Childhood Hodgkin's Lymphoma
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The lymphatic system helps the body fight infection. There are two main types of cancer associated with the lymphatic system: Hodgkin's Disease and Non-Hodgkin's Lymphoma (NHL). Both are rare in children aged under 3, and are more common in older children and adults. More boys than girls have childhood Hodgkin's disease.

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Hodgkin's Lymphoma (general / adut resources)

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Pandit S, Choudhury S, Das A, et al.
Cervical lymphadenopathy--pitfalls of blind antitubercular treatment.
J Health Popul Nutr. 2014; 32(1):155-9 [PubMed] Related Publications
Tuberculosis (TB) is the most common cause of cervical lymphadenopathy in the TB-endemic zone, like India but it can also mimic other diseases. Four cases of cervical lymphadenopathy presented to us as initial treatment failure after completion of six months of antitubercular drugs (ATD), including rifampicin, isoniazid, pyrazinamide, and ethambutol. All were diagnosed as having tuberculosis either by fine needle aspiration cytology or clinically from outside our institution. In one case, tuberculosis was the final diagnosis but, unfortunately, it was multidrug-resistant. In other three cases, Hodgkin disease, Non-Hodgkin lymphoma, and Kikuchi's disease were the diagnoses. In resource-poor countries, like India, which is also a TB-endemic zone, TB should be the first diagnosis in all cases of chronic cervical lymphadenopathy, based on clinical and/or cytological evidences. So, they were correctly advised antitubercular therapy (ATT) initially. Sometimes, TB mimics other aetiologies where apparent initial improvement with ATT finally results in treatment failure. Hence, investigations for microbiological and histopathological diagnosis are warranted, depending on the resources and feasibility. If these tests are not routinely available, the patients should be under close monitoring so that lymphoma, drug-resistant TB, or other aetiologies of cervical lymphadenopathy are not missed. Patients with cervical lymphadenopathy rarely presents acutely; so, a physician can take the opportunity of histopathological study of lymphnode tissue.

Related: Non Hodgkin's Lymphoma

Shankar A, Hayward J, Kirkwood A, et al.
Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma--results of the UK HD3 relapse treatment strategy.
Br J Haematol. 2014; 165(4):534-44 [PubMed] Related Publications
The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005, 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4-6 cycles of EPIC [etoposide, prednisolone, ifosfamide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5-year overall survival [OS] and progression-free survival from relapse was 75·8% [64·8-83·9] and 59·9% [48·3-69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19-1·18] for those with a time from end of treatment to relapse of 3-12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04-0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse. Survival outcome in children with primary refractory HL is poor.

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Maraldo MV, Jørgensen M, Brodin NP, et al.
The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma.
Pediatr Blood Cancer. 2014; 61(4):717-22 [PubMed] Related Publications
BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique.
PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I–II classical HL patients <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow-up, treating death from other causes as competing risks. The corresponding LYL were derived from the estimated excess risks. Statistical analyses were performed with repeated measures ANOVA.
RESULTS: Both a reduction in field size and in prescribed radiation dose significantly lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL.
CONCLUSIONS: Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.

Koh YW, Park C, Yoon DH, et al.
CSF-1R expression in tumor-associated macrophages is associated with worse prognosis in classical Hodgkin lymphoma.
Am J Clin Pathol. 2014; 141(4):573-83 [PubMed] Related Publications
OBJECTIVES: The aim of this study was to determine the prognostic relevance of colony-stimulating 1 receptor (CSF-1R) expression in both Hodgkin/Reed-Sternberg (HRS) cells and the surrounding cells (non-HRS cells) in patients with classical Hodgkin lymphoma (CHL) .
METHODS: Diagnostic tissues from 112 patients with CHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively by immunohistochemical analysis for CSF-1R and CD68 and CD163 for tissue-associated macrophages.
RESULTS: High numbers (≥30%) of non-HRS cells expressing CSF-1R conferred inferior event-free survival and overall survival in univariate and multivariate analysis. High numbers of non-HRS cells expressing CSF-1R were significantly associated with a high number of tumor-associated macrophages as detected by CD163 expression (P < .001). In particular, coexpression of CSF-1R and CD163 was associated with a worse survival outcome than either CSF-1R or CD163 expression alone or no expression.
CONCLUSIONS: Our data demonstrate that a high number of non-HRS cells expressing CSF-1R are correlated with an increased tumor macrophage content and worse survival.

