Case presentation

Clinical presentation

A 33-year-old man with a history of BCR::ABL1-positive chronic-phase chronic myeloid leukemia (CML) presented for evaluation of persistent disease approximately nine years after his initial diagnosis. He was first diagnosed with CML in 2017 at 24 years of age after marked leukocytosis was incidentally identified during routine blood donation screening. Initial laboratory studies revealed a white blood cell count of 187.8 ×10³/µL, hemoglobin of 10.3 g/dL, and platelet count of 418 ×10³/µL. Peripheral blood smear demonstrated marked leukocytosis with left-shifted myeloid maturation, basophilia, and approximately 2% circulating blasts. Bone marrow evaluation showed a hypercellular marrow with granulocytic hyperplasia and left-shifted myeloid maturation consistent with chronic-phase CML. Cytogenetic analysis identified a variant Philadelphia chromosome translocation, t(6;9;22)(q34;q11.2;p21), and fluorescence in situ hybridization (FISH) confirmed BCR::ABL1 fusion positivity in 94.5% of analyzed cells, establishing the diagnosis of BCR::ABL1-positive chronic-phase CML. Table 1 summarizes the timeline from 2017 until current presentation.

Date | Clinical course | Key findings | Treatment | Response/outcome
Apr 2017 | Incidental leukocytosis during blood donation | WBC 206.7×10³/µL, BM: chronic-phase CML, variant t(6;9;22), BCR::ABL1 94.5% | Imatinib initiated | Hematologic response
Dec 2017 | Insurance interruption | Lost access to imatinib | Treatment held ~1 month | Re-established care
Jan 2018 | Hematology follow-up | Tolerating therapy | Restarted imatinib 400 mg daily | Continued response
Mar 2018 | Follow-up | BCR::ABL1 58.8% | Continued imatinib | Stable chronic phase
Aug 2019 | Lost follow-up | Stopped imatinib because of insurance | No treatment | Prolonged treatment interruption
Jul 2023 | Hospitalization for hyperleukocytosis | WBC 443.5×10³/µL, BCR::ABL1 35.2% | Hydroxyurea, allopurinol; imatinib resumed | Cytoreduction achieved
Sept 2023 | Right knee abscess | No abnormal myeloid cells on flow cytometry | Antibiotics | Infection resolved
Dec 2023 | Neck cellulitis | CT neck with extensive soft tissue edema | IV antibiotics; temporary interruption of TKI | Restarted imatinib after discharge
May 2026 | Current admission | Headache, intermittent fever, fatigue, abdominal distention, early satiety, massive splenomegaly, WBC 545×10³/µL | Hydroxyurea, TLS prophylaxis, bone marrow biopsy, flow cytometry | Persistent chronic-phase disease confirmed
May 2026 | Definitive management | BM: MF-2 fibrosis, no blast transformation | Dasatinib planned/initiated | Outpatient hematology follow-up

Initial assessment and physical examination

Upon presentation, the patient reported several weeks of progressively worsening headaches accompanied by intermittent subjective fevers, abdominal distention, reduced appetite, fatigue, and early satiety. Initial vital signs demonstrated a low-grade fever (maximum temperature 38.0°C) and mild sinus tachycardia (heart rate approximately 105 beats/min), while blood pressure, respiratory rate, and oxygen saturation remained stable. He was alert, oriented, and in no acute distress.

Physical examination demonstrated tachycardia with a regular rhythm and normal respiratory effort without evidence of acute cardiopulmonary compromise. The abdomen was distended with marked splenomegaly but remained soft and non-tender without guarding or rebound tenderness. Bilateral thigh ecchymoses were noted without evidence of active bleeding. Neurologic examination was nonfocal, and no generalized lymphadenopathy was appreciated. Given the constellation of constitutional symptoms, massive splenomegaly, and persistent hematologic abnormalities, a comprehensive diagnostic evaluation was undertaken to assess disease status and exclude progression to advanced-phase CML.

