Clinical Significance of Tumor-Associated Macrophages in Early-Stage Hodgkin's Lymphoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2638-2638
Author(s):  
Manuel Gotti ◽  
Marta Nicola ◽  
Valeria Fiaccadori ◽  
Elisa Bono ◽  
Marco Lucioni ◽  
...  
Keyword(s):  
Complete Remission ◽  
Clinical Outcome ◽  
Clinical Significance ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Tumor Associated Macrophages ◽  
Eortc Criteria ◽  
Group A ◽  
Diagnostic Biopsies

Abstract Abstract 2638 Although patients with early-stage Hodgkin's lymphoma (HL) overall have a high rate of cure, they cannot be considered as a homogeneous group. In fact, a portion of these patients are resistant to or may relapse after standard treatment. Current prognostic criteria based on clinical and laboratory parameters at diagnosis do not allow to accurately identify the subset of patients with less favorable clinical outcome. In a study aimed at defining new biomarkers for risk stratification, an increased number of tumor-associated macrophages was found to be strongly associated with shortened survival in patients with classic Hodgkin's lymphoma [N Engl J Med. 2010 Mar 11;362(10):875-85]. The aim of this study was to evaluate the clinical significance of the proportion of CD68-positive infiltrating macrophages in patients with early-stage Hodgkin's lymphoma. By using an immunohistochemistry method, we analyzed diagnostic biopsies of 63 patients followed at our institution between 2006 and 2010, and uniformly treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. Thirty-nine (62%) patients were males and 24 (38%) were females; median age at diagnosis was 30 years (range 17–85). Histological subtype was nodular sclerosis HL in 55 cases, mixed cellularity HL in 3 cases, lymphocyte-rich HL in 3 cases, and not classified in 2 cases. Five patients had subdiaphragmatic disease while 58 had supradiaphragmatic localizations. Forty-four patients with supradiaphragmatic disease were classified in the EORTC unfavorable subset: in detail, 25 patients had B symptoms and ESR ≥30, or ESR ≥50 despite the absence of B symptoms, 29 patients had bulky disease, 7 patients were older than 50 years, and 6 patients had more than 3 nodal areas involved. Thirty-six out of 63 (59%) patients received radiotherapy as a consolidation treatment after chemotherapy. After completion of the therapeutic program, 54 out of 63 (86%) patients obtained complete remission, while 9 (14%) had refractory disease; 15 out of 54 (28%) patients in complete remission relapsed during follow up. Diagnostic biopsies were reviewed by expert hematopathologists and classified into 3 groups according to the intensity of CD68 expression [N Engl J Med. 2010 Mar 11;362(10):875-85]. CD68-positive infiltrate was lower than 5% in 14 patients (group A), between 5 and 25% in 43 patients (group B), and greater than 25% in 6 patients (group C). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method with observation time calculated from diagnosis. Comparison between survival curves was performed by means of the Gehan-Wilcoxon test. The 2-year OS and PFS in the entire cohort were 98% and 79%, respectively. There was a difference in the 2-year PFS between patients with favorable and those with unfavorable prognosis according to the EORTC risk criteria (100% vs 72%, P<.05). CD68 expression had a significant effect on 2-year PFS, which was 86%, 84% and 33% in group A, B and C, respectively (P<.004). After merging group A and B, there was a significant difference in 2-year PFS between patients having up to 25% and those with more than 25% CD68-positive infiltrating macrophages (84% vs 33%, P<.002). All patients with favorable EORTC criteria had CD68 expression lower than or equal to 25%. Within those with unfavorable EORTC criteria, patients with CD68 expression greater than 25% had a worse 2-year PFS compared with patients having values up to 25% (33% vs 77%, P<.012). In conclusion, the findings of this study suggest that a proportion of CD68-positive infiltrating macrophages greater than 25% is associated with unfavorable clinical outcome in patients with early-stage Hodgkin's lymphoma. However, for CD68 expression to be used as a prognostic factor in these patients, both technical standardization of the immunohistochemistry method and prospective validation of the prognostic biomarker in a clinical trial are clearly required. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin's lymphoma

2012 ◽  
Vol 23 (3) ◽  
pp. 736-742 ◽  
Author(s):  
D. Azambuja ◽  
Y. Natkunam ◽  
I. Biasoli ◽  
I.S. Lossos ◽  
M.W. Anderson ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Tumor Associated Macrophages

Lymphocyte-Predominant and Classical Hodgkin's Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group

2008 ◽  
Vol 26 (3) ◽  
pp. 434-439 ◽  
Author(s):  
Lucia Nogová ◽  
Thorsten Reineke ◽  
Corinne Brillant ◽  
Michal Sieniawski ◽  
Thomas Rüdiger ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Treatment Strategies ◽  
Hodgkin's Lymphoma ◽  
Tumor Control ◽  
Study Group ◽  
Advanced Stage ◽  
German Hodgkin Study Group

