scholarly journals Bendamustine and Rituximab Treatment, Chronic Lymphocytic Leukemia, Direct Antiglobulin Test, and false negative

Author(s):  
Won Sriwijitalai ◽  
Viroj Wiwanitkit
Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4183-4183
Author(s):  
Wei Xu ◽  
Jianyong Li ◽  
Xin Cao ◽  
DAN-Xia Zhu ◽  
Lin Yao ◽  
...  

Abstract Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemias in the Western countries, however, infrequent in the Eastern. Autoimmune hemolytic anemia (AHA) is a complication in chronic lymphocytic leukemia (CLL). The direct antiglobulin test (DAT) may be positive at some time during the disease course in up to 35% of cases, but overt AHA occurs less frequently. The aim of the study was to explore the prognostic impact of positive DAT in Chinese patients with CLL and its correlation with other prognostic factors, including Binet stages, lymphocyte count in peripheral blood, lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), IgVH mutation status, ZAP-70, CD38 and cytogenetic abnormalities. Out of the 80 Chinese patients with CLL, positive DAT was found in 21 (30.6%) cases. The incidence of positive was 12.5% in Binet A, 23.8% and 44.4% in Binet B and C, respectively. The incidence of positive DAT was significantly increased at Binet C, compared with Binet A (P=0.006), and the presence of higher LDH and β2-MG levels correlated strongly with positive DAT (P=0.006 and P=0.004, respectively). Patients with unmutated IgVH genes had higher incidence of positive DAT than did patients with IgVH mutations (P=0.042), and positive DAT was also associated with higher level of ZAP-70 and CD38 (P=0.004 and P<0.001, respectively). We also analyzed positive DAT in different cytogenetic subgroups. Higher incidence of positive DAT was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22) in contrast to lower level in good risk cytogenetics (deletion in 13q as the sole abnormality) (P = 0.002). Positive DAT was associated with poor outcome. Survival analysis showed that the patients with positive DAT had significantly shorter OS (mean, 106.3 months) (95% CI, 74.7 to 137.8 months) than the patients negative DAT (mean, 151.5 months) (95% CI, 122.3 to 180.6 months) (P=0.024). Patients treated with fludarabine were not likely to remain DAT positive and to change from negative to positive (P=0.209). In conclusion, DAT status provides a new prognostic indicator and correlates with other clinical or laboratory prognostic factors, and might be applied for the assessment of prognosis in patients with CLL.


2013 ◽  
Vol 13 (4) ◽  
pp. 441-446 ◽  
Author(s):  
Francesca Ricci ◽  
Alessandra Tedeschi ◽  
Eleonora Vismara ◽  
Chiara Colombo ◽  
Silvio Veronese ◽  
...  

2014 ◽  
Vol 90 (1) ◽  
pp. E5-E8 ◽  
Author(s):  
Anne Quinquenel ◽  
Chadi Al Nawakil ◽  
Fanny Baran-Marszak ◽  
Virginie Eclache ◽  
Remi Letestu ◽  
...  

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1820-1826 ◽  
Author(s):  
Claire Dearden ◽  
Rachel Wade ◽  
Monica Else ◽  
Sue Richards ◽  
Don Milligan ◽  
...  

Autoimmune hemolytic anemia (AHA) is a common complication in chronic lymphocytic leukemia (CLL). The UK LRF CLL4 trial is the largest prospective trial in CLL to examine the prognostic impact of both a positive direct antiglobulin test (DAT) and AHA. Seven-hundred seventy-seven patients were randomized to receive chlorambucil or fludarabine, alone or with cyclophosphamide (FC). The incidence pretreatment of a positive DAT was 14%. Ten percent developed AHA. The DAT correctly predicted the development, or not, of AHA after therapy in 83% of cases, however only 28% of DAT-positive patients developed AHA. Of 299 patients tested both before and after treatment, those treated with single-agent fludarabine were most likely to remain DAT positive and to change from negative to positive. Patients treated with chlorambucil or fludarabine were more than twice as likely to develop AHA as those receiving FC. In a multivariate analysis, stage C disease and high β2 microglobulin were independent predictors of a positive DAT result. AHA, or a positive DAT, with or without AHA, independently predicted for reduced overall survival (OS). Four deaths, all on fludarabine monotherapy, were attributed to AHA. In conclusion, DAT status at the time of initiation of therapy provides a new prognostic indicator, although FC may protect against AHA. This trial was registered at http://isrctn.org as no. 58585610.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2329-2329
Author(s):  
Marian J.P.L. Stevens-Kroef ◽  
Annet Simons ◽  
Michael Egmont Petersen ◽  
Hanneke Gorissen ◽  
Yvonne Nanciu ◽  
...  

Abstract B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Characteristic genomic abnormalities have shown to provide highly significant prognostic information (Dohner NEJM 2000). However, karyotyping and/or FISH are laborious and expensive techniques. Although other prognostic markers (like mutation status of VH-genes and expression of CD38 and ZAP70) have been noted, these fail to identify all patients with a cytogenetic high-risk profile. We have performed multiplex ligation-dependent probe amplification (MLPA) analysis on 37 CLL patients, using the P037 and P038 kits (mrc-holland, http://www.mlpa.com/pages/indexpag.html), which allow the simultaneous identification of 56 genomic CLL-specific targets. The MLPA data obtained were compared with interphase FISH data in a blinded fashion using the ATM, centromere 12, RB1, D13S319, and TP53 specific probes (Vysis). By doing so, a good correlation was revealed in those cases in which the percentage of abnormal cells was at least 27%. We diagnosed six cases with loss of the ATM locus, six cases with trisomy 12, twenty cases with loss of chromosome 13q14 (three of them with a biallelic deletion), and three cases with loss of the TP53 locus. In three cases the genetic abnormality was detected by interphase FISH only. In these latter cases, the percentages of abnormal cells were 13%, 20% and 20%, respectively, which may explain the false negative results of the MLPA analyses. Since multiple probes were used for the 13q14 loci, a critical region of genomic loss could be identified which excluded the RB1 gene but included the KCNRG, DLEU2 and DLEU1 genes and miRNA15A. Also for the TP53 and ATM genes multiple probes were tested and, based on these results, one patient is suspected to have an intragenic ATM deletion. Also, additional abnormalities were detected by MLPA as e.g. trisomy 19. In conclusion, MLPA appears to be a useful technique for the identification of clinically relevant genetic abnormalities in a diagnostic setting.


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