JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
considered in the differential diagnoses. Broad spectrum antibiotics were continued and diuretics as well as non-invasive ventilation with bi-level positive airway pressure (BiPAP) were applied. Despite aggressive medical management, patient’s condition deteriorated rapidly and he died from multi-organ failure within forty-eight hours of his presentation.
DISCUSSION
Chronic lymphocytic leukemia (CLL) is themost common formof adult leukemia in the western hemisphere. The treatment of CLL is associated with a high incidence of secondary malignancies including non-melanoma skin cancer, Kaposi sarcoma, melanoma, cancers of the lung, gastrointestinal tract, breast, prostate, kidney, bladder, head and neck, and transformation to an aggressive large B-cell lymphoma (Richter’s syndrome). It is noteworthy that AML developing in a background of CLL is extremely rare. Among those with treatment-associated AML (t-AML), exposure to topoisomerase II inhibitors (mainly Etoposide), alkylating agents and ionizing radiation are among the main contributing factors. Cases of AML have also been reported in patients treated with other topoisomerase II inhibitors such as Mitoxantrone 7 and Bimolane. 8 AML after treatment with DNA-topoisomerase 2 inhibitors has a short latency period, presents without a prior myelodysplastic syndrome, and is associated with 11q23 translocation. In 2006, there were two reports of concurrent AML with CLL in untreated patients. Gottardi et al 9 documented simultaneous CLL and AML (FAB-M2) based on morphological and immunologic features. The AML component was CD34+/ CD13+/HLA-DR+/CD7+, and the CLL expressed VH3-53/ D3-22/JH4 Ig with 3.9% IgVH mutations. Further evaluation with IgH gene rearrangement on CD34+/CD19- and CD34-/ CD19+ immunomagnetically sorted cell populations revealed a shared molecular signature suggesting that genomic DNA from the CD34-/CD19+ cell fraction demonstrated IgH gene rearrangement, resulting in expansion of two independent clones and concomitant presentation of CLL and AML. In the case reported by Lu et al, 10 cytogenetic analysis revealed inv(16) (p13.1q22) and trisomy 22 in a second clone. Fluorescence in situ hybridization confirmed the CBFβ rearrangement associated with inv(16) in myeloblasts and myelomonocytic cells but not in CLL cells, confirming that the AML and CLL did not share clonality. The association between APL and CLL is even rarer. Molero et al reported a case of APL that developed two years after radiotherapy for prostate cancer in a patient with chronic lymphocytic leukemia.11 Although no treatment was given for the patient’s CLL, radiotherapy for prostate cancer in this patient might have contributed to the development of APL and is considered therapy-related. It has been suggested that there is a 0.1 – 0.2% risk of developing AML within 10 years in patients receiving radiation therapy, and the incidence is higher in patients with a mean bone marrow dose of greater than 3.5 Gy. 12 To date, no report in the literature has been found on simultaneous occurrence of APL and CLL in patients without
Treatment for APL with All-trans retinoic acid (ATRA) and hydroxyurea was started immediately along with dexamethasone for prevention of differentiation syndrome. Anthracycline or arsenic trioxide-based therapy was not initiated concomitantly due to concern for cardiotoxicity in the context of recent NSTEMI. Twenty-four hours after his initial presentation and six hours after initiation of ATRA, he developed respiratory distress. X-Ray showed extensive patchy opacities in bilateral lung fields. WBC count further increased to 130,000 /µL. Acute pulmonary edema due to recent NSTEMI, bilateral pneumonia (blood culture later reported as positive for Staphylococcus epidermidis), leukostasis, and differentiation syndrome were Figure 1. Peripheral smears, bone marrow aspirate, H&E and IHC staining show two distinct populations of leukemic cells. 1A. Peripheral blood smear showing CLL lymphocytes (Wright-GiemsaX1000). 1B. Peripheral bloodsmear showinga leukemic promyelocyte, CLL lymphocyte, and a smudge cell (Wright-Giemsa, X 1000). 1C. Bone marrow aspirate showing several leukemic promyelocytes and a single CLL cell (Wright-Giemsa stain, X1000). 1D. Bone marrow aspirate. Positive FISH result with PML/RARA fusion identified in leukemic promyelocytes (15q22-24 LSI PML Spectrum Orange/17q21 LSI RARA Spectrum Green, X1000). 1E. Bone marrow clot section with a central focus of CLL surrounded by leukemic promyelocytes (Hematoxylin & Eosin, X 100). 1F. Bone marrow clot section showing the interface between CLL and APL (Hematoxylin and Eosin, X 400). 1G-H. Bone marrow clot section showing the interface between APL cells stained positive for myeloperoxidase (G) and CLL cells stained positive for CD79a (H) (Immunohistochemical staining for Myeloperoxidase and CD79a, X 400).
J La State Med Soc VOL 169 MAY/JUNE 2017 69
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