Prognostic Value of Serum Free Light Chain in Multiple Myeloma.

The measurement of serum free light chain (sFLC) has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. The aim of the present work was to study the prognostic value of sFLC in multiple myeloma in relation to other serum biomarkers, response to therapy and survival. Forty five newly diagnosed patients with MM were included in the study. Patients were divided into responders and non-responders groups according to response to therapy. sFLC and serum Amyloid A (SAA) were measured by immunonephelometry. The non-responders group showed a statistically significant higher kappa/lambda or lambda/kappa ratio and higher ß2 microglobulin level, but lower albumin level at presentation, as compared to the responders group (P < 0.001). However, no statistically significant difference was detected between the two groups regarding SA A or calcium levels. Comparison between sFLC ratio obtained before and after therapy revealed significant decrease after treatment in the responders group (P = 0.05). Survival was significantly inferior in patients with an FLC ratio of ≥ 2.6 or ≤ 0.56 compared with those with an FLC ratio that was between 0.56 and 2.6 (P = 0.002).

MTHFR C677T polymorphism: association with lymphoid neoplasm and effect on methotrexate therapy.

The aim of this study was to detect the possible role of methylene tetrahydrofolate reductase gene polymorphism (MTHFR C677T) in the pathogenesis of lymphoid neoplasms and to investigate the influence of this polymorphism on methotrexate toxicity in adult ALL patients treated with methotrexate maintenance therapy. There was a statistically significant increase in the risk of non-Hodgkin lymphoma in patients with CT genotype (OR, 2.9; 95% CI, 1.3-6.3; P = 0.007) and combined CT + TT genotype (OR, 3.2; 95% CI, 1.5-6.6; P = 0.006). While no significant association was found between this polymorphism and ALL risk. The patients with ALL treated with methotrexate during maintenance therapy were observed for signs of toxicity. MTHFR 677C>T polymorphism (CT + TT) was significantly overrepresented among cases with hepatic toxicity (OR = 15.6; 95% CI, 2.6-81.3; P = 0.001). In addition, they were overrepresented among cases with mucositis, anemia, thrombocytopenia, and leukopenia. However, it did not reach statistical significance level. Further studies on larger number of subjects are necessary. Additional studies on the role of MTHFR gene polymorphism with environment (folate intake) interaction are needed to confirm the role of these genetic polymorphisms.

Angiogenic factor VEGF and its relationship with biological prognostic markers in chronic lymphocytic leukemia.

B-CLL is a heterogeneous disease, distinguishing between good and poor prognosis represents a challenge to hematologists. The present study aimed to assess the relative merit of VEGF as a prognostic factor in CLL and to correlate it with other prognostic factors as CD38 & sP53 in the different stages of the disease. The median values of CD38%, sP53 and VEGF were significantly higher in both high and intermediate risk subgroups of the modified Rai staging system when compared to low risk subgroup. There was a statistically significant positive correlation between CD38% and VEGF in all subgroups. However, positive correlation between VEGF and sP53 was only observed in the high risk subgroup. The strong correlation between CD38 and VEGF in CLL patients, suggests the possibility that angiogenic factors might contribute to the more aggressive clinical behavior of CD38+ CLL. This could provide a rationale for the use of antiangiogenic agents in CD38+ CLL.

Changes of serum growth factors (IGF-I & IGFBP-2) and prediction of response to chemotherapy in patients with acute myeloid leukemia.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) possess mitogenic properties promoting cellular proliferation and inhibiting cellular apoptosis. Thus, IGF-system may play a role in tumor proliferation. In the present study, we investigated IGF-I and IGFBP-2 in patients with acute myeloid leukemia (AML) for their predictive value to identify patients who could be responsive to conventional induction chemotherapy. Serum levels of IGF-I and IGFBP-2 were measured (using commercial ELISA kits) in 22 patients with AML. Following treatment, patients were followed up 14 days after the induction cycle to determine if they achieved hematological remission or not. Accordingly, patients were divided into two groups: Responders (10 patients) and Non-Responders (12 patients). No significant difference was observed in IGF-1 between Responders and Non-Responders, neither before (79.26 +/- 4.568 pg/ml vs 72.225 +/- 3.62 pg/ml, respectively) nor after induction cycle (74.87 +/- 3.669 pg/ml vs 69.783 +/- 4.329 pg/ml, respectively). However, IGFBP-2 was significantly lower in Responders than in Non-Responders both at diagnosis (4250 +/- 155.099 pg/ml vs 6866.67 +/- 352.122 pg/ml, respectively) as well as after induction cycle of chemotherapy (4130 +/- 324.225 pg/ml vs 7150.00 +/- 265.290 pg/ml, respectively). It is concluded that, serum IGFBP-2 is considered as an independent factor that adds additional information for the prediction of relapse or treatment failure and patients with concentration > or = 4900 pg/ml at diagnosis are suspected to be nonresponders to conventional induction chemotherapy.