Related: CSF1R

Terezakis SA, Metzger ML, Hodgson DC, et al.
ACR Appropriateness Criteria Pediatric Hodgkin Lymphoma.
Pediatr Blood Cancer. 2014; 61(7):1305-12 [PubMed] Related Publications
Pediatric Hodgkin lymphoma is a highly curable malignancy and potential long-term effects of therapy need to be considered in optimizing clinical care. An expert panel was convened to reach consensus on the most appropriate approach to evaluation and treatment of pediatric Hodgkin lymphoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Four clinical variants were developed to assess common clinical scenarios and render recommendations for evaluation and treatment approaches to pediatric Hodgkin lymphoma. We provide a summary of the literature as well as numerical ratings with commentary. By combining available data in published literature and expert medical opinion, we present a consensus to the approach for management of pediatric Hodgkin lymphoma.

Rossi C, Kanoun S, Berriolo-Riedinger A, et al.
Interim 18F-FDG PET SUVmax reduction is superior to visual analysis in predicting outcome early in Hodgkin lymphoma patients.
J Nucl Med. 2014; 55(4):569-73 [PubMed] Related Publications
UNLABELLED: PET performed after 2 cycles of chemotherapy (PET2) allows prediction of outcome in most patients with Hodgkin lymphoma (HL). Visual analysis using a 5-point scale was proposed to assess PET response, but a semiquantitative approach using maximum standardized uptake value (SUVmax) reduction between baseline and interim PET was shown to be superior to the 5-point scale in patients with diffuse large B-cell lymphoma and may also improve the accuracy of interim PET interpretation in HL. To compare the clinical usefulness of both methods in HL patients, we analyzed PET2 according to visual and ΔSUVmax criteria in a retrospective single-center study.
METHODS: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated with 4-8 cycles of anthracycline-based chemotherapy. Radiotherapy was performed in 19 responding patients with localized disease. PET was done at baseline (PET0) and after 2 cycles of chemotherapy, and treatment was not modified according to the PET2 result. PET2 was interpreted using the 5-point scale (positivity for score 4 or 5). The SUVmax reduction between PET0 and PET2 (ΔSUVmax) was computed for all patients, and patients with a ΔSUVmax greater than 71% were considered good responders.
RESULTS: When the 5-point scale was used, 46 patients (78%) achieved a negative PET2 result, 7 of whom failed treatment (negative predictive value, 85%). Forty-nine patients (83%) had a ΔSUVmax greater than 71%, 6 of whom failed treatment (negative predictive value, 88%). The PET2 positive predictive value was significantly better for ΔSUVmax (70%) than for the 5-point scale (46%). When ΔSUVmax was used, 6 (46%) of the 13 PET2-positive patients could be reclassified as good responders. Although visual PET2 positivity was related to a lower 4-y progression-free survival (45%) compared with PET2 negativity (81%, P < 0.002), ΔSUVmax (>71 vs ≤71%) was more accurate for identifying patients with different 4-y progression-free survivals (82% vs. 30%; P < 0.0001). In multivariate analysis using the international prognosis score and ΔSUVmax as covariates, ΔSUVmax remained the unique independent predictor for progression-free survival (P = 0.0001; relative risk, 8.1).
CONCLUSION: Semiquantitative analysis was more accurate than visual analysis based on the 5-point scale to interpret PET2 and predict the outcome of HL patients. These encouraging results warrant further confirmation in larger and prospective series.

Huppmann AR, Nicolae A, Slack GW, et al.
EBV may be expressed in the LP cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in both children and adults.
Am J Surg Pathol. 2014; 38(3):316-24 [PubMed] Article available free on PMC after 01/03/2015 Related Publications
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (CHL) are classified separately because of their distinct clinical and pathologic features. Whereas Epstein-Barr virus (EBV) is detected in the neoplastic cells of 25% to 70% of CHL, NLPHL is generally considered to be EBV(-). We assessed EBV status in 302 pediatric and adult cases of NLPHL. A total of 145 pediatric (age 18 y or younger) and 157 adult cases of NLPHL were retrieved from 3 North American centers and tested for EBV by in situ hybridization (EBV-encoded small RNA). Clinical and pathologic features were analyzed. Five (3.4%) pediatric and 7 (4.5%) adult NLPHL cases contained EBV(+) lymphocyte-predominant (LP) cells. Although all 12 cases met the criteria for diagnosis of NLPHL, atypical features were present, including capsular fibrosis, atrophic germinal centers, and pleomorphic or atypical LP cells. CD20 and OCT-2 were strongly and diffusely positive in all except 1 case. However, PAX5 and CD79a were weak and/or variable in 7/8 and 6/6 cases tested, respectively. EBV(+) cases were more likely to be CD30(+) (75%) compared with EBV(-) cases (25%) (P=0.0007); CD15 was negative in all cases. Our results show that EBV(+) LP cells may occur in NLPHL. Distinguishing EBV(+) NLPHL from CHL can be challenging, as EBV(+) NLPHL can have partial expression of CD30 and weak PAX5 staining as well as pleomorphic-appearing LP cells. However, the overall appearance and maintenance of B-cell phenotype, with strong and diffuse CD20 and OCT-2 expression, support the diagnosis of NLPHL in these cases.

