Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.
Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment.
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Pediatric Oncology, Langone Medical Center, New York University, New York, NY, USA. Electronic address: kschmiegelow@rh.dk.
Kjeld
K
Schmiegelow
Department of Pediatric Hematology and Oncology, St Anna Children's Hospital, Vienna, Austria; Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
Andishe
A
Attarbaschi
Schneider Children's Medical Center of Israel, Department of Pediatric Hematology Oncology, Petah-Tikva, Israel.
Shlomit
S
Barzilai
University Medical Center Eppendorf, Clinic of Pediatric Hematology and Oncology, Hamburg, Germany.
Gabriele
G
Escherich
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
Thomas Leth
TL
Frandsen
Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Christina
C
Halsey
University College London's NHS Foundation Trust, London, UK.
Rachael
R
Hough
St Jude Children's Research Hospital, Memphis, TN, USA.
Sima
S
Jeha
Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Motohiro
M
Kato
Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
Der-Cherng
DC
Liang
Department of Pediatrics, Aarhus University Hospital, Aarhus N, Denmark.
Torben Stamm
TS
Mikkelsen
Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Department of Pediatrics, Kiel, Germany.
Anja
A
Möricke
Department of Pediatrics, Oulu University Hospital, Oulu, Finland.
Riitta
R
Niinimäki
EORTC Children's Leukemia Group and University Department of Pediatric Oncology CHR Citadelle, Liège, Belgium.
Caroline
C
Piette
Clinic of Pediatric Hematology Oncology, Department of Women's and Children's Health, Padova, Italy.
Maria Caterina
MC
Putti
University of Utah, Department of Pediatrics and Huntsman Cancer Institute, Salt Lake City, UT, USA.
Elizabeth
E
Raetz
Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
Lewis B
LB
Silverman
Department of Paediatric and Adolescent Haematology/Oncology, and Children's Haemopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, UK.
Roderick
R
Skinner
Department of Pediatrics, Aalborg University Hospital, Aalborg, Denmark.
Ruta
R
Tuckuviene
Dutch Childhood Oncology Group, The Hague, Netherlands; Erasmus Medical Center, Sophia Children's Hospital, Department of Pediatric Hematology-Oncology, Rotterdam, Netherlands.
Inge
I
van der Sluis
University Hospital Motol, Department of Pediatric Hematology/Oncology, Prague, Czech Republic.
Ester
E
Zapotocka
D002648:Child; D003131:Combined Modality Therapy / Q000009:adverse effects*; D003697:Delphi Technique; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011836:Radiation Tolerance; D023382:Toxicity Tests, Acute