A rare pediatric presentation of myeloproliferative neoplasm: unexpected diagnosis of chronic myeloid leukemia in a 4-year-old girl—a case report

Introduction

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm defined by the Philadelphia chromosome and the resulting BCR-ABL1 fusion. It accounts for fewer than 3% of all pediatric leukemias and is exceptionally rare in children younger than 5 years. Affected children may present with non-specific features such as fatigue, splenomegaly, and weight loss, or may be entirely asymptomatic, with the diagnosis prompted incidentally by leukocytosis on a routine complete blood count (CBC). In such asymptomatic patients the differential with a leukemoid or infection-related reaction can be challenging, and the dynamic behavior of morphological clues on the peripheral smear (most notably the trajectory of toxic granulation relative to the leukocyte count) can be diagnostically pivotal (1,2).

While CML is a well-recognized entity in adults, with a median age at diagnosis between 50 and 60 years, it is exceptionally rare in the pediatric population (3). Pediatric CML accounts for less than 3% of all childhood leukemias, with an estimated annual incidence of approximately 0.6–1.0 cases per million children under the age of 15 years (4,5). The incidence is even lower in very young children, with cases diagnosed under 5 years of age considered exceptional rarities (6). Most pediatric patients are diagnosed after the age of 8 years, with a slight male predominance (1).

The clinical presentation of pediatric CML can differ from that in adults. Children and adolescents often present with more aggressive disease features, including significantly higher white blood cell (WBC) counts, more pronounced splenomegaly, and lower hemoglobin levels (7). However, a subset of pediatric patients, particularly very young children, may be asymptomatic at diagnosis, with the abnormality discovered incidentally on routine blood tests. This asymptomatic presentation, coupled with hematologic findings that can overlap with common pediatric conditions, creates a significant diagnostic challenge. Marked leukocytosis with a left shift is frequently attributed to a leukemoid reaction secondary to infection or inflammation, which are far more prevalent in this age group (5).

Key hematologic clues that point toward CML, such as basophilia and the persistent absence of toxic granulation (or its rapid disappearance after a presumed infectious trigger has been treated) despite high and rising WBC counts, can be subtle and easily overlooked. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the management of CML, transforming it from a fatal disease requiring stem cell transplantation into a manageable chronic condition for most patients (8,9). Given the profound impact of early treatment on prognosis, timely and accurate diagnosis is crucial.

We report the case of a 4-year-old girl diagnosed with chronic-phase CML following an incidental finding of leukocytosis during a preoperative workup. This case underscores the diagnostic dilemma of differentiating reactive leukocytosis from an underlying myeloproliferative neoplasm in young children and highlights the importance of vigilant follow-up and appropriate molecular testing for persistent hematologic abnormalities.

Although pediatric CML has been increasingly reported, descriptions of asymptomatic CML diagnosed incidentally in preschool-aged children (<5 years) are scarce. The present report contributes a rare example in which the diagnostic pathway was uniquely informed by the temporal dissociation between toxic granulation (which resolved after antibiotics) and leukocytosis with basophilia (which paradoxically worsened). To our knowledge, this dynamic morphological clue has not been emphasized in previous pediatric reports and serves as a practical, smear-based signal to escalate to BCR-ABL1 testing in young children. The case also illustrates a rapid early molecular response on a standard imatinib dose, supporting the applicability of adult-derived response milestones to very young patients. We present this article in accordance with the CARE reporting checklist (available at https://aob.amegroups.com/article/view/10.21037/aob-2026-0022/rc).

Case presentation

A previously healthy 4-year-old girl (weight 13.6 kg, height 100 cm, body surface area 0.61 m²) was referred for preoperative evaluation prior to adenoidectomy for adenoid hypertrophy. She had no fever, bleeding, weight loss, night sweats, fatigue, hepatosplenomegaly, or lymphadenopathy. Routine preoperative CBC showed a WBC count of 30,000/µL (age-specific reference 5,500–15,500/µL) with neutrophilia, basophilia, monocytosis, an initial left shift with 1% blasts, and toxic granulation. Erythrocyte sedimentation rate (ESR) was within the normal range (6 mm/h; reference <15 mm/h). Given the marked leukocytosis with left shift and toxic granulation in the context of adenoid hypertrophy, a presumptive diagnosis of bacterial infection was made despite a normal ESR, and she received intravenous ceftriaxone for 2 days followed by oral cefdinir to complete a 5-day antibiotic course. An interim CBC after 2 days of intravenous ceftriaxone showed a transient decrease in the WBC count to 25,000/µL (Table 1). All procedures performed in this study were in accordance with the ethical standards of the institutional research committee at NMC Royal Hospital, Sharjah, UAE, and with the Helsinki Declaration and its subsequent amendments. Written informed consent for publication of clinical details and accompanying images was obtained from the patient’s parents/legal guardians. A copy of the written consent is available for review by the editorial office of this journal.

