Discussion:
Pediatric chronic myeloid leukemia (PCML) is a rare hematologic
malignancy in children (2-3% of pediatric leukemias) [1], resulting
from clonal expansion of granular lineage progenitors leading to an
accumulation of immature, non-functioning myeloid cells. CML tumor cells
are characterized by a t (9; 22) translocation, which leads to the
formation of the Philadelphia (ph) chromosome. This translocation, which
leads to the formation of the BCR-ABL fusion gene, is responsible for
the disease through its dysregulated tyrosine kinase activity [2,3].
The diagnosis of pediatric CML is based on clinico-biological data: the
disease can be revealed by isolated splenomegaly or associated with
hepatomegaly with other lymph node and visceral determinations in the
advanced phases. It comprises three evolutionary phases: a first chronic
phase of progressive installation which can be asymptomatic in many
patients at the time of diagnosis suspected in front of a haemogram
which shows a hyperleukocytosis, usually higher than 250,000/mm³,
thrombocytosis in 30 to 50% of the cases with basophilia on the
myelogram, a hyper-cellularity with an increase in the ratio of
erythroblasts to granules and in the number of megakaryocytes, and less
than 10% of blasts and promyelocytes. The first case of our observation
was diagnosed at the chronic stage by a clinical and biological picture
in favor of the disease. Accelerated phase characterized by the presence
of blood or marrow blasts lower than 20% with blood basophilia higher
than 20% and thrombocytopenia lower than 100,000/mm³ not related to the
treatment, this phase corresponds to the transition between the chronic
phase and the blastic phase being then explosive defined by the presence
of more than 20% of marrow blasts [4,5]. The immunophenotypic study
by flow cytometry makes it possible to confirm the acutisation and the
myeloid or lymphoid nature of the blasts, as in the case of the second
observation diagnosed for pediatric CML in the acutisation phase with
36% of blasts of a myeloid nature with strong expression of the
CD13CD33CD117 markers and a postive myeloperoxidase (Egil score greater
than 2 in favour of the myeloid lineage).
The biological diagnosis is based on the realization of the haemogram,
the key examination allowing to evoke the diagnosis by the
hyperleucocytosis, observed in the two cases of our observation with a
normochromic normocytic anaemia and a thrombopenia. The myelogram shows
a hypercellular marrow with marked granular hyperplasia and the presence
or absence of blasts to confirm the phase of the disease.
The cytological study is completed by the genetic study, a fundamental
tool of the diagnosis by the realization of a RT-PCR (reverse
transcriptase polymerase chain reaction) which highlights the BCR-ABL1
fusion transcript in the medullary or peripheral blood, indispensable
test for diagnosing pediatric CML and which allows the differential
diagnosis with juvenile myelomonocytic leukemia: borderline entity
between myelodysplastic syndrome and myeloproliferative syndrome with
the presence of cytological signs of myelodysplasia and hyperleukytosis,
with reactive myelmia and with acute lymphocytic leukemia with
Philadelphia chromosome in the acute phase.
The treatment of pediatric CML is based primarily on the use of tyrosine
kinase inhibitors such as imatinib, which is currently considered the
best treatment for CML, even though it poses significant side-effect
problems, including growth restriction and the possibility of developing
resistance to the treatment, which has an impact on the treatment
decision. However, in case of treatment failure, the research of other
mutations of the tyrosine kinase domain is recommended in view of the
new therapeutic possibilities [6, 7].