Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America.
To assess trends in survival and geographic disparities among children (0-14 years) with chronic myeloid leukaemia (CML) before and after the introduction of molecular therapy, namely tyrosine kinase inhibitors (TKIs) in Southern-Eastern European (SEE) countries and the USA.



We calculated survival among children with CML, acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) in 14 SEE (1990-2014) cancer registries and the U.S. Surveillance, Epidemiology and End Results Program (SEER, 1990-2012). We used Kaplan-Meier curves and multivariate Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).



Among 369 CML cases, substantial improvements were noted in 2-year survival during the post-TKI (range: 81-89%) compared to pre-TKI period (49-66%; HR: 0.37, 95% CI: 0.23-0.60). Risk of death was three times higher for <5-year-old children versus those aged 10-14 years (HR: 3.03, 95% CI: 1.85-4.94) and 56% higher for those living in SEE versus SEER (HR: 1.56, 95% CI: 1.01-2.42). Regardless of geographic area and period of TKI administration, however, age seems to be a significant determinant of CML prognosis (pre-TKI period, HR0-4y: 2.71, 95% CI: 1.53-4.79; post-TKI period, HR0-4y: 3.38, 95% CI: 1.29-8.85). Noticeably, post-TKI survival in CML overall approximates that for ALL, whereas therapeutic advancements for AML remain modest.



Registry data show that introduction of molecular therapies coincides with revolutionised therapeutic outcomes in childhood CML entailing dramatically improved survival which is now similar to that in ALL. Given that age disparities in survival remain substantial, offering optimal therapy to entire populations is an urgent priority.
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, 75 Mikras Asias Str, Athens, 11527, Greece.
Maria A
MA
Karalexi
Department of Pediatric Hematology-Oncology, "Pan & Agl. Kyriakou" Children's Hospital, Thivon and Papadiamantopoulou Str, 11527, Athens, Greece.
Margarita
M
Baka
National Cancer Registry of Ukraine, National Institute of Cancer, Lomonosova str, 33/43, Kyiv, 03022, Ukraine.
Anton
A
Ryzhov
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Childhood Cancer Subregistry of Belarus, Lesnoe-2, 223040, Minsk Region, Belarus.
Anna
A
Zborovskaya
Bulgarian National Cancer Registry, National Oncology Hospital, 6, Plovdivsko Pole Street, Sofia, 1756, Bulgaria.
Nadya
N
Dimitrova
Institute of Public Health of Serbia, Dr Subotica 5, Belgrade, 11000, Serbia.
Snezana
S
Zivkovic
Izmir Cancer Registry, Izmir Hub, Izmir & Hacettepe University Institute of Public Health, Zubeyde Hanim Caddesi No:100, Karsiyaka, Izmir, 35067, Turkey.
Sultan
S
Eser
North Region Cancer Registry of Portugal (RORENO), Portuguese Oncology Institute of Porto, Rua António Bernardino da Almeida, Porto, 4200-072, Portugal.
Luis
L
Antunes
Croatian National Cancer Registry, Croatian Institute of Public Health, Rockefellerova 7, Zagreb, 10000, Croatia.
Mario
M
Sekerija
Cancer Registry of Republic of Slovenia, Institute of Oncology, Zaloška cesta 2, SI-1000, Ljubljana, Slovenia.
Tina
T
Zagar
Central Region Cancer Registry of Portugal (ROR-Centro), Portuguese Oncology Institute of Coimbra, Av. Bissaya Barreto 98, 3000-075, Coimbra, Portugal.
Joana
J
Bastos
Cyprus Cancer Registry-Health Monitoring Unit, Ministry of Health, 1 Prodromou Str & 17 Chilonos Str, Nicosia, 1448, Cyprus.
Anna
A
Demetriou
Malta National Cancer Registry, Department of Health Information and Research, 95, Guardamangia Hill, Guardamangia, MSD 08, Malta.
Domenic
D
Agius
Regional Cancer Registry of Iasio, National Institute of Public Health, 14 Victor Babes Street 700465, Iasi, Romania.
Margareta
M
Florea
Regional Cancer Registry of Cluj, Oncological Institute "Ion Chiricuta", Republicii Str no. 34-36, Cluj Napoca, 400015, Romania.
Daniela
D
Coza
Department of Pediatric Haematology-Oncology, "Aghia Sophia" Children's Hospital, Thivon and Livadias, Goudi, Athens, 115 27, Greece.
Sophia
S
Polychronopoulou
Department of Pediatric Hematology-Oncology, University of Crete, University Hospital of Heraklion, Arsinois 23, Heraklion Crete, 71303, Greece.
Eftichia
E
Stiakaki
Haematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, "Aghia Sophia" Children's Hospital, Thivon and Livadias, Goudi, Athens, 115 27, Greece.
Maria
M
Moschovi
2nd Department of Pediatrics, Aristotelion University of Thessaloniki, AHEPA General Hospital, Thessaloniki, Greece.
Emmanuel
E
Hatzipantelis
Department of Pediatric Hematology and Oncology, Hippokration Hospital, Konstantinoupoleos Str 49, Thessaloniki, 54642, Greece.
Maria
M
Kourti
Stem Cell Transplantion Unit, Aghia Sophia Children's Hospital, Thivon and Livadias, Goudi, Athens, 115 27, Greece.
Stelios
S
Graphakos
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rua Andre Cavalcanti, 37, Rio de Janeiro, 20230-130, Brazil.
Maria S
MS
Pombo-de-Oliveira
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard T.H., Chan School of Public Health, Boston, MA, USA; Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Kirkeveien 166, Frederik Holsts hus, Oslo, 0450, Norway.
Hans Olov
HO
Adami
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, 75 Mikras Asias Str, Athens, 11527, Greece. Electronic address: epetrid@med.uoa.gr.
Eleni Th
ET
Petridou
D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005061:Europe, Eastern; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000401:mortality*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality; D008297:Male; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012042:Registries; D018426:SEER Program; D015996:Survival Rate / Q000639:trends*; D014481:United States
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
Cancer registration; Child; Chronic myeloid leukaemia; Inequalities; Survival; Tyrosine kinase inhibitors