Two Leukemias at Once: Doctors Report a Rare Case of CML and CLL in One Elderly Man

In an extraordinary case that reads like a biological paradox, physicians have documented a 79-year-old man whose blood carried not one but two distinct leukemias at the same time. The report, published in Clinical Case Reports, describes the simultaneous diagnosis of chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL), a coincidence so rare that only about 62 cases have ever been documented in the medical literature, and just seven of those involved both malignancies appearing simultaneously. The case offers a striking window into how two fundamentally different cancers can coexist within a single circulatory system, and it raises unresolved questions about whether such dual malignancies spring from a common ancestral stem cell or from two independent oncogenic accidents.

The patient’s story began insidiously. For six months, the 79-year-old man experienced mild fatigue and generalized weakness that remained stable before worsening dramatically in the final month. He described episodes of his legs giving out, new-onset muscle cramping, dizziness, unintentional weight loss, night sweats, early satiety, anorexia, and nocturia. He denied any recent fever. Two weeks before admission, his primary care physician detected anemia and marked leukocytosis, an abnormally high white blood cell count, prompting referral for specialist evaluation. The patient had no significant past medical history, which made the laboratory findings that followed all the more alarming.

On admission, the numbers were staggering. His white blood cell count reached 292.74 × 10³/μL, roughly thirty times the upper limit of the normal range of 4 to 10 × 10³/μL. The differential count revealed a chaotic mixture: 42% neutrophils, 24% lymphocytes, 12% myelocytes, 8% band cells, 5% metamyelocytes, 1% promyelocytes, and 4% blasts, immature cells that should rarely appear in circulating blood. He was also profoundly anemic, with hemoglobin of 8.5 g/dL against a reference range of 12.3 to 15.3 g/dL, and an elevated red cell distribution width of 18.2% indicating marked variation in red cell size. His platelet count remained deceptively normal at 343 × 10³/μL. Lactate dehydrogenase, an enzyme released when cells die rapidly, was elevated at 890 U/L, signaling the intense cellular turnover characteristic of proliferative hematologic malignancies.

A peripheral blood smear provided the first major clue. The slide showed a full spectrum of myeloid precursors, including myelocytes, metamyelocytes, promyelocytes, and occasional blasts, a picture highly suggestive of chronic myeloid leukemia. Yet the lymphocyte percentage of 24% appeared deceptively normal on its face. The absolute lymphocyte count told a different story: with total leukocytosis of 292.74 × 10³/μL, the 24% fraction corresponded to an absolute lymphocyte count of 70.26 × 10³/μL, a figure dramatically above normal. This distinction between relative and absolute counts proved pivotal, as it flagged the presence of a second proliferative disorder hiding behind the dominant myeloid picture. Recognizing the myeloproliferative emergency, clinicians started the patient on hydroxyurea from the first day, and over an 18-day course his leukocyte count fell significantly to 11.8 × 10³/μL.

Molecular testing then confirmed the myeloid diagnosis. The patient expressed strong levels of the BCR::ABL1 p210 transcript, the hallmark fusion gene generated by the t(9;22)(q34;q11) chromosomal translocation, along with weak expression of the p190 variant. This translocation fuses the ABL1 gene on chromosome 9 with the BCR gene on chromosome 22, creating the infamous Philadelphia chromosome. The resulting fusion protein exhibits constitutive tyrosine kinase activity, driving uncontrolled proliferation of myeloid cells. Based on these findings, the patient began imatinib, a targeted tyrosine kinase inhibitor, on day 10 of admission at 400 mg daily.

But the diagnostic workup was not finished. Flow cytometry of the peripheral blood, performed to assess blast percentage, revealed a clonal B-cell population expressing CD5, CD19, and CD20, an immunophenotype classic for chronic lymphocytic leukemia. The test was repeated for confirmation and yielded identical results. CLL is defined by the clonal expansion and progressive accumulation of mature B lymphocytes, most of which express the CD5 antigen, infiltrating the peripheral blood, bone marrow, lymphatic tissues, and spleen. Imaging studies added further evidence: abdominal and pelvic ultrasonography identified multiple pathologic lymph nodes, including portacaval nodes up to 15 mm and left mesenteric nodes up to 12 mm in short-axis diameter, all round, lacking the central echogenic hilum of healthy nodes. Splenomegaly was also noted, with a cranio-caudal diameter of 205 mm.

