Evangelia M. Dimitriadou

Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma

The prognostic value of baseline serum free light chain ratio (sFLCR) was investigated in 94 multiple myeloma (MM) patients. sFLCR was calculated as κ/λ or λ/κ, depending on the patients’ dominating monoclonal light chain. Median baseline sFLCR was 3·57 in κ‐MM patients, 45·09 in λ‐MM. ‘High’ sFLCR (≥ the observed median value for κ‐ and λ‐MM respectively) correlated with elevated serum creatinine and lactate dehydrogenase, extensive marrow infiltration and light chain type MM. The 5‐year disease‐specific survival was 82% and 30% in patients with sFLCR lower than and equal or greater than the median, respectively (P = 0·0001). sFLCR was an independent prognostic factor.

Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib

Bortezomib is a proteasome inhibitor producing high response rates in patients with relapsed/resistant multiple myeloma patients. This study investigates the effect of bortezomib on circulating angiopoietins levels, and shows that the normalization of the angiopoietin-1/angiopoietin-2 ratio reflects the response to treatment. Neoangiogenesis is involved in the pathophysiology of multiple myeloma and angiopoietins possibly contribute to myeloma-induced neovascularization. Bortezomib’s antineoplastic potential includes an anti-angiogenic effect. We determined serum levels of angiopoietin-1 and angiopoietin-2 with ELISA pre- and post-bortezomib administration in 35 patients with relapsed/refractory multiple myeloma. Pre-bortezomib, serum angiopoietin-1 levels did not differ in patients and in healthy individuals, while serum angiopoietin-2 levels were elevated. Corresponding serum angiopoietin-1/angiopoietin-2 ratio was reduced in patients compared with controls. After treatment, serum angiopoietin-1 levels increased, while serum angiopoietin-2 levels decreased, therefore the angiopoietin-1/angiopoietin-2 ratio increased and normalized. This increase was significant in patients who responded to treatment. In conclusion, angiopoietin-1/angiopoietin-2 ratio normalization reflected response to bortezomib.

Topoisomerase IIα Expression as an Independent Prognostic Factor in Hodgkin's Lymphoma

Purpose: To correlate the immunohistochemical expression of topoisomerase IIα (topoIIα) in Hodgkins lymphoma (HL) with clinicopathological parameters, the expression of Ki-67 and the outcome of patients, who had been homogenously treated with ABVD or equivalent regimens. Experimental Design: Immunohistochemistry using the monoclonal antibody Ki-S1 (topoIIα) was performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238. Results: The mean ± SD percentage of topoIIα- and Ki-67–positive Hodgkin-Reed-Sternberg (HRS) cells was 63 ± 19% (5%-98%) and 73 ± 19% (8%-99%), respectively. The median percentage of topoIIα-positive HRS cells was 64% (interquartile range, 51-78%). There was no correlation between topoIIα expression and patient characteristics. TopoIIα and Ki-67 expression were correlated (Spearmans Rho 0.255, P < 0.001). TopoIlα expression within the highest quartile of this patient population was predictive of failure free survival (FFS) (10-year rates 82 ± 3% vs 68 ± 7%, P = 0.02 for patients falling into the quartiles 1-3 and 4 respectively). In multivariate analysis topoIIα expression was independently predictive of FFS. Conclusion: TopoIIα was expressed in all cases of HL showing a correlation with Ki-67 expression. Under current standard therapy including drugs inhibiting its activity, topoIIα was an independent adverse predictor of FFS with no statistically significant correlation with other established prognostic factors.

Immunotherapeutic and immunoregulatory drugs in haematologic malignancies.

A better understanding of the biology and pathogenesis of hematological malignancies has led to the development of immunotherapeutic and immunoregulatory drugs. Many of these agents have revolutionized the current treatment modalities, while others are under investigation. Rituximab (anti-CD20 antibody) has been established as the gold standard of treatment for aggressive B-cell lymphomas in combination with CHOP and has shown significant activity as monotherapy in the treatment of indolent B-cell lymphomas. In follicular lymphomas the combination of Rituximab with chemotherapy improves the outcome compared to chemotherapy alone. CD 20-based radioimmunotherapy, with the advantage of the bystander effect, represents an additional therapeutic alternative in B-cell lymphomas and may produce tumor regression in Rituximab resistant patients. The anti-CD52 monoclonal antibody, alemtuzumab, further expands the armamentarium against lymphoid malignancies producing high response rates in these entities. Antibody-targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33 antibody combined to calicheamicin, has shown efficacy in the treatment of refractory acute myeloid leukemia; exact indications, timing and dosing schedule for optimized efficacy remain to be determined. Interferons have proven significant activity in cutaneous lymphomas, hairy cell leukemia and chronic myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic cells microenvironment and lead to disease control in multiple myeloma as well as in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor, displays significant anti-tumor activity, especially in multiple myeloma and lymphoproliferative disorders. The addition of these agents in therapeutic regimens has improved considerably the treatment of hematological malignancies.