Huynh-Le MP, Walker AJ, Kominers SD, et al.
Patterns of failure after involved field radiation therapy for pediatric and young adult Hodgkin lymphoma.
Pediatr Blood Cancer. 2014; 61(7):1210-4 [PubMed] Related Publications
BACKGROUND: Involved field radiation therapy (IFRT) is integral in curative therapy for Hodgkin lymphoma (HL), although primarily used in patients with intermediate/high-risk HL. We present failure patterns and clinical outcomes in a cohort of pediatric and young adult patients with HL treated with IFRT at the Johns Hopkins Hospital.
PROCEDURE: Patients ≤40 years old with intermediate/high-risk HL who received chemotherapy and IFRT from 1997 to 2012 were included in this retrospective analysis. Patients were evaluated for failure patterns, overall survival (OS), and event-free survival (EFS) using Kaplan-Meier curves, descriptive statistics, and Cox proportional hazard regressions.
RESULTS: We reviewed 74 patients (45 pediatric and 29 young adult) with a median follow-up of 4.4 years. The mean age at diagnosis was 21.4 years. Patients received a median of 29.75 Gy of IFRT (range 15-39.6 Gy). The majority of pediatric patients received ABVE-PC chemotherapy (n = 25) and <30 Gy of radiation (n = 33) while most young adults received ABVD chemotherapy (n = 24) and ≥30 Gy (n = 25). Estimated 5-year OS and EFS were 96% and 81%, respectively. Thirteen patients had recurrence; eight were pediatric. Distant relapse alone comprised 83% of failures in patients receiving ≥30 Gy. Of the seven patients who received <30 Gy and had recurrence, six had local failure as a component of their recurrence. Caucasian race (P = 0.02) and nodular sclerosing histology (P = 0.01) predicted for increased EFS. Late effects were minimal and all deaths (n = 4) were from HL.
CONCLUSIONS: In this series, pediatric and young adult patients were treated with differing chemoradiation and had distinct recurrence patterns.

Michaelson EM, Chen YH, Silver B, et al.
Thyroid malignancies in survivors of Hodgkin lymphoma.
Int J Radiat Oncol Biol Phys. 2014; 88(3):636-41 [PubMed] Related Publications
PURPOSE: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes.
METHODS AND MATERIALS: Thyroid cancer cases were retrospectively identified from a multi-institutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model.
RESULTS: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, ≥10 years, ≥15 years, and ≥20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively.
CONCLUSIONS: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and ≥10 years from HL treatment owing to their higher risk, which increases over time.

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Advani RH, Horning SJ, Hoppe RT, et al.
Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma.
J Clin Oncol. 2014; 32(9):912-8 [PubMed] Related Publications
PURPOSE: Universal expression of CD20 by malignant cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) led us to evaluate rituximab (R) as a therapeutic option.
PATIENT AND METHODS: Patients with previously treated or newly diagnosed NLPHL were treated with R (375 mg/m(2) once per week for 4 weeks) or, after a protocol amendment, with R plus R maintenance (MR; administered once every 6 months for 2 years). Primary and secondary outcome measures were progression-free survival (PFS) and overall response rate (ORR), respectively.
RESULTS: A total of 39 patients were enrolled (R, n = 23; R + MR, n = 16). After four once-per-week treatments, ORR was 100% (complete response, 67%; partial response, 33%). At median follow-ups of 9.8 years for R and 5 years for R + MR, median PFS were 3 and 5.6 years (P = .26), respectively; median overall survival (OS) was not reached. Estimated 5-year PFS and OS for patients treated with R versus R + MR were 39.1% (95% CI, 23.5 to 65.1) and 95.7% (95% CI, 87.7 to 100) versus 58.9% (95% CI, 38.0 to 91.2) and 85.7% (95% CI, 69.2 to 100), respectively. Nine of 23 patients experiencing relapse had evidence of transformation to aggressive B-cell lymphoma; six of these patients had infradiaphragmatic involvement at study entry.
CONCLUSION: R is an active agent in NLPHL. Although responses are not durable in most patients, a significant minority experience remissions lasting > 5 years. R + MR results in a nonsignificant increase in PFS compared with R. R may be considered in the relapsed setting for NLPHL. The potential for transformation of NLPHL to aggressive B-cell lymphoma underscores the importance of rebiopsy and long-term follow-up.

