Impact of Additional Cytogenetic Abnormalities and Variant t(9;22) at Diagnosis on Prognosis of Childhood Chronic Myelogenous Leukemia : The Experience of the International Registry for CML in Children and Adolescents (I-CML-Ped Study)
Authors: Millot Frédéric , Guilhot Joelle , Suttorp Meinolf , Sedlacek Pietr , de Bont Eveline S.J.M. , Li Chi Kong , Kalwak Krzysztof , Lausen Birgitte , Srdjana Culic , Dresse Marie-Francoise , Biondi Andrea , Baruchel André , Brizard Françoise 
Published: November 2019

Abstract

Introduction. Chronic myeloid leukemia(CML) is a very rare disease in children and adolescents. The international registry of CML in children and adolescents gives us the opportunity to assess the prognostic relevance of variant t(9 ;22) and additional cytogenetic abnormalities at diagnosis on prognosis.
Patients and Methods. We used clinical and biological characteristics and outcome of 239 children and adolescents less than 18 years to assess the impact of additional cytogenetic abnormalities and variant t(9 ;22) on the rate and the time to achieve a complete cytogenetic response (CCyR). Cytogenetic analysis was performed 24 or 48 hour culture on G-banded metaphases.
Results. Overall, 17/239 children (7.1%) presented with additional cytogenetic finding at diagnosis: 5/239 children (2.1%) had a variant of the t(9;22), 10 children (4.2%) had other additional cytogenetic (numerical/structural) abnormalities (ACA), and 2/239 (0.8%) had both. Characteristics of the patients and phase of the disease are reported in Table 1. In the 7 patients with variant t(9;22), one (chromosome 1 in 3 patients, chromosome 8 in 2 patients and chromosome 14 in one patient) or two further chromosomes (chromosomes 8 and 17) were involved in 6 and one patient(s), respectively. In the 12 patients with ACA, 9 patients have one type of ACA, 2 patients have 2 type of ACA and one patient have 3 type of ACA. Regarding the patients in chronic phase at diagnosis (n=219), the cumulative incidence of complete cytogenetic response at 18 months was 88% (95% CI: 82 % - 93%) and 70% (95% CI: 42% - 93%) for patients without variant t(9;22) or ACA and for those with variant t(9;22) and/or ACA (p=0.151), respectively. Three deaths were recorded (among them one patient had ACA at initial diagnosis). With a median follow up of 43 months (range 1 – 161) the probability of 3 years overall survival was 99% (95% CI: 94 % - 100%) and 88% (95% CI: 39 % - 98%) for patients in chronic phase without variant t(9;22) or ACA and for those with variant t(9;22) and/or ACA (p=0.042), respectively.
Conclusion. Additional chromosomal abnormalities at diagnosis in children with CML in chronic phase may have an impact on the outcome. A larger cohort of patient and a longer follow up is needed to confirm such findings.
Table 1. Cytogenetic No variant t(9;22) or ACA Variant t(9;22) ACA Variant t(9;22) and ACA Number of patients 222 5 10 2 Sex (% males) 56% 60% 50% 100% Median age, yrs (range) 12 (1-18) 14 (9-17) 12 (5-16) 6 and 17 Phase of the disease (n) chronic accelerated blastic 208 12 2 3 1 1 7 1 2 1 0 1
Acknowledgment: The I-CML Ped study is supported by an unrestricted grant from Novartis Pharmaceutical Company

Disclosures
No relevant conflicts of interest to declare.