Prognostic Impact of Positive Direct Coombs Test in Chronic Lymphocytic Leukemia (CLL)

2017 ◽  
Vol 17 ◽  
pp. S298
Author(s):  
Mostafa F. Mohammed Saleh ◽  
Shimaa Abdelallah ◽  
Mai M. Aly ◽  
Ghada Elsayed ◽  
Yomna Refaat ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Coombs Test ◽  
Direct Coombs Test ◽  
Positive Direct

The Prognostic Significance of Positive Direct Antiglobulin Test in Chinese Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4183-4183
Author(s):  
Wei Xu ◽  
Jianyong Li ◽  
Xin Cao ◽  
DAN-Xia Zhu ◽  
Lin Yao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Lymphocytic Leukemia ◽  
Direct Antiglobulin Test ◽  
Chinese Patients ◽  
Prognostic Impact ◽  
Antiglobulin Test ◽  
Positive Direct

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.

The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1820-1826 ◽  
Author(s):  
Claire Dearden ◽  
Rachel Wade ◽  
Monica Else ◽  
Sue Richards ◽  
Don Milligan ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Single Agent ◽  
Prospective Trial ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Direct Antiglobulin Test ◽  
Prognostic Impact ◽  
Antiglobulin Test ◽  
Positive Direct

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.

scholarly journals AB0007 STAT4 RS7574865 G/T POLYMORPHISM AS MARKER OF PREDISPOSITION TO SYSTEMIC LUPUS ERYTHEMATOSUS WITH JUVENILE ONSET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1038.2-1039
Author(s):  
M. Kaleda ◽  
M. Krylov ◽  
I. Nikishina
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Pilot Study ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Control Group ◽  
Coombs Test ◽  
Systemic Lupus ◽  
Direct Coombs Test ◽  
Positive Direct ◽  
Cutaneous Lupus

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a significant genetic predisposition. Recent studies have identified STAT4 (signal transducers and transcription activators 4) as a susceptibility gene for SLE.Objectives:To investigate the hypothesis of the association of STAT4 rs7574865 G/T polymorphism with the predisposition to SLE in children and its relationship with some of SLE manifestations.Methods:The case-control pilot study included 143 children (39 with SLE and 103 healthy unrelated volunteers as a control group). Diagnosis of SLE was based on 2012 SLICC criteria. STAT4 rs7574865 G/T polymorphism was investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results:The group of pts with SLE consisted of 29 girls and 10 boys, with an average age of 11.8±3.7 years (from 3 to 17 years) and an average disease duration of 4.1±2.4 years. 79.5% pts had acute cutaneous lupus at the onset, 46.1% - nonscarring alopecia, 71.8% - arthritis, 23.1% - oral and nasal ulcers, 23.1% - serositis, 43.6% - renal involvement, 35.9% –neuropsychiatric disorders. Leucopenia/lymphopenia was found in 71.8% of pts, thrombocytopenia – in 23,1%. ANA were detected in 100% pts, anti-dsDNA – in 79.5%, anti-Sm – in 31.6%, antiphospholipid antibodies - in 7,3%, hypocomplementemia – in 61.5%, positive direct Coombs test – in 35.9 %. Macrophage activation syndrome at the onset was documented in 15.4 % of pts. The distribution of rs7574865 genotypes in the control group showed no significant deviations from the Hardy-Weinberg equilibrium. The distribution of genotype frequencies among pts had statistically significant differences compared to the control (χ2=12.95, p=0.0015): GG-30.8% and 63.1% (p=0.001), GT-56.4% and 33.0% (p=0.018), TT-12.8% and 3.9% (p=0.114), GT+TT - 69.2% and 36.9% (p=0.0005). The frequency of the mutant STAT 4 allele T (polymorphism), was significantly higher in the SLE group than in the control group (41% and 20.4%, respectively; p=0.0007). We identified an association of the T allele with some clinical, laboratory, and immunological disorders in SLE: arthritis (OR 3.9, p=0.0002), acute cutaneous lupus (OR 2.47, p=0.003), nonscarring alopecia (OR 3.12, p=0.002), renal involvement (OR 2.42, p=0.022), leucopenia (OR 2.72, p=0.003), thrombocytopenia (OR 4.88, p=0.002), anti-dsDNA (OR 2.82, p=0.0006), hypocomplementemia (OR 2.34, p=0.012), positive direct Coombs test (OR 3.38, p=0.002).Conclusion:Our pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of SLE in children and some of SLE manifestations.Disclosure of Interests:None declared

The prognostic impact of autologous stem cell transplantation in patients with chronic lymphocytic leukemia: a risk-matched analysis based on the VH gene mutational status

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2850-2858 ◽  
Author(s):  
Peter Dreger ◽  
Stephan Stilgenbauer ◽  
Axel Benner ◽  
Matthias Ritgen ◽  
Alexander Kröber ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Lymphocytic Leukemia ◽  
Study Entry ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Mutational Status

Abstract To assess the therapeutic value of sequential high-dose therapy (SHDT) including autologous stem cell transplantation in chronic lymphocytic leukemia (CLL) we performed a risk-matched comparison between 66 patients who had undergone a uniform SHDT regimen and a database of 291 patients treated conventionally. Matching variables were age, Binet stage, IgVH (variable region of the immunoglobulin heavy chain) gene mutational status, and lymphocyte count. Forty-four pairs fully matched for all 4 variables were identified. Patient groups were well balanced for additional risk factors including adverse genomic abnormalities and CD38 expression. With an overall median follow-up time of 70 and 86 months, respectively, survival was significantly longer for the SHDT patients than for the conventionally treated patients when calculated from diagnosis (hazard ratio [HR] 0.39; P = .03 [log rank]) or from study entry (HR 0.32; P = .006). The benefit for the SHDT group remained significant when the analyses were restricted to those 58 patients who had an unmutated VH status. Cox regression analysis confirmed SHDT as independent favorable prognostic factor for survival from diagnosis (HR 0.38, P = .04) as well as from study entry (HR 0.38, P = .03). These data suggest a survival benefit for patients with poor-risk CLL receiving SHDT during the course of their disease. (Blood. 2004;103:2850-2858)

scholarly journals Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG)