Related: Rituximab (Mabthera)

Fromm JR, Wood BL
A six-color flow cytometry assay for immunophenotyping classical Hodgkin lymphoma in lymph nodes.
Am J Clin Pathol. 2014; 141(3):388-96 [PubMed] Related Publications
OBJECTIVES: We have recently demonstrated that classical Hodgkin lymphoma (CHL) can be immunophenotyped by flow cytometry (FC), thus obviating the need for immunohistochemistry in many cases. The previously described nine-color assay, however, cannot be used by laboratories that do not have access to a nine- or ten-color flow cytometer. Therefore, a six-color FC tube was designed employing the following combination: CD64-FITC/CD30-PE/CD40-PeCy5.5/CD20-PECy7/CD95-APC/CD3-APC-H7.
METHODS: To validate this assay, we analyzed 408 tissue specimens (including 55 CHL cases, 26 of which had been previously cryopreserved). Specimen inclusion criteria included the identification of an abnormal population by FC or (if no abnormal population was identified) greater than 50,000 viable events and specimen age less than 4 days. All FC studies were examined blinded to any clinical, laboratory, or histologic information.
RESULTS: The diagnostic sensitivity and specificity of the six-color FC assay was 85.4% and 99.7%, respectively.
CONCLUSIONS: Taken together, these results suggest that the six-color FC assay has acceptable sensitivity and specificity for clinical use, allowing more FC laboratories to immunophenotype CHL by this method.

Venkatramani R, Kamath S, Wong K, et al.
Pulmonary outcomes in patients with Hodgkin lymphoma treated with involved field radiation.
Pediatr Blood Cancer. 2014; 61(7):1277-81 [PubMed] Related Publications
BACKGROUND: Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols.
PROCEDURES: Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained.
RESULTS: The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving >25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes.
CONCLUSION: In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes.

Eichenauer DA, Thielen I, Haverkamp H, et al.
Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group.
Blood. 2014; 123(11):1658-64 [PubMed] Related Publications
Therapy-related acute myeloid leukemia and myelodysplastic syndromes (t-AML/MDS) represent severe late effects in patients treated for Hodgkin lymphoma (HL). Because more recent data are scarce, we retrospectively analyzed incidence, outcome, and risk factors for the development of t-AML/MDS after HL. A total of 11,952 patients treated for newly diagnosed HL within German Hodgkin Study Group trials between 1993 and 2009 were considered. At a median follow-up of 72 months, t-AML/MDS was diagnosed in 106/11,952 patients (0.9%). Median time from HL treatment to t-AML/MDS was 31 months. The median age of patients with t-AML/MDS was higher than in the whole patient group (43 vs 34 years, P < .0001). Patients who received 4 or more cycles of BEACOPP(escalated) had an increased risk to develop t-AML/MDS when compared with patients treated with less than 4 cycles of BEACOPP(escalated) or no BEACOPP chemotherapy (1.7% vs 0.7% vs 0.3%, P < .0001). The median overall survival (OS) for all t-AML/MDS patients was 7.2 months. However, t-AML/MDS patients proceeding to allogeneic stem cell transplantation had a significantly better outcome with a median OS not reached after a median follow-up of 41 months (P < .001).

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Oki Y, Chuang H, Chasen B, et al.
The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma.
Br J Haematol. 2014; 165(1):112-6 [PubMed] Related Publications
The prognostic value of interim positron emission tomography (PET) was evaluated after 2 cycles of doxorubicin, bleomycin, vinblastin and dacarbazine in classical Hodgkin lymphoma patients (n = 229), based on Deauville criteria. In early stage non-bulky disease, bulky stage II disease, advanced stage low International Prognostic Score (IPS ≤2) and advanced stage (IPS ≥3), 3-year progression-free survival rates in PET2-negative vs. PET2-positive groups were 95·9% vs. 76·9% (P < 0·0018), 83·3% vs. 20·0% (P = 0·017), 77·0% vs. 30·0% (P < 0·001) and 71·0% vs. 44·4%(P = 0·155), respectively. The outcome after positive PET2 was better than previously reported. The results from non-randomized studies of PET2-guided therapy would be valuable with careful interpretation.