Laboratory and diagnostic testing

Serial laboratory studies during hospitalization demonstrated persistent marked leukocytosis characterized by neutrophilia, basophilia, eosinophilia, monocytosis, and numerous immature granulocytic precursors. White blood cell counts remained markedly elevated, reaching approximately 342 ×10³/µL. Concurrent anemia was present, with hemoglobin measuring 7.4 g/dL and hematocrit 24.5%. Platelet counts remained preserved at approximately 398 ×10³/µL (Table 2).

Parameter (unit) | Admission | Peak/nadir during hospitalization | Discharge | Reference range
WBC (×10³/µL) | 342.0 | 545.2 (peak) | 243 | 4.0-11.0
Hemoglobin (g/dL) | 7.4 | 7.4–8.5 | 8.1 | 13.5-17.5
Platelets (×10³/µL) | 261 | 585 (peak) | 400 | 150-400
Blasts (%) | 0–1 | 6 (peak) | 2 | <1
Basophils (%) | 4 | 10 (peak) | 8 | <1
Eosinophils (%) | 4 | 6 (peak) | 4 | 0-5
Absolute basophils (×10³/µL) | 13.68 | 21.81 (peak) | 20.57 | <0.20
LDH (U/L) | 1,720 | 3,037 (peak) | 645 | 140-280
Uric acid (mg/dL) | 7.1 | 10.2 (peak) | 4.3 | 3.5-7.2
AST (U/L) | 37 | 180 (peak) | 56 | 10-40
ALT (U/L) | 20 | 180 (peak) | 93 | 7-56
Creatinine (mg/dL) | 0.90 | 1.00 | 0.90 | 0.7-1.3
CRP (mg/dL) | 4.9 | 4.9 | 0.8 | <1.0

Comprehensive infectious disease testing was negative, including HIV-1/2 antigen-antibody screening, HIV RNA testing, hepatitis B surface antigen, hepatitis B core IgM antibody, hepatitis C antibody, and hepatitis C viral RNA testing. Blood cultures showed no documented microbiologic growth (Table 3).

Test | Result | Interpretation
HIV-1/2 antigen/antibody screen | Nonreactive | Negative for HIV infection
HIV-1 RNA PCR | Not detected | No evidence of active HIV infection
Hepatitis B surface antigen (HBsAg) | Nonreactive | No evidence of active hepatitis B infection
Hepatitis B core IgM antibody (HBcAb IgM) | Nonreactive | No evidence of acute hepatitis B infection
Hepatitis C antibody (Anti-HCV) | Nonreactive | Negative hepatitis C screening
Hepatitis C virus RNA PCR | Not detected | No evidence of active hepatitis C infection
Blood cultures | No growth | No microbiologic evidence of bacteremia

Repeat bone marrow examination confirmed persistent/recurrent chronic myeloid leukemia without evidence of progression to accelerated-phase or blast-phase disease. Histopathologic evaluation demonstrated a markedly hypercellular marrow with an overall cellularity of approximately 95%, showing trilineage hematopoiesis with prominent myeloid hyperplasia and markedly decreased erythroid precursors. Myeloid elements exhibited complete maturation with left shift and no overt dysplasia. Megakaryocytes were scattered and included occasional small hypolobated forms. Peripheral blood smear examination demonstrated marked neutrophilia with left-shifted granulopoiesis and basophilia. Immunohistochemical staining identified rare CD34-positive blasts representing approximately 1% of marrow cellularity, while PAX5 and CD34 immunostains were otherwise negative. Collectively, these findings were consistent with persistent chronic-phase CML without morphologic evidence of leukemic transformation (Table 4).

