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Haematologica 2019 Volume 104(10):1974-1983
Bone Marrow Failure
Immunosuppressive therapy for pediatric aplastic anemia: a North American Pediatric Aplastic Anemia Consortium study
Zora R. Rogers,1 Taizo A. Nakano,2 Timothy S. Olson,3 Alison A. Bertuch,4
Winfred Wang,5 Alfred Gillio,6 Thomas D. Coates,7 Anjulika Chawla,8
Paul Castillo,9 Peter Kurre,10 Christopher Gamper,11 Carolyn M. Bennett,12
Sarita Joshi,13 Amy E. Geddis,14 Jessica Boklan,15 Grzegorz Nalepa,16
Jennifer A. Rothman,17 James N. Huang,18 Gary M. Kupfer,19 Michaela Cada,20
21 22 23 24 Bertil Glader, Kelly J. Walkovich, Alexis A. Thompson, Rabi Hanna,
25 26 27 28 Adrianna Vlachos, Maggie Malsch, Edie A. Weller, David A. Williams and
Akiko Shimamura28
1Pediatric Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Center for Cancer and Blood Disorders, Department of Pediatrics, Children's Hospital Colorado and the University of Colorado School of Medicine, Aurora, CO, USA; 3Children's Hospital of Philadelphia, Philadelphia, PA, USA; 4Baylor College of Medicine, Houston, TX, USA; 5Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA; 6Hackensack University Medical Center, Hackensack, NJ, USA; 7Children's Hospital Los Angeles, Los Angeles, CA, USA; 8Brown University, Providence, RI, USA; 9University of Florida, Gainesville, FL, USA; 10Oregon Health and Science University, Portland, OR, USA; 11Johns Hopkins University, Baltimore, MD, USA; 12Emory University, Atlanta, GA, USA; 13Nationwide Childrens Hospital, Columbus, OH, USA; 14Seattle Children's Hospital, Seattle, WA, USA; 15Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA; 16Indiana University School of Medicine, Indianapolis, IN, USA; 17Duke Children’s Hospital, Durham, NC, USA; 18UCSF Benioff Children's Hospital, San Francisco, CA, USA; 19Yale, New Haven, CT, USA; 20Sick Kids Hospital, Toronto, Ontario, Canada; 21Stanford University School of Medicine, Palo Alto, CA, USA; 22University of Michigan, Ann Arbor, MI, USA; 23Lurie Children's Hospital, Chicago, IL, USA; 24Cleveland Clinic, Cleveland, OH, USA; 25Hofstra Northwell School of Medicine, Hempstead, NY, USA; 26Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, MA, USA; 27Division 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 and 28Boston Children’s Hospital and Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA
ABSTRACT
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 ≥50x109L. 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 syn- drome 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 treat- ment 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.
Correspondence:
AKIKO SHIMAMURA
akiko.shimamura@childrens.harvard.edu
Received: November 5, 2018. Accepted: March 28, 2019. Pre-published: April 4, 2019.
doi:10.3324/haematol.2018.206540
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/10/1974
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