Serum Soluble TACI, a BLyS Receptor, Is a Powerful Prognostic Marker of Outcome in Chronic Lymphocytic Leukemia

BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells' surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients' outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS ( = −0.000021), b2-microglobulin ( = 0.005), anemia ( = −0.03), thrombocytopenia ( = 0.04), Binet stage ( = 0.02), and free light chains ratio ( = 0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT ( = 0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival ( = 0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS

Prognostic impact of serum free light chain ratio on multiple myeloma patients and biological mechanisms regulating free light chain secretion by neoplasmatic plasma cells

Multiple Myeloma (MM) is the most common hematological malignancy. It emerges through the clonal change of Plasma cells, that is B – Lymphocytes that have reached their final stadium of differentiation. Clonal Plasma cells secrete monoclonal Immunoglobulin, of which light chains are produced in excess and can be detected in serum as free light chains (FLC) with special techniques that were developed in the last years. Serum Free Light Chain Ratio (sFLCR) has been proven to be an independent prognostic survival factor and has been also implicated in the new disease response criteria after treatmentIn this study we measured serum levels of s-synd-1, VEGF, BLyS, IL – 6 and sIL – 6R. These cytokines have been object of investigation in MM as they are elements of the bone marrow microenvironment, with which malignant Plasma cells interact. It was found that s-synd-1 and VEGF levels correlate with sFLCR, implying a possible relation in their physiology. Furthermore it was shown that serum levels of s-synd-1 and BLyS at diagnosis constitute prognostic factors for survival, although only s-synd-1 is an independent prognostic factor.Next, in a multicentral study we analyzed the importance of sFLCR in the prognosis of MM patients. We confirmed previous findings and demonstrated its importance. Trying to improve it use in clinical practice we created three prognostic models combining sFLCR and established prognostic disease parameters. Finally we analyzed the prognostic impact of sFLCR and other established prognostic disease parameters in patients that received treatment with novel agents. Results showed that the patients’ group that benefits the most out of the treatment with novel agents are those, who suffer from aggressive disease, that presents with high ISS stadium, high sFLCR and abnormal high LDH. In accordance treatment with novel agents obscures the negative prognostic impact of the aforementioned factors.Το Πολλαπλούν Μυέλωμα είναι η συχνότερη αιματολογική κακοήθεια. Προέρχεται από την κλωνική εξαλλαγή των πλασματοκυττάρων, Β – λεμφοκυττάρων που βρίσκονται στο τελευταίο στάδιο διαφοροποίησης τους. Τα κλωνικά πλασματοκύτταρα παράγουν μονοκλωνική ανοσοσφαιρίνη, της οποίας οι ελαφρές άλυσοι εκκρίνονται σε περίσσεια και ανιχνεύονται στον ορό με ειδικές τεχνικές που τελειοποιήθηκαν τα τελευταία έτη.Ο λόγος των ελεύθερων ελαφρών αλύσεων έχει αποδειχθεί ότι αποτελεί ανεξάρτητο προγνωστικό παράγοντα επιβίωσης ενώ έχει ενσωματωθεί και στα νέα κριτήρια ανταπόκρισης της νόσου μετά από θεραπεία.Στη μελέτη αυτή έγινε μέτρηση των κυτταροκινών s-synd-1, VEGF, BLyS, IL – 6 και sIL – 6R. Οι παραπάνω ουσίες αποτελούν αντικείμενο μελέτης στο ΠΜ καθώς αποτελούν βασικά συστατικά του μικροπεριβάλλοντος του μυελού με το οποίο αλληλεπιδρούν τα μυελωματικά πλασματοκύτταρα. Βρέθηκε ότι τα επίπεδα του s-synd-1 και του VEGF σχετίζονται με το λόγο των ελεύθερων ελαφρών αλύσεων, υποδηλώνοντας πιθανή σχέση στη φυσιολογία τους. Επιπλέον διαπιστώθηκε ότι τα επίπεδα των κυτταροκινών s-synd-1 και BLyS κατά τη διάγνωση αποτελούν προγνωστικό παράγοντα επιβίωσης, παρόλο που μόνο ο s-synd-1 αποδείχθηκε ανεξάρτητος προγνωστικός παράγοντας.Στη συνέχεια στα πλαίσια πολυκεντρικής μελέτης αναλύθηκε η σημασία του ΛΕΕΑ στην επιβίωση των ασθενών με ΠΜ. Επιβεβαιώθηκε η προγνωστική του σημασία. Στο πλαίσιο της προσπάθειας βελτίωσης της κλινικής πρακτικής δημιουργήθηκαν τρία προγνωστικά μοντέλα συνδυάζοντας τον ΛΕΕΑ με γνωστές προγνωστικές παραμέτρους της νόσου.Τέλος δόθηκε ιδιαίτερη βαρύτητα στη μελέτη της επίδρασης του ΛΕΕΑ και άλλων καθιερωμένων προγνωστικών παραμέτρων στους ασθενείς που λαμβάνουν θεραπεία με τους νέους παράγοντες. Τα αποτελέσματα έδειξαν ότι ότι οι ασθενείς που ωφελούνται περισσότερο από τη θεραπεία με ΝΠ είναι εκείνοι με επιθετική νόσο που εκδηλώνεται με υψηλό στάδιο ISS, υψηλό ΛΕΕΑ και παθολογική LDH. Κατ’ επέκταση η θεραπεία με ΝΠ μετριάζει την αρνητική προγνωστική σημασία των παραπάνω παραγόντων

Efficacy-safety of Facilitated Subcutaneous Immunoglobulin in Immunodeficiency Due to Hematological Malignancies. A Single-Center Retrospective Analysis

Background/Aim: Hematological malignancies are frequently complicated by secondary immunodeficiency (SID). Immunoglobulin replacement with intravenous gamma globulins (IVIg) reduces infection incidence, antibiotics’ need and hospitalization days in these patients. Facilitated subcutaneous immunoglobulin replacement (fSCIg) has been studied in primary immunodeficiency patients and is equally efficacious with several advantages (self-administration, same bioavailability, long infusion intervals, fewer adverse drug reactions). fSCIg has been less extensively studied in SID. We present our retrospective single-center data of fSCIg administration to hematological patients with SID, focusing on efficacy and safety issues. Patients and Methods: Overall, 33 hematological patients with hypogammaglobulinemia were treated with fSCIg according to ESMO 2015 guidelines, between mid-October 2015 and mid-January 2018 in our Department. Results: The infection rate was very low (18.1%). Shorter infusion intervals further reduced it. ADRs were rare (9%) and mild (grade 1). fSCIg managed to reduce the everyday nursery/hospital burden of our tertiary hospital. Conclusion: fSCIg compares favorably to IVIg replacement in SID patients

Serum Soluble TACI, a BLyS Receptor, Is a Powerful Prognostic Marker of Outcome in Chronic Lymphocytic Leukemia

BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells’ surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients’ outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P=-0.000021), b2-microglobulin (P=0.005), anemia (P=-0.03), thrombocytopenia (P=0.04), Binet stage (P=0.02), and free light chains ratio (P=0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P=0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P=0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS