Philadelphia chromosome mosaicism at diagnosis in chronic myeloid leukemia: clinical correlates and effect on imatinib mesylate treatment outcome

In chemotherapy-treated patients with chronic myeloid leukemia (CML), the karyotypic detection of Philadelphia chromosome (Ph)-negative metaphases at diagnosis (i.e. Ph mosaicism) is not considered significant as a prognostic factor for survival. In the current retrospective study, clinical correlates and prognostic relevance of Ph mosaicism were evaluated in 63 Ph-positive patients with CML, including 59 in chronic phase and 4 in accelerated phase, receiving imatinib mesylate as either first (n = 46) or second (n = 17) line therapy. Thirteen patients (21%) displayed Ph-negative metaphases at diagnosis and, compared to the other 50 patients with 100% Ph-positive metaphases, presented with significantly lower leukocyte count (p = 0.0004), circulating blast percentage (p = 0.02), and incidence of palpable splenomegaly (p = 0.02). Ph mosaicism did not correlate with other CML-pertinent prognostic factors including Sokal score (p = 0.4) or the presence of additional chromosome changes (p = 0.96) found in 10 patients (16%). Neither Ph mosaicism nor the presence of additional chromosome changes affected complete or partial cytogenetic remission rates to IM. Multivariable analysis identified Ph mosaicism as a risk factor for shortened survival. Due to the small sample size, the current preliminary observations require validation in a larger group of patients.