Concurrent Chronic Myeloid Leukemia and Chronic Lymphocytic Leukemia at Initial Presentation: A Case Report and Review of the Literature

Abstract

Introduction

Concurrent chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) in the same patient are rare and may be overlooked when leukocytosis is attributed to a single hematologic process. We report a case of synchronous CML and CLL identified at initial presentation, highlighting the diagnostic value of integrating morphology, immunophenotyping, cytogenetics, and molecular testing.

Case Presentation

A 44-year-old man presented with progressive weight loss and back pain and was found to have leukocytosis with neutrophilia, absolute lymphocytosis, eosinophilia, and basophilia. Peripheral blood smear and flow cytometry supported CLL, whereas reverse-transcription polymerase chain reaction and cytogenetics demonstrated e13a2 BCR::ABL1 and t(9;22)(q34;q11.2), confirming concomitant CML in chronic phase. Bone marrow examination showed hypercellularity with granulocytic hyperplasia and nodular lymphoid infiltrates, and fluorescence in situ hybridization detected 13q14.3 deletion in the lymphoid clone. Imatinib 400 mg daily was initiated but was replaced with dasatinib 100 mg daily because of intolerance. At 14 months of follow-up, the patient remained clinically stable on dasatinib, with early molecular response at 3 months and major molecular response at 12 months, while the CLL remained under observation without indication for CLL-directed therapy.

Conclusion

This case highlights the diagnostic complexity of synchronous hematologic malignancies and the importance of comprehensive multimodal evaluation when clinical, morphologic, and laboratory findings are not fully explained by a single diagnosis. Treating the clinically dominant clone while monitoring the second clone may be appropriate when the latter is asymptomatic.

Introduction

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion gene created by the Philadelphia chromosome translocation t(9;22)(q34;q11.2) [1]. Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by a clonal population of mature CD5-positive B lymphocytes with a highly variable clinical course [2].

The coexistence of CML and CLL in the same patient is rare and has been described mainly in isolated case reports and small series [3–11]. Reported patterns include CLL preceding CML, CML preceding CLL, and synchronous presentation. Because treatment decisions are usually disease-specific, prompt recognition of both clones is important when the blood count, smear, or marrow findings are not fully explained by a single diagnosis. Most published cases involve older patients and sequential rather than synchronous presentation, and management guidance remains limited when both clones are identified at diagnosis. We report a patient with synchronous CML and CLL identified at initial presentation and provide a focused review of the published literature.

Case Presentation

A previously healthy 44-year-old man presented with progressive weight loss and back pain for 5 months. He reported an 8-kg weight loss during the 3 months before presentation. He denied fever, night sweats, or other constitutional symptoms. On examination, his oral temperature was 36.6°C, heart rate was 97 beats/min, respiratory rate was 17 breaths/min, blood pressure was 139/96 mm Hg, and oxygen saturation was 99% on room air. He had splenomegaly and generalized lymphadenopathy.

Initial laboratory investigations are summarized in Table 1. The results demonstrated leukocytosis with neutrophilia, absolute lymphocytosis, eosinophilia, and basophilia without anemia or thrombocytopenia.

Table 1.

Initial laboratory investigations

Test	Result	Unit	Normal reference range
Leukocyte count	39.3	× 109/L	3.5–10.8
Neutrophils (absolute)	18.9	× 109/L	1.8–7.7
Lymphocytes (absolute)	12.6	× 109/L	1.0–4.8
Monocytes (absolute)	0.8	× 109/L	0.1–0.9
Eosinophils (absolute)	1.18	× 109/L	0.0–0.5
Basophils (absolute)	1.96	× 109/L	0.0–0.1
Hemoglobin	14.2	g/dL	13.5–17.5
Platelet count	349	× 109/L	150–400

Bone marrow aspirate and biopsy demonstrated a hypercellular marrow with increased granulopoiesis, decreased erythropoiesis, and nodular lymphoid infiltrates (Fig. 1, 2). Immunostains highlighted the distinct myeloid and lymphoid marrow components (Fig. 3). Reverse-transcription polymerase chain reaction detected the e13a2 BCR::ABL1 fusion transcript. Testing for JAK2 and CALR was negative. Immunophenotyping identified a clonal B-cell population expressing CD19, CD20 (dim), CD5, CD23, CD43, CD200, IgD, and IgM with lambda light-chain restriction; partial expression of CD79b and FMC7 was present in a minority of monotypic cells. Cytogenetic analysis showed 46,XY,t(9;22)(q34;q11.2)[16]/46,XY[25]. Fluorescence in situ hybridization demonstrated deletion of 13q14.3 (D13S319) in 48% of analyzed cells. These findings established concomitant CML in chronic phase and CLL/small lymphocytic lymphoma involving the bone marrow.

Fig. 1.

