Chronic myeloid leukaemia (CML) is a clonal illness that affects all hematopoietic stem cell lineages. CML often affects individuals between the age group of 60 and 65 in western countries whereas it affects age group of 40-60 years in Indian scenario. Although it can present in paediatric age group but this is rare in India. (1) CML constitutes 2% of all leukaemia in less than 15 years of age and 9% of all leukaemia between 15 and 19 years of age. The annual incidence rates for these two age groups are 1 and 2.2 cases per million, respectively. (2) Paediatric CML differs biologically and clinically from adult CML and presents with higher leukocyte count and symptoms related to splenomegaly. (3) Paediatric CML has a faster progression; higher risk of accelerated/blast phase whereas adult CML shows a slower disease course. Krumbholz M et al have shown that breakpoint distribution in BCR is different in paediatric CML compared with adult CML. These differences in the genomic landscape may contribute to the more aggressive clinical characteristics in paediatric CML compared with adult CML. (4) Children have immature skeletons and longer life expectancies than adult patients, and the current standard practice of continuing TKI indefinitely can lead to significant long-term morbidities in growing children. Taking into account all of these issues, it is clear that an important goal of paediatric CML management should be the avoidance of lifelong treatment with TKIs. One potential solution is to stop TKIs after a certain period of deep molecular remission. (5) We present series of paediatric CML in 5 children which adds useful insights into this rare disease in our setting.

Case 1: A 16-year-old boy presented with weight loss in the last 2 months. On examination splenomegaly was present. Case 2: A 15-year-old male presented with complaints of generalized weakness and pain in the lower and upper limbs for 3 months. On examination hepatosplenomegaly was present. Case 3: A 10-year-old boy presented with complaints of fever for 10 days with generalized weakness. On examination no organomegaly or lymphadenopathy present. Case 4: A 14-year-old girl presented with complaints of fever on and off, cough, generalized weakness and reduced appetite since last 6 months. On examination splenomegaly was present. Case 5: A 12-year-old female presented with complaints of generalized weakness for one week. On examination hepatosplenomegaly was present. Clinical features. Complete blood count (CBC) findings and Peripheral blood Film findings are shown in table 1 and 2. Bone marrow aspiration and trephine biopsy examination in all the five patients revealed hypercellular bone marrow with relative erythroid hyperplasia, myeloid predominance with blast count < 5% and adequate to increased megakaryocytes. Dwarf megakaryocytes were seen in all five bone marrows. BCR/ABL fusion was positive in all the patients (5/5, 100%). Table1: Clinical features in Pediatric CML cases Cases Age/Sex Fever Weight loss Generalized weakness Splenomegaly Hepatomegaly 1. 16Y/M Absent Present Absent Present Present 2. 15Y/M Absent Absent Present Present Present 3. 10Y/M Present Absent Present Absent Absent 4. 14Y/F Present Absent Absent Absent Present 5. 12Y/F Absent Absent Present Present Present Table 2: CBC and Peripheral blood findings Cases Hb (g/dL) TCL (/cu.mm) Platelets (/cu.mm) Blasts Left shift Basophilia Eosinophilia 1. 7.7 3,86,000 5,49,000 2% Present Present Present 2. 13.2 3,16,000 4,68,000 4% Present Present Present 3. 10.9 40,200 6,32,000 0% Present Present Present 4. 7.6 3,64,400 7,03,000 3% Present Present Present 5. 8.2 4,45,500 3,49,000 3% Present Present Present

Chronic Myeloid Leukemia (CML) in children is uncommon, comprising about 2-3% of all childhood leukemias, and has distinct clinical, hematologic, and morphologic features, especially at presentation, compared to adults. Our findings, while based on a small cohort, are largely consistent with the clinical and hematological characteristics described in larger paediatric CML series, while also highlighting some subtle distinctions. (6) The median age of presentation of our patients (14 years) is similar to that reported by Dinesh C et al. who also noted a median age of 16 years at diagnosis. (7) We noted a male preponderance with male to female ration of 2:1 which was similar to the findings by Dinesh et al who reported male to female ratio of 2.6:1. We observed that the constitutional symptoms like generalized weakness in 60% patients (3/5), fever was seen in 40 % patients (2/5) and weight loss was seen in only 20% (1/5) patients which is a lower frequency than some reports in adult populations but is within the range seen in other paediatric series. (7) The heterogeneity of presenting symptoms further emphasizes the need for a high index of suspicion in children with unexplained organomegaly and or cytoses. Clinically, 60% (3/5) of our patients had the most common finding of splenomegaly, a hallmark sign of CML while Madabhavi I et al found splenomegaly in all the patients (8). The initial laboratory findings from the complete blood count (CBC) and peripheral blood smears in our patients were characteristic of the chronic phase of CML. All five patients exhibited leucocytosis with a left-shifted myeloid series, including the presence of myelocytes, metamyelocytes, and an absolute eosinophilia and basophilia. The WBC count was very high in 4 out of 5 patients (80%) i.e. > 3,00,000/cu.mm which was similar to the finding by Tanizawa who also noted high WBC count of (median WBC=3,10,000/cu.mm). Platelet counts were elevated in all five patients, a finding consistent with the thrombocytosis commonly associated with CML. In our study, the peripheral smear also revealed a minimal percentage of blasts (<5%), confirming the chronic phase of the disease. This was in contrast to Pushpam D et al who observed higher percentage of blasts. (9) Bone marrow examination was pivotal for confirming the diagnosis and assessing the disease phase in all our cases. The bone marrow was consistently hypercellular with relatively depressed erythropoiesis, marked myeloid predominance and a characteristic decrease in the myeloid-to-erythroid ratio. Megakaryocytes were adequate to increase with presence of dwarf megakaryocytes. These morphological findings are considered classical for CML and were mirrored in our patient cohort. The absence of a significant increase in blasts (<5%) in the bone marrow was a critical finding that further supported the diagnosis of chronic-phase CML in all our patients (100%, 5/5) whoever Sangita V et al noted Chronic phase of CML in 79.5% (35/44) patients. (10) These bone marrow findings, combined with the peripheral blood features, provide a comprehensive picture of the disease state and are essential for guiding initial management and prognostication.

In conclusion, the clinical, hematological, and bone marrow findings in our paediatric CML case series are largely congruent with the established literature on the disease. The consistent presentation of splenomegaly, leucocytosis with left shift, and characteristic bone marrow changes underscores the reproducibility of these diagnostic features even in a small cohort. While the rarity of the disease in children makes large-scale studies challenging, small case series like this one are vital for adding to the collective knowledge base. Our findings reinforce the importance of a meticulous evaluation of both peripheral blood and bone marrow morphology in the diagnosis of CML in the paediatric population. Further research, particularly multi-institutional collaborations, is necessary to better understand the long-term outcomes and treatment responses in this distinct patient group.

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