Herraiz S, Novella-Maestre E, Rodríguez B, et al.
Improving ovarian tissue cryopreservation for oncologic patients: slow freezing versus vitrification, effect of different procedures and devices.
Fertil Steril. 2014; 101(3):775-84 [PubMed] Related Publications
OBJECTIVE: To compare slow freezing (SF) with four vitrification techniques (VT) for cryopreservation of ovarian tissue (OT) and to evaluate the best protocol for human OT in a xenograft model.
DESIGN: Experimental study.
SETTING: University hospital.
PATIENT(S): Patients undergoing fertility preservation.
ANIMAL(S): Ovariectomized nude mice.
INTERVENTION(S): Cryopreservation of bovine OT after SF and four VTs (VT1, VT2, VT3, and VT4) by combining two cryoprotectant vitrification solutions (VS1 and VS2) and two devices (metallic grid and ethyl vinyl acetate bag), after which the cryopreservation of human OT by SF and VT1 and xenograft into nude mice.
MAIN OUTCOME MEASURE(S): Follicular densities, proliferation, vascularization, fibrosis, apoptosis, tissue viability.
RESULT(S): The in vitro study in bovine OT showed a lower percentage of quiescent follicles in the SF group but not in the vitrification groups (VT1-VT4). Apoptosis increased and cell proliferation decreased in all the experimental groups except VT1 (20% ethylene glycol, 20% dimethyl sulfoxide, 0.5 M sucrose, and 20% synthetic serum substitute in HEPES-buffered M199 culture media with Cryotissue metallic grids). Tissue viability was diminished in VT3, and the SF-xenografted human samples showed reduced primordial and secondary densities and unbalanced follicular populations when compared with fresh and VT1 tissue.
CONCLUSION(S): VT1 offers similar conditions to fresh tissue for follicular density, proliferation, viability, and cell death and preserves a larger population of quiescent follicles than SF after transplantation, thus ensuring the maintenance of graft potential fertility.

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Castellanos EM, Barrantes JC, Báez LF, et al.
A chemotherapy only therapeutic approach to pediatric Hodgkin lymphoma: AHOPCA LH 1999.
Pediatr Blood Cancer. 2014; 61(6):997-1002 [PubMed] Related Publications
BACKGROUND: AHOPCA is a collaborative group that designs uniform treatment regimens (protocols) for children diagnosed with cancer in Central America. Based on a preliminary report from one of the AHOPCA centers, AHOPCA adopted a treatment regimen to maintain a good event-free survival (EFS) as well as eliminate radiation therapy from the treatment of children with Hodgkin lymphoma.
PROCEDURE: Newly diagnosed patients with histologically proven Hodgkin lymphoma were staged according to the Ann Arbor classification and divided into favorable (stage I, stage IIA, and IIIA) and unfavorable (stage IIB, IIIB, and IV) groups. Subjects classified as group 1 (favorable) were treated with six 28-day cycles of chemotherapy (COPP/COPP ± ABV). Subjects classified as group 2 (unfavorable) were treated with eight 28-day cycles of COPP/ABV chemotherapy.
RESULTS: Of 269 patients registered, 216 were eligible for evaluation. The mean age at diagnosis was 7.5 years with a male to female ratio of 3.7-1. The predominant histology was nodular sclerosis (44%) but with a relatively high proportion of mixed cellularity (35.2%) The EFS at 5 and 10 years was 71% and 68%, respectively. There was a 14% rate of abandonment of therapy.
CONCLUSION: This treatment regimen for children with Hodgkin lymphoma, when applied as a multi-institutional regimen, had poorer outcome than our previously reported preliminary data and was inferior to the EFS reported in high-income countries. The major contributor adversely affecting EFS in this report is abandonment of therapy. Given these results, AHOPCA initiated a concerted effort to decrease abandonment of therapy.

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Brodin NP, Maraldo MV, Aznar MC, et al.
Interactive decision-support tool for risk-based radiation therapy plan comparison for Hodgkin lymphoma.
Int J Radiat Oncol Biol Phys. 2014; 88(2):433-45 [PubMed] Related Publications
PURPOSE: To present a novel tool that allows quantitative estimation and visualization of the risk of various relevant normal tissue endpoints to aid in treatment plan comparison and clinical decision making in radiation therapy (RT) planning for Hodgkin lymphoma (HL).
METHODS AND MATERIALS: A decision-support tool for risk-based, individualized treatment plan comparison is presented. The tool displays dose-response relationships, derived from published clinical data, for a number of relevant side effects and thereby provides direct visualization of the trade-off between these endpoints. The Quantitative Analyses of Normal Tissue Effects in the Clinic reports were applied, complemented with newer data where available. A "relevance score" was assigned to each data source, reflecting how relevant the input data are to current RT for HL.
RESULTS: The tool is applied to visualize the local steepness of dose-response curves to drive the reoptimization of a volumetric modulated arc therapy treatment plan for an HL patient with head-and-neck involvement. We also use this decision-support tool to visualize and quantitatively evaluate the trade-off between a 3-dimensional conformal RT plan and a volumetric modulated arc therapy plan for a patient with mediastinal HL.
CONCLUSION: This multiple-endpoint decision-support tool provides quantitative risk estimates to supplement the clinical judgment of the radiation oncologist when comparing different RT options.

