Presentations

Abstract

Introduction:

Acute lymphoblastic leukemia (ALL) is characterized by the uncontrolled proliferation of immature lymphoid cells within the bone marrow and peripheral blood. The BCR-ABL fusion gene can occur in up to 30 percent of adults with ALL and is a marker of poor prognosis. Such patients are routinely treated with allogeneic hematopoietic cell transplantation (HCT) after remission induction. We present a case of a patient who was first suspected to have ALL by having a positive BCR-ABL1 quantitative blood test by Reverse transcription (RT) PCR.

Case Presentation:

A 28-year-old woman with recent endometritis following an abortion, presented to the emergency department with complaints of abdominal distension, weight gain, malaise, orthopnea, exertional dyspnea, and bilateral lower extremity edema. She also reported chills, nausea, and a decreased appetite. Her systolic blood pressure ranged from 180 to 200 mmHg despite no history of hypertension. Examination revealed hepatosplenomegaly and spontaneous bruising, Labs disclosed anemia (7.9 g/dL), thrombocytopenia (110,000/mm3), elevated proBNP (2,021 pg/mL) as well as elevated LDH. The initial assessment suggested new-onset heart failure and volume overload due to hypertensive urgency. She responded to diuretics and antihypertensive therapy. Hematology was consulted due to anemia, thrombocytopenia, and hepatosplenomegaly on ultrasound. Labs ruled out sickle cell anemia, thalassemia, and porphyria. The patient was discharged with close follow-up after a quantitative BCR-ABL1 test was drawn. Nine days later, the patient returned to the emergency department due to worsening bilateral leg pain, primarily concentrated in the upper thighs, along with nausea, vomiting, and dyspnea. Blood work revealed continued anemia (8.4 g/dL), thrombocytopenia (12,000/mm3), and CT imaging confirmed hepatosplenomegaly. In the interim, her quantitative BCR-ABL1 test had returned markedly positive. A bone marrow biopsy confirmed extensive B-lymphoblastic leukemia/lymphoma, accompanied by BCR-ABL1 fusion leading to immediate initiation of chemotherapy.

Discussion:

The Philadelphia (Ph) chromosome, a fusion between chromosomes 9 and 22 resulting in the BCR-ABL fusion protein, was first discovered in Chronic Myeloid Leukemia (CML). The Ph chromosome is also implicated in Acute Lymphoblastic Leukemia (ALL), predominantly within the adult population, constituting approximately up to 30 % of cases.

Because RT-PCR quantitative BCR-ABL testing is low-cost, sensitive, rapid, and not labor intensive, it is the diagnostic test of choice for Ph-positive leukemia. It can also be used to assess response to treatment and to detect measurable residual disease (MRD) following allogeneic bone marrow transplantation. Identifying BCR-ABL positive ALL subtype early is pivotal. Tyrosine kinase inhibitors (TKIs) have notably curbed MRD, a pivotal prognostic marker in Ph-positive ALL. Dasatinib, a TKI, is commonly favored based on prospective studies and potential CNS penetration.

Our patient received dasatinib with a subsequent bone marrow biopsy showing no disease and has continued follow-up with hematology.

Conclusion:

This case highlights the utility of the blood RT-PCR BCR-ABL test and teaches us about the presence of it not just in CML but also in ALL. It might in time, in the right patient, become a tool useful to hospitalists as well as outpatient physicians while awaiting input from hematologists.