Patient With Myelofibrosis and Monoclonal B-Cell Lymphocytosis—What Is Causing the Leukocytosis?

Presentation

Mr. O is a pleasant and friendly 75-year-old man with a JAK2-mutated primary myelofibrosis causing splenomegaly and a monoclonal B-cell lymphocytosis with mild thoracic lymphadenopathy. On initial consult, he stated that for several years, he had known he had splenomegaly but the cause was not entirely clear. Previously, he had been worked up with a CT scan of the chest/abdomen/pelvis, which demonstrated mild thoracic lymphadenopathy, largest node 2.1 cm, enlarged spleen measuring 19 cm, and no evidence of chronic liver disease. A CBC also performed at that time demonstrated an absolute lymphocyte count (ALC) of 3.4 x 109. 

Additional Work-Up

The CBC revealed a mild anemia, hemoglobin ~12.5 g/dL. White blood cell count and platelets were within normal range, 9.09 x 10⁹/L and 199 x 10⁹/L, respectively. Additional laboratory testing was notable for an increased lactate dehydrogenase (LDH) of 508 U/L. Workup for causes of anemia was negative. 

Peripheral blood flow cytometry demonstrated a monoclonal B-cell population with a characteristic chronic lymphocytic leukemia (CLL) immunophenotype in 11.6% of cells. ALC was 3.2-4.2. A CLL FISH panel on the peripheral blood demonstrated deletion of 13q (9% of cells). Based on these findings, Mr. O met criteria for monoclonal B lymphocytosis or, at most, small lymphocytic lymphoma based on the small volume thoracic lymphadenopathy previously seen on the CT scan.  

Bone marrow aspiration and biopsy demonstrated the following:  

• 60%-70% cellular marrow, trilineage hematopoiesis, marked atypical megakaryocytic hyperplasia, grade 2 moderate reticulin fibrosis 
• Clonal B-cell population accounting for 5% of the marrow nucleated cells 

• Cytogenetics analysis demonstrated an abnormal karyotype 46,XY,del(20)(q11.2q13.1)[10]/46,XY,t(1;20)(q21;p13)[3]/46,XY[7] 
• A molecular panel demonstrated JAK2 V617F mutation 

In addition to monoclonal B lymphocytosis, based on the bone marrow biopsy, he was diagnosed with JAK2-mutated primary myelofibrosis, as the JAK2 mutation is diagnostic for an underlying myeloproliferative neoplasm. Symptoms at the time of diagnosis included abdominal discomfort and early satiety related to splenomegaly and fatigue. 

Treatment Initiation and Laboratory Changes

Mr. O was started on ruxolitinib 5 mg twice daily and this dose was increased three months later to 10 mg twice daily due to unchanged splenomegaly and increased leukocytosis. One month after the dose increase, he started to note improvement in abdominal discomfort and felt his spleen was less prominent. Objectively, Mr. O’s palpable spleen reduced by 50% (8 cm to 4 cm) after 1 month on ruxolitinib 10 mg twice daily.  

Interestingly, Mr. O’s white blood cell (WBC) count continued to increase, despite the higher dose of ruxolitinib. Differential was consistent with lymphocyte predominance, which was unexpected.  Lymphocytosis is uncommon in myelofibrosis given myeloid predominance. There were no apparent underlying causes for reactive lymphocytosis. Peripheral blood flow cytometry was repeated and detected 19% monoclonal B cells (previously 11.6%).   

Interim Labs

Discussion 

Mr. O’s case is unique, and at first sight, without careful attention to the WBC differential, one may think leukocytosis is related to myelofibrosis and progressing despite treatment with ruxolitinib. However, given the increased ALC and flow cytometry demonstrating an increase in monoclonal B cells to 19%, this is deemed unrelated to his underlying myelofibrosis.  

The consideration is that the monoclonal B-cell population is expanding as we are treating myelofibrosis. Mr. O does not have clinical evidence of progression of the monoclonal B-cell lymphocytosis; no increased lymphadenopathy, new cytopenias, or changes in LDH.  

If lymphocytosis were to progress or the patient developed new symptoms, it may be reasonable to repeat a bone marrow to evaluate for increased monoclonal B-cell population and CT neck/chest/abdomen/pelvis. The co-existence of a myeloproliferative neoplasm and CLL is rare, with only 28 cases reported in the literature to date.¹ It is important for the advanced practitioner to be astute in disease monitoring and pursing additional testing when unexpected results occur.  

Reference

1. Angotzi F, et al. Primary Myelofibrosis occurring during targeted therapy for chronic lymphocytic leukemia: a report of two cases. Curr Oncol. 2022;29:1455-1460.