ADDITIONAL TRISOMIES AMONGST PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA CARRYING TRISOMY 12: THE PARTNER CHROMOSOME MAKES A DIFFERENCE

Konference: 2015 20th Congress of the European Hematology Association - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Poster

Číslo abstraktu: P586

Autoři: Panagiotis Baliakas; Anna Puiggros; Aliki Xochelli; Lesley-Ann Sutton; Florence Nguyen-Khac; Anne Gardiner; Mgr. Karla Plevová (roz. Malinová), Ph.D.; Margarita Ortega; Rosa Collado; Teresa González; Isabel Granada; Dr. Elisa Luno; Mgr. Jana Kotašková; Zadie Davis; Dr. Achilles Anagnostopoulos; BSc. Jonathan C. Strefford, PhD; prof. RNDr. Šárka Pospíšilová, Ph.D.; MD Frederic Davi, PhD; Anastasia Athanasiadou; Prof. MD Richard Rosenquist (Brandell), PhD; Prof. David Graham Oscier; Blanca Espinet Sola; MD Kostas Stamatopoulos

Background
Trisomy 12 (+12), the second most frequent recurrent chromosomal aberration in chronic lymphocytic leukemia (CLL), is associated with clinical and biological heterogeneity. We and others previously reported a minor fraction of +12 cases with co-existence of trisomy 19 displaying distinctive clinicobiological characteristics. However the respective cohorts were small, precluding definitive conclusions.

Aims

Detailed characterization of cases with multiple trisomies in a large series of CLL patients carrying +12, aiming to identify distinctive profiles that would assist in further dissecting the heterogeneity of this major cytogenetic subgroup.



Methods

Within a multi-institutional series of 4486 CLL patients with available classic cytogenetic data, we identified 713 cases (16%) with trisomy 12, of whom 87 (12%) harbored multiple trisomies. Sixty-eight of these 87 cases (78%) had co-existing +19 (group A: +12,+19 CLL), while the remaining 19/87 cases (22%) had other co-existing extra chromosome(s)  (group B: +12,+other trisomy CLL). The median time from diagnosis to karyotype analysis was 1.5 months (range, 0-194); the great majority of cases with available treatment/survival information were untreated prior to testing (73/78 cases, 94%). FISH data for the Döhner model aberrations was available in 67/87 (77%) cases. Within the same CLL series, we identified 68 cases with isolated +12 and available clinicobiological data, which were used as a control group for the survival analysis (group C).



Results
In group A, 43/68 (63%) cases also harbored +18. Extra structural abnormalities were detected in 12/63 (18%) cases, mostly concerning deletions and/or translocations involving the 13q chromosome in 7/12 (58%) cases. Interestingly, the great majority of cases harboring extra structural abnormalities (10/12, 83%) displayed +12+18+19 highlighting an association between +18 and clonal evolution. In contrast, no structural abnormalities were observed in group B, within which trisomy 3 predominated, being detected in 8/19 (42%) cases, followed by trisomies 18 and 22 in 6 (32%) and 4 (21%) cases respectively Moreover, different clinicobiological profiles were observed between the two groups. In particular, group A displayed (i) higher incidence of M-CLL (42/45, 95% vs 6/8, 75%, p=0.045); (ii) younger median age at diagnosis (59 years vs 67 years, p=0.007); (iii) ubiquitous surface IgG expression (23/23, 100% vs 2/8, 25%, p<0.0001); (iv) higher incidence of del(13q) (27/51, 53% vs 0/11, 0%, p=0.0002); and (v) higher incidence of monoclonal gammopathy (23/37, 62% vs 2/8, 25%, p=0.05). Group B displayed higher incidence of: (i) clinical/laboratory autoimmunity (5/10, 50% vs 2/33, 6% in group A, p=0.0009); and (ii) other malignancies (6/11, 55% vs 4/48, 8% in group A, p=0.0002). Furthermore, each group displayed significant differences (p<0.05) when compared to control group C regarding the aforementioned features. Regarding survival analysis, Groups A and B exhibited longer overall survival compared to Group C (median OS: not reached for Groups A and B vs 8 years in Group C; log-rank test, group A vs C, p=0.08, and group B vs C, p=0.036). 

Summary

The presence of extra trisomies defines subgroups of cases with distinctive clinicobiological profiles within +12 CLL cases, further highlighting their heterogeneous biological background and clinical outcome.

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Datum přednesení příspěvku: 13. 6. 2015