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.

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.

Identification of Prognostic Factors in Patients with Early Stage Unfavorable Hodgkin’s Lymphoma: An Individual Patient Data Meta-Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5577-5577
Author(s):  
Julia Bohlius ◽  
Heinz Haverkamp ◽  
Volker Diehl ◽  
Houchingue Eghbali ◽  
Jeremy Franklin ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Missing Data ◽  
Hodgkin’S Lymphoma ◽  
Individual Patient Data ◽  
Early Stage ◽  
Patient Data ◽  
Hodgkin's Lymphoma ◽  
Cochrane Library ◽  
Bulky Disease ◽  
Laboratory Parameters

Abstract Background: In patients with early stage unfavorable Hodgkin’s lymphoma (HL) event-free-survival (EFS) is low compared to patients with early favorable or advanced stage disease. An international collaborative study was initiated to identify prognostic factors that could help to define among early stage unfavorable patients those who might benefit from more intensive treatment. Methods: Medline and Cochrane Library were systematically searched for randomized controlled trials in stage I/II HL. Trials should concern patients with one or more risk factors (age, sex, stage, B-symptoms, bulky disease, number of areas involved, laboratory parameters) receiving 4–6 cycles of ABVD or similar chemotherapy and radiotherapy. Only trials with ≥ 100 patients per study arm were considered. Individual patient data were collected. Results: Six studies were identified: GHSG: HD5, HD8, HD11; EORTC: H6U, H7U, H8U. Data from 4,235 patients enrolled between 08/1982 and 01/2003 were available for analysis. The proportion of missing data was very low for demographic and clinical characteristics (&lt; 1%); it was acceptable (1.5–9%) for laboratory parameters with the exception of albumin (41% missing values, not recorded in 3 trials). Patient characteristics are listed below. The median follow up was 58.4 months (95% CI 56–61). At the time of analysis 612 patients had experienced an event (disease progression, relapse or death) leading to a 5-year EFS rate of 85%. Using an univariate Cox-regression stratified by study and treatment arm several parameters showed significant influence on EFS. Conclusion: The data set available is sufficiently powered to identify relevant prognostic factors. A multivariate analysis using updated data will be presented. Baseline parameter of inlcuded studies Age (median years) Male sex Sage (I/II) B symptoms Bulky disease Hb (median g/dL) All patients, n=4,325 32 2,039 (48.1%) I: 546 (12.9%), II: 3,688 (87.1%) 1,490 (35.2%) 1,936 (45.7%) 12.9 Missing data 1 (&lt; 1%) 0 1 (&lt; 1%) 35 (&lt; 1%) 0 82 (1.9%)

Combined VBM Chemotherapy and Involved Field (IF) Radiotherapy in Early Stage Hodgkin’s Lymphoma (HL): A Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4463-4463
Author(s):  
Emilia Cocorocchio ◽  
Fedro A. Peccatori ◽  
Federica Gigli ◽  
Simona Bassi ◽  
Luca Nassi ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Alkylating Agents ◽  
Performance Status ◽  
Low Risk ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Before And After

Abstract Early stage HL patients (pts) benefit from a short course of chemotherapy combined with IF radiotherapy. In our previous experience six courses of VBM chemotherapy (Stanford regimen) were administered with IF radiotherapy. However, despite good clinical results, the schedule was modified in terms of total chemotherapy cycles delivered, in order to reduce the risk of long term toxicities. PET and CT scan were performed at staging to identify a low risk patients (pts) group. From May 2001 to November 2006, 32 treatment naïve Hodgkin’s lymphoma pts (18 male, 14 female) were treated with four courses of VBM chemotherapy (D1, 8: Vinblastine 6 mg/sm, Bleomycin 10 mg/sm, Methotrexate 30 mg/sm, repeated every 28 days) followed by IF radiotherapy. Median age was 37 years (range 16–73). Main histology was classical HL in 26 pts, while lymphocyte predominant was observed in 6 pts. Pts were all stage I-IIA (no bulky disease), no more than three sites involved, performance status 0–1 and ESR < 50. CT scans were performed before and after chemotherapy and radiotherapy. PET scans were performed before and after chemotherapy in 26 pts, and after radiotherapy if not performed before or in case of positivity after chemotherapy. Chemotherapy was usually well tolerated: three pts experienced G3-4 neutropenia while the main non- haematological toxicities recorded were G3 transaminitis in 3 pts and G1-2 neuroconstipation/abdominal pain in 18 pts. IF radiotherapy was performed one month after the last chemotherapy cycle; median dose administered was 30Gy (range 26–30.4). At the end of chemotherapy 7 pts were PET positive. While one patient developed progressive disease, the other six pts became negative after radiotherapy and are still in complete remission (CR). 29 pts (90%) completed the whole program obtaining a CR. Two pts progressed before radiotherapy, while one patient shifted to an anthracycline containing schedule after two cycles due to stable disease. With a median follow-up of 42 months (range: 7–73), all pts are alive. 1 out of 29 CR pts progressed and is now receiving intensive chemotherapy program with autologous stem cell transplant. In our experience four cycles of VBM chemotherapy combined with IF radiotherapy is an effective program. Furthermore this regimen that doesn’t contain alkylating agents or anthracyclines avoids alopecia and decreases the risk of long term toxicity. PET scan effectively helps to identify low risk early stage HL pts that can take advantage of this therapeutic approach.

