Concomitant Acute Promyelocytic Leukemia and Chronic Lymphocytic Leukemia: Molecularly Two Distinct Diseases

Introduction: Acute myeloid leukemia (AML) developing in chronic lymphocytic leukemia (CLL) patients is very uncommon and is usually treatment-related. Acute promyelocytic leukemia (APL) occurring concurrently with CLL is extremely rare and there is only one published case of treatment-related APL. No case of concomitant APL and CLL in patients without history of malignancy has been found in the literature. We report such a case of coexisting CLL and APL.

Case report: A 52-years-old Caucasian male with past medical history of hypertension, diabetes mellitus, and coronary artery disease, presented to an outside facility with chest pain and dyspnea for two day duration. He had lymphocytosis (WBC 31,500 /µL and 66 % lymphocytes) one year prior, however, was lost to follow up and no further workup was pursued. On examination, he was pale with no petechiae or ecchymosis. There was no lymphadenopathy or hepatosplenomegaly. Labs showed WBC 17,000/µL with 97% lymphocytes and 2% blasts, Hemoglobin 6.0 g/dL, and platelet 16,000/µL. Serum troponin was 0.30 ng/mL. EKG revealed ST-depression in lateral leads concerning for non-ST elevation MI (NSTEMI). Patient was admitted and received packed red blood cells and platelet transfusion with resolution of chest pain. Upon transfer to our hospital, he was afebrile and hemodynamically stable. Lab work showed WBC of 72,000/µL and platelet count of 9,000/µL. Slides from outside facility were reviewed and immunohistochemistry from bone marrow specimen revealed dense staining of myeloperoxidase (MPO) on sheets of myeloid blasts and strong CD79a staining on clumps of lymphocytes. Peripheral blood, bone marrow aspiration and biopsy showed two distinct morphological abnormalities including immature myeloid blasts with prominent cytoplasmic granules as well as increased number of small lymphocytes. Flow cytometry demonstrated a clonal B-cell population consistent with chronic lymphocytic leukemia. Further evaluation with fluorescent in-situ hybridization (FISH) revealed presence of a t(15;17) (q22;q12), PML-RARA translocation consistent with acute promyelocytic leukemia. Co-existence of CLL and APL was confirmed. Treatment with All-trans-retinoic acid (ATRA) and hydroxyurea was started immediately along with dexamethasone for prevention of differentiation syndrome. Shortly after initiation of ATRA, patient developed acute hypoxic respiratory failure with extensive patchy opacities in bilateral lungs on chest radiography. WBC further increased to 130,000/µL. Respiratory failure worsened despite bi-level positive airway pressure (BiPAP) and diuretics, and he was subsequently transferred to intensive care unit (ICU). Patient's clinical condition deteriorated rapidly, developed disseminated intravascular coagulation (DIC), and eventually died from cardiopulmonary arrest.

Discussion: CLL is the most common hematologic malignancy in adults in western countries and the treatment of CLL is associated with increased incidence of secondary malignancies. However, transformation of CLL into AML is uncommon and most reported cases were therapy-related (t-AML). In patients with t-AML, exposure to topoisomerase II inhibitors (mainly Etoposide), alkylating agents and ionizing radiation are among the main causative factors. AML after treatment with DNA-topoisomerase II inhibitors has a short latency period, presents without a prior myelodysplastic syndrome, and is associated with 11q23 translocation. There was only one reported case of APL which developed 2 years after radiotherapy for prostate cancer in a patient with chronic lymphocytic leukemia. Although no treatment was given for CLL, radiotherapy for prostate cancer in that patient might have contributed to the development of APL, which is considered therapy-related. High dose of radiation has also been considered to increase the risk of t-AML. To date, no report in literature has been found on simultaneous occurrence of CLL and APL in patients without any previous treatment, either for CLL or for other co-existing conditions. We report here the first case of CLL co-existing with APL, diagnosed as two separate disease entities based on evidence from molecular testing and immunohistochemistry staining. APL is a hematological emergency. Management of APL, regardless of it being de novo or therapy-related, is the same.