A Study to Evaluate the Utility and Appropriateness of Diagnostic Workup for Leukocytosis in the Hematology Clinic

Background: Leukocytosis is a common abnormality in the complete blood count (CBC) that is often first noted by general practitioners. In addition to many benign causes of leukocytosis, malignant causes such as CML, myeloproliferative neoplasms (MPNs), and MDS/MPN overlap syndromes, must be evaluated for select patients by a hematology specialist. While some recommendations for evaluation and diagnostic workup for leukocytosis exist, the real-world appropriateness and utility of further serologic tests or diagnostic procedures, including bone marrow biopsy, remain largely unknown. The aim of this study is to determine hematological parameters in patients referred for evaluation of leukocytosis that are associated with MDS/MPN diagnoses and are therefore useful to the hematologist in selecting appropriate patients for further diagnostic testing.

Methods: A retrospective chart review was conducted of 803 adult patients referred to the hematology clinic at a single institution between 2016-2021. 487 patients were included based on the inclusion criteria that they were referred for evaluation of leukocytosis and did not have a prior established hematologic diagnosis. Demographic and laboratory data were collected including CBCs, anemia workup, leukocytosis workup, JAK2 V617F mutation and BCR-ABL mutation results, and bone marrow biopsy results. Clinician notes were reviewed from the medical record to verify appropriate patient selection and data points. Statistical analyses were performed using Chi-Square/Fisher exact tests to evaluate for hematological parameters that are associated with the identification of MDS/MPNs as well as other hematologic malignancies, and a multivariable logistic regression model was used to analyze the association between hematological parameters and diagnosis of MDS/MPN.

Results: 487 patients were included in analysis: 70% female, 44.6% white, 30% black or African American, and 25.5% Hispanic or Latino. After evaluation by a hematologist, 14.6% of patients were diagnosed with a hematologic malignancy, and 8% were diagnosed with MDS/MPN. Higher WBC, particularly greater than 15 x 109/L, was associated with diagnosis of MDS/MPN, any hematologic malignancy, and testing positive for BCR/ABL or JAK2 V617F (p <0.0001). Patients with an absolute neutrophil count (ANC) > ULN (7.8), absolute eosinophil count (AEC) > ULN (0.6), absolute basophil count (ABC) > ULN (0.3), platelet count >600, ferritin >50, and vitamin B12 > ULN (920) were more likely to be diagnosed with MDS or MPN (p <0.0001, <0.0001, <0.0001, <0.0001, 0.02, and 0.0006 respectively). These laboratory findings were also significantly associated with diagnosis of any hematologic malignancy, and many were associated with testing positive for BCR/ABL or JAK2 V617F mutations (ANC, AEC, ABC, and platelet count). Multivariable analysis results shows that ABC >= 0.3 (OR=27.7, 95% CI=3 - 255.3), platelet count >= 600 (OR=16.9, 95% CI=1.9 - 146.4), and vitamin B12 > 920 (OR=5.8, 95% CI=1.2 - 28.4) significantly increase the risk of being diagnosed with MDS/MPN.

Conclusions: This retrospective study identified hematological parameters in patients referred for evaluation of leukocytosis including elevated ANC, AEC, ABC, and platelet count that were significantly associated with testing positive for BCR/ABL mutation or JAK2 V617F mutation. These parameters, in addition to vitamin B12 and ferritin, were associated with positive identification of hematologic neoplasms and specifically MDS/MPNs. These parameters may guide hematologists in selecting appropriate patients for further serologic or procedural testing, such as JAK2 V617F and BCR/ABL mutation testing and bone marrow biopsy, in order to avoid unnecessary testing and decrease the financial cost of evaluation.

Shammo:Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; CTI Pharma: Research Funding; Stemline Therapeutics: Research Funding; Kartos Pharma: Research Funding; Takeda: Consultancy, Current equity holder in private company, Current equity holder in publicly-traded company, Honoraria, Research Funding; Abbvie: Current equity holder in private company, Research Funding; Baxter: Current holder of stock options in a privately-held company; Sanofi: Consultancy, Honoraria, Speakers Bureau; NS Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Research Funding.