Involved-Field Radiotherapy Is Equally Effective and Less Toxic Compared With Extended-Field Radiotherapy After Four Cycles of Chemotherapy in Patients With Early-Stage Unfavorable Hodgkin’s Lymphoma: Results of the HD8 Trial of the German Hodgkin’s Lymphoma Study Group

2003 ◽  
Vol 21 (19) ◽  
pp. 3601-3608 ◽  
Author(s):  
Andreas Engert ◽  
Petra Schiller ◽  
Andreas Josting ◽  
Richard Herrmann ◽  
Peter Koch ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Survival Rates ◽  
Observation Time ◽  
Hodgkin's Lymphoma ◽  
Bulky Disease ◽  
Acute Side Effects ◽  
Extended Field ◽  
Lymphoma Study Group ◽  
Involved Field

Purpose: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy. Patients and Methods: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). Results: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm. Conclusion: Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.

Evaluation of Early Stage Hodgkin’s Lymphoma Treatment: Two Decades of Progress.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4581-4581
Author(s):  
Eyad F. Alsaeed ◽  
Rajiv Samant ◽  
Gallant Victor ◽  
Lother Huebsch ◽  
Wayne Kendal
Keyword(s):  
Overall Survival ◽  
Treatment Modality ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Hodgkin's Lymphoma ◽  
Combined Modality Treatment ◽  
Combined Modality ◽  
Involved Field ◽  
Disease Free

Abstract Introduction The treatment of early stage Hodgkin’s lymphoma is controversial. Radiotherapy alone, chemotherapy alone or a combination of radiotherapy and chemotherapy are all considered effective options. Purpose The purpose of this study is to review the treatment approaches and outcomes used for early stage Hodgkin’s lymphoma over the past two decades at ORCC Methods Retrospective chart review of all patients with stage IA /IIA treated from 1984–2002 was performed. Patients were separated into three groups according to initial treatment modality: radiation alone (Rads), chemotherapy alone (Chemo), or combined modality (Combined). Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis. Result Between May 1984 and January 2003, 172 patients with newly diagnosed Hodgkin’s lymphoma (28% stage 1A, 72% stage 2A) were seen at our centre. Treatment was as follows: 49% Rads, 13% Chemo and 38% Combined. The median age was 33.7 years (range: 17 – 82 years) and the median follow-up of 73 months (range: 3 – 204 months). The 5-year disease free and overall survival rates for the entire group were 90% and 96 % respectively. The 5-year disease-free and overall survival by treatment modality was: Rads 87% and 93 %; Chemo 80 % and 100 %; Combined 97 % and 98%. In the Combined group, there was no difference in outcome between patients receiving involved-field radiation and those receiving extended-field radiotherapy. The relapse rate in a patient who received abbreviated chemotherapy and greater than four cycles was 4.3% (1 out of 23) and 2.4% (1 out of 41) respectively. The incidence of acute Grade 3 and 4 toxicities were 9 % and 0.5% respectively. Conclusions Our data confirms the excellent prognosis of early stage Hodgkin’s lymphoma with all the approaches used at our centre. At present, we favour combined modality treatment with involved-field radiotherapy and our results support its continued use.