Parameter | Finding | Reference/normal
Bone marrow diagnosis | Persistent/recurrent chronic myeloid leukemia without increase in blasts | N/A
Marrow cellularity | Approximately 95% (hypercellular) | Age-adjusted expected: ~30-70%
Hematopoiesis | Trilineage hematopoiesis present | Normal finding
Myeloid series | Marked myeloid hyperplasia with left-shifted maturation | No significant myeloid hyperplasia
Erythroid series | Markedly decreased | Normal trilineage representation
Megakaryocytes | Scattered, including occasional small hypolobated forms | Normal morphology
Lymphocytes | Small mature lymphocytes without atypical aggregates | Normal
CD34-positive blasts (IHC) | Approximately 1% of marrow cellularity | <5% consistent with chronic phase
PAX5 | Negative | Negative
Reticulin fibrosis | MF-2 (moderate fibrosis) | MF-0
Ring sideroblasts | Not detected | Absent
Marrow dysplasia | No overt dysplasia identified | Absent
Blast transformation | Not identified | Absent
Bone marrow aspirate differential | Not performed due to inadequate aspirate smear | N/A
Pathologist interpretation | Persistent chronic-phase CML without increase in blasts | N/A

Additional marrow studies demonstrated moderate reticulin fibrosis (MF-2), indicative of ongoing chronic myeloproliferative activity. Bone marrow aspirate differential analysis could not be performed because of inadequate aspirate smears; however, concurrent peripheral blood studies revealed marked leukocytosis (235 ×10³/µL) with neutrophilia, immature myeloid forms (17%), eosinophilia (5%), and basophilia (6%). Correlation with cytogenetic and molecular studies was recommended for comprehensive assessment of persistent disease burden and therapeutic planning (Table 4).

Peripheral blood flow cytometry identified an abnormal population of CD34-positive/CD117-positive myeloid blasts comprising 3.16% of analyzed leukocytes. These cells demonstrated aberrant expression characterized by decreased CD33 and CD13 expression and were interpreted as abnormal myeloid blasts supporting the presence of an underlying myeloid neoplasm. No abnormal B-cell or T-cell populations were detected. The blast population showed an immature myeloid immunophenotype with expression of CD34, CD117, HLA-DR, CD13, and CD33, while lacking immunophenotypic evidence of lymphoid malignancy. Basophils were also increased, accounting for approximately 3.3% of analyzed events. Taken together with the bone marrow morphology, these findings supported persistent chronic-phase CML without evidence of accelerated-phase or blast-phase transformation (Figure 1 and 2; Table 5).

Figure 1: Flow cytometric immunophenotypic analysis of peripheral blood at hospital presentationRepresentative multiparameter flow cytometry of the peripheral blood obtained during the patient's 2026 hospitalization. Sequential gating was performed to exclude debris and doublets, followed by identification of the CD45-positive leukocyte population. Analysis demonstrated a small population of CD34-positive blasts (approximately 1%) expressing CD13, CD33, CD117, HLA-DR, and CD10, consistent with chronic-phase chronic myeloid leukemia (CML). The predominant cell population consisted of mature and maturing myeloid cells without immunophenotypic evidence of acute leukemic transformation.

Figure 2: Immunophenotypic characterization of the CD34-positive blast population by multiparameter flow cytometryRepresentative multiparameter flow cytometric analysis of the gated CD34-positive blast population from peripheral blood obtained during the patient's 2026 hospitalization. Sequential gating identified the CD34-positive population, which accounted for approximately 4.7% of the gated events. The blast population demonstrated expression of CD34, HLA-DR, CD13, CD33, CD117, and CD10, while lacking aberrant expression of lymphoid markers including CD3, CD4, CD7, and CD19. This immunophenotypic profile is consistent with chronic-phase chronic myeloid leukemia and shows no evidence of immunophenotypic features suggestive of acute leukemic transformation.

