Fuchs, Ephraim; Holdhoff, Matthias; Loeb, David M.; Symons, Heather J.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 12, 01.12.2017, p. 2127-2136.

Research output: Contribution to journalArticle

Llosa, NJ, Cooke, KR, Chen, AR, Gamper, CJ, Klein, OR, Zambidis, ET, Luber, B, Rosner, G, Siegel, N, Holuba, MJ, Robey, N, Hayashi, M, Jones, RJ, Fuchs, E, Holdhoff, M, Loeb, DM & Symons, HJ 2017, 'Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients', Biology of Blood and Marrow Transplantation, vol. 23, no. 12, pp. 2127-2136. https://doi.org/10.1016/j.bbmt.2017.08.012
Llosa, Nicolas J. ; Cooke, Kenneth R. ; Chen, Allen R. ; Gamper, Christopher J. ; Klein, Orly R. ; Zambidis, Elias T. ; Luber, Brandon ; Rosner, Gary ; Siegel, Nicholas ; Holuba, Mary Jo ; Robey, Nancy ; Hayashi, Masanori ; Jones, Richard J. ; Fuchs, Ephraim ; Holdhoff, Matthias ; Loeb, David M. ; Symons, Heather J. / Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients. In: Biology of Blood and Marrow Transplantation. 2017 ; Vol. 23, No. 12. pp. 2127-2136.
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T1 - Reduced-Intensity Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Solid Tumors in Pediatric and Young Adult Patients

AU - Llosa, Nicolas J.

AU - Cooke, Kenneth R.

AU - Chen, Allen R.

AU - Gamper, Christopher J.

AU - Klein, Orly R.

AU - Zambidis, Elias T.

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

AU - Holdhoff, Matthias

AU - Loeb, David M.

AU - Symons, Heather J.

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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.

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