Salvage Treatment with Ofatumumab and ESHAP (O-ESHAP) for Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma After First-Line Chemotherapy: Interim Analysis of a Phase II Trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1630-1630
Author(s):  
Carmen Martinez ◽  
Mercedes Rodriguez-Calvillo ◽  
María José Terol ◽  
Blanca Xicoy ◽  
Ramón García-Sanz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Phase Ii Trial ◽  
Hodgkin's Lymphoma ◽  
Hematological Toxicity ◽  
Published Data ◽  
High Dose ◽  
First Line ◽  
Bulky Disease ◽  
Line Chemotherapy

Abstract Abstract 1630 The management of recurrent or refractory Hodgkin's lymphoma (HL) remains challenging. Previous published data have suggested that infiltrating normal B lymphocytes in classic HL lesions may contribute to the survival of Hodgkin and Reed-Sternberg cells in vivo. The objective of this prospective, multicenter, phase II trial was to investigate the activity of an anti-CD20 monoclonal antibody, ofatumumab, in combination to a standard platinum-based salvage regimen, ESHAP (O-ESHAP) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) for patients with classical HL failing to first line chemotherapy. Forty- five patients (25 M / 21 F, median age 34 years, range 18–66) were enrolled in the study between June 2010 and June 2012. Treatment consisted on three cycles of ESHAP plus ofatumumab 1,000 mg days 1 and 8 on first cycle and day 1 on second and third cycles. At the time of study entry, 66% of patients had III-IV Ann Arbor stage, 16% bulky disease, 18% B symptoms, 40% extranodal HL and 52% ≥3 involved nodal areas. We respect to response to first-line therapy, 46% patients had achieved a completed response (CR) and then relapsed, 6% had a partial remission (PR), whereas the remaining 48% were primary refractory. Eighty-one percent patients have received 3 cycles of O-ESHAP as scheduled, three patients 2, and five 1 cycle (1 patient due to toxicity, 1 patient's decision, 2 HL progression, and 4 treatments ongoing). Grade 3–4 WHO hematological toxicity was observed in 16%, 19%, and 20% after cycles 1, 2, and 3, respectively. Non-hematological toxicity was reported in 32%, 10%, and 20%, respectively. Overall response (OR) rate was 63% (49% CR and 14% PR). Response to O-ESHAP according to prior response to first-line chemotherapy is shown in table 1. Adequate PBSCs collection was achieved in 94% mobilized patients. Twenty-six out of 33 patients have already proceeded to ASCT. Two patients died of neutropenic sepsis after ASCT and HL progression, respectively. Preliminary results of this ongoing trial suggest that addition of ofatumumab to ESHAP is safe and has a promising clinical activity in patients with relapsed/refractory HL candidates to ASCT. Table 1. Response to O-ESHAP according to previous response to first-line treatment Response to first-line chemotherapy Relapsed or partial response (n=17) Refractory (n=16) Response after O-ESHAP OR 16 (94%) 7 (44%) CR 14 (82%) 3 (22%) PR 2 (12%) 4 (22%) Refractory 1 (6%) 9 (56%) Disclosures: No relevant conflicts of interest to declare.

Combined Modality Treatment of Two or Four Cycles of ABVD Followed by Involved Field Radiotherapy in the Treatment of Patients with Early Stage Hodgkin’s Lymphoma: Update Interim Analysis of the Randomised HD10 Study of the German Hodgkin Study Group (GHSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2673-2673 ◽  
Author(s):  
Andreas Engert ◽  
Annette Pluetschow ◽  
Hans T. Eich ◽  
Richard Herrmann ◽  
Bernd Doerken ◽  
...  
Keyword(s):  
Overall Survival ◽  
Interim Analysis ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Combined Modality Treatment ◽  
Involved Field ◽  
Radiotherapy Dose ◽  
Involved Field Radiotherapy

