scholarly journals Presenting features and prognosis of chronic lymphocytic leukemia in younger adults [see comments]

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1545-1551 ◽  
Author(s):  
E Montserrat ◽  
F Gomis ◽  
T Vallespi ◽  
A Rios ◽  
A Romero ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Risk Groups ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Younger Adults ◽  
Female Ratio ◽  
Prognostic Features ◽  
The Impact

Abstract We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.

scholarly journals Presenting features and prognosis of chronic lymphocytic leukemia in younger adults [see comments]

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1545-1551 ◽  
Author(s):  
E Montserrat ◽  
F Gomis ◽  
T Vallespi ◽  
A Rios ◽  
A Romero ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Risk Groups ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Younger Adults ◽  
Female Ratio ◽  
Prognostic Features ◽  
The Impact

We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.

scholarly journals Impact of Berberine on the Expression of Apollon Gene in Chronic Lymphocytic Leukemia

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Niloofar Ghanizade ◽  
Maral Hemati ◽  
Habib Jaafarinejad ◽  
Mehrnoosh Pashaei ◽  
Parviz Kokhaei
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Blood Mononuclear Cells ◽  
The Impact

Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.

Select High-Risk Genetic Features Predict Earlier Progression Following Chemoimmunotherapy With Fludarabine and Rituximab in Chronic Lymphocytic Leukemia: Justification for Risk-Adapted Therapy

2006 ◽  
Vol 24 (3) ◽  
pp. 437-443 ◽  
Author(s):  
John C. Byrd ◽  
John G. Gribben ◽  
Bercedis L. Peterson ◽  
Michael R. Grever ◽  
Gerard Lozanski ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Prognostic Factors ◽  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Interphase Cytogenetics ◽  
Mutational Status ◽  
The Impact

Purpose Several new prognostic factors predicting rapid disease progression in chronic lymphocytic leukemia (CLL) have been identified, including unmutated Ig VH mutational status, del(11)(q23), del(17)(p13.1), and p53 mutations. To date, the impact of these same prognostic factors have not been examined relative to treatment outcome with chemoimmunotherapy. Methods We examined the impact of these new prognostic factors on predicting treatment outcome in symptomatic, untreated CLL patients who received chemoimmunotherapy with fludarabine and rituximab as part of a completed, randomized phase II study, Cancer and Leukemia Group B (CALGB) 9712. Results Eighty-eight patients treated as part of CALGB 9712 had detailed prognostic factor assessment performed. Using Ig VH mutational status to classify risk, there was no association between complete response rate with either unmutated Ig VH mutational status or high-risk interphase cytogenetics. However, the median progression-free survival (PFS; P = .048) and overall survival (OS; P = .01) were shorter among the Ig VH unmutated patients as compared with the Ig VH mutated patients. Using the hierarchical classification of Döhner, PFS (P = .005) and OS (P = .004) were significantly longer as the classification moved from high risk [del (11)(q22.3) or del (17)(p13.1)] to low risk. Conclusion These data demonstrate that high-risk CLL patients characterized by Ig VH unmutated (≥ 98%) or high-risk interphase cytogenetics, including either del(17p) or del(11q), appear to have a shorter PFS and OS with chemoimmunotherapy. Larger prospective studies will be required to determine the independent influence of Ig VH mutational status and interphase cytogenetics on treatment outcome.

scholarly journals Detailed Clinical, Immunological and Molecular Analysis of NOTCH1, SF3B1 and MYD88 mutations in Chronic Lymphocytic Leukemia Patients Reveals Accumulation of Negative Prognostic Features in NOTCH1 and SF3B1 mutated Individuals

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5570-5570
Author(s):  
Maciej Putowski ◽  
Marta Podgórniak ◽  
Marta Piróg ◽  
Joanna Knap ◽  
Jacek Zawislak ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Sanger Sequencing ◽  
Prognostic Markers ◽  
Lymphocytic Leukemia ◽  
Complete Analysis ◽  
Prognostic Features ◽  
Ighv Gene ◽  
Gene Status ◽  
Notch1 Mutations