By discharge, the white cell count had normalized to 10.7 × 10³/μL and lactate dehydrogenase had fallen to 363 U/L, indicating reduced cellular turnover. However, anemia had worsened to 7.5 g/dL and thrombocytopenia had developed, with platelets dropping to 69 × 10³/μL, possibly reflecting disease burden or cytotoxic effects of therapy. The lymphocyte percentage was markedly elevated at 82.2%, supporting the concurrent lymphoproliferative diagnosis. After two months of continuous imatinib treatment, the patient showed significant clinical and hematological response, with marked reduction in white cell count and notable improvement in performance status, though persistent lymphocytosis remained. Tragically, approximately two months after treatment initiation, he developed severe community-acquired pneumonia and died of respiratory failure, cutting follow-up short.

The simultaneous occurrence of CML and CLL presents a fascinating biological puzzle. CLL is the most prevalent leukemia in adults across Western countries, with an estimated incidence of 4 to 6 cases per 100,000 individuals annually, and over 70% of patients diagnosed at 65 years or older. CML is the most common myeloproliferative disorder characterized by the BCR::ABL1 fusion gene. Despite both conditions preferentially affecting elderly populations, their coexistence is exceedingly uncommon. Documented presentations include sequential diagnoses, where one malignancy follows the other, and synchronous onset, in which both are identified at the same time. In over half of reported cases, CLL preceded CML, and many of those patients had received chemoimmunotherapy with agents such as fludarabine or chlorambucil, raising the possibility that DNA damage or selection pressures from CLL therapy might contribute to subsequent CML. Notably, the present patient had no history of cytotoxic therapy, making his simultaneous presentation even more enigmatic.

Several hypotheses attempt to explain this biclonal leukemic phenomenon. Cytogenetic studies in some cases show that the two malignancies arise from separate hematopoietic clones: researchers have demonstrated BCR::ABL1 fusion confined exclusively to the myeloid fraction, while monoclonal immunoglobulin gene rearrangement was found only in the lymphoid CLL cells, supporting two distinct malignant clones coexisting rather than a single clone transforming along two lineages. Conversely, other authors speculate that both neoplasms may originate from a single pluripotent hematopoietic stem cell that acquires mutations enabling both myeloid and lymphoid transformation. If BCR::ABL1 occurred in an early progenitor, it could theoretically give rise to both myeloid and lymphoid clones, though direct proof remains lacking. A third mechanism involves microenvironmental effects: BCR::ABL1-positive cells produce cytokines such as interleukin-3, which can stimulate CD34⁺ progenitors and B-lymphoid cells, meaning a CML clone could in theory secrete factors that drive expansion of a B-lymphoid clone, or vice versa.

This case underscores the critical importance of comprehensive diagnostic evaluation when patients present with atypical hematological findings. The peripheral blood smear, flow cytometry, and molecular studies were all pivotal in unraveling the dual diagnosis, and the distinction between relative and absolute lymphocyte counts proved essential to recognizing the second malignancy. The pathogenesis of such rare co-occurrence remains under active debate, with the consensus being that it is heterogeneous: some patients demonstrably arise from separate clones, while others are best explained by a shared stem-cell origin. Genetic instability, environmental triggers, or stochastic events may all contribute to this rare dual leukemogenesis. As the population ages and diagnostic techniques grow more sensitive, clinicians may encounter such dual malignancies more frequently, making awareness of this phenomenon increasingly relevant for hematologists managing elderly patients with complex blood disorders.

Subject of Research: Rare co-occurrence of chronic myeloid leukemia and chronic lymphocytic leukemia in a single patient

Article Title: A Rare Case of Chronic Lymphocytic Leukemia and Chronic Myeloid Leukemia in an Elderly Patient: A Case Report

Article References: Kamandi, M., & Alvandi Fard, M. M. (2026). A Rare Case of Chronic Lymphocytic Leukemia and Chronic Myeloid Leukemia in an Elderly Patient: A Case Report. Clinical Case Reports, 14(10), Article e73136. https://doi.org/10.1002/ccr3.73136

Image Credits: AI Generated

DOI: 10.1002/ccr3.73136

Keywords: chronic myeloid leukemia, chronic lymphocytic leukemia, BCR::ABL1, flow cytometry, hematology, case report, Rare, Case, Chronic, Lymphocytic, Leukemia, Myeloid