Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia

Meinolf Suttorp,Stephanie Sembill,Markus Metzler,Frédéric Millot,Hélène Deutsch

doi:10.3390/cancers13040798

Meinolf Suttorp, Stephanie Sembill + Show 3 more

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https://doi.org/10.3390/cancers13040798

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Abstract

Simple SummaryThe low incidence (1:1,000,000) of chronic myeloid leukemia (CML) in the first two decades of life presents an obstacle to accumulation of pediatric experience and knowledge on this leukemia. Biological features of CML are shared but also differing between adult and pediatric patients. This review aims; (i) to define the disease based on an unified terminology, (ii) to list the diseases to be considered as a differential diagnosis in children, (iii) to outlines the morphological, histopathological and immuno-phenotypical findings of pediatric CML, (iv) to illustrate rare but classical complications resulting from high white cell and platelet counts at diagnosis, and (v) to recommend a uniform approach for the diagnostic procedures to be applied. Evidently, only a clear detailed picture of all relevant features can lay the basis for standardized treatment approaches.Depending on the analytical tool applied, the hallmarks of chronic myeloid leukemia (CML) are the Philadelphia Chromosome and the resulting mRNA fusion transcript BCR-ABL1. With an incidence of 1 per 1 million of children this malignancy is very rare in the first 20 years of life. This article aims to; (i) define the disease based on the WHO nomenclature, the appropriate ICD 11 code and to unify the terminology, (ii) delineate features of epidemiology, etiology, and pathophysiology that are shared, but also differing between adult and pediatric patients with CML, (iii) give a short summary on the diseases to be considered as a differential diagnosis of pediatric CML, (iv) to describe the morphological, histopathological and immunophenotypical findings of CML in pediatric patients, (v) illustrate rare but classical complications resulting from rheological problems observed at diagnosis, (vi) list essential and desirable diagnostic criteria, which hopefully in the future will help to unify the attempts when approaching this rare pediatric malignancy.

Highlights

For a long time, the rarity of chronic myeloid leukemia (CML) in minors has hampered the accumulation of in-depth knowledge from cases presenting in the first two decades of life
Given the enormous improvement of therapeutic success achieved by tyrosine kinase inhibitors (TKI), the interest in the long-term outcome of this novel treatment especially in pediatric patients resulted in foundation of the International Registry on Pediatric CML (IR-PCML) at Poitiers/France in the year 2010 [4]
This article, as the first part of a series on pediatric CML, aims to provide precise definitions and to unify the terminology in relation to the World Health Organization (WHO) International Classification of Diseases (ICD) codes and the methods applied for diagnosis of pediatric CML

Summary

Introduction

The rarity of chronic myeloid leukemia (CML) in minors has hampered the accumulation of in-depth knowledge from cases presenting in the first two decades of life. Given the enormous improvement of therapeutic success achieved by TKIs, the interest in the long-term outcome of this novel treatment especially in pediatric patients resulted in foundation of the International Registry on Pediatric CML (IR-PCML) at Poitiers/France in the year 2010 [4]. The information depicted from a registry on a rare disease like CML in minors offers the enormous benefit to enable treating physicians to apply a uniform approach to diagnose and follow-up this leukemia. Based on the collected data and the shared experience in very small subcohorts (e.g., CML at very young age, diagnosis in advanced stage of disease, treatment failure) this article recommends a uniform approach for the diagnostic procedures to be applied in the management of CML in children and young adolescents

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