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).

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.

Related: Lung Cancer Non Hodgkin's Lymphoma Mesothelioma

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.

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

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

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.

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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.

Greaves P, Clear A, Owen A, et al.
Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells.
Blood. 2013; 122(16):2856-63 [PubMed] Related Publications
CD4(+) T-helper cells (THs) dominate the classical Hodgkin lymphoma (CHL) microenvironment, but their role is poorly understood. Advances in flow cytometry and immunohistochemistry permit more detailed investigation of this aspect of CHL pathophysiology. To address the hypothesis that the TH-infiltrate, rather than being TH2-enriched, senescent and hypofunctional, is TH1 and activation marker-rich, cytokine-secretory and proliferative, we applied comprehensive flow cytometric immunophenotyping and functional assays of cytokine secretion/proliferation to TH cells from 18 CHL-derived single-cell suspensions (SCSs) compared to reactive lymph nodes (RLNs). CHL-derived TH cells express TH1-associated CXCR3/CCR5 and TNFα/IFNγ/interleukin-2 (IL-2) and less TH2-associated CCR3/CCR4, with no IL-4/IL-13. They lack exhaustion-/suppression-associated PD1, CD57 and terminally differentiated effector memory cells, with more central memory cells, activation-associated partners of Hodgkin Reed Sternberg (HRS) cell-expressed CD30/OX40-L/ICOS-L, and other activation markers. TH cell lines established from CHL and RLN-derived SCSs remain cytokine-secretory. We confirmed and extended these studies using tissue microarray immunohistochemistry (TMA-IHC) from a large CHL tissue bank (n = 122) and demonstrate TH1-associated TBET is abundant in CHL, and TH2-associated CMAF/GATA3 and exhaustion-associated PD1 expressed at significantly lower levels. These molecular insights into the CHL-associated TH offer potential diagnostic, prognostic and pharmacologically modifiable therapeutic targets and do not support the established view of a TH2-enriched, senescent/exhausted, hypofunctional, hypoproliferative infiltrate.

Related: Cytokines

Di Napoli A, Al-Jadiri MF, Talerico C, et al.
Epstein-Barr virus (EBV) positive classical Hodgkin lymphoma of Iraqi children: an immunophenotypic and molecular characterization of Hodgkin/Reed-Sternberg cells.
Pediatr Blood Cancer. 2013; 60(12):2068-72 [PubMed] Related Publications
BACKGROUND: Classical Hodgkin lymphoma (cHL) in children is often associated with EBV infection, more commonly in developing countries.
PROCEDURE: Here we describe the histological, immunohistochemical, and molecular features of 57 cases of HL affecting Iraqi children under 14 years of age.
RESULTS: Histologically, 51 cases were classified as cHL of Mixed Cellularity and Nodular Sclerosis subtypes (MC = 69%; NS = 31%), and 6 cases as Nodular Lymphocyte Predominant HL (NLP-HL). EBV infection of H/RS cells was demonstrated in 44 of 51 cases of cHL (86%), and was more common in MC than in NS (97% vs. 63%; P = 0.0025). The immunophenotypic profile of H/RS cells was similar in MC and NS, and was not influenced by EBV infection; H/RS cells were consistently positive for PAX-5 and to a lesser degree for other B cell markers including CD20/CD79a, OCT-2, and BOB-1. Clonal IGH rearrangements were detected in 14 of 38 cHL (37%), with no significant difference between MC and NS cases, and with no association with the EBV status. Oligoclonal/monoclonal TCRγ rearrangements were present in 28 of 38 cases (74%), suggestive of restricted T cell responses.
CONCLUSIONS: Our findings indicate that cHL occurring in Iraqi children is characterized by immunohistochemical and molecular features undistinguishable from those present in cHL occurring elsewhere in the world. Moreover, the high incidence of EBV-infected H/RS cells and frequent occurrence of restricted T cell responses might be indicative of a defective local immune response perhaps related to the very young age of the children.

Yamada M, Kamberos N, Grose C
Breakthrough varicella in a cancer patient with persistent varicella antibody after one varicella vaccination.
J Pediatr. 2013; 163(5):1511-3 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
A boy with Hodgkin disease contracted breakthrough varicella from his father, who had chickenpox. The boy had received a single varicella vaccination and was seropositive by enzyme-linked immunosorbent assay before being diagnosed with breakthrough varicella. Seropositivity after a single varicella vaccination does not guarantee complete protection in an immunocompromised child.

Maraldo MV, Brodin P, Aznar MC, et al.
Doses to carotid arteries after modern radiation therapy for Hodgkin lymphoma: is stroke still a late effect of treatment?
Int J Radiat Oncol Biol Phys. 2013; 87(2):297-303 [PubMed] Related Publications
PURPOSE: Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates.
METHODS AND MATERIALS: We included a cohort of 46 supradiaphragmatic stage I-II classical HL patients. All patients were initially treated with chemotherapy and INRT delivered as 3D-CRT (30 Gy). For each patient, we simulated MF (36 Gy) and INRT plans using VMAT and PT (30 Gy). Linear dose-response curves for the 20-, 25-, and 30-year risk of stroke were derived from published HL data. Risks of stroke with each technique were calculated for all patients. Statistical analyses were performed with repeated measures analysis of variance.
RESULTS: The mean doses to the right and left common carotid artery were significantly lower with modern treatment compared with MF, with substantial patient variability. The estimated excess risk of stroke after 20, 25, and 30 years was 0.6%, 0.86%, and 1.3% for 3D-CRT; 0.67%, 0.96%, and 1.47% for VMAT; 0.61%, 0.96%, and 1.33% for PT; and 1.3%, 1.72%, and 2.61% for MF.
CONCLUSIONS: INRT reduces the dose delivered to the carotid arteries and corresponding estimated risk of stroke for HL survivors. Even for the subset of patients with lymphoma close to the carotid arteries, the estimated risk is low.