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Chirieac LR, Barletta JA, Yeap BY, et al.
Clinicopathologic characteristics of malignant mesotheliomas arising in patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma.
J Clin Oncol. 2013; 31(36):4544-9 [PubMed] Related Publications
PURPOSE: Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established.
PATIENTS AND METHODS: We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival.
RESULTS: We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age ≤ 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001).
CONCLUSION: Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM.

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Hawkes EA, Barton S, Cunningham D, et al.
GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma.
Ann Hematol. 2014; 93(5):827-34 [PubMed] Related Publications
Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m(2) day (D)1, D8 and D15; methylprednisolone 1,000 mg D1-5; and cisplatin 100 mg/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.

Related: Cisplatin Gemcitabine

Lüders H, Rühl U, Marciniak H, et al.
The impact of central review and central therapy planning on the treatment of children and adolescents with Hodgkin lymphoma.
Eur J Cancer. 2014; 50(2):425-33 [PubMed] Related Publications
PURPOSE: The multicentre response-adapted paediatric Hodgkin lymphoma trial GPOH-HD95 (1995-2001, 925 patients) was followed by the 'HD-Interval' period (2001-2002, 203 patients). During this period, treatment was recommended according to GPOH-HD95 protocol with only minor changes. Central review and treatment planning as in HD95, however, had to be omitted in the absence of funding. Results of both periods were compared to evaluate the impact of central review on staging, stratification, treatment planning and outcome.
METHODS: Pre- and post-chemotherapy computed tomography and magnetic resonance imaging of HD-Interval patients were evaluated with respect to reliability of staging, response assessment and subsequent treatment stratification.
RESULTS: Despite more favourable patient characteristics and treatment group stratifications, the 10-year progression-free survival (PFS) was inferior in HD-Interval patients compared to GPOH-HD95 patients with nearly identical therapy (86% versus 91%, P=0.01). Of 142 patients without guidance by the reference centre, 56 (39%) received a treatment deviating from protocol recommendations: chemotherapy doses were either lower or higher than recommended in 17% of patients, and deviations concerning radiotherapy dose and treatment volume occurred in 25% and 20%, respectively. In both periods, the 10-year PFS was lower in patients with diminished therapy compared to those with adequate treatment according to the given recommendations (HD-Interval: 72% versus 89%, P=0.02; GPOH-HD95: 80% versus 92%, P=0.04).
CONCLUSIONS: Deviations from protocol treatment may influence negatively the outcome in paediatric oncology. Protocol enrolment and compliance including timely and correct treatment are crucial. Central reference and consultation centres offer quality assurance, support protocol adherence, and hence influence PFS.

Klimm B, Goergen H, Fuchs M, et al.
Impact of risk factors on outcomes in early-stage Hodgkin's lymphoma: an analysis of international staging definitions.
Ann Oncol. 2013; 24(12):3070-6 [PubMed] Related Publications
BACKGROUND: In early-stage Hodgkin's lymphoma (HL), treatment according to the early favorable or unfavorable subgroup is guided by staging definitions, which differ between various study groups worldwide. We analyzed risk factors used in different international staging systems and their impact on the outcome of early-stage HL patients.
PATIENTS AND METHODS: In 1173 early-stage HL patients treated homogenously within the German Hodgkin Study Group (GHSG) trials HD10 and HD11, the impact of three staging systems developed and used by the GHSG, the European Organization for Research and Treatment of Cancer (EORTC), and the National Comprehensive Cancer Network (NCCN) in discriminating risk groups for progression-free survival (PFS) and overall survival (OS) was assessed and the relevance of their single risk factors was investigated.
RESULTS: All the three staging systems defined an unfavorable risk group out of early-stage patients of comparable size (56%, 55%, and 57%), having a significantly poorer PFS and OS as compared with the corresponding favorable group; 5-year differences between early favorable and early unfavorable in terms of PFS were 9.4% (HR 2.61, 95% CI 1.74-3.91), 6.7% (HR 2.10, 95% CI 1.41-3.13), and 8.6% (HR 2.14, 95% CI 1.45-3.16) with the GHSG, EORTC, and NCCN definition, respectively. Sensitivity was high for all systems (84%, 79%, and 83%); however, there was a low specificity with high rates of false-positive results (1-specificity 54%, 53%, and 55%, respectively). Models of high sensitivity included risk factors associated with large tumor burden and high tumor activity. Most risk factors for tumor-specific end points were also predictive of OS.
CONCLUSIONS: Differentiating between a favorable and an unfavorable risk group has significant impact on PFS and OS in early-stage HL patients in the modern treatment era. Risk-adapted treatment strategies using new risk factors with higher specificity are needed.