On repeat CBC at the end of the antibiotic course, the toxic granulation had disappeared, but the WBC count had paradoxically risen to 42,000/µL with persistent basophilia (absolute basophil count 1,763/µL; age-specific reference <100/µL) and a sustained left shift. This discordance between resolving morphologic signs of infection and worsening leukocytosis redirected the work-up toward a primary myeloproliferative neoplasm.

Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for BCR-ABL1 was positive at 100% on the International Scale (IS), identifying the major-breakpoint p210 transcript (e13a2). The peripheral blood smear demonstrated marked leukocytosis with a spectrum of granulocytic precursors at various stages of maturation (myelocytes, metamyelocytes, band and segmented neutrophils) together with basophilia, consistent with chronic-phase CML (Figure 1). Bone marrow aspirate and trephine biopsy showed a hypercellular marrow with marked granulocytic hyperplasia, 3% blasts, basophilia and eosinophilia—consistent with chronic-phase CML [<10% blasts per the 2022 World Health Organization (WHO) 2022 criteria]. Conventional karyotyping demonstrated t(9;22)(q34;q11), confirming the Philadelphia chromosome. Additional baseline ABL1 kinase domain mutation screening was not performed at diagnosis, in line with current guidelines that reserve mutation analysis for cases of inadequate response or loss of response on TKI therapy.

Figure 1 Peripheral-blood smear showing marked leukocytosis with myeloid left shift, absolute basophilia, and absence of toxic granulation at re-evaluation (original magnification ×1,000, Romanowsky stain).

Imatinib mesylate was initiated on 29/10/2025 at 200 mg orally once daily, corresponding to approximately 340 mg/m²/day for her body surface area (BSA) of 0.61 m². However, a repeat CBC after completion of the full 5-day antibiotic course revealed re-escalation of the WBC count to 42,000/µL with persistent basophilia and a sustained left shift, while the previously observed toxic granulation had completely disappeared (Figure 1).

Within 2 weeks, the WBC count normalized to 11,000/µL and the BCR-ABL1 transcript decreased to 2.6% IS (Table 1). Treatment was well tolerated, with no cytopenias or significant adverse events. A long-term monitoring plan was put in place: qRT-PCR monthly for the first 3 months and until achievement of major molecular response (MMR), then every 3 months thereafter, in accordance with the 2025 European LeukemiaNet recommendations (2) and the international pediatric chronic myeloid leukemia expert panel recommendations (10).

Table 1 summarizes the key laboratory parameters of the patient at different time points: at initial presentation, during and after antibiotic treatment, and following the initiation of imatinib therapy. The data illustrate the initial diagnostic challenges and the subsequent rapid response to targeted treatment.

Discussion

This case report describes an extremely rare presentation of CML in a 4-year-old girl, whose diagnosis was made incidentally. The case highlights several critical aspects of pediatric CML, including its rarity in very young children, the diagnostic challenge of distinguishing it from reactive conditions, and the efficacy of targeted therapy.

Epidemiology and clinical features of pediatric CML

CML is predominantly a disease of adulthood, and its occurrence in children is infrequent, representing only 2–3% of all pediatric leukemias (5). The incidence is lowest in the first decade of life, making a diagnosis in a 4-year-old child a notable event (6). While many pediatric patients present with classic symptoms such as fatigue, weight loss, and symptomatic splenomegaly, our patient was entirely asymptomatic, a presentation seen in up to 40% of cases, often discovered through routine blood work (10).

The absence of splenomegaly in our patient is also noteworthy, as splenomegaly is a common finding in pediatric CML, often more pronounced than in adults (7). This atypical, subtle presentation underscores the need for clinicians to consider CML even in the absence of its classic signs and symptoms.

The diagnostic dilemma: CML versus leukemoid reaction

The primary diagnostic challenge in this case was the differentiation of CML from a leukemoid reaction. A leukemoid reaction, defined as a reactive hyperleukocytosis exceeding 50,000/µL with a significant left shift, is a common response to severe infection, inflammation, or certain malignancies in children (5). Our patient’s initial presentation—marked leukocytosis, left shift, and toxic granulation in the context of adenoid hypertrophy—was highly suggestive of a reactive process. The initial management with antibiotics was therefore appropriate.

However, the failure of the leukocytosis to resolve, and its subsequent increase after the course of antibiotics, was the pivotal clue that pointed away from a transient reactive state and toward a primary bone marrow disorder.

