3 research outputs found
Immunoglobulin mutational status detected through single-round amplification of partial VH region, represents a good prognostic marker for the clinical outcome in chronic lymphocytic leukemia
No full textThe immunoglobulin (Ig) mutational status in B-cell chronic lymphocytic leukemia (CLL) distinguishes two subsets of patients with different prognosis. Ig status detection is commonly performed with a panel of VH family-specific primers. Although this method detects clonal VDJ rearrangement in virtually all cases, it is technically cumbersome and therefore not widely used clinically. Here, we describe a simple and rapid method to establish the mutational status of IgVH in CLL. The method is based on a consensus VH FR2 primer, used in both polymerase chain reaction (PCR) and sequencing reactions. Overall, monoclonal B-cell populations were detected in 163 of 189 CLL patients (86%). The prognostic value of IgVH mutational status was then evaluated by analyzing survival in 146 CLL cases using different VH homology cutoffs. CLL prognostic groups were best separated by the classical 98% cutoff: median survival was 127 and 206 months in unmutated and mutated CLL cases, respectively (P = 0.0023). VH FR2 consensus and VH family PCR were compared in 41 cases, correctly assigning all cases by both methods. Therefore, we suggest a sequential strategy to detect immunoglobulin mutational status in CLL patients by first using the approach described in this study followed by alternative VH family-specific PCRs for negative cases
The length of treatment of aggressive non-Hodgkin's lymphomas established according to the international prognostic index score: long-term results of the GISL LA03 study
No full textObjectives: To compare two different schedules of two different anthracycline-containing regimens, where length of treatment is modulated according to the international prognostic index (IPI) in patients with aggressive non-Hodgkin's Lymphoma (NHL). Methods: In 1993 the Gruppo Italiano per lo Studio dei Linfomi (GISL) started a randomized 2 x 2 factorial phase III clinical trial for patients with newly diagnosed aggressive NHL comparing ProME(Epidoxorubicin)CE-CytaBOM (PE-C) to ProMI(Idarubicin)CE-CytaBOM (PI-C) and a fixed to a flexible treatment schedule where anthracycline dose was to be modulated according to observed hematological toxicity. Patients with low or low-intermediate IPI (IPI 0-2) and those with intermediate-high or high IPI (IPI 3-5) should receive six or eight courses, respectively. Involved-field radiotherapy was allowed for patients with initial bulky disease or with residual masses. Results: Three hundred and fifty-six patients were registered into the study and randomized. Patients were well balanced among the four study arms in terms of clinical characteristics and prognostic factors. Three hundred and forty-five patients were available for evaluation of study endpoints. At the end of induction therapy complete remission rate was 61%, 5-year failure-free survival (FFS) rate was 40% and 5-year overall survival (OS) rate was 59%; no differences were observed according to treatment arms. Patients in the flexible arm received higher dose intensity of anthracycline (P < 0.001) with no apparent increase in toxicity. However, the flexible schedule was not superior to the fixed one. Patients with IPI 3-5 showed lower response rates (45% vs. 67%: P < 0.0001) and lower 5-year FFS (29% vs. 45%: P < 0.0001) compared to those with IPI 0-2. Conclusions: six courses of fixed or flexible PE-C or PI-C can determine a promising success rate in patients with advanced aggressive NHL with IPI 0-2, whereas the same regimens are less effective in patients with IPI 3-5, even if two additional courses are delivered. For the latter group of patients innovative approaches are warranted
Paraneoplastic endocrine-metabolic syndromes
No full textBACKGROUND The paraneoplastic syndromes (PS) are characterized by the presence of biochemical alterations, signs and symptoms expressive of cancer distance action into the patient’s organism. Sometimes these syndromes can precede the evidence of malignancy even of some years or can correspond to cancer relapse. PS, even being characterized by general symptoms (fever, anorexia, cachexia), may occur with neurological, rheumathological, osteoarticular, vascular, haematological, nephrological and endocrinological/metabolic symptoms; the latter ones are discussed in this article. AIM OF THE STUDY Here we will focus on the most common PS: paraneoplastic hypercalcemia, inappropriate secretion of antidiuretic hormone (SIADH) and paraneoplastic Cushing syndrome. CONCLUSIONS Our work can be useful in the diagnosis and therapeutic management of paraneoplastic syndromes