Qiu L, Chen Y, Wu J
The role of 18F-FDG PET and 18F-FDG PET/CT in the evaluation of pediatric Hodgkin's lymphoma and non-Hodgkin's lymphoma.
Hell J Nucl Med. 2013 Sep-Dec; 16(3):230-6 [PubMed] Related Publications
Pediatric lymphomas (PL) are the third most common malignancy and account for 10% to 15% of all cancers in the pediatric age group. Accurate classification and staging are important for appropriate prognosis and treatment of pediatric Hodgkin's lymphoma (PHL) and non-Hodgkin's lymphomas (PNHL) and impact patient prognosis significantly. The role of fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and 18F-FDG PET/computed tomography (18F-FDG PET/CT) in diagnosis, staging, localization of tumor radiotherapy, evaluation of treatment response and detection of recurrent tumors of PHL and PNHL is reviewed in this paper. The results of published 18F-FDG PET and 18F-FDG PET/CT studies in pediatric patients with HL and NHL were promising for initial diagnosis, for the localization of tumors, for radiation treatment and for early assessment of treatment response. However, as the sample size of these original articles was often small and a unified study design standard is lacking, more data are needed to better specify the role of 18F-FDG PET and 18F-FDG PET/CT in the management of PHL and PNHL. In conclusion, the 18F-FDG PET and 18F-FDG PET/CT appear superior to other imaging methods such as X-rays, CT, MRI and ultrasound, other nuclear medicine methods and bone marrow biopsy for the evaluation of pediatric lymphomas.

Related: Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology

Gibb A, Greystoke A, Ranson M, et al.
A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity.
Br J Cancer. 2013; 109(10):2560-5 [PubMed] Article available free on PMC after 12/11/2014 Related Publications
BACKGROUND: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1-3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured.
METHODS: Dose escalation of doxorubicin in cycles 1-3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m(-2)) with doxorubicin reduced to 25 mg m(-2) or omitted in cycles 4-6 to maintain cumulative exposure of 103-130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD.
RESULTS: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m(-2), so 45 mg m(-2) was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD.
CONCLUSION: Escalated ABVD incorporating doxorubicin at 45 mg m(-2) in cycles 1-3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Udupa K, Philip A, Rajendranath R, et al.
Spontaneous regression of primary progressive Hodgkin's lymphoma in a pediatric patient: a case report and review of literature.
Hematol Oncol Stem Cell Ther. 2013 Sep-Dec; 6(3-4):112-6 [PubMed] Related Publications
Spontaneous regression of malignancies is a very rare phenomenon. Our research of existing literature yielded only 16 cases of Hodgkin's lymphoma which regressed spontaneously. The outcome of primary progressive Hodgkin's lymphoma is poor even with salvage chemotherapy and autologous bone marrow transplantation. Here we present a case of primary progressive Hodgkin's lymphoma, which regressed spontaneously after failure of salvage chemotherapy. To our knowledge, this is the first case report of primary progressive Hodgkin's lymphoma undergoing spontaneous regression.

Ghosh J, Singh RK, Saxena R, et al.
Prevalence and aetiology of anaemia in lymphoid malignancies.
Natl Med J India. 2013 Mar-Apr; 26(2):79-81 [PubMed] Related Publications
BACKGROUND: We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies.
METHODS: Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the prevalence and a subgroup of 46 patients was analysed for the cause of anaemia.
RESULTS: Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients.
CONCLUSION: Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out.

Related: Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology Non Hodgkin's Lymphoma

Wang KL, Liu CL, Zhuang Y, Qu HY
Breastfeeding and the risk of childhood Hodgkin lymphoma: a systematic review and meta-analysis.
Asian Pac J Cancer Prev. 2013; 14(8):4733-7 [PubMed] Related Publications
PURPOSE: Numerous observational epidemiological studies have evaluated associations between breastfeeding and the risk of childhood Hodgkin lymphoma; however, the existing results are inconsistent. We therefore conducted a systematic review and meta-analysis.
METHODS: Medical literature was searched in the Pubmed and Embase databases to identify all English-language relevant studies up to April 10, 2013. Reference lists were thereafter hand-searched for additional articles. Studies that reported relative risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were included. This meta-analysis was conducted in accordance with the guidelines for the meta-analysis of observational studies in epidemiology.
RESULTS: We finally included 10 case-control studies in our meta-analysis, involving 1,618 childhood Hodgkin lymphoma cases and 8,181 controls. Overall, we did found a borderline significant association between breastfeeding and reduced risk of childhood Hodgkin lymphoma comparing ever breastfed children to never breastfed children (pooled OR =0.79; 95%CI, 0.58-1.08; P=0.13), with limited evidence for between-study heterogeneity (P =0.12, I2 = 35.70%).
CONCLUSION: There is limited evidence for an inverse association between breastfeeding and risk of childhood Hodgkin lymphoma.