Parameter | Finding | Reference/interpretation
Specimen | Peripheral blood | -
Flow cytometry panel | Acute myeloid leukemia (AML) screen | -
Abnormal myeloid blasts | 3.16% of analyzed leukocytes | Elevated; chronic-phase CML typically <10% blasts
Blast phenotype | CD34+, CD117+ immature myeloid blasts | Consistent with myeloid progenitors
CD33 expression | Decreased | Aberrant expression
CD13 expression | Decreased | Aberrant expression
Basophils | 3.3% of analyzed events | Increased
Abnormal B-cell population | Not detected | Negative
Abnormal T-cell population | Not detected | Negative
Evidence of lymphoid malignancy | Not identified | Negative
Overall interpretation | Findings support persistent myeloid neoplasm | Consistent with persistent chronic-phase CML
Blast-phase transformation | Not identified | Blasts <10%
Accelerated-phase transformation | Not identified by flow cytometry | No immunophenotypic evidence

Fluorescence in situ hybridization (FISH) analysis for BCR::ABL1 rearrangement was performed on 200 interphase nuclei and demonstrated persistent cytogenetic evidence of disease. The predominant signal pattern was 1F2R2G, identified in 143 of 200 cells (71.5%), with additional abnormal fusion signal patterns observed in smaller subclones. Overall, more than 70% of analyzed cells demonstrated evidence of BCR::ABL1 rearrangement, confirming persistence of the Philadelphia chromosome-positive leukemic clone despite prior therapy. These findings correlated with the morphologic and hematologic evidence of ongoing chronic-phase CML. Table 6 and Figure 3 summarize FISH analysis.

FISH signal pattern | Interpretation | Number of cells (n=200) | Percentage (%)
1F2R2G | Typical dual-fusion BCR::ABL1-positive pattern | 143 | 71.5
1F2R1G | Variant BCR::ABL1-positive pattern | 18 | 9.0
R1G2F1 | Variant BCR::ABL1-positive pattern | 16 | 8.0
2R2G | Normal signal pattern | 9 | 4.5
2F1R1G | Variant BCR::ABL1-positive pattern | 8 | 4.0
Other abnormal fusion patterns* | Variant BCR::ABL1-positive patterns | 6 | 3.0
Total abnormal cells | Evidence of BCR::ABL1 rearrangement | 182 | 91.0
Total normal cells | No detectable rearrangement | 9 | 4.5
Unclassified/rare patterns | Miscellaneous signal configurations | 9 | 4.5

Figure 3: Fluorescence in situ hybridization (FISH) analysis demonstrating persistent BCR::ABL1-positive chronic myeloid leukemiaRepresentative interphase nuclei stained with dual-color dual-fusion BCR::ABL1 probes are shown. Red signals represent ABL1, green signals represent BCR, and yellow signals represent fusion events. Panels A-H illustrate representative abnormal signal configurations observed during analysis. The dominant signal pattern was 1F2R2G, detected in 71.5% of analyzed nuclei, with additional variant fusion patterns identified in smaller subclonal populations. Overall, 91.0% of analyzed cells demonstrated abnormal BCR::ABL1 fusion signals, confirming persistence of the Philadelphia chromosome–positive clone despite maintenance of chronic-phase morphology.

Additional diagnostic studies were performed to assess disease burden and evaluate associated symptoms. Contrast-enhanced computed tomography (CT) of the abdomen and pelvis demonstrated massive splenomegaly measuring approximately 31.9 cm in maximal craniocaudal dimension, occupying a substantial portion of the abdominal cavity and exerting significant mass effect on adjacent viscera (Figure 4). Borderline enlarged pelvic lymph nodes were also identified. The marked splenic enlargement was consistent with persistent myeloproliferative disease activity.

Figure 4: Massive splenomegaly on contrast-enhanced computed tomography in persistent chronic myeloid leukemiaCoronal contrast-enhanced computed tomography (CT) images of the abdomen and pelvis demonstrating massive splenomegaly in a patient with persistent chronic myeloid leukemia. (A) Coronal CT image showing marked enlargement of the spleen extending from the left upper quadrant into the pelvis. (B) Coronal CT image at a different level further illustrating the extent of splenic enlargement and associated displacement of adjacent abdominal viscera. The spleen measured approximately 31.9 cm in maximal craniocaudal dimension. White arrows indicate the enlarged spleen and its mass effect on surrounding structures.

