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Showing papers by "Constance M. Yuan published in 2013"


Journal ArticleDOI
14 Feb 2013-Blood
TL;DR: It is concluded that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL.

514 citations


Journal ArticleDOI
TL;DR: There is a need for prospectively validated models to characterize individual patient risk of transformation to MM by comparing the distribution of patients with SMM classified as low, medium and high risk for progression.
Abstract: The risk of progression to multiple myeloma (MM) from the precursor condition smoldering MM (SMM) varies considerably among individual patients. Reliable markers for progression to MM are vital to advance the understanding of myeloma precursor disease and for the development of intervention trials designed to delay/prevent MM. The Mayo Clinic and Spanish PETHEMA have proposed models to stratify patient risk based on clinical parameters. The aim of our study was to define the degree of concordance between these two models by comparing the distribution of patients with SMM classified as low, medium and high risk for progression. A total of 77 patients with SMM were enrolled in our prospective natural history study. Per study protocol, each patient was assigned risk scores based on both the Mayo and the Spanish models. The Mayo Clinic model identified 38, 35 and four patients as low, medium and high risk, respectively. The Spanish PETHEMA model classified 17, 22 and 38 patients as low, medium and high risk, respectively. There was significant discordance in overall patient risk classification (28.6% concordance) and in classifying patients as low versus high (p < 0.0001), low versus non-low (p = 0.0007) and high versus non-high (p < 0.0001) risk. There is a need for prospectively validated models to characterize individual patient risk of transformation to MM.

87 citations


Journal ArticleDOI
TL;DR: Hairy cell leukemia-v is resistant to traditional HCL therapy, making accurate diagnosis imperative, and FCM criteria for differentiation of HCL-v from HCL and SMZL is defined.

81 citations



Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: Ibrutinib effectively reduces the clonal light chain, a correlate of tumor control, while the non-clonal light chains, presumably in part reflecting normal B-cells, are low pre-treatment and increase during treatment, suggesting a beginning recovery of humoral immunity.

22 citations


Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: This investigator-initiated phase II, single-center trial of ibrutinib monotherapy prospectively addressed the possible role of IbrutinIB in DEL 17p CLL irrespective of the pts’ prior treatment history.

21 citations


Journal ArticleDOI
TL;DR: Quantification of antigens might be useful in evaluating new antigen to target for therapy and may provide a systematic approach to selecting individualized therapy in CLL.
Abstract: Objectives: Anti-CD20 (rituximab), anti-CD52 (alemtuzumab), anti-CD22 (BL22, HA22), and anti-CD25 (Oncotac) are therapeutic options that are the mainstay or in preclinical development for the treatment of chronic lymphocytic leukemia (CLL). Studies suggest that levels of surface antigen expression may affect response to monoclonal antibody–based therapy. Methods: Using the flow cytometric Quantibrite method (BD Biosciences, San Jose, CA) to determine antibodies bound per cell, we quantified the levels of surface expression of CD20, CD22, CD25, and CD52 in CLL cells from 28 untreated patients. Results: The CLL cells in all cases expressed CD20, CD22, and CD52 but 4 (14%) cases were negative for CD25. Although the ranking of levels of expression from highest to lowest was CD52, CD20, CD22, and CD25, the level of antigen expression on any specific case could not be accurately predicted. Conclusions: Quantification of antigens might be useful in evaluating new antigens to target for therapy and may provide a systematic approach to selecting individualized therapy in CLL.

16 citations


Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: This phase II single arm pilot study treats high risk SMM patients ≥18 years old with 8 cycles of CRd therapy with well tolerated with manageable toxicities and none have progressed to clinical symptomatic multiple myeloma.

11 citations


Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: The association of HLC, FLC, and other prognostic factors to predict early CR and MRD in the ongoing prospective clinical CRd trials for multiple myeloma (MM) and high risk smoldering MM (SMM) patients is reported.

3 citations


Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: In this paper, the utility of cell free tumor DNA (cf-VDJ) in monitoring disease burden in myeloma patients receiving combination chemotherapy was discussed. But, there was no correlation between the pre-treatment level of cf-VDj and disease burden estimated based on the % CD138+ plasma cells in BM, the proportion of VDJ DNA in BM and the M-protein concentration in blood/urine.

2 citations


Journal ArticleDOI
31 May 2013
TL;DR: FC assessment of MFI detects subtle changes in antigen expression not entirely apparent by visual examination of dot plots or immunohistochemistry, and is a means of uncovering subtle but unique immunophenotypic features in both well-known, and less well-defined neoplastic hematolymphoid entities.
Abstract: Follicular lymphoma (FL) is a relatively common, well-characterized lymphoma with recognizable morphologic and immunophenotypic features. Nevertheless, close examination of its immunophenotypic profile by mean fluorescent intensity (MFI) and potential relationship between antigens, as well as histologic grade, has not been extensively assessed by flow cytometry immunophenotyping (FC). We examined the immunophenotypic profile, including heavy and light chain analysis, of 41 nodal FL cases with FC analysis and tissue diagnosis. Additionally, MFI of CD45, CD19, CD20, CD22, and CD10 were examined. The relationship between the antigen expression on FL cells and normal B cells in the same sample, and any association with each other or with histologic grade, were analyzed statistically. We observed brighter CD45 and CD20 expression in FL than normal B cells (P , 0.0001); dimmer CD19 in FL than normal B cells (P = 0.03); brighter CD20 in grade 2 than grade 1 histology (P = 0.0023). No correlation was observed between CD10 MFI and other antigens. Increased expression of CD20, CD45, and dim expression of CD19 are features of nodal FL. FC assessment of MFI detects subtle changes in antigen expression not entirely apparent by visual examination of dot plots or immunohistochemistry. MFI is a means of uncovering subtle but unique immunophenotypic features in both well-known, and less well-defined neoplastic hematolymphoid entities.

Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: The use of modern CRd combination therapy including Carfilzomib (CFZ)-Lenalidomide (LEN)-Dexamethasone (DEX) would significantly lower the rates of HPC product contamination and thus allow for adequate collection in a single apheresis procedure.

Journal ArticleDOI
15 Nov 2013-Blood
TL;DR: A prospective clinical study designed to characterize patterns of cProt in peripheral blood from MGUS, SMM and MM patients found chymotrypsin-and caspase-like activity of circulating proteasome in asymptomatic gammopathies is related to tumoral mass and immunoparesis degree.