Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning

The URTH Trial

Shalini Shenoy*, Mark C. Walters, Alex Ngwube, Sandeep Soni, David Jacobsohn, Sonali Chaudhury, Michael Grimley, Kawah Chan, Ann Haight, Kimberley A. Kasow, Suhag Parikh, Martin Andreansky, Jim Connelly, David Delgado, Kamar Godder, Gregory Hale, Michael Nieder, Michael A. Pulsipher, Felicia Trachtenberg, Ellis Neufeld & 2 others Janet L. Kwiatkowski, Alexis A Thompson

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI,.64% to.92%) and 79% (95% CI,.6% to.9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.

Original languageEnglish (US)
Pages (from-to)1216-1222
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Unrelated Donors
Thalassemia
Graft vs Host Disease
Fetal Blood
Hematopoietic Stem Cell Transplantation
Transplantation
Bone Marrow
Allografts
Incidence
Immunosuppression
Multicenter Studies
Pneumonia
Neutrophils
Blood Platelets
Hemorrhage
Lung
Survival

Keywords

  • Hematopoietic stem cell transplant
  • Reduced-intensity conditioning
  • Thalassemia
  • Unrelated donor

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Shenoy, Shalini ; Walters, Mark C. ; Ngwube, Alex ; Soni, Sandeep ; Jacobsohn, David ; Chaudhury, Sonali ; Grimley, Michael ; Chan, Kawah ; Haight, Ann ; Kasow, Kimberley A. ; Parikh, Suhag ; Andreansky, Martin ; Connelly, Jim ; Delgado, David ; Godder, Kamar ; Hale, Gregory ; Nieder, Michael ; Pulsipher, Michael A. ; Trachtenberg, Felicia ; Neufeld, Ellis ; Kwiatkowski, Janet L. ; Thompson, Alexis A. / Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning : The URTH Trial. In: Biology of Blood and Marrow Transplantation. 2018 ; Vol. 24, No. 6. pp. 1216-1222.
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abstract = "Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82{\%} (95{\%} CI,.64{\%} to.92{\%}) and 79{\%} (95{\%} CI,.6{\%} to.9{\%}), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24{\%} and 44{\%}; the 2-year cumulative incidence of chronic extensive GVHD was 29{\%} and 21{\%}, respectively; 71{\%} of BM and 91{\%} of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.",
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Shenoy, S, Walters, MC, Ngwube, A, Soni, S, Jacobsohn, D, Chaudhury, S, Grimley, M, Chan, K, Haight, A, Kasow, KA, Parikh, S, Andreansky, M, Connelly, J, Delgado, D, Godder, K, Hale, G, Nieder, M, Pulsipher, MA, Trachtenberg, F, Neufeld, E, Kwiatkowski, JL & Thompson, AA 2018, 'Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning: The URTH Trial', Biology of Blood and Marrow Transplantation, vol. 24, no. 6, pp. 1216-1222. https://doi.org/10.1016/j.bbmt.2018.01.023

Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning : The URTH Trial. / Shenoy, Shalini; Walters, Mark C.; Ngwube, Alex; Soni, Sandeep; Jacobsohn, David; Chaudhury, Sonali; Grimley, Michael; Chan, Kawah; Haight, Ann; Kasow, Kimberley A.; Parikh, Suhag; Andreansky, Martin; Connelly, Jim; Delgado, David; Godder, Kamar; Hale, Gregory; Nieder, Michael; Pulsipher, Michael A.; Trachtenberg, Felicia; Neufeld, Ellis; Kwiatkowski, Janet L.; Thompson, Alexis A.

In: Biology of Blood and Marrow Transplantation, Vol. 24, No. 6, 01.06.2018, p. 1216-1222.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning

T2 - The URTH Trial

AU - Shenoy, Shalini

AU - Walters, Mark C.

AU - Ngwube, Alex

AU - Soni, Sandeep

AU - Jacobsohn, David

AU - Chaudhury, Sonali

AU - Grimley, Michael

AU - Chan, Kawah

AU - Haight, Ann

AU - Kasow, Kimberley A.

AU - Parikh, Suhag

AU - Andreansky, Martin

AU - Connelly, Jim

AU - Delgado, David

AU - Godder, Kamar

AU - Hale, Gregory

AU - Nieder, Michael

AU - Pulsipher, Michael A.

AU - Trachtenberg, Felicia

AU - Neufeld, Ellis

AU - Kwiatkowski, Janet L.

AU - Thompson, Alexis A

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI,.64% to.92%) and 79% (95% CI,.6% to.9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.

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KW - Hematopoietic stem cell transplant

KW - Reduced-intensity conditioning

KW - Thalassemia

KW - Unrelated donor

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