Abstract The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, from stable to a rapidly progressive. The variety of prognostic factors has been already described, nevertheless they are not fully efficient in predicting the course of CLL, especially when the disease is diagnosed at an early stage. Recently, beside well established cytogenetic prognostic factors, novel molecular mutations of predictive value have been identified. Many of them have been thoroughly characterized, including TP53 mutation, which is commonly considered as a strong, negative prognostic factor. The use of next-generation sequencing technology has also revealed previously unknown genomic alterations, such as neurogenic locus notch homolog protein1 (NOTCH1), splicing factor 3B subunit 1 (SF3B1) or myeloid differentiation primary response 88 (MYD88). These new mutations could partly explain the CLL heterogeneity and help in identifying clinically relevant groups of patients. The aim of the study was to characterize CLL patients with NOTCH1, MYD88 and SF3B1 mutations with regard to molecular and immunological prognostic markers in CLL. Peripheral blood mononuclear cells (PBMCs) were obtained from 369 CLL patients at the moment of diagnosis and the median age reached 65 years. Sixty percent of the patients were male. Distribution of disease stages according to the Rai classification was the following: 0 stage=93, I stage=52, II stage=69, III stage=14, IV stage=26. Clinically, the prognostic significance in terms of time to first treatment (TTFT) was assessed for 202 CLL patients. DNA samples were extracted from PBMCs obtained after Ficoll density gradient centrifugation. NOTCH1 c.7544_7545delCT (n=316) in PEST domain (exon 34) and MYD88 L265P (n=323) mutations were investigated by ARMS PCR. Screening for SF3B1 (n=364) mutations K700, E622/R625 and H662/K666 (exons 14 and 15) were performed using HRM analysis and the results were confirmed by Sanger sequencing. The IGHV gene mutations were investigated by Sanger sequencing. NOTCH1 mutations were found in 19/316 (6.0%) patients. Patients harbouring NOTCH1 mutations prevalently have unfavourable prognostic factors including unmutated IGHV gene status, expression of CD38 (>30%) and expression of ZAP-70 (>20%). The complete analysis of correlations between NOTCH1, MYD88 and SF3B1 mutations and prognostic markers in CLL are presented in Table 1. Analysis of IGHV subsets in patients with NOTCH1 mutation revealed frequent presence of subset #1 in n=2/19 (10.5%), which is associated with particularly poor prognosis in CLL. Patients belonging to subsets #5, #6, #201 and #202 were also present, each in single NOTCH1 mutated CLL case (5.2%). MYD88 mutation occurred in 12/323 (3.7%), of whom one patient was characterized as subset #2 and another as subset #4. MYD88 mutations were nearly equally distributed in patients with mutated/unmutated IGVH status (5 vs. 7). SF3B1 mutations occurred in 17/364 (4.7%) patients, furthermore two of them carrying negative prognostic features of subsets #2 and one subset #1. Patients belonging to subsets #3 and #6 were also present. Certain negative prognostic factors accompany poor clinical outcome. The assessment of median TTFT revealed the significant differences between patients from various prognostic groups (Fig. 1). Patients with unmutated IGHV gene status were characterized by significantly shorter TTFT than patients harbouring the mutation (p<0.0001). The similar correlation occurs in patients with ZAP-70 positive (p=0.04) and CD38 positive (p=0.0003). There were no significant differences in patients with mutated and unmutated NOTCH1 and MYD88, while in patients harbouring SF3B1 mutation the tendency to lower median TFTT was revealed (p=0.08). Interestingly, the significant difference in median TTFT was observed in groups of men and women, showing the better outcome in female patients (median 10 vs 28 months, p=0.01). NOTCH1 and SF3B1 mutations accompany certain biological markers of unfavourable prognosis. Undeniably, the mutations may contribute to the identification of poor-risk CLL patients and in combination with conventional lesions of CLL may be the key to accurate estimation of the disease prognosis. Acknowledgments: This work was supported by Polish Ministry of Science and Higher Education Scientific Grant "The best from the best" ("Najlepsi z Najlepszych") No. 506-0000-39-0000. Disclosures No relevant conflicts of interest to declare.