Purpose Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL patients registered in the German Hodgkin Study Group (GHSG) database, comparing patient characteristics and treatment outcome with cHL patients. Patients and Methods We analyzed retrospectively 8,298 HL patients treated within the GHSG trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL. Results Complete remission and unconfirmed complete remission after first-line treatment was achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced stages of LPHL compared with cHL, respectively. Tumor control (freedom from treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50 months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%, respectively (P = .0166). In LPHL patients, negative prognostic factors were advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia (P = .010) for FFTF. Age ≥ 45 years (P = .0125), advanced stage (P = .0153), and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS. Conclusion The better prognosis of LPHL as compared with cHL might allow different treatment strategies, particularly for early-stage LPHL patients.

Treatment of Early Stage Classic Hodgkin's Lymphoma Outcome: Kuwait Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4948-4948
Author(s):  
Salem H Alshemmari ◽  
Rehab S Elhagracy ◽  
Amany Elbasmy
Keyword(s):  
Survival Rate ◽  
Regression Model ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Bulky Disease ◽  
Early Stages ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Abstract 4948 Treatment of early stage classical Hodgkin's lymphoma (CHL) I&II had been changed over the last decades. This study evaluated the treatment outcome for early stages CHL patients who were treated by 6 versus 4 ABVD cycles with or without radiotherapy (RT) to the residual or bulky sites. The study retrospectively analyzed cases with early stage CHL patients diagnosed & treated in Kuwait Cancer Control Center from 2001–2010. Staging confirmed by computed tomography, nuclear studies:Gallium or recently Positron emission tomography. Data analyzed by SPSS version 15 & described using mean and standard deviation (SD) or frequencies according to data type. Chi square test was used for comparison of qualitative variables; survival analysis was performed by Kaplan-Meir analysis and regression model performed with Cox regression model. Significance considered if p ≤0.05 & highly significant if ≤0.01. The study included 105 patients that were further subdivided into Group A included 34 patients treated with 4 cycles and group B included 71 patients were treated by 6 cycles. Table(1)demonstrated cases characteristics. There were 61 males and 44 female with male:female ratio 1.3:1. Nodular sclerosis attributed to 66.6%, mixed cellularity 26.6%, lymphocyte rich 5.7% and lymphocyte depleted 0.9% of cases.Table (1):Characteristic Differences between group A & B.ParametersGroup A n=34Group B n=71pAge mean±SD37.41±16.15928.44±11.4740.005Sex female/males n (%)13(38.2)/21(61.7)31(43.6)/40(56.3)0.675B symptoms positive n (%)6 (17.6)32 (45)0.009Stage I n (%) II n (%)13 (38.2) 21 (61.7)7 (9.8) 64 (90.1)0.001IA 18 (17.1%)12 (35.2)6 (8.4)IIA 49 (46.6%)16 (47)33 (46.4)IB 2 (1.9%)1 (2.9)1 (1.4)IIB 36 (24%)5 (14.7)31 (43.6)Presence of Bulky disease n (%)5 (14.7)21 (29.5)0.146Presence of Extranodal site n (%)4 (11.7)4 (5.6)0.329Groups of lymph node ≥412(35.3)41(57.7%)ESR ≥ 50mm/hr n (%)36(34.28)6(17.6)30(42.2)mean±SDmean±SDTLC X109/L8.09± 3.10810.42±4.4580.007HB g/L12.36±2.1211.67±1.900.09Plat X109/L349.21±88.429400.17±151.4880.033Lymphocytes X109/L1.65±0.6711.74±0.7900.491ESR mm/hr28.21±22.15347.69±33.4500.001Max mass size by CM4.94±2.7955.39±3.0260.464Albumin g/L39.59±4.65936.62±6.0320.013LDH IU/L178.41±46.639183.90±85.3420.727 Age was significantly lower in group B (p=0.005), that may attributed to the heterogeneity of population. Group B significantly had more B symptoms, higher platelets, ESR, TLC & lower albumin level. RT was delivered to total 60(57.1%) cases; 28(82.3%) in group A and 32(45%) in group B. Thirty six of cases received 30 Gy and 20 received 36 Gy. The commonly radiated sites were cervical nodes 53.3% followed by the mediastinum in 41.6%. Complete remission (CR) achieved in 84 (80%) of cases, while 6 (5.7%) showed residual disease (RD) & progression (PD) on therapy and 15 (14.3%) of cases developed relapse on follow up. In group A; 82.2% of patients achieved CR compared to 76.1%. Relapse incidence was 16.9%(12) in group B compared to 8.8%(3) in group A. Thirteen patients were treated by high dose chemotherapy followed by ASCT; 7 with relapse (2 from A & 5 from B) & 6 cases with SD/PD (1 from A & 5 from B). Among relapsed cases 6 died (4 from group B & 2 from group A). Four patients with RD/PD died (3 from group B, 1 from group A). No significant difference was found between the two groups regarding CR, PD or relapse incidence (p=0.40). Kaplan-Mayer survival study showed 5-years survival rate was 86%; without significant difference between group A 85 % or group B 87% (p=0.51). Those without B symptoms had significantly better 5-years survival rate 92% compared to those with B symptoms 73 % (p=0.02). Although those patients with bulky disease showed inferior 5-years survival rate 77 % compared to those without bulky disease 89%,the difference was not statistically significant (p=0.1). Lower ESR < 50 mm/hr had better 5-years survival 89 % compared to high ESR ≥ 50 mm/hr 82 % with no significant difference (p=0.51). Events free survival time was difficult to determine attributed to minor events among patients. There were no cardiopulmonary toxicities or secondary malignancy detected in patients on 5-years follows up. This suggests that treatment of early stage CHL by combined chemo-radiotherapy associated with better survival. ABVD 4 cycles is adequate as 6 cycles in early stages. Disclosures: No relevant conflicts of interest to declare.

