Clonal Chromosomal Abnormalities in Philadelphia negative cells (Ph-) of Chronic Myeloid Leukemia (CML) patients during Tyrosine Kinase Inhibitors (TKIs) treatment: Argentine Experience

LABARTA D; VARELA A; FIGUEROA; ZARATE T; PAVLOVSKY C; GIERE I; VERRI V; GONZALEZ J ; FLORES G; LARRIPA I; MERCADO GUZMAN V; OTERO I; ARDAIZ M; MOIRAGHI E

Cancun

Congreso; XXXIV World Congress of the International Society of Hematology (ISH); 2012

International Society of hematology

Introduction: Clonal cytogenetic abnormalities in Ph- cells of CML patients  during á-Interferon and TKI  treatment have been previously described. These are evaluable only in patients who achieve some type of cytogenetic response. This is different from clonal evolution that refers to additional chromosomal changes in Ph+ cells. Objective: To evaluate  the frequency and significance of Ph- chromosomal abnormalities in  a cohort of Argentinian  CML patients one during first or second line TKI therapy: Imatinib (IM), Dasatinib (D) and Nilotinib (N) Material and methods:  A retrospective analysis was performed in order to calculate the frequency of Ph- abnormalities. Cytogenetics: Chromosome analysis of unstimula- ted Bone marrow(BM) or Peripheral blood(PB) cultures and PHA-stimulated PB cultures (constitutional karyotype) was performed by GTG-banding . FISH: CEP 8,  cytocell  probe and double fusion bcr/abl, LIVE-LEXEL. Results: 193 patients were analysed:  79.8% (154/193) treated with IM; 15%  (29/193) with  Dasatinib  and   5.2%  (10/193) with Nilotinib, with a median follow up of 28 months   (range: 13-41)  Data for each ITK are shown in table 1.  Total frequency of Ph- abnormalities was: 5.7% (11/193). Some  of these abnormalities disappeared  during the patients’ follow up. Some patients presented cytopenia and/ or evolution to advanced phases CML. Conclusions: -Some of the abnormalities described in this  cohort have  already been  reported (Trisomies 6 , 8, XYY and monosomy 7), being T8 and -7 the most frequent. Trisomy  6  has been reported in one patient under IM treatment but our patient received N. This is the first report of Trisomy 6  in patients receiving second generation ITKs. We found not reports of Trisomy 11 and 13 in the literature. - Monosomy 7 , as previously reported was related poor prognosis. Trisomy 11 and 13  as sole abnormalities  are indicators of poor prognosis in other hematologic malignancies.Our patient with Trisomy 11 had a poor outcome. - All this indicates the importance that patients on TKIs, that have achieved some grade of cytogenetic response, should be regularly followed with cytogenetic  techniques besides of RT-PCR  for bcr/abl, not only to evaluate the decrease of Ph+ cells, but also to look for Ph- chromosomal abnormalities.