Circulating Angiogenic Cytokines in Chronic Lymphocytic Leukemia: Relationship to Modern Prognostic Factors and Effect of Fludarabine-Based Treatment

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4186-4186
Author(s):  
Lukas Smolej ◽  
Ctirad Andrys ◽  
Sona Pekova ◽  
Lenka Kucerova ◽  
Monika Hrudkova ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Growth Factor ◽  
Chronic Lymphocytic Leukemia ◽  
Clinical Course ◽  
Angiogenic Factors ◽  
Lymphocytic Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Angiogenic Markers ◽  
Angiogenic Cytokines

Abstract Angiogenesis has been studied in chronic lymphocytic leukemia (CLL) since mid 1990s. Given the extraordinary heterogeneity of clinical course of CLL patients, angiogenesis assessment may potentially improve prognostic stratification. There are numerous reports on increased markers of angiogenesis in CLL; however, data on possible association of angiogenic markers with modern prognostic factors are very scarce. Therefore, we evaluated prognostic significance of angiogenic cytokines, namely basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), endostatin, and angiopoietin-2 (Ang-2) in patients with untreated CLL. Plasma levels of angiogenic factors were quantified using enzyme-linked immunosorbent assay (bFGF, VEGF, n=106; endostatin, n=83, Ang-2, n=55). Eighty healthy donors served as control group. Relationship of angiogenic markers to modern prognostic factors (IgVH mutation status, cytogenetic aberrations detected by fluorescent in situ hybridization [FISH]) was also analyzed. Results: bFGF, VEGF, and endostatin were significantly elevated in CLL patients when compared to controls (bFGF, VEGF: p&lt;0.0001, endostatin: p=0.039); Ang-2 levels were not different from the control (p=0.192). There were no differences in angiogenic factors with regard to gender, clinical course or modified Rai stage. Similarly, no association of angiogenic factors with IgVH or FISH was identified. Interestingly, in a pilot subgroup of 16 patients with serial measurements before and after successful fludarabine-based combination treatment, levels of bFGF as well as VEGF decreased significantly (p&lt;0.0001 and p=0.0027, respectively). In conclusion, our study confirms that angiogenic signaling is intensive in CLL. Fludarabine-based treatment may have intrinsic antiangiogenic properties. Further research is needed for better understanding of angiogenic processes, especially with respect to possible refinement of individual patient’s prognosis in this disease.

scholarly journals Chronic Lymphocytic Leukemia: Prognostic Factors at Presentation in a Resource-Limited Center

2021 ◽  
pp. 56-62
Author(s):  
Kaladada Ibitrokoemi Korubo ◽  
Uchechukwu Prince Okite ◽  
Sampson Ibekwe Ezeugwu
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Prognostic Markers ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Resource Limited ◽  
Binet Stage ◽  
Wbc Count

PURPOSE Determining chronic lymphocytic leukemia (CLL) prognosis using the International Prognostic Index markers such as TP53 and immunoglobulin heavy-chain variable region gene mutation in a resource-limited setting is difficult to achieve because of cost and equipment unavailability. The aim of this study is to determine prognostic factors easily available to hematologists in low- or medium-income countries. MATERIALS AND METHODS This was a retrospective study conducted at the University of Port Harcourt Teaching Hospital, Nigeria. Data were retrieved from CLL patient records from January 2004 to December 2019 (15 years). Data collected were analyzed using SPSS software version 25. RESULTS A total of 46 records were reviewed, with a median age of 55 years and a male:female ratio of 1:1.2. All patients were symptomatic at presentation, with splenomegaly (91.3%), anemia (82.6%), and lymphadenopathy (76.1%) predominating. About 89.1% of the patients presented at Binet stage C and/or high-risk Rai (Rai stages III and IV) with 10.9% presenting at Binet stage B and/or intermediate-risk Rai (Rai stage II). Only 13% of the patients had immunophenotyping done with 6.5% being done for the Matutes CLL score. The 5-year overall survival (OS) was 15.7% with a median survival of 26 months. WBC count and absolute lymphocyte count (ALC) > 100 × 109/L were significant poor prognostic markers ( P = .013 and .021, respectively). Thirty-five (76.1%) received chemotherapy, and they had a better median survival than those who did not (26 v 17.5 months). The most common regimen used was cyclophosphamide, vincristine, and prednisolone for 15 (42.9%) patients. CONCLUSION WBC count and ALC > 100 × 109/L were poor prognostic markers. Patients who received chemotherapy had a better OS.

