A chart review of patients with myeloproliferative neoplasms (MPN) who developed unexplained leukocytosis or thrombocytosis demonstrated that these patients should be evaluated for chronic myelogenous leukemia (CML), according to a case series described in a published abstract from the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.1
Myeloproliferative neoplasms (MPN) are classified by the presence of the Philadelphia chromosome (Ph). Ph-negative MPN typically possesses driver mutations of JAK-2, MPL, and CALR genes. CALR is involved with apoptosis and cell proliferation, and MPL leads to thrombopoietin receptor stimulation. JAK-2 mutations render hematopoietic stem cells more sensitive to growth.
Cases of patients with essential thrombocythemia (ET) who later develop chronic myelogenous leukemia (CML) are infrequent, with the true incidence of this unknown. However, CALR, MPL, and JAK-2 mutations are believed to have some role in determining whether these are separate events or clonally derived.
For this case series, Shahina Patel, MD, of Providence Hospital in Southfield, Michigan, and colleagues reviewed charts of 3 patients with MPN who later developed CML.
Patient 1 had ET, treated with hydroxyurea. Twenty-one years after diagnosis, the patient developed rising WBC and platelet counts prompting a marrow biopsy that detected Ph+ CML, and CALR positive. Next-generation sequencing (NGS) was negative for nondriver mutations. Platelets initially declined from 3 million to 975,000 with tyrokine kinase inhibitor (TKI) therapy, and a major molecular response (MMR) was achieved. However, the inability to control his thrombocytosis required adding ruxolitinib.
Patient 2 had ET and was treated with P32. Nine years later, CML was diagnosed and TKI administration achieved a MMR. Subsequently, a profound anemia evaluation diagnosed paroxysmal nocturnal hemoglobinuria (PNH) requiring eculizumab. The patient did not respond to treatment and repeat marrow with NGS revealed a MPL mutation and post-ET myelofibrosis.
Patient 3 presented with a JAK-2 positive mutation and polycythemia vera (PV). After 4 years of treatment with hydroxyurea, extreme leukocytosis led to a marrow biopsy revealing a diagnosis of Ph+ CML. MMR was achieved promptly with dasatinib. NGS revealed KIT D618 V, coinciding with a diagnosis of systemic mastocytosis (SM).
Although the patients in this series had different lead times and different mutations, Dr Patel’s team concludes that these cases illustrate the importance of evaluating for CML in patients with MPN who develop unexplained leukocytosis or thrombocytosis.
The researchers plan to retrieve archival tissue for serial genetic analyses. They note that further work is required to determine whether these events are random, unpredictable events or if they represent clonal evolution of disease.
1. Patel S, Kim SH, Shammo JM, Radich JP, Terebelo HR. Patient with myeloproliferative neoplasms (MPN) who later develop ph+ chronic myelogenous leukemia (CML): a case series. J Clin Oncol. 2017;35(suppl):e18563.
This article originally appeared on ONA