Therapy-Related Acute Megakaryoblastic Leukemia in a Lung Cancer Patient

Therapy-related AML (t-AML) is one of the newly expanded disease entities in the 2008 WHO classification, accounting for 1020% of all cases of AML, and its incidence is increasing worldwide because of improved survival rates following treatment for other primary cancers [1, 2]. Acute megakaryoblastic leukemia (AMKL) (M7) is the least common of the t-AML French-American-British (FAB) subtypes, and only two such cases have been reported to date [3, 4], neither of which was in Korea. AMKL accounts for about 7-10% of childhood AML cases (frequently associated with Down syndrome), but only about 1% of adult AML cases [5]. Here, we describe a rare case of therapy-related acute megakaryoblastic leukemia (t-AMKL) with chromosome 5 and 7 abnormalities that presented ten years after chemoradiotherapy in an elderly lung cancer patient. A 72-yr-old man with lung cancer (non-small cell lung cancer [NSCLC], right lower lobe [RLL], squamous cell cancer, stage T2N1M0) was treated with a combination of radiotherapy and a repeated chemotherapy regimen (4 trials, 13 cycles) consisting of docetaxel, cisplatin, gemcitabine, vinorelbine, gefitinib, irinotecan, and carboplatin, between March 2003 and February 2005 (Table 1). Subsequently, in April 2005, he underwent surgical resection (RLL lobectomy) of the cancer and thereafter achieved complete remission. He was asymptomatic until being referred to our hospital for further evaluation of pancytopenia discovered at a local hospital, to which he had been admitted for fever persisting for three days, upper respiratory infection symptoms, and aggravated dyspnea. He had signs of anemic conjunctiva, but no lymphadenopathy or organomegaly on physical examination. Abdominal sonography revealed hepatomegaly but no splenomegaly. A complete blood count (CBC) revealed Hb level of 5.2 g/dL; white blood cell counts of 1.7 ×10/L (absolute neutrophil count 0.78×10/L); and platelet counts of 34×10/L. A peripheral blood smear showed macrocytic normochromic anemia with teardrop cells, a shift to the left in the neutrophilic series together with dysplastic features such as hypogranulation and the PelgerHuët anomaly in segmented neutrophils, irregularly segmented monocyte nuclei, and giant platelets (Fig. 1A).The plasma Hb (19.5 mg/dL; reference interval [RI], 0.0-5.0 mg/dL) and D-dimer (4.59 μg/mL; RI, 0-0.5 μg/mL) levels were both elevated. Most biochemical tests were normal, except for elevated levels of serum lactate dehydrogenase (513 IU/L; RI, 0-480 IU/L), beta-2 microglobin (2.9 mg/L; RI, 0-2.4 mg/L), and C-reactive protein (22.24 mg/L; RI, 0-5.0 mg/L). Vitamin B12 was raised at 19,030 pg/mL (RI, 160-970 pg/mL), but the folate level was within the RI. Bone marrow (BM) aspirate smears and a touch print preparation of the BM biopsy revealed hypercellular marrow, dysplastic changes in all three hematopoietic cell lineages, and 23.5% blasts (Fig. 1B). The blasts were medium to large sized and had round, slightly irregular or indented nuclei, fine