Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia
Charlotte M. Niemeyer,
Mignon L. Loh,
Annamaria Cseh,
Todd Cooper,
Christopher C. Dvorak,
Rebecca Chan,
Blanca Xicoy,
Ulrich Germing,
Seiji Kojima,
Atsushi Manabe,
Michael Dworzak,
Barbara De Moerloose,
Jan Starý,
Owen P. Smith,
Riccardo Masetti,
Albert Catala,
Eva Bergstraesser,
Marek Ussowicz,
Oskana Fabri,
André Baruchel,
Hélène Cavé,
Michel Zwaan,
Franco Locatelli,
Henrik Hasle,
Marry M. van den Heuvel-Eibrink,
Christian Flotho,
Ayami Yoshimi
Affiliations
Charlotte M. Niemeyer
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University of Freiburg, Germany
Mignon L. Loh
Department of Pediatrics and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USA
Annamaria Cseh
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University of Freiburg, Germany
Todd Cooper
Aflac Cancer and Blood Disorders Center/Children’s Healthcare of Atlanta/Emory University, Atlanta, GA, USA
Christopher C. Dvorak
Division of Pediatric Allergy, Immunology, and Bone Marrow Transplant, Benioff Children’s Hospital, University of California, San Francisco, CA, USA
Rebecca Chan
Department of Pediatrics, The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
Blanca Xicoy
Department of Hematology, Hospital Germans Trias i Pujol and Institut Català d’Oncologia-José Carreras Leukemia Research Institute, Badalona, Spain
Ulrich Germing
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany
Seiji Kojima
Department of Pediatrics, Nagoya University Graduate School of Medicine, Japan
Atsushi Manabe
Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan
Michael Dworzak
St. Anna Children’s Hospital and Children’s Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Austria
Barbara De Moerloose
Department of Pediatric Hemato-Oncology, Ghent University Hospital, Belgium
Jan Starý
Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Czech Pediatric Hematology Working Group, Prague, Czech Republic
Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I–II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia.