Bone marrow aspirate showing increased small mature lymphoid cells with occasional smudge cells (red arrow) and left-shifted granulocytic forms with basophils/eosinophils (blue arrows).

Fig. 2.

Bone marrow biopsy showing hypercellular marrow with nodular lymphoid infiltrates (orange arrows) and granulocytic hyperplasia (green arrow). Insets show monotonous small lymphoid cells and diffuse granulocytic proliferation.

Fig. 3.

Immunostains highlighting distinct marrow components in concurrent CML and CLL. a Myeloperoxidase staining highlights granulocytic hyperplasia. b CD61 demonstrates increased megakaryocytes, including dwarf forms. c CD20 highlights nodular B-cell infiltrates. d CD5 shows positive staining in the lymphoid infiltrates, supporting CLL.

The patient was started on imatinib 400 mg orally once daily. Because of intolerance, including dysgeusia and additional weight loss, treatment was changed to dasatinib 100 mg once daily. He remains on dasatinib and is tolerating it well. At 14 months of follow-up, his weight improved from 61 kg before treatment to 71 kg, and his back pain significantly improved. The most recent complete blood count showed a leukocyte count of 16 × 10⁹/L, with an absolute neutrophil count of 1.9 × 10⁹/L, absolute lymphocyte count of 13.1 × 10⁹/L, monocytes 0.6 × 10⁹/L, eosinophils 0.3 × 10⁹/L, basophils 0.3 × 10⁹/L, hemoglobin 15.2 g/dL, and platelet count 321 × 10⁹/L. Serial quantitative BCR::ABL1 monitoring demonstrated an early molecular response at 3 months (≤10% IS) and major molecular response at 12 months (≤0.1% IS). The persistent absolute lymphocytosis was considered consistent with the untreated CLL clone. As the patient remained clinically stable without clear indications for CLL-directed therapy, the CLL continued to be managed with watchful waiting.

Discussion and Literature Review

This case highlights the importance of reconsidering a unifying diagnosis when the differential count, peripheral smear, flow cytometry, and marrow findings point to more than one hematologic process. In our patient, absolute lymphocytosis with a characteristic monotypic CD5-positive/CD23-positive B-cell population supported CLL/small lymphocytic lymphoma, whereas neutrophilia, eosinophilia, basophilia, and detection of BCR::ABL1 established concomitant CML in chronic phase [1, 2].

The coexistence of CML and CLL is rare. A non-systematic review of published case reports and small series was performed to contextualize the present case. A recent published blood/ASH conference abstract summarizing reported cases identified 26 cases in the literature [12]. In that pooled cohort, the mean age was 63.1 years and men were slightly predominant. CLL preceded CML in 50% of cases, synchronous presentation accounted for 27%, and CML preceded CLL in 23%. Among reports with available data, splenomegaly was present in 62% and B symptoms in 57%, underscoring both the heterogeneity of presentation and the fact that most reported patients were older than our patient [12]. Published case reports and small series likewise show that diagnosis usually depends on integrating morphology, immunophenotyping, cytogenetics, and molecular testing [3–11]. A focused review of selected individual reports is summarized in Table 2.

Table 2.

Selected published reports of concomitant CML and CLL

No.	Citation	Pattern	What was reported	Practice message
[3]	Bhagavathi et al. [3] (2008)	CML before CLL	A 71-year-old man developed CLL 7 years after Philadelphia chromosome-positive CML in morphologic, cytogenetic, and molecular remission; molecular studies supported separate myeloid and lymphoid clones	Distinct genomic findings can support independent clonal origins
[4]	Katović et al. [4] (2010)	Synchronous	A simultaneous diagnosis of CLL and CML was established in a previously healthy 50-year-old man; the patient remained clinically well at 4 years	Simultaneous presentation can follow an indolent course
[5]	Rahman et al. [5] (2013)	Synchronous	Abnormal differential-count findings prompted immunophenotyping and cytogenetic testing; early hematologic improvement was reported after TKI therapy	Multimodal workup helps avoid missed dual diagnoses
[6]	Crişan et al. [6] (2015)	CML before CLL	CLL was diagnosed 60 months after CML, while the myeloid clone was in complete cytogenetic and major molecular response; progressive CLL later required treatment	Control of one clone does not preclude later expansion of the second clone
[7]	Boddu et al. [7] (2019)	Mixed patterns	Two additional cases illustrated heterogeneous temporal patterns of coexisting CML and CLL and emphasized individualized management when both diseases coexist	Co-occurrence may be sequential or synchronous and management must be tailored to the clinically dominant clone
[8]	Armarego et al. [8] (2021)	CLL before CML	In a five-patient series, all patients had preceding CLL, all received TKIs for CML, none required subsequent CLL therapy, and all remained alive with molecular response	Treating the dominant clone may allow observation of the second disease
[9]	Przespolewski et al. [9] (2023)	Synchronous	Concomitant venetoclax and imatinib were used successfully when treatment for both CLL and CML was required	Dual targeted therapy can be feasible with careful interaction monitoring
[10]	James et al. [10] (2024)	CML before CLL	A patient with imatinib-treated CML subsequently required ibrutinib for high-risk CLL, with successful comanagement reported	Drug-drug interactions and overlapping toxicities should be considered
[11]	Elazab et al. [11] (2025)	CML before CLL	A patient with controlled CML on nilotinib later developed asymptomatic CLL and continued nilotinib, while the CLL was observed	Observation is reasonable for indolent CLL without treatment indications

CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor.

