Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation: Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium

Eneida R. Nemecek, Ralf A. Hilger, Alexia Adams, Bronwen E. Shaw, Deidre Kiefer, Jennifer Le-Rademacher, John E. Levine, Gregory Yanik, Wing Leung, Julie An Talano, Paul Haut, David Delgado, Neena Kapoor, Aleksandra Petrovic, Roberta Adams, Rabi Hanna, Hemalatha Rangarajan, Jignesh Dalal, Joseph Chewning, Michael R. VernerisStacy Epstein, Lauri Burroughs, Evelio D. Perez-Albuerne, Michael A. Pulsipher, Colleen Delaney

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ .5 m2), 12 g/m2/day (BSA > .5 to 1.0 m2), or 14 g/m2/day (BSA > 1.0 m2) on days −6 to −4; fludarabine 30 mg/m2/day on days −6 to −2; and a single fraction of 200 cGy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

treosulfan
Whole-Body Irradiation
Body Surface Area
Myelodysplastic Syndromes
Cell Transplantation
Acute Myeloid Leukemia
Young Adult
Bone Marrow
Pediatrics
Transplants
Graft vs Host Disease
Fetal Blood
Disease-Free Survival
Pharmacokinetics
Mycophenolic Acid
Mortality
Tacrolimus
Methotrexate
Cyclosporine
Multicenter Studies

Keywords

  • Acute myeloid leukemia
  • Conditioning regimen
  • Myelodysplastic syndromes
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation : Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium. / Nemecek, Eneida R.; Hilger, Ralf A.; Adams, Alexia; Shaw, Bronwen E.; Kiefer, Deidre; Le-Rademacher, Jennifer; Levine, John E.; Yanik, Gregory; Leung, Wing; Talano, Julie An; Haut, Paul; Delgado, David; Kapoor, Neena; Petrovic, Aleksandra; Adams, Roberta; Hanna, Rabi; Rangarajan, Hemalatha; Dalal, Jignesh; Chewning, Joseph; Verneris, Michael R.; Epstein, Stacy; Burroughs, Lauri; Perez-Albuerne, Evelio D.; Pulsipher, Michael A.; Delaney, Colleen.

In: Biology of Blood and Marrow Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Nemecek, ER, Hilger, RA, Adams, A, Shaw, BE, Kiefer, D, Le-Rademacher, J, Levine, JE, Yanik, G, Leung, W, Talano, JA, Haut, P, Delgado, D, Kapoor, N, Petrovic, A, Adams, R, Hanna, R, Rangarajan, H, Dalal, J, Chewning, J, Verneris, MR, Epstein, S, Burroughs, L, Perez-Albuerne, ED, Pulsipher, MA & Delaney, C 2018, 'Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation: Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium', Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2018.04.025
Nemecek, Eneida R. ; Hilger, Ralf A. ; Adams, Alexia ; Shaw, Bronwen E. ; Kiefer, Deidre ; Le-Rademacher, Jennifer ; Levine, John E. ; Yanik, Gregory ; Leung, Wing ; Talano, Julie An ; Haut, Paul ; Delgado, David ; Kapoor, Neena ; Petrovic, Aleksandra ; Adams, Roberta ; Hanna, Rabi ; Rangarajan, Hemalatha ; Dalal, Jignesh ; Chewning, Joseph ; Verneris, Michael R. ; Epstein, Stacy ; Burroughs, Lauri ; Perez-Albuerne, Evelio D. ; Pulsipher, Michael A. ; Delaney, Colleen. / Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation : Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium. In: Biology of Blood and Marrow Transplantation. 2018.
@article{2ee6812019fb4d009cfdbb459d53f33d,
title = "Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation: Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium",
abstract = "This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ .5 m2), 12 g/m2/day (BSA > .5 to 1.0 m2), or 14 g/m2/day (BSA > 1.0 m2) on days −6 to −4; fludarabine 30 mg/m2/day on days −6 to −2; and a single fraction of 200 cGy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80{\%}, 73{\%}, and 3{\%}, respectively. One-year relapse was 38{\%} for AML and 13{\%} for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22{\%} and 40{\%}, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3{\%}) in children and young adults with AML and MDS.",
keywords = "Acute myeloid leukemia, Conditioning regimen, Myelodysplastic syndromes, Stem cell transplantation",
author = "Nemecek, {Eneida R.} and Hilger, {Ralf A.} and Alexia Adams and Shaw, {Bronwen E.} and Deidre Kiefer and Jennifer Le-Rademacher and Levine, {John E.} and Gregory Yanik and Wing Leung and Talano, {Julie An} and Paul Haut and David Delgado and Neena Kapoor and Aleksandra Petrovic and Roberta Adams and Rabi Hanna and Hemalatha Rangarajan and Jignesh Dalal and Joseph Chewning and Verneris, {Michael R.} and Stacy Epstein and Lauri Burroughs and Perez-Albuerne, {Evelio D.} and Pulsipher, {Michael A.} and Colleen Delaney",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2018.04.025",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation

T2 - Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium

AU - Nemecek, Eneida R.

AU - Hilger, Ralf A.

AU - Adams, Alexia

AU - Shaw, Bronwen E.

AU - Kiefer, Deidre

AU - Le-Rademacher, Jennifer

AU - Levine, John E.

AU - Yanik, Gregory

AU - Leung, Wing

AU - Talano, Julie An

AU - Haut, Paul

AU - Delgado, David

AU - Kapoor, Neena

AU - Petrovic, Aleksandra

AU - Adams, Roberta

AU - Hanna, Rabi

AU - Rangarajan, Hemalatha

AU - Dalal, Jignesh

AU - Chewning, Joseph

AU - Verneris, Michael R.

AU - Epstein, Stacy

AU - Burroughs, Lauri

AU - Perez-Albuerne, Evelio D.

AU - Pulsipher, Michael A.

AU - Delaney, Colleen

PY - 2018/1/1

Y1 - 2018/1/1

N2 - This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ .5 m2), 12 g/m2/day (BSA > .5 to 1.0 m2), or 14 g/m2/day (BSA > 1.0 m2) on days −6 to −4; fludarabine 30 mg/m2/day on days −6 to −2; and a single fraction of 200 cGy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.

AB - This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ .5 m2), 12 g/m2/day (BSA > .5 to 1.0 m2), or 14 g/m2/day (BSA > 1.0 m2) on days −6 to −4; fludarabine 30 mg/m2/day on days −6 to −2; and a single fraction of 200 cGy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.

KW - Acute myeloid leukemia

KW - Conditioning regimen

KW - Myelodysplastic syndromes

KW - Stem cell transplantation

UR - http://www.scopus.com/inward/record.url?scp=85047460893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047460893&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2018.04.025

DO - 10.1016/j.bbmt.2018.04.025

M3 - Article

C2 - 29753157

AN - SCOPUS:85047460893

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

ER -