Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study.
There is no standard therapy for steroid-refractory chronic graft-versus-host disease (GVHD). This problem is particularly daunting in children with chronic GVHD, whereby the effects of the disease and its treatment may impair normal growth and development. Children are also particularly vulnerable to failure and/or toxicity of therapy; for example, joint contractures or joint damage may result in life-long disability. The Pediatric Blood and Marrow Transplant Consortium performed a phase 2 trial of pentostatin for steroid-refractory chronic GVHD in 51 children (median age, 9.8 years) from 24 institutions. Overall response was 53% (95% confidence interval, 40%-64%), with a response of 59% (95% confidence interval, 42%-75%) in sclerosis. Thirteen subjects (25%) had toxicity requiring them to stop pentostatin. The drug had a significant steroid-sparing effect in those that responded. A trend was also observed toward increased survival at 3 years in responders versus nonresponders (69% vs 50%; P = .06). The intravenous administration of the drug ensures compliance in a patient group in which oral therapy is difficult to monitor. Pentostatin has activity in refractory chronic GVHD in children, and future studies, including treatment of children newly diagnosed with high-risk chronic GVHD, are warranted. The trial was registered at www.Clinicaltrials.gov as #NCT00144430.
Jacobsohn
David A
DA
Robert H. Lurie Comprehensive Cancer Center, Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital, Chicago, IL 60614, USA. djacobsohn@childrensmemorial.org
Gilman
Andrew L
AL
Rademaker
Alfred
A
Browning
Brittan
B
Grimley
Michael
M
Lehmann
Leslie
L
Nemecek
Eneida R
ER
Thormann
Kimberly
K
Schultz
Kirk R
KR
Vogelsang
Georgia B
GB
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000601:surgery; D015649:Pentostatin / Q000627:therapeutic use*; D033581:Stem Cell Transplantation / Q000009:adverse effects; D055815:Young Adult
D000970:Antineoplastic Agents; D015649:Pentostatin