title: Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia.
abstract: 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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University of Freiburg, Germany charlotte.niemeyer@uniklinik-freiburg.de.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Niemeyer
authors.affiliation: Department of Pediatrics and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Mignon L
authors.initials: ML
authors.lastname: Loh
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University of Freiburg, Germany.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cseh
authors.affiliation: Aflac Cancer and Blood Disorders Center/Children's Healthcare of Atlanta/Emory University, Atlanta, GA, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Cooper
authors.affiliation: Division of Pediatric Allergy, Immunology, and Bone Marrow Transplant, Benioff Children's Hospital, University of California, San Francisco, CA, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Department of Pediatrics, The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Chan
authors.affiliation: Department of Hematology, Hospital Germans Trias i Pujol and Institut Català d'Oncologia-José Carreras Leukemia Research Institute, Badalona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Xicoy
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.affiliation: St. Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.affiliation: Department of Pediatric Hemato-Oncology, Ghent University Hospital, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Moerloose
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Czech Pediatric Hematology Working Group, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Starý
authors.affiliation: Pediatric Oncology and Hematology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Owen P
authors.initials: OP
authors.lastname: Smith
authors.affiliation: Department of Pediatric Oncology and Hematology, University of Bologna, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Department of Hematology, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Catala
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital, Zurich, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Bergstraesser
authors.affiliation: Department of Pediatric Oncology, Hematology and BMT, Wroclaw Medical University, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Ussowicz
authors.affiliation: Department of Hematology and Transfusiology, Comenius University, Bratislava, Slovakia.
authors.forename: Oskana
authors.initials: O
authors.lastname: Fabri
authors.affiliation: Department of Pediatric Hematology of Robert Debré Hospital and Paris Diderot University, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: Department of Genetics, Hôpital Robert Debré, and Paris Diderot University, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.affiliation: ErasmusMC-Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, and the Netherlands and ITCC.
authors.forename: Michel
authors.initials: M
authors.lastname: Zwaan
authors.affiliation: Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, University of Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.affiliation: ErasmusMC-Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, and Dutch Childhood Oncology Group, The Hague, The Netherlands.
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University of Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Flotho
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University of Freiburg, Germany.
authors.forename: Ayami
authors.initials: A
authors.lastname: Yoshimi
mesh_terms: D002648:Child; D002986:Clinical Trials as Topic / Q000592:standards*; D003131:Combined Modality Therapy; D006801:Humans; D054429:Leukemia, Myelomonocytic, Juvenile / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D017410:Practice Guidelines as Topic / Q000592:standards*; D011379:Prognosis; D015996:Survival Rate