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1245 Long Term Survival of Chronic Myeloid Leukemia Patients with Chromosomal Aberrations in Philadelphia Negative Cells Treated with Tyrosine Kinase InhibitorsClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster I
Hematology Disease Topics & Pathways:
Biological, CML, Diseases, Therapies, Myeloid Malignancies, Clinically relevant, TKI
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Christos Varelas, MD, MSc1*, Anastasia Athanasiadou, MD PhD1*, Eleni Gavriilaki, MD2, Maria Gkaitatzi1*, Georgios Papaioannou1*, Tasoula Touloumenidou2*, Chrysanthi Vadikoliou1*, Chrysavgi Lalayanni1*, Niki Stavroyianni1*, Lila Papalexandri, MD1*, Ioannis Batsis1*, Ioanna Sakellari, MD PhD2* and Achilles Anagnostopoulos2

1Hematology Department - HCT Unit, George Papanikolaou Hospital, Thessaloniki, Greece
2Hematology Department and HCT Unit, George Papanikolaou General Hospital, Thessaloniki, Greece

Background: The emergence of novel clonal aberrations (NCAs) in Ph- metaphases of chronic myeloid leukemia (CML) patients (pts) has surfaced as a significant finding in the era of tyrosine kinase inhibitors (TKIs). Nevertheless, the biological and clinical impact of NCAs remains unclear.

Aims: We prospectively investigated the frequency and prognostic significance of NCAs among consecutive CML pts treated with TKIs in our center from 2002 to 2019.

Methods: We studied CML pts diagnosed and treated with TKIs according to relevant recommendations. Cytogenetic analyses were conducted on unstimulated bone marrow cells after cultures (24 & 48 hours) and at least 20 metaphases were analyzed. Data from patients with NCAs were recorded in detail (demographics, treatment, time to complete cytogenetic response/CCyR, time to major molecular response/MMR, survival).

Results: Among 200 CML pts, 21 (10,5%) developed NCAs in Ph- cells, with a median time from initiation of treatment with TKIs at 58 months (range 3-204). Fourteen pts received only imatinib, 1 dasatinib, 4 imatinib and as a second line of treatment nilotinib, and 2 imatinib followed by dasatinib. Patients’ data are presented in Table 1.

In 21 patients with NCAs, 15 had 1 abnormality, 4 had 2, 1 pt had 3 and 1 pt had 5 NCAs (in 2 pts the abnormalities were found in two different clones and in 1, in three clones). Ten pts without additional chromosomal abnormalities received only TKIs before the emergence of Ph (-) clone, while 11 pts received 1-5 (lines of treatment) prior to initiation of TKIs. Thus, number of abnormalities was associated with number of treatments before TKIs (p=0.030). Among these pts, 3 had undergone autologous hematopoietic cell transplantation (HCT), while 3 others received allogeneic HCT – 2 with persistent monosomy 7 and 1 with trisomy 8 and an extra X chromosome - after the emergence of these NCAs. Time to CCyR and MMR was significantly higher in pts that received allogeneic HCT, and pts with 3 abnormalities (Figure 1).

Eighteen pts had only numerical abnormalities, 1 only structural, and 2 both numerical and structural. We found abnormalities of chromosome Y in 9 pts; in 1 as an extra chromosome and 8 as a less chromosome (as a single abnormality in 7). Trisomy 8 was revealed in 9 pts, and monosomy 7 in 3. We also found other abnormalities as +X,+9, +13, +21, add(6)(q27),del(20)(q11), t(4;15)(q31;q26) and t(2;10)(q23;q24). Two pts had the same NCAs (-Y, +8) in Ph+ and Ph- cells. Three pts (2 with two different NCAs and 1 with three NCAs) maintained only one of them as persistent.

Eight out of 16 pts had a persistent clone for a median time of 76 months (range 2-192), 5 loss of chromosome Y, 2 trisomy 8 and 1 pt del(20q). All 16 pts had an optimal response (16/16 in CCyR, 2/16 in MMR and 14/16 in MR4.5).

With a follow-up of 156 months (range 20-300), 10-year overall survival was 87.1% (Figure 2). None of the studied factors was associated with poor survival. No evidence of myelodysplastic syndrome or acute leukemia has been described. All pts that received allogeneic HCT are alive.


We found NCAs in 10, 5% of CML pts treated with TKIs after long term follow up. Beyond previously reported NCAs, we also describe novel NCAs such as add(6)(q27), t (4;15)(q31;q26) and t(2;10)(q23;q24) that have never been reported. The significance of –Y needs to be further elucidated, since our study reports it in rather young pts. Importantly, our study confirms that NCAs do not impact outcomes of CML. However, the potential of cure with allogeneic HCT in pts with monosomy 7 should be kept in mind. Larger cohorts are needed to define the significance of NCAs, since the underlying pathophysiology remains unknown.

Disclosures: Gavriilaki: Omeros Pharmaceuticals: Consultancy.

*signifies non-member of ASH