Antiphospholipid Antibodies Are Not Associated with Clinical Parameters or Prognostic Outcomes in Patients with Non-Hodgkin's Lymphoma

2020 ◽  
Vol 40 (05) ◽  
pp. 662-670
Author(s):  
Rimesh Pal ◽  
Subhash Varma ◽  
Jasmina Ahluwalia ◽  
Gaurav Prakash
Keyword(s):  
Overall Survival ◽  
Treatment Response ◽  
Antiphospholipid Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Significant Difference

Abstract Background Antiphospholipid antibodies (APAs) are found quite frequently in patients with non-Hodgkin’s lymphoma (NHL). However, the clinical significance of these antibodies is largely unknown. This study aims to delineate the clinical and prognostic role of APAs in NHL patients. Patients and Methods  Consecutive patients of NHL were screened for lupus anticoagulant (LA), IgG/IgM anticardiolipin antibody, and IgG/IgM anti-β2-glycoprotein I at the time of diagnosis. Baseline investigations, staging, and treatment were done as per institutional protocol. Patients were followed up until the last known outpatient visit or death. All were screened at each visit for any thromboembolic event. The association of APA status with baseline NHL characteristics and treatment response was evaluated by univariate analysis. Kaplan–Meier survival analysis was used to compare the final outcome in patients with or without APAs. Patients who were initially APA positive were retested for the corresponding antibody at the end of chemotherapy. Results Twenty-four out of 105 patients (22.8%) were APA positive at diagnosis. The presence of APA was not significantly associated with NHL stage, histology, International Prognostic Index score, activated partial thromboplastin time, or treatment response. The median duration of follow-up was 15 months. Only four patients developed venous thrombosis; none was APA positive. There was no statistically significant difference in overall survival between the two groups (p = 0.471). Patients, who were APA positive initially, tested negative at the end of treatment, irrespective of treatment response. Conclusion APAs are encountered more frequently in NHL patients than in the general population. However, APAs do not correlate with disease severity, thrombosis risk, treatment outcome, or overall survival.

Presentation Serum Selenium Predicts for Overall Survival, Dose Delivery, and First Treatment Response in Aggressive Non-Hodgkin’s Lymphoma

2003 ◽  
Vol 21 (12) ◽  
pp. 2335-2341 ◽  
Author(s):  
Kim W. Last ◽  
Victoria Cornelius ◽  
Trevor Delves ◽  
Christine Sieniawska ◽  
Jude Fitzgibbon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Response ◽  
Hodgkin’S Lymphoma ◽  
Selenium Concentration ◽  
Hodgkin's Lymphoma ◽  
Serum Selenium ◽  
Dose Delivery ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Serum Selenium Concentration

Purpose: This study was undertaken to test the hypothesis that serum selenium concentration at presentation correlates with dose delivery, first treatment response, and overall survival in patients with aggressive B-cell non-Hodgkin’s lymphoma.Patients and Methods: The patients presented between July 1986 and March 1999 and received anthracycline-based chemotherapy, radiotherapy, or both. The total selenium content was retrospectively analyzed in 100 sera, frozen at presentation, using inductively coupled plasma mass spectrometry.Results: The serum selenium concentration ranged from 0.33 to 1.51 μmol/L (mean, 0.92 μmol/L; United Kingdom adult reference range, 1.07 to 1.88 μmol/L). Serum selenium concentration correlated closely with performance status but with no other clinical variable. Multivariate analysis revealed that increased dose delivery, summarized by an area under the curve, correlated positively with younger age (P < .001), advanced stage (P = .001), and higher serum selenium concentration (P = .032). Selenium level also correlated positively with response (odds ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.90; P = .011) and achievement of long-term remission after first treatment (log-rank test, 4.38; P = .036). On multivariate analysis, selenium concentration was positively predictive of overall survival (hazard ratio [HR], 0.76 for 0.2 μmol/L increase; 95% CI, 0.60 to 0.95; P = .018), whereas age indicated negative borderline significance (HR, 1.09; 95% CI, 0.99 to 1.18; P = .066).Conclusion: Serum selenium concentration at presentation is a prognostic factor, predicting positively for dose delivery, treatment response, and long-term survival in aggressive non-Hodgkin’s lymphoma. Unlike most existing prognostic factors in aggressive non-Hodgkin’s lymphoma, selenium supplementation may offer a novel therapeutic strategy in this frequently curable malignancy.

Antiphospholipid Antibodies: Prevalence, Clinical Significance and Correlation to Cytokine Levels in Acute Myeloid Leukemia and Non-Hodgkin’s Lymphoma

1993 ◽  
Vol 70 (04) ◽  
pp. 568-572 ◽  
Author(s):  
Roberto Stasi ◽  
Elisa Stipa ◽  
Mario Masi ◽  
Felicia Oliva ◽  
Alessandro Sciarra ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Significance ◽  
Antiphospholipid Antibodies ◽  
Myeloid Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Tnf Alpha ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Acute Myeloid

SummaryThis study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and highgrade non-Hodgkin’s lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p <0.0001). APA titres became normal in all patients responding to treatment, whereas nonresponders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from Controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to Controls (p = 0.003, p = 0.009 and p = 0.024 respectively). In addition, the levels of these cytokines correlated with IgG-ACA at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.

