Recently, t-MN has been recognized as one of the most serious challenges facing clinical oncology, due to improved survival rates following primary malignancies [6
]. Many studies have addressed various aspects of t-MN; however, this is the largest study to address the clinical and cytogenetic characteristics of the disease in Korea [17
The previous WHO classification emphasized 2 different t-MNs: one that occurs after exposure to alkylating agents or radiation therapy (typically with abnormalities of chromosomes 5 or 7) and the other that occurs after exposure to topoisomerase 2 inhibitors (typically with balanced translocations involving 11q23 or 21q22) [4
]. However, most patients who develop t-MNs are treated with both alkylating agents and topoisomerase 2 inhibitors; therefore, a division according to the type of therapy is usually not practical and not recommended in the revised classification [1
]. In our study, only 4 patients received topoisomerase 2 inhibitors without alkylating agents, and only 2 patients received alkylating agents without topoisomerase 2 inhibitors; hence, it was not useful to compare these 2 groups in terms of latency or survival.
We found that recurring translocations or balanced rearrangements were significantly more common in patients who had previously undergone therapy to treat a solid tumor. In particular, 6 of 9 patients with primary breast cancer had recurring chromosomal rearrangements; 5 patients had t(11q23) and 1 had inv(16). Additionally, most patients with balanced translocations and other recurrent rearrangements were overt t-AML patients (11 of 13 patients, 84.6%) rather than t-MDS patients (2 of 13 patients, 15.4%). Smith et al. [4
] also documented these patterns, which were subsequently confirmed by others [17
Previous studies on t-MN have shown that the number of patients with a history of treatment for a previous hematological malignancy was nearly equal to that for a previous solid tumor [4
]. Of primary hematologic malignancies, lymphoma (non-Hodgkin lymphoma and Hodgkin lymphoma) was the most common [3
]. In our study, 14 patients had a primary hematologic malignancy and 25 had a solid tumor. Notably, 4 patients developed t-MN after treatment for de novo
AML/MDS, which has rarely been reported. This may be due to improvement of long-term disease-free survival after treatment for AML. In the present study, altered cytogenetic and/or molecular abnormalities were present in all patients with t-MN developing from de novo
AML/MDS, and dysplastic changes were observed. One patient (H12 in ) developed t-MN from AML with t(8;21) (q22;q22), which is well known to be associated with a good prognosis. He had received CT that included idarubicin and cytosine arabinoside, followed by autologous peripheral blood stem cell transplantation. This patient developed t-MN after 5 yr, despite the absence of factors associated with a poor prognosis, such as CD56 expression or the presence of the KIT
Several previous studies have investigated the clinical presentation of t-MN. These studies have consistently found that the majority (60-80%) of patients were diagnosed with t-MDS with or without subsequent progression to t-AML [2
]. However, our data showed that t-AML (66.7%) was more common than t-MDS. This suggests the possibility of delayed diagnosis of t-MDS after progression to t-AML. Indeed, we observed that cytopenia preceded the diagnosis of t-AML in more than half of the 15 patients whose regular CBC data were available. Of these cases, persistent cytopenia was observed in 5 patients for 6 months before the diagnosis of t-AML, and in 2 patients for more than 1 yr.
Although our data do not demonstrate the survival rate of t-MN patients due to incomplete data regarding clinical outcome and a short follow-up period, it is well known that the survival of patients with t-MN is often poor despite prompt diagnosis and treatment [26
]. Poor survival of patients with t-MN is associated with multiple competing risks, including persistence of primary malignant disease, significant organ dysfunction from previous therapies, prolonged immunocompromised status, and lack of uniform treatment [4
]. Therefore, early diagnosis or prevention of this late complication of otherwise curative cancer therapies is critical, and close monitoring for signs of bone marrow dysfunction, such as progressive cytopenia, is necessary.
This study described the clinical and cytogenetic characteristics of Korean patients with t-MN. Although our results were generally consistent with those of previous reports, we found that t-MN from de novo leukemia was common and that t-AML was more common than t-MDS at presentation. Multi-institutional studies involving a larger number of patients and additional parameters are required to investigate the epidemiology, genetic predisposition, and survival rate of t-MN in Korea.