Isolated clonal cytogenetic abnormalities after high-dose therapy

Therapy-related myeloid neoplasms (t-MN) are well-recognized complications of high-dose cytotoxic therapy (HDT), such as autologous stem cell transplantation (ASCT). Clonal marrow cytogenetic abnormalities (CMCA) in the setting of normal bone marrow pathology have also been reported after HDT, but their significance remains unclear. We retrospectively evaluated occurrences of CMCA and t-MN in 785 patients treated with HDT at Johns Hopkins University between 1997 and 2007. Most patients received ASCT, but 106 patients who received high-dose cyclophosphamide without ASCT were also included in this study, as this is our institutional standard for malignant and nonmalignant lymphoproliferative disorders in need of HDT. Twenty-two patients developed t-MN, with an estimated cumulative incidence of 3.5% at 4 years. Eleven patients developed isolated CMCA, either transient or persistent without pathologic evidence of t-MN. Altogether, only 20 of the patients with reported CMCA subsequently developed t-MN during the follow-up period. Therefore, in the absence of pathologic evidence of t-MN, CMCA should not be considered diagnostic of t-MN.