Therapy-related acute myeloid leukemia in a patient with chronic lymphocytic leukemia treated with rituximab–bendamustine

Abstract

Dear Editor, Therapy-related neoplasms account for 10–20 % of all cases of acute myeloid leukemias (AMLs). Two subsets of therapy-related acute myeloid leukemias are generally recognized. The most common occurs 5–10 years after exposure to alkylating agents and/or ionizing radiation. The second category has a latency period of about 1–5 years and follows treatment with agents that interact with DNA topoisomerase II. Herein, we present the clinical case of a patient with chronic lymphocytic leukemia (CLL) who developed acute myeloid leukemia after treatment with bendamustine, an alternative agent with both alkylating and purine-like qualities. To our knowledge, this is the first report of acute myeloid leukemia induced by bendamustine. A 62-year-old patient was diagnosed with CLL, clinical stage I-A Rai–Binet in December 2009; however, absolute lymphocytosis had previously been detected in October 2006. Bone marrow infiltration reached 59 % of atypical lymphocytes with a Matutes score of 3/5 in immunophenotype. Peripheral blood and bone marrow had atypical lymphocytes, but no dysplastic morphologic alteration was observed. Cytogenetic aberrations were detected in 50 % of cells with 46,XY, der (3)(p?),-8. FISH analysis detected del (13)(q14) in 73 % of the analyzed nuclei without del (11q), del (17p), or trisomy 12. CLL lymphocytes used the gene IGHV330-3 with only 93.4 % of homology. The patient remains in observation with a diagnosis of CLL with genomic aberrations (13q deletion) and mutated IGHV genes without symptoms and good prognosis (Table 1). In October 2011, he received treatment with four cycles of rituximab (375mg/m, day 1) and bendamustine (90 mg/m, days 1–2) for severity of CLL characterized by progressive lymphadenopathy, massive splenomegaly (23 cm), and a lymphocyte count of 71,000/μl. The last cycle was administered at a lower dose of bendamustine (70mg/m, days 1–2). The patient reached a complete response evaluated by CT (ESM Fig. 1) and negative minimal residual disease in bone marrow measured by flow cytometry in February 2012. Interestingly, severe T cell lymphopenia was detected even at 8 months after treatment (Table 2). In July 2012, mild thrombocytopenia and monocytosis (platelets 92,000/μl, monocytes of 4,800/μl) without symptoms were detected. A peripheral blood smear showedmonocytosis but without blasts. Two months later, the patient presented worsening of the pancytopenia with Hb 10.1 g/dl, 98,000 platelets/μl and leukocytes 12,000/μl, neutrophils 700/μl, lymphocytes 6,200/μl, and monocytes 5,700/μl as well as mild asthenia. At this moment, the patient presented 20 % of blasts with only mild signs of dysplasia in peripheral blood smear (Fig. 1). A bone marrow aspiration was performed demonstrating infiltration of 89 % of monoblasts and promonocytes with abundant cytoplasm and azurophilic granules. Mild signs of dysplasia were seen occasionally in BM (Figs. 2 and 3). Multiparametric flow Electronic supplementary material The online version of this article (doi:10.1007/s00277-013-1844-8) contains supplementary material, which is available to authorized users. R. Garcia-Munoz (*) :D. K. Garcia :V. Roldan-Galiacho : A. Campeny-Najara : P. Rabasa Hematology Service, Hospital San Pedro, Calle Piqueras 98, 26006 Logrono, La Rioja, Spain e-mail: rgmunoz@riojasalud.es