JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
Acute Promyelocytic Leukemia and Chronic Lymphocytic Leukemia: Concomitant Presentation of Two Molecularly Distinct Entities
Jingdong Su, MD, Diana Veillon, MD, Rodney Shackelford, MD, James Cotelingam, MD, Hazem El-Osta, MD, Glenn Mills, MD, Reinhold Munker, MD, and Srinivas Devarakonda, MD
Acute myeloid leukemia (AML) developing in patients with chronic lymphocytic leukemia (CLL) is very uncommon and usuallyassociatedwithprior treatment.Acutepromyelocytic leukemia (APL) accounts for a very small proportion of treatment-associated AML. So far, there has been only one reported case of APL occurring post radiation for prostate cancer in a patient with CLL. We report herein the first case of APL and CLL presenting concomitantly in an untreated patient. Evaluation of peripheral blood and bone marrow aspirate with immunohistochemistry, flow cytometry, and FISH to confirm two morphologically, molecularly and genetically distinct leukemic populations characteristic of APL and CLL is required. APL is a hematologic emergency, and aggressive management is vital to a successful therapeutic outcome. Standard treatment is with All-trans retinoic acid (ATRA) and anthracycline-based regimen, whether the process is de novo or therapy-related. Due to increased incidence of secondary malignancies in CLL patients, active surveillance is necessary.
count showed a white blood cell count (WBC) of 17,000 /µL comprised of 97% lymphocytes and 2% blasts, hemoglobin of 6.0 g/dL, and a platelet count of 16,000 /µL. He was found to have an elevated serum troponin 0.30 ng/mL (normal range 0 - 0.05 ng/mL). Other laboratory studies were unremarkable. Electrocardiogram (ECG) revealed ST-depression in lateral leads suspicious for a non-ST elevationmyocardial infarction (NSTEMI). On admission, he received packed red blood cell and platelet transfusions with resolution of chest pain. NSTEMI was conservatively managed due to thrombocytopenia. Work up for infection was negative. WBC count further increased to 69,000 /µL and platelet count decreased to 9,000 /µL. Coagulation studies revealed a slightly elevated prothrombin time (PT) of 16.7 seconds, normal activated partial thromboplastin time (aPTT), and normal fibrinogen. Peripheral blood smear examination revealed conspicuous atypical lymphocytes and occasional promyelocytes (Figure 1A and 1B). Microscopic examination of the bone marrow aspirate (Figure 1C) and bone marrow clot sections (Figure 1E and 1F) revealed a hypercellular bone marrow with a marrow cellularity of 100%. 65% of the marrow cellularity was comprised of leukemic promyelocytes. On immunohistochemical staining (BenchMark ULTRA automated stainer, antibodies from Ventana Medical Systems, Inc., Tucson, AZ), these cells were positive for myeloperoxidase (Figure 1G) and CD117, but negative for CD34. The remaining 35% of the marrow cellularity was comprised of small atypical B lymphocytes. These cells expressed CD79a (Figure 1H) and BOB-1 on immunohistochemical staining, but did not express CD20. Other hematopoietic elements were virtually absent. Flow cytometric studies performed on the bone marrow aspirate revealed a prominent population of leukemic promyelocytes with expression of CD13, CD15, CD33, CD56, and CD117. CD45 expression was dim. CD34 and HLA- DR were negative. A population of clonal B cells was identified that expressed CD5, CD19, CD20 (dim), CD22, CD23, CD45, and HLA-DR, and were kappa light chain restricted. Molecular genetic studies by fluorescence in situ hybridization (FISH) were positive for PML/RARA with PML/RARA fusion signals identified in 122/200 cells (Figure 1D). Molecular genetic studies by FISH for CLL associated prognostic abnormalities detected a deletion in 13q. Morphologic features, flow cytometric findings, and molecular genetic studies were diagnostic of an acute promyelocytic leukemia (APL) with t(15;17)(q22;q21); PML/RARA and concomitant B cell chronic lymphocytic leukemia (CLL).
INTRODUCTION
Secondary malignancies following treatment of chronic lymphocytic leukemia (CLL) and other malignancies are common. These include solid tumors as well as hematologic malignancies. 1,2 Acute myeloid leukemia (AML) occurring after treatment for other malignancies is frequently reported. However, AML following treatment of CLL patients is extremely rare. Although acute promyelocytic leukemia (APL) accounts for 12-15% of therapy-related AML (t-AML), these cases typically occur following chemotherapy with topoisomerase II inhibitor and only occasionally following radiation therapy. 3-6 To our knowledge, concomitant APL and CLL in untreated patient have not been found in literature, prompting this report.
CASE REPORT
A 52-year-old Caucasian male with a past medical history of hypertension, insulin-dependent diabetes mellitus, and coronary artery disease status post stent placement presented initially to an outside facility with substernal chest pain and dyspnea for two days. He did not report any fatigue, drenching night sweats or weight loss. On examination, there was no evidence of lymphadenopathy, splenomegaly or hepatomegaly. No petechiae or ecchymosis were evident. Complete blood
68 J La State Med Soc VOL 169 MAY/JUNE 2017
Made with FlippingBook Digital Publishing Software