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Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biol Blood Marrow Transplant 2014 Feb;20(2):229-35

Date

11/13/2013

Pubmed ID

24216185

DOI

10.1016/j.bbmt.2013.11.001

Scopus ID

2-s2.0-84893106561   146 Citations

Abstract

Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2A ??A 10(6) hMSCs/kg for 4A weeks, with an additional 4 weekly infusions after dayA +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8A yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30A d (range, 2 to 1639A d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3A organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at dayA +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at dayA +28 was 58.5% for the gastrointestinal system, 75.6% for skin, and 44.4% for liver. Collectively, overall response at dayA +28 for patients treated for severe refractory aGVHD was 61.3%, and this response was correlated with statistically significant improved survival at dayA +100 after hMSC infusion. Patients who responded to therapy by dayA +28 had a higher Kaplan-Meier estimated probability of 100-d survival compared with patients who did not respond (78.1% versus 31.0%; PA <A .001). Prochymal infusions were generally well tolerated, with no evidence of ectopic tissue formation.

Author List

Kurtzberg J, Prockop S, Teira P, Bittencourt H, Lewis V, Chan KW, Horn B, Yu L, Talano JA, Nemecek E, Mills CR, Chaudhury S

Author

Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Child
Child, Preschool
Female
Graft vs Host Disease
Humans
Infant
Male
Mesenchymal Stem Cell Transplantation
Prospective Studies
Transplantation, Homologous