Last Updated: 2009-11-23 16:47:38 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Pentostatin is effective for refractory chronic graft-versus-host disease (GVHD) in children, according to a Pediatric Blood and Marrow Transplant Consortium study.
"There is hope for patients with severe chronic GVHD, especially for patients with sclerotic chronic GVHD," Dr. David A. Jacobsohn told Reuters Health. Dr. Jacobsohn, from Northwestern University in Chicago, was the lead author of the Consortium's report, which appears in the November 12 issue of Blood.
"This is a great advancement for children with chronic GVHD," he added.
The 24-center study involved 51 pediatric patients with corticosteroid-refractory chronic GVHD after stem cell transplantation. The patients ranged from 0.9 to 20.7 years at the time of study enrollment (median age, 9.8 years), with a median duration of chronic GVHD of 6.2 months.
Pentostatin, which inhibits adenosine deaminase, was given by IV infusion every 2 weeks. Overall, 27 patients (53%) responded to treatment, including 20 with partial responses and 7 with complete responses. In 23 patients, responses were observed within 90 days. In the others, responses were first observed at the 180-day or 365-day visit.
Fifteen children had no response at all, whereas nine had transient responses but later progressed.
The response rate was 50% among the 40 patients with skin rash/lichenoid involvement and 59% among the 27 patients with sclerotic manifestations, but there were no responses in patients with liver or lung manifestations.
Responders had significant decreases in their daily prednisone requirement, but there was no change in prednisone dose in nonresponding patients.
Infection was the most common adverse event, occurring in 15 patients. Thirteen patients withdrew from the study for reasons that included leukoencephalopathy, renal compromise, pancreatitis/abdominal pain, autoimmune hemolytic anemia, and allergic reaction.
At three years after enrollment, projected survival was 69% for patients who responded to pentostatin compared with 50% for nonresponders.
"It would be ideal to study pentostatin in combination with other less toxic therapies, such as photopheresis," Dr. Jacobsohn said. "We may see better response when we combine agents with non-overlapping mechanisms of action and non-overlapping toxicity profiles."
"Pentostatin is also easy to administer and by giving it in the clinic every two weeks, one can assure compliance, which is very difficult to do if we prescribe medications patients are supposed to take at home daily or multiple times a day," Dr. Jacobsohn added.
"In the future we would like to look at using pentostatin earlier in the course of chronic GVHD," he continued. "For example, we could study it in patients with newly-diagnosed high-risk chronic GVHD, who tend to have a very poor outcome with conventional therapy."
Blood 2009;114:4354-4360.
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