Clonal Chromosomal Abnormalities in Philadelphia Negative Cells during Dasatinib Treatment in Five Patients with Chronic Myeloid Leukemia.

The emergence of clonal chromosomal abnormalities in Philadelphia negative cells was reported during Imatinib treatment in several patients with chronic myeloid leukemia (CML) in different phases (chronic phase, accelerated phase and blastic crisis). Recently, new tyrosine kinase inhibitors were used in treatment of Imatinib-resistant or Imatinib-intolerant chronic myeloid leukemia. We describe 5 patients with chromosomal abnormalities in Philadelphia negative cells during treatment with Dasatinib. At the beginning of treatment, 4 patients were in chronic phase, 1 patient was in accelerated phase. All patients were in cytogenetic relapse. Additional cytogenetic abnormalities were described in Philadelphia positive cells only in one case (accelerated phase). Clonal cytogenetic abnormalities (4 trisomy 8, 1 monosomy 7) appeared in Philadelphia negative cells during Dasatinib treatment (after 6 months in 1 patient, 9 months in 4 patients).At this time, 4 patients (Imatinib- resistant) received Dasatinib at the dose of 40 mg twice daily (dose reduction due to hematological toxicity); 1 patient (Imatinib cutaneous intolerance in chronic phase) received 140 mg daily. Two patients were in complete cytogenetic response, 2 patients were in partial cytogenetic response (10% and 8.5% Philadelphia positive cells) and obtained a complete cytogenetic response 3 months later, and 1 patient was in minor cytogenetic response. For 2 patients, the presence of trisomy 8 was transient, for 3 patients chromosomal abnormalities were persistent; none showed myelodysplastic changes. At present, all patients are still treated by Dasatinib with the same dosage. Cytogenetic abnormalities occur in Philadelphia negative cells in a fraction of patients with CML treated with Dasatinib. Philadelphia negative abnormal clone can persist despite complete cytogenetic response achievement. Their incidence, etiology and prognosis remain to be clarified and with a short follow-up, no clear clinical consequences can be identified.