Impact of Age on Survival after Intensive Therapy in Newly Diagnosed Multiple Myeloma. The Nordic Myeloma Study Group (NMSG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 924-924
Author(s):  
Stig Lenhoff ◽  
Martin Hjorth ◽  
Peter Gimsing ◽  
Jon Magnus Tangen ◽  
Jan Westin
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Median Survival ◽  
Intensive Therapy ◽  
Population Based ◽  
Control Group ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Historic Control ◽  
The Impact

Abstract Introduction: Intensive therapy (IT) including autologous stem cell transplantation (ASCT) is considered superior to conventional therapy in newly diagnosed myeloma pts <60 yrs. For older pts the benefit of IT is less clear. In 1998 the NMSG started a population-based, prospective trial (#7/98) aiming to study the impact of age on event-free survival (EFS) and survival after IT, and to compare survival to a conventionally treated historic control group. Patients: Newly diagnosed symptomatic pts <65 yrs were included into a protocol with four phases; I) VAD x 3–4; II) cyclophosphamide 2g/sqm, G-CSF (filgrastim) and stem cell harvest; III) melphalan 200 mg/sqm, stem cell infusion and G-CSF; IV) interferon maintenance. Double ASCT was optional. From Jan 1998 to June 2000, 452 pts were registered and 414 (92%) of these were included into the IT protocol (=Intensive Therapy Group (ITG)). 294 were <60 yrs (=ITG-60) and 120 were 60–64 yrs (=ITG-65). The historic control group was derived from a previous population-based, randomized NMSG study (#4/90) where melphalan and prednisone +/− interferon was given as initial therapy. Of the 281 pts <65 yrs registered in this trial, 243 (86%) fulfilled the eligibility criteria for IT stated in the #7/98 protocol and constituted the Control Group (CG). 146 were <60 yrs (=CG-60) and 97 were 60–64 years (=CG-65). Results: In the ITG-60, 261 pts (89%) were actually transplanted (80% single ASCT, 18% double ASCT and 2% allogeneic SCT). In the ITG-65, 98 pts (82%) were transplanted (84% single and 16% double ASCT). Median follow-up is 50 months. Major response rate (CR+PR) was 88% in the ITG-60 and 81% in the ITG-65. EFS at 4 yrs for the ITG-60 was 37% and median EFS 36 months, while the corresponding figures for the ITG-65 were 19% and 24 months (P=.005). Survival at 4 yrs for the ITG-60 was 67% and median survival 67 months, while the corresponding figures for the ITG-65 was 50% and 48 months (P=.004). In a multivariate analysis of the entire ITG, two variables were significantly associated with EFS and survival; beta-2-microglobulin at diagnosis and age < or ≥ 60 yrs. The survival in the ITG-60 was prolonged compared to the CG-60 with a risk ratio (RR) of 0.50 (95%CI 0.38–0.67; p<.0001). Survival at 4 yrs was 67% in the ITG-60 and 44% in the CG-60, with a median survival of 67 and 43 months, respectively. The survival advantage persisted (RR 0.57, 95%CI 0.42–0.78; p=.0004) after statistical analysis of prognostic factors and correction for differences between the groups. Also for patients 60–64 yrs old survival was prolonged in the ITG compared to the CG with a RR of 0.65 (95%CI 0.42–0.92; p=.02). Survival at 4 yrs was 50% in the ITG-65 and 40% in the CG-65 with a median survival of 48 and 28 months, respectively. However, after correction for the difference in prognostic factors between the groups there was no significant difference in survival (RR 0.80, 95%CI 0.55–1.16; p=.23). Conclusions: In this population-based study older age was found to have a negative influence on outcome after IT. Our results indicate that there is an upper age limit that remains to be defined for superiority of IT over conventional chemotherapy.

scholarly journals Serum Vitamin D3 Levels in Chronic Lymphocytic Leukemia and Its Relevance with Clinical Prognostic Factors