Several hematologic features were critical in raising the suspicion of CML. First, the persistence of basophilia is a key hallmark of CML and is uncommon in typical leukemoid reactions (5). Second, the disappearance of toxic granulation while leukocytosis persisted indicated that the inflammatory stimulus had resolved, yet the myeloproliferation continued unabated. Third, the sheer magnitude and persistence of the left shift, including a small percentage of blasts, are more characteristic of a clonal disorder.

Other conditions in the differential diagnosis for a young child with myeloproliferation include juvenile myelomonocytic leukemia (JMML). However, JMML typically presents with monocytosis, hepatosplenomegaly, skin rash, and often features elevated fetal hemoglobin and the absence of the Philadelphia chromosome, none of which were consistent with our patient’s profile (11).

Ultimately, the definitive diagnosis of CML relies on the detection of the BCR-ABL1 fusion gene, making molecular testing indispensable when suspicion arises (12).

Diagnostic workup and prognostication

The diagnostic workup followed established guidelines, including a CBC with differential, bone marrow examination, cytogenetics, and molecular testing (13). The 2022 World Health Organization classification defines CML by the presence of the t(9;22)(q34.1;q11.2) translocation resulting in the BCR::ABL1 fusion gene (14). Our patient’s diagnosis was confirmed by both conventional karyotyping showing the Philadelphia chromosome and qRT-PCR detecting the BCR-ABL1 transcript.

The most critical prognostic indicators in the current era, for both children and adults, are the achievement of early treatment milestones. An early molecular response, defined as BCR-ABL1 transcript levels ≤10% IS at 3 months, is strongly associated with superior long-term outcomes, including higher rates of deep molecular response and better event-free survival (15,16). Our patient’s remarkable response, with a drop to 2.6% IS in just 2 weeks, is a highly encouraging prognostic sign.

Management and long-term considerations in pediatric CML

Imatinib remains the standard first-line TKI for chronic-phase pediatric CML at a usual dose of 260–340 mg/m²/day (8); our patient was started on 200 mg once daily, corresponding to approximately 340 mg/m²/day for her BSA of 0.61 m², which falls within this recommended range. Clinical trials in children have demonstrated efficacy and safety profiles comparable to those in adults (17,18). Our patient’s rapid early molecular response (BCR-ABL1 2.6% IS at 2 weeks) is consistent with the favorable kinetics generally reported in pediatric series and supports the applicability of adult-derived response milestones to very young children, while underscoring the need for vigilant long-term monitoring of growth, endocrine function, and bone health on prolonged TKI therapy (19).

While TKIs are highly effective, the prospect of lifelong therapy starting from a young age raises unique long-term concerns. The most well-documented long-term side effect in prepubertal children is growth retardation, as these agents can interfere with bone metabolism and growth plate function (20).

The success of therapy has also opened the door to the possibility of treatment-free remission. Data on treatment-free remission in children are emerging and appear promising, offering the potential to avoid lifelong therapy and its associated toxicities.

This case serves as a powerful reminder for pediatricians and hematologists to include CML in the differential diagnosis of any child with persistent, unexplained leukocytosis, even if they are asymptomatic and very young. A simple peripheral blood smear review by an experienced hematopathologist, followed by definitive molecular testing, can prevent diagnostic delays and ensure the timely initiation of therapy.

Limitations

Several limitations of this report should be acknowledged. First, this is a single-patient case report, which limits generalizability. Second, although the patient has now completed 9 months of imatinib therapy with a sustained response, the follow-up remains relatively short, and longer-term confirmation of sustained deep molecular response will require ongoing observation according to the schedule outlined above.

Conclusions

We have presented a case of Philadelphia chromosome-positive CML in a 4-year-old girl, a diagnosis that is exceptionally rare in this age group. The disease was discovered incidentally during a preoperative assessment, and its initial hematologic features mimicked a reactive leukemoid state, highlighting a critical diagnostic pitfall in pediatric practice. The persistence of marked leukocytosis with basophilia, despite the resolution of potential infectious triggers, was the key indicator that prompted further investigation and led to the correct diagnosis. This case underscores that CML can present subtly in young children without the classic constitutional symptoms or splenomegaly.

A high index of suspicion and careful interpretation of peripheral blood smear findings are essential for early detection. The rapid and profound hematologic and molecular response to therapy observed in our patient reaffirms the transformative impact of treatment in the management of pediatric CML. Early diagnosis and treatment are paramount to optimizing long-term outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://aob.amegroups.com/article/view/10.21037/aob-2026-0022/rc

Peer Review File: Available at https://aob.amegroups.com/article/view/10.21037/aob-2026-0022/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://aob.amegroups.com/article/view/10.21037/aob-2026-0022/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee at NMC Royal Hospital, Sharjah, UAE, and with the Helsinki Declaration and its subsequent amendments. Written informed consent for publication of clinical details and accompanying images was obtained from the patient’s parents/legal guardians. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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