Loss of response to azacitidine is associated with deletion 12p13 in a patient with myelodysplastic syndrome with unique translocation t(13;17)(q12;q25) after prior breast cancer and acute promyelocytic leukemia

Dear Editor, With increasingly successful treatment of malignancies, therapy-related leukemia (TRL) and myelodysplastic syndrome (MDS) are increasingly observed, especially in association with prior radiotherapy and the use of alkylating agents or topoisomerase-II inhibitors [1, 2]. They are characterized by lesions of chromosomes 5 and 7 and poor survival (median 7–10 months) [3, 4]. Azacitidine may be a reasonable treatment choice [5] although safety concerns in patients with complex cytogenetics [6] or previous acute promyelocytic leukemia (APL) exist [7]. Here, we present a case of two consecutive, individually rare TRLs following initial solid tumor and subsequent treatments with the development of unique translocation (13;17)(q12;q25). Azacitidine was successfully used achieving 1-year-long remission when patient relapsed, revealing a distinctive karyotype (Fig. 1). A female patient aged 61 was diagnosed with breast cancer in 2006. She had mastectomy, received four cycles of doxorubicin/cyclophosphamide, four cycles of paclitaxel, and radiotherapy accomplishing remission. In 2009, APL was diagnosed, PML/RARα positive (47, XX,+8,t(15;17)(q24;q21)[10]). Antracycline/ATRA-based induction and three consolidation therapies were followed by 2year ATRA/6-MP/methotrexate maintenance. Remission was soon achieved, and patient remained without detectable PML/ RARα transcript thereafter. In 2013, the patient developed anemia requiring transfusion support. MDS (18 % blasts) with complex cytogenetics (45,XX,del(5)(q22q33),-7,t(13;17)(q12;q25), del(12)(p13),add(20)(q11)[cp15]) was diagnosed. Azacitidine was instituted as salvage therapy, and the patient became transfusion independent, achieving hematological remission. After 11 cycles, azacitidine had to be stopped due to the development of anemia and thrombocytopenia. Repeated revisions showed increased number of blasts (15 % progressing to 72 %) and alt e r ed cy togene t i c s (45 ,XX,de l (5 ) (q22q33 ) , 7 , t(13;17)(q12;q25),del(12)(p13)[20]). Fluorescence in situ hybridization (FISH) was performed on the actual sample and retrospectively (at the time of MDS diagnosis) revealing 12p13 deletion was initially present in a subclone comprising 35 % of cells and now prevailing in 90 % of cells. 17p13 deletion was absent in both samples. The patient receives supportive treatment and remains alive more than 18 months since diagnosis. * Ozren Jaksic ojaksic@kbd.hr