Pentostatin: Efficacy in Refractory Chronic GVHD in Children.
Authors: Jacobsohn David A. , Browning Brittan , Thormann Kimberly , Higman Meghan , Phelps Michele L. , Chen Allen R. , Vogelsang Georgia B. 
Published: October 2019

Abstract
Pentostatin, one of the purine nucleoside analogues, is known to decrease lymphocyte number and function. We are currently investigating pentostatin for refractory chronic graft-vs.-host disease (cGVHD). Within an adult/pediatric phase II study, 16 patients under age 20 are evaluable. All children presented here failed at least two immunosuppressive regimens (including steroids at a dose equivalent to at least 1 mg/kg/day prednisone for one month) before enrollment. The treatment protocol consists of adding pentostatin 4 mg/m2/dose IV every 2 weeks for 6 months. Patients with improving disease are permitted to continue pentostatin therapy at a 3 to 4 week interval. To reduce the risk of infection, steroids are tapered early in all patients. At the end of 3 months, patients with stable or improving cGVHD are weaned off their other medications but maintained on calcineurin inhibitor. Pentostatin is stopped at 6 months if complete response (CR) is achieved or continued if partial response (PR). Patients are followed for improvement in the skin, mouth, and liver. The severity of GVHD is scored for each system on a scale from 0 to 4. Major response is defined as an improvement in symptom score of 2 points or more without worsening in any system. Minor response is a 1 point improvement. Mixed response is improvement in 1 system but worsening in another. Patients have received a median of 15 doses (range 5–30). Median age of the pediatric cohort is 14.5 years (range 5 to 19). Diagnoses include AML/MDS (6), ALL (5), hemoglobinopathy (2), T-cell leukemia (1), aplastic anemia (1), and lymphohistiocytosis (1). Ten had HLA-identical sibling donors (7 BM/3 PBSC) and 6 had HLA-matched unrelated donors (4 BM/2 PBSC). Median time since transplant to start of Pentostatin is 20.5 months (range 8–72). Most patients were on calcineurin inhibitor, eleven on prednisone, seven on MMF, one on rapamycin, and one was receiving ECP at entry on the study. Five patients attained a CR, eight a major response, and three patients have progressed. The overall response rate is 81%. Since some patients had multiple organ involvement, response rate by organ (PR or CR for individual organ) is below. Therapy has been well-tolerated. There has been only one toxicity likely due to pentostatin (creatinine elevation to 4.8 in a patient with a single kidney), and this required the patient to withdraw from the study. There have been no severe infections. There have been 2 deaths, both cGVHD-related, in patients who did not respond. Of the 11 patients on prednisone, 8 were weaned completely off steroids or to <1/4 of original dose at the end of the course of pentostatin. The results suggest that pentostatin has activity in the treatment of cGVHD and may be especially beneficial in children and adolescents. These data form the basis for an ongoing phase II, pediatric-only study through the Pediatric Blood and Marrow Transplant Consortium.
Response by specific organs involved
System Partial Response Complete Response Progression Total Skin 7 3 2 12 --Mainly lichenoid --1 --1 --0 --2 --Mainly scleroderma --5 --2 --1 --8 --Mainly fasciitis --1 --0 --1 --2 Oral 5 1 1 7 Liver 0 3 1 4