Clinical Leukemia最新文献

Concurrent occurrence of 2 specific chromosome translocations is a relatively rare phenomenon and only occasionally has been described in hematologic malignancies. Individual cases concurrently harboring c-MYC/immunoglobulin (Ig)H and Bcl-6/IgH rearrangements have been previously reported in B-cell malignancies; however, the occurrence of 3-way translocations simultaneously affecting 3 key genes involved in the pathogenesis was described only in individual cases. This report describes a patient diagnosed with acute lymphoblastic leukemia with genetic alterations concurrently affecting the c-MYC, Bcl-6, and IgH loci in addition to the rearrangement of the long arm of chromosome 1. Our case might be of interest because of the: (1) concurrent translocations of Bcl-6 and c-MYC oncogenes to the same IgH loci as a result of a 3-way recombination; (2) disruption of the bcl-6 gene because of the cryptic insertion of IgH in 3q27; (3) presence of jumping translocation affecting the long arm of chromosome 1; and (4) further illustration of the utility of fluorescence in situ hybridization studies in the identification of cryptic and complex translocations in routine diagnosis. Concurrent translocations of 2 key oncogenes to the same immunoglobulin loci demonstrate novel features of instability of bcl-6 and IgH genes and might present a novel mechanism of gene activation in B-cell malignancies.

Myelodysplastic syndromes (MDS) have undergone a therapeutic revolution in the past decade that has redefined treatment strategies for this disease. Patients with early-stage MDS who harbor a clonal chromosome 5q deletion (del[5q]) represent a distinct subset of MDS that is clinically, pathologically, and often prognostically distinct. While the vast majority of patients with MDS are red blood cell transfusion dependent, natural history of the disease varies from indolent (with a low-risk of leukemia evolution), in patients with isolated del(5q), to a high-risk of leukemia and poor survival in patients with a complex karyotype. Lenalidomide, which specifically targets the del(5q) clone, selectively suppresses the clone to yield transfusion independence and a cytogenetic response in approximately two thirds of patients, a response that is sustained for a median of 2.2 years. Features associated with a higher likelihood of transfusion independence include early treatment-related cytopenias and lower baseline transfusion needs, whereas the expectation for extended overall survival and freedom from leukemia evolution is greatest in cytogenetic responders. Future applications of lenalidomide will target patients with del(5q) with more advanced disease, will exploit the potentiation effects of lenalidomide's interaction with other agents, and will target novel pathways.

Dasatinib is a new tyrosine kinase inhibitor which is approved by the FDA for the treatment of patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. Dasatinib can cause fluid retention in some patients, leading to peripheral edema and pleural effusion. Herein, we report 2 patients with chronic phase CML who developed significant scrotal and penile edema while on treatment with dasatinib. In both patients, transient dasatinib interruption and use of diuretics helped alleviate the symptoms. Both patients had the dose schedule of dasatinib switched to once daily from twice daily. Scrotal and penile edemas are unusual manifestations of fluid retention that, to our knowledge, have not been reported in patients treated with dasatinib. Recognition of these symptoms as a potential complication of dasatinib will help prevent unnecessary investigations, facilitate adequate management, and help alleviate patient anxiety.

The association of myelodysplastic syndromes with lymphoid malignancies has rarely been reported. To our knowledge, there are only 5 reported cases of chronic lymphocytic leukemia (CLL) and chronic myelomonocytic leukemia (CMML) occurring in the same patient. Herein, we describe the case of an 80-year-old woman diagnosed with CLL. She declined chemotherapy and began weekly rituximab 375 mg/m² intravenously. She initially had a solid partial response to treatment. However, after 2 treatments with rituximab her white blood cell count increased, and a peripheral smear was remarkable for large, cleaved, folded cells, identified as monocytes. The previous bone marrow biopsy was retrieved and restained with an α-naphthol butyl esterase for monocytes. An increased atypical monocytic population was exposed, indicative of an evolving CMML. Her 2 malignancies probably arose from 2 different clones by chance. Treatment was begun with decitabine, but with no response. The patient remains transfusion dependent although relatively asymptomatic on hydroxyurea.

The International Prognostic Scoring System (IPSS) for myelodysplastic syndromes (MDS) identifies bone marrow (BM) blasts, cytogenetics, and the number of cytopenias as major variables with impact on disease outcome. Weighting of these variables defines distinct subgroups using multivariate analysis approaches. Recent studies, including the work of our group, indicate an underestimation of unfavorable cytogenetics in the IPSS. To delineate the prognostic impact of poor-risk karyotypes in relation to blast counts, we studied clinical outcome of cytogenetic and blast count subgroups in a large cohort of 1440 patients with MDS. Using univariate analytic tools, median survival times of 158 patients with poor-risk cytogenetics and 66 patients with blast counts of > 20% were 11.1 months and 9 months, respectively. Median survival times of patients with poor-risk cytogenetics and normal blast counts (n = 60; median survival, 17 months) were not significantly different from those of good-risk karyotypes and highly elevated BM blasts (11%–20%: n = 89; median survival, 22 months; P = .098; > 20%: n = 32; median survival, 13 months; P = .892). Our data indicate an equal prognostic significance of poor-risk cytogenetics compared with highly elevated BM blasts and suggest a higher score for unfavorable karyotypes in future integrative prognostic systems in MDS.