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2598-2607 ◽  
Author(s):  
Sonia Jaramillo ◽  
Andreas Agathangelidis ◽  
Christof Schneider ◽  
Jasmin Bahlo ◽  
Sandra Robrecht ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Early Stage ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Multicenter Clinical Trials

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinicobiological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: i) early-stage patients (watch-and-wait arm of the CLL1 trial) (n=592); ii) patients in need of treatment, enrolled in 3 phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1861). Subset #1 was associated with del(11q), higher CLL international prognostic index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (HR: 4.2, CI: 2-8.6, p<0.001), and shorter time-to-next-treatment (TTNT) in the advanced-stage cohort (HR: 2, CI: 1.2-3.3, p=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger age at diagnosis; in both cohorts, these patients showed a trend towards better outcomes versus other M-CLL. U-CLL subset #8 was associated with trisomy 12. Overall, this study shows that major stereotyped subsets have distinctive characteristics. For the first time in prospective multicenter clinical trials, subset # 2 appeared as an independent prognostic factor for earlier TTFT and TTNT and should be proposed for risk stratification of patients.

scholarly journals V H mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1410-1416 ◽  
Author(s):  
Alexander Kröber ◽  
Till Seiler ◽  
Axel Benner ◽  
Lars Bullinger ◽  
Elsbeth Brückle ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Expression Level ◽  
Chain Gene ◽  
P Value ◽  
Prognostic Impact ◽  
Survival Times ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Genomic Aberrations

In chronic lymphocytic leukemia (CLL), biologic risk factors such as immunoglobulin variable heavy chain gene (VH) mutation status, CD38 expression level, and genomic aberrations have recently been identified, but the relative prognostic impact of the individual parameters is unknown. In the current study, we analyzed VH mutation status by polymerase chain reaction and sequencing (n = 300), genomic aberrations by fluorescence in situ hybridization (+3q, 6q−, +8q, 11q−, +12q, 13q−, t(14q), 17p−) (n = 300), and CD38 expression by triple-color FACS (CD5, CD19, CD38) (n = 157) in a unicentric CLL cohort. The prognostic influence of VH mutation rate and CD38 expression level was tested by maximally selected log-rank statistics. A corrected P value (Pcor) for a cutoff level allowing the best separation of 2 subgroups with different survival probabilities was identified at 97% VH homology (95% confidence interval [CI], 96%-98% homology,Pcor &lt;.001) and at 7% CD38 expression (95% CI, 20%-71% expression, Pcor = .02). In univariate analyses, unmutated VH genes and high CD38 expression levels predicted for shorter survival times. The overall incidence of genomic aberrations was similar in theVH unmutated and VHmutated subgroups. High-risk genomic aberrations such as 17p− and 11q− occurred almost exclusively in the VHunmutated subgroup, whereas favorable aberrations such as 13q− and 13q− as single abnormalities were overrepresented in theVH mutated subgroup. In multivariate analysis, unmutated VH, 17p deletion, 11q deletion, age, WBC, and LDH were identified as independent prognostic factors, indicating a complementary role of VH mutation status and genomic aberrations to predict outcome in CLL.

scholarly journals CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression

Blood ◽  
2020 ◽  
Vol 135 (15) ◽  
pp. 1244-1254 ◽  
Author(s):  
Erika Tissino ◽  
Federico Pozzo ◽  
Dania Benedetti ◽  
Chiara Caldana ◽  
Tamara Bittolo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Prognostic Biomarker ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Clinical Behavior ◽  
Cutoff Value ◽  
Sequential Samples ◽  
Homogeneous Pattern ◽  
Over Time

Abstract CD49d is a remarkable prognostic biomarker of chronic lymphocytic leukemia (CLL). The cutoff value for the extensively validated 30% of positive CLL cells is able to separate CLL patients into 2 subgroups with different prognoses, but it does not consider the pattern of CD49d expression. In the present study, we analyzed a cohort of 1630 CLL samples and identified the presence of ∼20% of CLL cases (n = 313) characterized by a bimodal expression of CD49d, that is, concomitant presence of a CD49d+ subpopulation and a CD49d− subpopulation. At variance with the highly stable CD49d expression observed in CLL patients with a homogeneous pattern of CD49d expression, CD49d bimodal CLL showed a higher level of variability in sequential samples, and an increase in the CD49d+ subpopulation over time after therapy. The CD49d+ subpopulation from CD49d bimodal CLL displayed higher levels of proliferation compared with the CD49d− cells; and was more highly represented in the bone marrow compared with peripheral blood (PB), and in PB CLL subsets expressing the CXCR4dim/CD5bright phenotype, known to be enriched in proliferative cells. From a clinical standpoint, CLL patients with CD49d bimodal expression, regardless of whether the CD49d+ subpopulation exceeded the 30% cutoff or not, experienced clinical behavior similar to CD49d+ CLL, both in chemoimmunotherapy (n = 1522) and in ibrutinib (n = 158) settings. Altogether, these results suggest that CD49d can drive disease progression in CLL, and that the pattern of CD49d expression should also be considered to improve the prognostic impact of this biomarker in CLL.

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