Abstract Combined modality treatment is regarded as standard by most study groups for patients with early-stage Hodgkin’s lymphoma (HL). However, the optimal chemotherapy, the number of cycles needed and the optimal radiotherapy dose is still unclear. The GHSG thus conducted a randomised study for patients with early stage favourable Hodgkin’s lymphoma (HD10) in which these questions were addressed. A total of 1370 patients were randomised from 5/1998 to 1/2003 between two or four cycles of ABVD and independently to 20Gy or 30Gy involved field (IF) radiotherapy. For the second interim analysis at a median follow up of 28 months, 847 patients were available. Patients were equally balanced for age, gender, stage, histology, performance status and risk factors. Compared with two cycles, there was more toxicity in patients receiving four cycles of ABVD for leucopenia, hair loss and infection. Concerning radiotherapy dose, there was more toxicity associated with 30Gy for dysphagia, mucositis and leucopenia. The rate of complete remissions ranged between 98% and 99% with no significant differences among treatment arms. Freedom from treatment failure (FFTF) and overall survival showed no differences between the four treatment arms. The curves for overall survival and FFTF were nearly superimposable for all four arms. This analysis suggests that 2 chemotherapy cycles with involved field radiotherapy may be sufficient for patients with early favourable HL, but a reliable assessment must await the final analysis including all randomised patients and with adequate follow-up. The results of the third interim analysis (10/2005) including 1110 patients with a median follow up of more than 3 years will be presented.

Serum Levels of Soluble Interleukin 10 (IL-10) in Patients with Hodgkin’s Lymphoma: Predictive Value in Advanced Stage.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4590-4590 ◽  
Author(s):  
Mayda Navarrete ◽  
Andres Palacios ◽  
Maria J. Cruz ◽  
Adoracion Blanco ◽  
Isabel Caragol ◽  
...  
Keyword(s):  
Predictive Value ◽  
Hodgkin’S Lymphoma ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Hodgkin's Lymphoma ◽  
Advanced Stage ◽  
Nodal Disease ◽  
First Line ◽  
Bulky Disease ◽  
First Line Therapy

Abstract Introduction. Hodgkin’s lymphoma has a high rate of cure with current therapies; however, some patients do not respond or relapse after therapy. The aim of this study is to assess the predictive value of serum soluble Interleukin 10 (sIL-10) at diagnosis in these patients. Patients and Methods. Two cohorts of 80 consecutive patients with Hodgkin’s lymphoma (40 male and 40 female) diagnosed and treated in the same institution were evaluated. All of them were clinically staged according to Ann Arbor system. The following parameters were evaluate for prognosis: age, sex, histology, clinical symptoms, extra-nodal disease, stage, treatment, blood counts (hemoglobin, white blood cells, lymphocyte and platelets), blood chemistry (b-2-microglobulin, tymidine-kinase and LDH levels), serum soluble IL-10 and IL-6 levels by using an ELISA method. Statistics: Continuous variables were compared by using Wilcoxon signed-rank test, contingence tables were used for dichotomized variables; the optimal cut-off values were calculated by using CART method. Survival curves were estimated by Kaplan-Meier method and mantel-Cox were used to compare them. Cox multiple regression analysis was performed to determinate the independent contribution of the variables.Patients received COPP (n=16), hybrid schedule (n=21), ABVD (n=35), radiotherapy alone (n=6), surgery alone (n=1), and Stanford V (n=1) as first-line therapy. Results. Median patient age was 36 years (range: 15–85 years), predominant histology was nodular-sclerosis (70%), 27 patients (34%) presented B symptoms. Bulky disease was present in 14 (17%) and bone marrow involvement in 6%. Thirty-six patients were considered as having advanced stage (II-B or II + bulky disease. III-B or III + bulky disease, and IV). The overall response rate was 92% (85% CR/CRu, and 7% PR). Eleven out of 68 patients who achieved a CR/CRu relapsed. Serum IL-10 levels were significant higher in patients with B symptoms and extra-nodal disease and correlated with β-2-microglobulin, tymidine-kinase, and (inversely) hemoglobin levels. The optimal sIL-10 serum level cut-off was established in 13.8 pg/mL. %: 54 out of 57 patients (95%), and 14 out of 23 of patients below and above this level respectively achieved a CR/CRu (P<0.001). With a median follow-up of 86 months the OS and EFS are 77% and 69% respectively. Only sIL-10 > 13.8 pg/mL had independent predictive value for EFS in the multivariate analysis. Based on this study and combining stage a serum levels of sIL-10, three subgroups could have been identify:Patients with early disease: 85% EFS at 5 years;patients with advanced stage (according to the above mentioned definition ) and serum levels of sIL-10 less than 13.8 pg/mL: 72% EFS at 5 years.; andpatients with advanced stage and serum levels of sIL-10 superior to 13.8 pg/mL: 29% EFS at 5 years (P=0.0001). Conclusion. Serum levels of sIL-10 can help us to identify a subgroup of patients with advanced disease and poorer response and EFS who may benefit from more aggressive first-line therapy. Figure Figure

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