Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Παναγιώτης Παναγιωτίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Δερβενούλας, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πάγκαλης Γεράσιμος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία-Χριστίνα Κυρτσώνη, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Φλώρα Κοντοπίδου, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παναγιώτης Τσιριγώτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Στέλλα Κοκκόρη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Κυτταρογενετικές μεταβολές κατά τη πορεία του Πολλαπλού Μυελώματος, ΧΛΛ/SLL την εποχή των σύγχρονων θεραπευτικών προσεγγίσεων
Translated title:
Cytogenetic aberrations during the course of Multiple Myeloma, CLL/SLL in the era of new therapeutic approaches
Summary:
Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) are very different lymphoproliferative disorders that however share considerable clinical heterogeneity.
The purpose of the present study that started in 2010, was to evaluate the impact of cytogenetic abnormalities in disease course and prognosis. At that time the adverse significance of specific alterations such as abnormal karyotype or the presence of t(4;14), t(14;16), t(14;20), and deletion 17p by FISH in symptomatic MM at diagnosis had just been shown and were not included in the routine diagnostic workout; del13q was more widely tested. In CLL karyotypic studies were not performed, while the significance of mutational status, deletion p53 and 11q were used as prognostic markers.
More than 600 patients with CLL and MM at diagnosis were initially tested by FISH for del 17p and 11q in CLL and for del 13 and t(4;14) in MM. However, because of external reasons the study became on hold for a period of time and when it resumed, clinical practice regarding cytogenetic evaluation in both diseases had evolved; the prognostic significance of the former was proved, t(4;14), t(14;16), and del17p by FISH was mandatory for MM patients’ staging at diagnosis (RISS), while in CLL del 17p guided treatment choices.
Given that the initial study protocol had become out of date, we focused on 204 MM patients and 120 CLL and SLL relapsed/refractory patients and evaluated the prognostic significance of cytogenetic abnormalities evaluated at relapse, before treatment in MM patients receiving lenelidomide-dexamethasone (RD) and CLL/SLL patients under ibrutinib.
We showed that hyperdiploid karyotype was an adverse marker for relapsed MM patients treated with RD either they presented additional abnormalities or not. The presence of del 17p at a high percentage always deteriorated prognosis, while serum albumin, beta2-microglobulin LDH had no impact on prognosis in the present analysis.
In CLL/SLL, response indeed correlated with the longevity of treatment and survival. Of special interest was the finding that patients with at least two chromosomal alterations on karyotype had a statistically significant worse outcome than the others when treated with Ibrutinib. In the present analysis, mutational status and del 17p had no impact.
Further studies are needed to confirm our results, although already, shortly after us, the importance of karyotype at diagnosis in CLL patients treated at first line with Ibrutinib, was shown.
Main subject category:
Health Sciences
Keywords:
Multiple myeloma, Chronic lymphocytic leukemia/Small lymphocytic lymphoma, Cytogenetic aberrations, New therapeutic agents