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.

Early-Stage Hodgkin's Lymphoma

2010 ◽  
Vol 363 (23) ◽  
pp. 2267-2267
Author(s):  
Michele Bibas ◽  
Andrea Antinori
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma

Prognostic and predictive factors in early stages of classic Hodgkin’s lymphoma

2022 ◽  
pp. 7-15
Author(s):  
T. I. Bogatyreva ◽  
A. O. Afanasov ◽  
A. Yu. Terekhova ◽  
N. A. Falaleeva
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Cure Rate ◽  
First Line ◽  
Bulky Disease ◽  
Cox Regression Analysis ◽  
Early Stages

Rationale. In the early stages of classical Hodgkin’s lymphoma (cHL), the cure rate reaches 85–95 %, but the long-term effects of therapy can worsen overall survival. Current trials for early stages of Hodgkin’s lymphoma with favorable prognosis address the task of maintaining cure rates while reducing sequelae. For early unfavorable stages, the challenge is to improve cure rate without increasing toxicity.Purpose. To assess the potential significance of individual risk factors for optimal choice of the first line chemotherapy in early-stage Hodgkin lymphoma.Materials and methods. This single-center retrospective study included 290 patients with early stage cHL who had received ABVD – based (n = 249; 86 %) or BEACOPP‑21 – based (n = 41; 14 %) combined modality therapy from 2000 to 2017. Progression-free survival (PFS) and overall survival (OS) were assessed in Cox regression analysis including 12 clinical parameters.Main results. At a median follow up of 60 months for the entire group, OS was 95 % and PFS was 89 %. In a multivariate analysis PFS, at 5 years, was significantly inferior in patients with mediastinal bulk, baseline lymphocytopenia (≤ 0.6 × 109/L, р = 0.002; < 1.0 × 109/L, р = 0.000) and male gender; OS was inferior only in patients with an absolute lymphocytopenia (AL). In patients with AL, PFS after ABVD-based regimen was, respectively, 12 % in the high-risk group with mediastinal bulk and 56 % without it. PFS of patients without AL when treated with ABVD did not differ compared to BEACOPP‑21 within the same prognostic group: 95.2 % vs. 92.3 % for non-bulky and 86.4 % vs. 84.2 % for bulky disease. In the absence of AL, mediastinal bulk remained the main and only risk factor in multivariate analysis.Conclusions. The ABVD regimen is highly effective in the first line of chemotherapy for cHL, except for cases with baseline lymphocytopenia, in which the early usage of the BEACOPP regimen in the escalated or 14-day variants might be justified. In patients with mediastinal bulk, standard chemotherapy is not effective enough even in the absence of AL; therefore, if an intermediate PET/CT scan is available, it seems more appropriate to use a milder ABVD regimen on the first line and leave intensive therapy for patients with proven refractory disease. Prospects for improving the efficiency are opened with the new N-AVD and A-AVD schemes, the benefits of which should be evaluated, first of all, in patients with AL and mediastinal bulk.

Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial

The Lancet ◽  
2015 ◽  
Vol 385 (9976) ◽  
pp. 1418-1427 ◽  
Author(s):  
Karolin Behringer ◽  
Helen Goergen ◽  
Felicitas Hitz ◽  
Josée M Zijlstra ◽  
Richard Greil ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Open Label
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