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehdi Dehghani ◽  
Anush Khajeh ◽  
Reza Vojdani ◽  
Mozhdeh Sanei ◽  
Pedram Keshavarz ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Vitamin D3 ◽  
Normal Population ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Cross Sectional Study ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Cross Sectional

Background: Studies conducted in recent years have proposed a protective effect of vitamin D3 (VitD3) against various types of cancers. Thus, in this research, we investigated the serum levels of VitD3and its relation with prognostic clinical factors in chronic lymphocytic leukemia (CLL). Method: In this cross-sectional study, 86 CLL patients were investigated for a one-year period and evaluated for the relationship between Vit D3serum levels, Rai stages, age, gender, and pathological factors. A control group was added to the study in order to compare the VitD3 levels of CLL patients with that of the normal population. Results: The mean serum VitD3level in CLL patients was 29.76 ± 18.75 ng/ml, and most of the patients were in stage I and II. There was no significant association between age, sex, and Rai stages of CLL with VitD3 level. Except for splenomegaly (P < 0.001), the leukemia-related phenotypes, complications, and prognostic factors had no meaningful association with VitD3 (P > 0.05) level. VitD3 serum level was meaningfully different between case and control groups (P < 0.001). Conclusion: In the current research, there was no significant relationship between VitD3serum levels and investigated variables, except splenomegaly; these findings are in concordance with other studies.

scholarly journals Effect of anticancer therapy on Tn antigen exposure on the leucocyte membranes in patients with leukemia

2014 ◽  
Vol 5 (2) ◽  
pp. 99-103
Author(s):  
G. S. Maslak
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Polycythemia Vera ◽  
Blood Cells ◽  
Fluorescein Isothiocyanate ◽  
Anticancer Therapy ◽  
Carbohydrate Antigen ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Tn Antigen ◽  
The Impact

Tn-antigen (Thomsen-nouvelle antigen) is tumor-associated carbohydrate antigen with only one GalNAc residue attached to serine or threonine of polypeptide chain. There is not enough data about the expression of this glycotope in hematologic processes. But the correlations between increasing Tn-antigen expression on the cell surface and tumor growth progression, invasion, and activation of cell migration are well known. Therefore, the currently important area of modern research is studying of the impact of anticancer therapy by expression of this carbohydrate antigen in the onco-proliferative process. There are two types of cytostatic therapies in clinical hospitals of Ukraine: COP-therapy (cyclophosphamide, vincristine, prednisone) and FC-therapy (fludarabine, cyclophosphamide), which are the most popular due to their effectiveness and low price. The aim of our study was to investigate Tn-antigen exposure on the surface of lymphocytes, monocytes and granulocytes in polycythemia vera and subleukemic myelosis; to examine the influence of COP- and FC-therapies on Tn-antigen exponation in patients with chronic lymphocytic leukemia. The objects of the study were blood cells of patients with chronic lymphocytic leukemia (n = 25), polycythemia vera (n = 15) and subleukemic myelosis (n = 15) aged 58–66 years. Healthy hematologic volunteers (n = 15) aged 55 to 65 years were in the control group. Lymphocytes of patients with chronic lymphocytic leukemia (n = 25) were also studied after the chemotherapy treatment of patients divided into two groups: those who took COP-therapy (n = 13); and those who treated with FC-therapy (n = 12). Tn-antigen exposure on lymphocytes, monocytes and granulocytes was investigated by Beckman Сoulter EPICS flow cytometer with primary monoclonal Tn-antigen anybodies (Institute of Immunology, Moscow, Russia) and secondary fluorescein isothiocyanate labeled antybodies (Millipore, USA). The number of dead cells was monitored by binding them with propidium iodide. The result was analyzed with FC Express. According to our data, Tn-antigen exposure was not detected on the surface of blood cells (lymphocytes, monocytes and granulocytes) in the control group and in patients with polycythemia vera and subleukemic myelosis. Nevertheless, Tn-antigen was identified on the surface of more than 80% of lymphocytes in chronic lymphocytic leukemia patients. The intensity of this tumor-associated antigen exposure on lymphocytes membrane was 100 times higher compared with that in normal lymphocytes. In chronic lymphocytic leukemia patients after COP-treatment the number of lymphocytes with surface Tn-antigen was equal to 28,1 ± 0,8%, and after FC-treatment it decreased to 9,5 ± 0,5%. Moreover, positive effect of cytotoxic therapy used in treatment of patients with chronic lymphocytic leukemia on intensity of Tn-antigen exposure on the surface of lymphocytes was shown. FC-therapy (fludarabine, cyclophosphamide) is more effective; compared with the data prior to this treatment it 40 times reduced the relevant index. Therefore, it can be applied in Ukraine for chemotherapeutic treatment schemes effective against Tn-antigen.