scholarly journals Prognostic significance of bcl-2 protein expression in aggressive non- Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Independent Effect ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Abstract Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

scholarly journals Prognostic significance of bcl-2 protein expression in aggressive non- Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Independent Effect ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

scholarly journals International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1460-1463 ◽  
Author(s):  
J Hermans ◽  
AD Krol ◽  
K van Groningen ◽  
PM Kluin ◽  
JC Kluin-Nelemans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Population Based ◽  
Hodgkin's Lymphoma ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Non-Hodgkin's Lymphoma in the Elderly: A Retrospective Evaluation of Toxicity Related to Aggressive vs. Conservative Treatments

1988 ◽  
Vol 74 (4) ◽  
pp. 433-438 ◽  
Author(s):  
Umberto Tirelli ◽  
Vittorina Zagonel ◽  
Rachele Volpe ◽  
Mauro G. Trovo ◽  
Antonino Carbone
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
Randomized Trials ◽  
Survival Rates ◽  
The Elderly ◽  
Hodgkin's Lymphoma ◽  
Severe Toxicity ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Significant Difference

The outcome of 70 elderly patients aged 65 years or more (median, 71 years) with non-Hodgkin's lymphoma (NHL) treated between 1973 and 1981 with aggressive (AM) or conservative modalities (CM) was retrospectively evaluated. A significantly higher incidence of lethal and severe toxicity was observed in patients treated with AM than in those treated with CM (32 % vs 3 %, p < 0.01), with 10 % treatment related deaths in the AM group. Only 56 % of the deaths were attributed to NHL; other major causes were treatment-related deaths, infection and cardiac diseases. No significant difference in response and survival was found between AM and CM groups (complete remission rates were 35 % vs 42 %, and 10 year survival rates were 31 % vs 19 %, respectively), but the prevalence of stages III-IV in patients treated with AM makes these results meaningless. Prospective randomized trials with AM vs CM are clearly needed in elderly patients with advanced unfavorable NHL.

Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years.

1997 ◽  
Vol 15 (8) ◽  
pp. 2945-2953 ◽  
Author(s):  
Y Bastion ◽  
J Y Blay ◽  
M Divine ◽  
P Brice ◽  
D Bordessoule ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Parameters ◽  
Aggressive Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma. PATIENTS AND METHODS Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks. RESULTS The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death. CONCLUSION Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.

Role of a second transplant in the management of poor-prognosis lymphomas: a report from the European Blood and Bone Marrow Registry.

1997 ◽  
Vol 15 (4) ◽  
pp. 1595-1600 ◽  
Author(s):  
E Vandenberghe ◽  
R Pearce ◽  
G Taghipour ◽  
L Fouillard ◽  
A H Goldstone
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Refractory Disease ◽  
Myeloablative Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE Treatment of selected patients with poor-prognosis lymphomas with high-dose chemotherapy and marrow or peripheral stem-cell rescue improves prognosis. A second course of myeloablative chemotherapy has been given to some patients, but few data are available on the indications, morbidity, and overall survival associated with this approach. This study was undertaken to evaluate morbidity and identify subgroups of patients who may benefit from a second transplant. PATIENTS AND METHODS Thirty-four patients with lymphoma given two cycles of myeloablative chemotherapy and entered onto the European Blood and Bone Marrow Transplant (EBMT) registry between 1982 and 1995 were included in this study: Hodgkin's disease (HD), n = 12; intermediate/high-grade non-Hodgkin's lymphoma (HG-NHL), n = 17; and low-grade non-Hodgkin's lymphoma (LG-NHL), n = 5. The reason for second transplant, status at transplant, conditioning regimen, morbidity, and both progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS The second procedure was performed for the following reasons: (1) elective double procedure in four patients, (2) relapse after first transplant in 20, (3) partial remission (PR) after first transplant in eight, and (4) refractory disease after first transplant in two. The OS rate at 2 years for patients who underwent two transplants (estimated from the date of second transplant) was 49%, with a median follow-up time of 44 months. The OS rate at 2 years by histologic subtype was as follows; HD, 50%; HG-NHL, 60%; and LG-NHL, 0%. Seven of 15 patients with HD or HG-NHL who relapsed after they had achieved a posttransplant complete remission (CR) remain in CR 13 to 36 months after the second transplant, compared with two of 10 patients in CR (at 6 and 19 months after second transplant) who achieved a PR or had refractory disease after the first transplant. There were eight deaths (24%) before 3 months, of which three (9%) were transplant-related and the remainder due to persistent disease. Three late toxic deaths occurred: two of cardiovascular disease and one of secondary leukemia. CONCLUSION Selected patients with HD and HG-NHL whose disease recurs after one transplant may benefit from a second transplant. Patients with refractory disease and LG-NHL did not benefit from a second transplant.

Ifosfamide, Carboplatin, and Etoposide: A Highly Effective Cytoreduction and Peripheral-Blood Progenitor-Cell Mobilization Regimen for Transplant-Eligible Patients With Non-Hodgkin's Lymphoma

1999 ◽  
Vol 17 (12) ◽  
pp. 3776-3785 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Joseph R. Bertino ◽  
Jill R. Glassman ◽  
Eric E. Hedrick ◽  
Sonia Hunte ◽  
...  
Keyword(s):  
Overall Survival ◽  
Side Effects ◽  
Peripheral Blood ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Cancer Center ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cell Mobilization

PURPOSE: To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granuloctye colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL).PATIENTS AND METHODS: One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34+cells collected after treatment with ICE and G-CSF were evaluated.RESULTS: All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P = .003). The median number of CD34+cells/kg collected was 8.4 × 106. The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects.CONCLUSION: ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.

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