Our case differs from much of the published literature because both neoplasms were identified at initial presentation in a comparatively young 44-year-old patient. The marrow findings and ancillary studies support biologically distinct disease clones rather than a single neoplasm with lineage plasticity. The myeloid compartment harbored BCR::ABL1-positive CML, whereas the lymphoid population showed a classic CLL immunophenotype with 13q14.3 deletion. Earlier reports demonstrating separate molecular or cytogenetic abnormalities in the myeloid and lymphoid compartments similarly favor independent clonal origins [13, 14]. At the same time, the predominance of CLL-first cases in the published literature has raised questions about shared age-related susceptibility, treatment-related selection pressure in some previously treated patients, or simple coincidental coexistence; none of these mechanisms has been proven [8, 12].

Management should be individualized according to symptoms, disease burden, and treatment indications for each malignancy. Tyrosine kinase inhibitor therapy remains standard for chronic-phase CML [1], whereas contemporary CLL guidance recommends treatment only for active, symptomatic, or progressive disease [2]. Our patient therefore underwent CML-directed therapy while the CLL was observed. In our patient, the presenting weight loss and lymphadenopathy were attributed primarily to the overall initial presentation dominated by CML rather than definite progressive CLL, supporting initial observation of the lymphoid clone. Imatinib intolerance necessitated switching to dasatinib, after which tolerability improved. In this case, response to dasatinib should be interpreted as response of the CML clone rather than the CLL clone. During follow-up, serial quantitative BCR::ABL1 monitoring demonstrated molecular response of CML, whereas the persistent absolute lymphocytosis was consistent with the untreated CLL clone. Because no clear indication for CLL-directed therapy emerged during follow-up, the lymphoid clone continued to be managed with observation. Published experience supports this clone-directed strategy when one disease is clearly dominant. However, when both neoplasms require treatment, careful attention to drug-drug interactions and cumulative toxicities is essential, as illustrated by reports of concomitant imatinib with venetoclax or ibrutinib [9, 10].

The literature is limited by publication bias and by the fact that most evidence consists of single case reports; even the largest recent synthesis is available as a conference abstract rather than a full peer-reviewed review [12]. The current report is additionally limited by the relatively short duration of follow-up and by the inherent limitations of a single case report. Even so, the case emphasizes the value of a comprehensive diagnostic workup and careful disease-specific management when concurrent hematologic malignancies are encountered.

Conclusions

Concurrent CML and CLL can present at the time of initial diagnosis, even in a relatively young patient. Integrated use of morphology, flow cytometry, cytogenetics, and molecular testing is essential to establish both diagnoses accurately.

Published experience suggests that treating the clinically dominant leukemia while monitoring the second clone may be a reasonable initial strategy when the latter is asymptomatic. Additional case reports with longer follow-up are needed to clarify the biology and optimal management of this uncommon combination.

Acknowledgments

The authors thank Qatar National Library for publication support and the HMC internal medicine residency program for academic support.

Statement of Ethics

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. This case report was reviewed, and the need for ethical approval was waived by the Hamad Medical Corporation Medical Research Center. This case report was prepared in accordance with the CARE reporting guidelines, and the completed CARE checklist is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000552419).

Conflict of Interest Statement

The authors declare no conflicts of interest.

Funding Sources

Publication support was provided by Qatar National Library. The funder had no role in the design of the report, data collection, data analysis, manuscript preparation, or the decision to publish.

Author Contributions

Motaz Almahmood, Elmustafa Abdalla, Amin Saied, Dina Soliman, Ibrahim Almahdi A. Ganwo, Feryal Ibrahim, and Shehab Fareed contributed to the conception of the report, acquisition and interpretation of clinical data, drafting or critical revision of the manuscript, and final approval of the submitted version. Motaz Almahmood and Elmustafa Abdalla served as co-corresponding authors.

Funding Statement

Publication support was provided by Qatar National Library. The funder had no role in the design of the report, data collection, data analysis, manuscript preparation, or the decision to publish.

Data Availability Statement

The data supporting the findings of this case report are not publicly available due to patient privacy and confidentiality considerations but are available from the corresponding author upon reasonable request.