Jørgensen AY, Maraldo MV, Brodin NP, et al.
The effect on esophagus after different radiotherapy techniques for early stage Hodgkin's lymphoma.
Acta Oncol. 2013; 52(7):1559-65 [PubMed] Related Publications
INTRODUCTION: The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments.
MATERIAL AND METHODS: We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections.
RESULTS: Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001).
CONCLUSIONS: The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future.

Song MK, Chung JS, Lee JJ, et al.
Metabolic tumor volume by positron emission tomography/computed tomography as a clinical parameter to determine therapeutic modality for early stage Hodgkin's lymphoma.
Cancer Sci. 2013; 104(12):1656-61 [PubMed] Related Publications
Recent studies have shown that metabolic tumor volume (MTV) by positron emission tomography/computed tomography (PET/CT) is an important prognostic parameter in patients with non-Hodgkin's lymphoma. However, it is unknown whether doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone in early stage Hodgkin's lymphoma would lead to similar disease control as combined modality therapy (CMT) using MTV by PET/CT. One hundred and twenty-seven patients with early stage Hodgkin's lymphoma who underwent PET/CT at diagnosis were enrolled. The MTV was delineated on PET/CT by the area ≥SUV(max), 2.5 (standardized uptake value [SUV]). Sixty-six patients received six cycles of ABVD only. The other 61 patients received CMT (involved-field radiotherapy after 4-6 cycles of ABVD). The calculated MTV cut-off value was 198 cm(3) . Clinical outcomes were compared according to several prognostic factors (i.e. age ≥50 years, male, performance status ≥2, stage II, B symptoms, ≥4 involved sites, extranodal site, large mediastinal mass, CMT, elevated erythrocyte sedimentation rate and high MTV). Older age (progression-free survival [PFS], P = 0.003; overall survival [OS], P = 0.007), B symptoms (PFS, P = 0.006; OS, P = 0.036) and high MTV (PFS, P = 0.008; OS, P = 0.007) were significant independent prognostic factors. Survival of two high MTV groups treated with ABVD only and CMT were lower than the low MTV groups (PFS, P < 0.012; OS, P < 0.045). ABVD alone was sufficient to control disease in those with low MTV status. However, survival was poor, even if the CMT was assigned a high MTV status. The MTV would be helpful for deciding the therapeutic modality in patients with early stage Hodgkin's lymphoma.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Tudor CS, Distel LV, Eckhardt J, et al.
B cells in classical Hodgkin lymphoma are important actors rather than bystanders in the local immune reaction.
Hum Pathol. 2013; 44(11):2475-86 [PubMed] Related Publications
Recent studies, largely focusing on cellular immunity, have demonstrated that the composition of the abundant inflammatory background of Hodgkin lymphoma may affect outcome. This investigation aimed to characterize the potential role of infiltrating B cells and follicular dendritic cell networks in classical Hodgkin lymphoma (cHL) to better assess the role of components of humoral immunity. One hundred two cHL biopsies were investigated by immunohistochemistry with antibodies specific for CD20, CD138, activation-induced cytidine deaminase, and CD21 to characterize B cell distribution and follicular structures. To further subclassify B cells, analyses of tissue microarrays were performed investigating the expression of Mum1, Bcl6, IgD, IgG, IgG4, IgM, T-bet, CD38, CD5, and CD10. For evaluation a computer assisted quantification method was compared with a scoring system. Survival analysis and correlation analysis were performed. The B cell infiltrate was dominated by CD20+ B cells, followed by plasma cells, whereas only few AID+ cells were observed. High numbers of CD21+ follicular dendritic cell networks, CD20+ B cells, IgM+ cells, CD20+ aggregates, and Bcl6+ cells were associated with a better outcome of cHL patients, whereas Pax5+/CD38+ cells had an adverse prognostic impact. Other parameters showed no influence on survival. Our findings suggest that a complex network of B cells is present in the microenvironment of cHL and that B cells might actively contribute to a local anti- as well as pro-tumoral immune response. This indicates that the network of B cells in tumors is probably just as diverse as the T cellular infiltrate and probably functionally as heterogenous.

Related: SDC1

Monnereau A, Glaser SL, Schupp CW, et al.
Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis.
Blood. 2013; 122(20):3492-9 [PubMed] Article available free on PMC after 14/11/2014 Related Publications
Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets.

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