Chronic myeloid leukemia in a pediatric population in the Congo

Chronic myeloid leukemia (CML) is a positive Philadelphia chromosome clonal myeloproliferative disorder that affects mostly in adulthood. It is rare among children and accounts for 2-3 % of all childhood leukemia (1). Even though CML pediatric and adult population share the same fusion gene BCRABL, Krumbholz, et al have shown that breakpoint distribution in BCR in children is different than adult (2). Besides pediatric CML compared to adult one is described as more aggressive (3). Imatinib is, as in adults, an effective first line treatment in children and adolescents with CML (1). It has showed impressive complete cytogenetic response rates (1). In our knowledge only one study has described specifically the CML pattern in pediatrics population in Sub Saharan Africa (4). We are complementing it by describing the clinical, biological pattern of CML in children as well their response and adherence to imatinib. Patients and Methods


Results
Clinical and biological characteristics are shown in the table 1.Four children (7.69%) on 55 patients with chronic myeloid leukemia were included in the study.They were two males and two girls with an average age of 13.75 years (range 11.6 and 16.3 years).The delay diagnosis was 4 months (range 1 and 6 months).Abdominal pain was the most common symptoms.All patients presented a splenomegaly with a median size of 16.75 cm (range 14 and 19 cm).
Initial cell blood counts accounted for an average leukocytosis at 133.37 G/L (range 60.7 and 219 G/L).At the differential, blast accounted in average for 2.3% (range 1 and 5%).
All patients presented at the chronic phase.
Imatinib was initiated at 400 mg daily for all patients.The median time to achieve a complete hematological response was 8 weeks (4 and 9.5 weeks).All patients were not adherent to imatinib.They discontinued their treatment on themselves without the agreement of their medical providers.The average duration of the discontinuation was 98 non cumulative days (range 90 and 128 days).
At 6 months three patients (75%) showed minor cytogenetic responses and one (25%) did not respond to the treatment.

Discussion
Pattern of CML in the African continent have been broadly reported, however most of them were focused on the adult population.CML in children remain unexplored (4).Few reports in the region have been published.To our knowledge, no one of them debates the topic of adherence to the treatment (4,6).CML is also in the African continent a rare blood disorder in the childhood.In the Hematology department in Brazzaville, which is the unique department that manages hematological malignancies in the country, it constitutes 7.69% on a cohort of 52 patients.In Senegal CML in children accounts for 11% in and 1.2% in eastern India (4,7).
It appears that preteens and teenagers are more affected by CML in the pediatric population with an average age that ranges from 11.5 to 16 years (4,6,7).
Children from low and middles resources countries are older at the time of the diagnosis due to the long delay diagnosis of the CML (8,9).Consequent to the tardy diagnosis, children present with abdominal pain and voluminous splenomegaly that can confuse physicians to tropical splenomegaly in our region.They also have elevated white blood cell (WBC) counts.Fall et al showed an average count of 244G/L of WBC and a moderate anemia (4).Thrombocytosis is rare in children (3).Despite delayed diagnosis of the CML, children as well as adults in our cohort present at the hospital at chronic phase of the disease (8).
Cytogenetic responses monitored at 6 months of treatment showed poor performance of imatinib in our series since none complete cytogenetic responses (CCR) were noticed.El-Affy, Fall and Rault et al reported respectively 53, 55 and 75% of complete cytogenetic responses (4,6,7).Nonetheless, we should be cautious while comparing these rates.Indeed when we peruse the results of Rault et al, we can read that at 6 months of the treatment, the CCR was monitored only on 4 patients over 9 and sole one patient (25%) showed a CCR (7).Opimal response to imatinib is lower in the pediatric when we compare with adults (4).Poor adherence of children mainly adolescent is usually reported as cause of this low performance (10).

Conclusion
Chronic myeloid leukemia in children is a rare in the Congo.It shares clinical and biological feature with adults.However, the lower performance of the imatinib in this population related in some part to the poor adherence of the treatment, request specific interventions and management by the medical team.