Immunosuppressive therapy for pediatric aplastic anemia: a North American Pediatric Aplastic Anemia Consortium study
Zora R. Rogers,
Taizo A. Nakano,
Timothy S. Olson,
Alison A. Bertuch,
Winfred Wang,
Alfred Gillio,
Thomas D. Coates,
Anjulika Chawla,
Paul Castillo,
Peter Kurre,
Christopher Gamper,
Carolyn M. Bennett,
Sarita Joshi,
Amy E. Geddis,
Jessica Boklan,
Grzegorz Nalepa,
Jennifer A. Rothman,
James N. Huang,
Gary M. Kupfer,
Michaela Cada,
Bertil Glader,
Kelly J. Walkovich,
Alexis A. Thompson,
Rabi Hanna,
Adrianna Vlachos,
Maggie Malsch,
Edie A. Weller,
David A. Williams,
Akiko Shimamura
Affiliations
Zora R. Rogers
Pediatric Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Taizo A. Nakano
Center for Cancer and Blood Disorders, Department of Pediatrics, Children’s Hospital Colorado and the University of Colorado School of Medicine, Aurora, CO, USA
Timothy S. Olson
Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Alison A. Bertuch
Baylor College of Medicine, Houston, TX, USA
Winfred Wang
Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, USA
Alfred Gillio
Hackensack University Medical Center, Hackensack, NJ, USA
Thomas D. Coates
Children’s Hospital Los Angeles, Los Angeles, CA, USA
Anjulika Chawla
Brown University, Providence, RI, USA
Paul Castillo
University of Florida, Gainesville, FL, USA
Peter Kurre
Oregon Health and Science University, Portland, OR, USA
Christopher Gamper
Johns Hopkins University, Baltimore, MD, USA
Carolyn M. Bennett
Emory University, Atlanta, GA, USA
Sarita Joshi
Nationwide Childrens Hospital, Columbus, OH, USA
Amy E. Geddis
Seattle Children’s Hospital, Seattle, WA, USA
Jessica Boklan
Center for Cancer and Blood Disorders, Phoenix Children’s Hospital, Phoenix, AZ, USA
Grzegorz Nalepa
Indiana University School of Medicine, Indianapolis, IN, USA
Jennifer A. Rothman
Duke Children’s Hospital, Durham, NC, USA
James N. Huang
UCSF Benioff Children’s Hospital, San Francisco, CA, USA
Gary M. Kupfer
Yale, New Haven, CT, USA
Michaela Cada
Sick Kids Hospital, Toronto, Ontario, Canada
Bertil Glader
Stanford University School of Medicine, Palo Alto, CA, USA
Kelly J. Walkovich
University of Michigan, Ann Arbor, MI, USA
Alexis A. Thompson
Lurie Children’s Hospital, Chicago, IL, USA
Rabi Hanna
Cleveland Clinic, Cleveland, OH, USA
Adrianna Vlachos
Hofstra Northwell School of Medicine, Hempstead, NY, USA
Maggie Malsch
Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, MA, USA
Edie A. Weller
Division of Hematology and Oncology and Biostatistics and Research Design Center of the Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, MA, USA
David A. Williams
Boston Children’s Hospital and Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA
Akiko Shimamura
Boston Children’s Hospital and Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA
Quality of response to immunosuppressive therapy and long-term outcomes for pediatric severe aplastic anemia remain incompletely characterized. Contemporary evidence to inform treatment of relapsed or refractory severe aplastic anemia for pediatric patients is also limited. The clinical features and outcomes for 314 children treated from 2002 to 2014 with immunosuppressive therapy for acquired severe aplastic anemia were analyzed retrospectively from 25 institutions in the North American Pediatric Aplastic Anemia Consortium. The majority of subjects (n=264) received horse anti-thymocyte globulin (hATG) plus cyclosporine (CyA) with a median 61 months follow up. Following hATG/CyA, 71.2% (95%CI: 65.3,76.6) achieved an objective response. In contrast to adult studies, the quality of response achieved in pediatric patients was high, with 59.8% (95%CI: 53.7,65.8) complete response and 68.2% (95%CI: 62.2,73.8) achieving at least a very good partial response with a platelet count ≥50×109L. At five years post-hATG/CyA, overall survival was 93% (95%CI: 89,96), but event-free survival without subsequent treatment was only 64% (95%CI: 57,69) without a plateau. Twelve of 171 evaluable patients (7%) acquired clonal abnormalities after diagnosis after a median 25.2 months (range: 4.3-71 months) post treatment. Myelodysplastic syndrome or leukemia developed in 6 of 314 (1.9%). For relapsed/refractory disease, treatment with a hematopoietic stem cell transplant had a superior event-free survival compared to second immunosuppressive therapy treatment in a multivariate analysis (HR=0.19, 95%CI: 0.08,0.47; P=0.0003). This study highlights the need for improved therapies to achieve sustained high-quality remission for children with severe aplastic anemia.
