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1.  First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation 
Journal of Blood Medicine  2012;3:151-156.
The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of issues have emerged and partially obscured this scenario. First, it has become clear that a significant proportion of patients either present with primary resistance to imatinib or develop secondary resistance sooner or later during treatment. Second, although the drug is generally well tolerated, a percentage of patients eventually cease treatment because of toxicity. Bearing this in mind, second-generation tyrosine kinase inhibitors have been introduced, including nilotinib. Phase I and II studies indicate remarkable activity for this compound in CML cases resistant to imatinib, including some of those carrying BCR-ABL1 mutants. More recently, two Phase II studies and a III randomized Phase clinical trial demonstrated the superiority of nilotinib compared with imatinib in terms of complete cytogenetic and major molecular responses, which are two relevant surrogate measures of long-term survival in CML. In this paper, we review the most relevant data on nilotinib as first-line treatment for CML, and discuss the rationale for its routine use, as well as some possible future perspectives for CML patients.
doi:10.2147/JBM.S13067
PMCID: PMC3514971  PMID: 23226701
chronic myeloid leukemia; nilotinib; targeted therapy; BCR-ABL1
2.  Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience 
Diagnosis of B-non Hodgkin lymphomas (NHLs) is based on clinical, morphological and immunohistochemi-cal features. However, in up to 10-15% of cases, analysis of immunoglobulin heavy (IGH) or light (IGK/IGL) chains genes is required to discriminate between malignant and reactive lymphoid proliferations. In this study, we evaluated the feasibility and efficiency of IGK analysis in the routine diagnostic of B-cell lymphoproliferative disorders (B-LD) when applied to formalin-fixed paraffin-embedded (FFPE) tissues. Clonality patterns were studied in 59 B-LD using the BIOMED-2 protocol for IGK assays, after failure of the IGH assay. PCR products were evaluated by both heterodu-plex and GeneScan analysis. IGK analysis was technically successful in all cases. Overall, it supported the histopa-thological suspicion in 52/59 cases (88%), the sensitivity and specificity being 83% and 80%, respectively. Further, positive and negative predictive values were 95% and 50%, respectively. Interestingly, among various lymphoma subtypes, marginal zone lymphoma and follicular lymphoma most frequently required IGK analysis. In conclusion, IGK study according to the BIOMED-2 protocol resulted feasible and extremely useful in supporting challenging diagnosis of B-LD even if applied on FFPE samples. Accordingly, when NHL is suspected, negative results at IGH analysis should not be considered as conclusive and further investigation of IGK is appropriate.
PMCID: PMC3301430  PMID: 22432078
BIOMED-2; molecular diagnostic; IGK; non Hodgkin lymphoma; PCR

Results 1-2 (2)