Polymorphisms Of Human Leukocyte Antigen-G Gene and Clinical Outcome Of Patients With Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4151-4151
Author(s):  
Gabriela Klimkiewicz-Wojciechowska ◽  
Olga Grzybowska-Izydorczyk ◽  
Maciej Borowiec ◽  
Krystyna Wyka ◽  
Marta Chmielewska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Cell ◽  
Immune Escape ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Strong Linkage Disequilibrium ◽  
Cell Functions

Abstract Introduction The human leucocyte antigen-G (HLA-G) is a nonclassical class Ib molecule that suppresses various immune cell functions and may contribute to immune escape and cancer development. HLA-G polymorphisms, especially HLA-G-725(C/G/T) 5’URR and HLA-G 14bp del/ins 3’UTR, might influence the expression of HLA-G transcript and protein, and in consequence, affect the biological features of HLA-G. Therefore, we investigated whether these two polymorphisms, which seem to be functionally relevant, may play a role in susceptibility to chronic lymphocytic leukemia (CLL) and a clinical course of the disease. So far, no studies have reported any potentially impact of HLA-G polymorphisms on lymphoid neoplasms. Methods HLA-G725(C/G/T) 5’URR and HLA-G 14bp del/ins 3’UTR polymorphisms were genotyped in 167 previously untreated patients with CLL. The control group consisted of 98 randomly selected blood donors. Results Strong linkage disequilibrium between HLA-G-725(C/G/T) and HLA-G 14 bp del/ins was observed (D’=1.0 and r2=0.2). Six distinct haplotypes, including G/del, C/del, T/del, G/ins, C/ins, T/ins were found in the CLL patients. Among the controls only five haplotypes were found due to the T/ins haplotype not being observed. The probability of the occurrence of G/ins and T/ins haplotypes was higher in the CLL than in the controls (p= 0.01). The analysis of the prognostic significance of diplotypes, as well as the previously reported correlations between HLA-G genotypes and HLA-G expression in vitro and in vivo, allowed us to identify the HLA-G diplotype-based risk groups. The low-risk (LR) group comprised CC/del-del, CC/del-ins and CC/ins-ins diplotypes, and the high risk (HR) group included GG/del-del, GG/del-ins, GG/ins-ins, GC/del-del, GC/del-ins, GC/ins-ins, TT/del-del, TT/del-ins, TT/ins-ins and CT/del-ins diplotypes. The patients carrying LR diplotypes presented a higher 3-year treatment-free survival (TFS) (56.7%, 95% CI 47-66) than those with HR diplotypes (38.6%, 95% CI 27-52; p= 0.005). Additionally in the group of mutated IGHV patients, subjects carrying LR diplotypes presented a higher probability of 3-year TFS than those with HR diplotypes (68.5% vs 43.2%; p= 0.04). In regard to overall survival (OS), the estimated 5-year OS rates were 95.6% (95% CI 89-98) and 74.2% (95% CI 57-86) in the LR and HR group respectively (p= 0.005). Moreover, among the unmutated IGHV patients, those carrying LR diplotypes had a better 5-year OS compared to the patients with HR diplotypes (87.1% vs 71%; p= 0.02). Multivariate analysis demonstrated the IGHV mutation status (p= 0.005) and HLA-G diplotype-based risk groups (p= 0.01) to be independent factors predicting OS. Conclusions The results suggest the potential role of HLA-G and its polymorphisms in CLL. The inherited ability of the host to increase expression of the HLA-G antigen might contribute to the escape of CLL cells of the immuno-surveillance of the host and in turn to disease progression and the worse outcome for patients with CLL. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document