Cervical Lymphadenopathy in Concomitant CML and Tuberculosis: A Case Report Open Access

Chronic myeloid leukemia (CML) is one of the most well-known MPNs, marked by the dysregulated proliferation of granulocytes in the bone marrow and the presence of the Philadelphia chromosome, which results from the BCR::ABL1 translocation. CML typically progresses through chronic, accelerated, and blast phases, with lymphadenopathy being an uncommon finding in the chronic phase unless there is extramedullary hematopoiesis or disease progression [1].

Tuberculosis (TB) ranks among the leading causes of mortality attributable to a single infectious agent, with approximately one-third of the global population estimated to have been exposed to TB bacteria and potentially infected. Furthermore, South Asia has the highest TB burden with 587 million of 1.7 billion cases (45%) according to the 2023 WHO report. Given the high incidence of TB in such areas, it is crucial to consider TB in the differential diagnosis when CML patients present with lymphadenopathy. Although lymphadenopathy is uncommon in the chronic phase of CML, it may be seen during the blast phase or in cases with concurrent diseases, such as TB or lymphoma [2, 3].

The management of CML primarily involves tyrosine kinase inhibitors (TKIs). However, managing CML concurrently with TB poses a significant therapeutic challenge due to the potential interactions between TKIs and anti-TB medications, such as rifampicin and isoniazid. Despite the clinical importance of this scenario, guidelines addressing this overlap are lacking [4, 5].

This case report highlights the complexities of managing CML with concurrent TB, presenting the case of a 35-year-old male with chronic-phase CML who presented with left cervical lymphadenopathy. Initially presumed to be a manifestation of CML, further evaluation, including a lymph node biopsy, confirmed a diagnosis of TB. The treatment regimen was subsequently adjusted to address both CML and TB. Following this tailored approach, the lymphadenopathy resolved, and CML remained in remission. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000546368).

A 35-year-old Asian male with no significant past medical history presented with progressive swelling in the left cervical region that had been increasing in size over 3 months. The swelling was painless and not associated with systemic symptoms such as fever, night sweats, or weight loss. He denied any recent travel history, exposure to known TB cases, or significant occupational or environmental exposures. On physical examination, a firm, non-tender lymph node measuring approximately 3 × 2 cm was identified in the left cervical region, with no other palpable lymphadenopathy or organomegaly.

Initial laboratory investigations revealed leukocytosis, with a white blood cell count of 120 × 10⁹/L and a differential count showing an elevated proportion of myeloid precursors. Peripheral blood smear demonstrated a left shift with increased basophils and myeloblasts, raising suspicion for a myeloproliferative disorder. Bone marrow aspiration and cytogenetic analysis confirmed the diagnosis of chronic-phase CML, with the presence of the Philadelphia chromosome (t[9;22][q34;q11]) and BCR::ABL1 fusion on molecular testing.

The cervical lymphadenopathy was initially thought to represent extramedullary blast phase of CML, a rare but recognized presentation according to the WHO classification. However, as there was no improvement after 4 months of treatment with imatinib, a biopsy was performed for further evaluation. A lymph node biopsy revealed caseating granulomas on histopathology, consistent with TB. Mycobacterium tuberculosis was diagnosed through acid-fast bacilli (AFB) smear, polymerase chain reaction (PCR), and culture. Pulmonary TB was excluded through sputum analysis and imaging studies.

The patient was started on a standard four-drug anti-TB regimen, including rifampicin, isoniazid, pyrazinamide, and ethambutol. Recognizing the potential interaction between rifampicin and imatinib, the TKI dose was increased to 600 mg daily. The patient tolerated the adjusted regimen well, with no significant adverse effects or hepatotoxicity.

On regular follow-up, the patient demonstrated complete resolution of cervical lymphadenopathy and achieved hematological remission. Major molecular remission, with a corresponding BCR-ABL1 transcript level of ≤0.1%, was achieved at 6 months. He remained adherent to his anti-TB therapy and imatinib regimen, with regular monitoring scheduled every 3 months to ensure continued disease control.

CML is a myeloproliferative neoplasm caused by the Philadelphia chromosome, a genetic translocation (t(9;22)(q34;q11.2)) that fuses the ABL1 gene on chromosome 9 with the BCR gene on chromosome 22, producing the BCR::ABL1 oncoprotein [6]. CML typically presents in middle-aged to older adults, but it occurs at an earlier age in African and Asian populations, who are often diagnosed at more advanced stages, particularly during the blast phase, necessitating more aggressive treatment [7]. Compounding the challenge, these regions also bear the majority of the global TB burden, creating additional therapeutic complexities for CML patients with concurrent TB [8].

The relationship between TB and CML is not fully understood, although geographic and socio-economic factors may contribute to this complex association. Liu et al. [3] observed that the incidence of TB is significantly higher in male CML patients aged 60 and older, as well as in those who have undergone stem cell transplantation or interferon-α therapy. In a similar vein, Silva et al. [9] identified factors such as malnutrition, fludarabine use, and steroid therapy as contributing to increased TB rates in CML patients through multivariate analysis. Furthermore, several studies and case reports suggest that TKIs, particularly imatinib, can lead to the reactivation of TB [10‒12]. This reactivation is thought to result from TKI-induced alterations in the T-cell-mediated immune response, as evidenced by in vitro studies. TKIs weaken T cells’ ability to fight Mycobacterium tuberculosis, reducing their activity and cytokine release. Despite this, it helps control Mycobacterium tuberculosis growth in infected macrophages by enhancing lysosomal acidification, showing the importance of innate immunity [13, 14].

Lymphadenopathy in CML patients is an unusual finding that requires further investigation. It may indicate progression to the blast phase, necessitating more intensive treatment, or could be associated with secondary malignancies, such as lymphomas, as documented in several case reports [4, 15, 16]. Notably, lymphadenopathy has been linked to the use of dasatinib, one of the TKIs, but has not been reported with other TKIs [17]. While mycobacterial infections are frequently associated with TB, solitary lymphadenopathy in CML patients is a rare occurrence, presenting diagnostic and therapeutic challenges, as observed in previous studies [18, 19].

Patients starting on imatinib often require dose adjustments when undergoing treatment with rifampicin-based anti-TB regimens. Rifampicin is a strong inducer of cytochrome P450 3A4 (CYP3A4), the enzyme primarily responsible for metabolizing imatinib. Co-administration of rifampicin with imatinib leads to a significant reduction in imatinib plasma levels, potentially decreasing its therapeutic efficacy. Studies have shown that rifampicin can reduce imatinib exposure (measured as area under the curve) by up to 74%. To counteract this effect, increasing the imatinib dose by 50–100% is recommended, depending on the clinical response and tolerance of the patient [19, 20].

This case underscores the diagnostic and therapeutic challenges of managing CML with concurrent TB, highlighting the need for careful dosing adjustments of TKIs when combined with anti-TB medications. Early diagnosis and proper management of both conditions are crucial for optimal outcomes.

The case was approved by Hamad Medical Corporation Medical Research Center (MRC-4-25-012) and the patient signed written informed consent for the publication of any potentially identifiable images or data included in this article.

On behalf of all authors, the corresponding author states that there is no conflict of interest to declare.

The study will be funded by Qatar National Library if accepted.

Conception and design of the study: Dr. A. Alshurafa and Dr. M. Yassin. Acquisition of data and drafting the manuscript: Dr. A. Alshurafa and Dr. A. Aziz. Revising the manuscript for intellectual content: Dr. A. Aziz and Dr. M. Yassin. Approval of the version of the manuscript to be published: Dr. A. Aziz, Dr. A. Alshurafa, and M. Yassin.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.