Magnetic resonance imaging (MRI) of the brain was obtained because of persistent headaches and was limited by artifact from dental braces but revealed no gross intracranial mass, midline shift, or other acute abnormality.

Transthoracic echocardiography demonstrated preserved left ventricular systolic function with an estimated ejection fraction of 60-65%, mild right ventricular dilation, and no significant valvular abnormalities.

Chest radiography showed no acute cardiopulmonary abnormalities, and electrocardiography demonstrated sinus tachycardia without other significant abnormalities.

Multidisciplinary board discussion

The case was reviewed in a multidisciplinary setting involving hematology, pathology, and laboratory medicine specialists. The principal diagnostic consideration was distinguishing persistent chronic-phase disease from progression to accelerated or blast phase. Despite substantial leukocytosis and persistent marrow involvement, multiple pathologic assessments demonstrated blast counts below established thresholds for disease acceleration. Bone marrow morphology, immunohistochemistry, and flow cytometry consistently identified only 1-2% blasts, favoring persistent chronic-phase CML rather than transformation.

The presence of moderate reticulin fibrosis and sustained hypercellularity raised concerns regarding disease persistence despite therapy. The board concluded that the overall findings were most consistent with recurrent or persistent chronic-phase CML with associated myelofibrotic change and recommended correlation with cytogenetic and molecular studies to further characterize disease status and guide subsequent treatment decisions.

Management

Given the patient's marked leukocytosis and substantial disease burden, cytoreductive therapy with hydroxyurea was initiated upon admission. He was closely monitored with serial complete blood counts and metabolic panels to assess treatment response and detect potential complications. Due to the high risk of tumor lysis syndrome associated with rapid cytoreduction, prophylactic measures including aggressive intravenous hydration and allopurinol were implemented, with frequent monitoring of serum uric acid, electrolytes, phosphorus, calcium, creatinine, and lactate dehydrogenase levels throughout hospitalization.

Following diagnostic reassessment and confirmation of persistent chronic-phase disease, treatment with dasatinib 100 mg daily was initiated as definitive disease-directed therapy. Antimicrobial prophylaxis with acyclovir was also administered during treatment. Supportive care included ongoing monitoring of hematologic parameters, renal function, and treatment-related adverse effects. The patient remained under the care of a multidisciplinary hematology team, with therapeutic decisions guided by serial laboratory assessment and clinical response.

Outcome and follow-up

The patient demonstrated a favorable hematologic response to treatment during hospitalization. Following initiation of hydroxyurea and subsequent dasatinib therapy, his leukocyte count progressively declined from greater than 500 ×10³/µL at presentation to approximately 243 ×10³/µL by discharge. Concurrently, his presenting symptoms, including headache and abdominal discomfort, improved. Despite the substantial disease burden and rapid cytoreduction, no clinically significant tumor lysis syndrome developed, and renal function remained stable throughout the hospital course.

After stabilization, the patient was discharged on dasatinib 100 mg daily with close outpatient hematology follow-up. Ongoing surveillance was recommended, including serial complete blood counts, comprehensive metabolic panels, lactate dehydrogenase, uric acid, and quantitative BCR::ABL1 transcript monitoring by real-time PCR to assess molecular response, treatment efficacy, and disease control over time. Although longitudinal BCR::ABL1 transcript measurements were not available during the present hospitalization, serial molecular monitoring was recommended for subsequent follow-up in accordance with current CML management guidelines. Continued adherence to tyrosine kinase inhibitor therapy and longitudinal hematologic follow-up were emphasized to reduce the risk of disease progression and optimize long-term outcomes.