Cella L, Liuzzi R, Conson M, et al.
Multivariate normal tissue complication probability modeling of heart valve dysfunction in Hodgkin lymphoma survivors.
Int J Radiat Oncol Biol Phys. 2013; 87(2):304-10 [PubMed] Related Publications
PURPOSE: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD).
METHODS AND MATERIALS: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC).
RESULTS: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger.
CONCLUSIONS: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity.

Zhang R, Howell RM, Homann K, et al.
Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy.
Radiat Oncol. 2013; 8(1):184 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
BACKGROUND: Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB.
METHODS: In the treatment plans, each patient's heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed.
RESULTS: The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors.
CONCLUSIONS: We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study.

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Koh YW, Park C, Yoon DH, et al.
Prognostic significance of COX-2 expression and correlation with Bcl-2 and VEGF expression, microvessel density, and clinical variables in classical Hodgkin lymphoma.
Am J Surg Pathol. 2013; 37(8):1242-51 [PubMed] Related Publications
Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) play important roles in tumor angiogenesis. Recent reports found that COX-2 expression had prognostic value in classical Hodgkin lymphoma (cHL). The purpose of this study was to measure the expression of COX-2, B-cell lymphoma-2 (Bcl-2), VEGF, and CD31 and assess their prognostic significance and potential correlation with clinical variables in cHL. A total of 167 cHL specimens were evaluated retrospectively by immunohistochemical methods for COX-2, Bcl-2, and VEGF expression and for CD31 to measure the microvessel density (MVD). Correlations between COX-2, Bcl-2, VEGF, MVD, and clinicopathologic factors were assessed, and prognostic significance was determined. COX-2, Bcl-2, and VEGF were expressed in 27.5%, 8.3%, and 33.5% of the specimens, respectively. A positive correlation was found between COX-2 and VEGF expression (P<0.001). The MVD was significantly higher in tumors positive for both COX-2 and VEGF compared with that in tumors negative for both markers (P=0.047). COX-2 expression was associated with a lower overall survival rate (P=0.015). High MVD was associated with a lower event-free survival rate (P=0.014). COX-2 was an independent prognostic factor for overall survival on multivariate analysis (P=0.013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL.

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Tang H, Wei Q, Ge J, et al.
IMP3 as a supplemental diagnostic marker for Hodgkin lymphoma.
Hum Pathol. 2013; 44(10):2167-72 [PubMed] Related Publications
Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is ubiquitously expressed in embryos, mediating organogenesis, RNA trafficking, and cell growth, and is generally down-regulated in adult tissue. However, IMP3 has recently been shown to be overexpressed in some malignant epithelial neoplasms and to be a useful diagnostic and/or prognostic biomarker for several carcinomas. To determine whether IMP3 might also be an accurate biomarker of Hodgkin lymphoma, we examined 81 Hodgkin lymphomas for immunoreactivity to IMP3 as compared to commonly used markers such as CD30, CD15, PAX5, and MUM1. Consequently, in 98.8% (80/81) of Hodgkin lymphomas, the malignant Hodgkin and Reed-Sternberg cells were selectively reactive for IMP3, with 72.8% (59/81) of the tumors showing strong, diffuse cytoplasmic staining. Positive staining of the Hodgkin lymphomas was also seen for CD30 (82.7%, 67/81), CD15 (65.4%, 53/81), PAX5 (84.0%, 68/81), and MUM1 85.2% (69/81), but significantly fewer cells showed strong staining intensity for CD30 (32.1%, 26/81), CD15 (17.3%, 14/81), PAX5 (12.3%, 10/81), and MUM1 (29.6%, 24/81). Furthermore, the IMP3 staining was selectively restricted to Hodgkin and Reed-Sternberg cells, with a clearly negative background, and complementary to CD30 staining. Our findings show that IMP3 may be a useful diagnostic marker of Hodgkin lymphoma, helping to improve diagnostic accuracy for this malignancy.

Koh YW, Kang HJ, Yoon DH, et al.
Changing trend of Epstein-Barr virus association in Hodgkin lymphoma in the Republic of Korea.
Ann Hematol. 2013; 92(12):1653-60 [PubMed] Related Publications
Hodgkin lymphoma (HL) in resource-poor population shows an early childhood peak with predominance of mixed cellularity (MCHL) and high Epstein-Barr virus (EBV) association, whereas HL in resource-rich population has a peak in ages 15-29 years with the predominance of nodular sclerosis (NSHL) and low EBV association. We examined the changing trend of HL in association with EBV in Korea in 385 cases of HL (1980-2011). Data from 1980-1995 and 1996-2011 were compared. Age distribution showed a marked decrease in children (age < 15 years) (21.0 % to 8.6 %, p = 0.004) and sharp increase in young adults (ages 15-29 years) and ages 30-59 years. Male predominance decreased from 3.04 to 1.57. Predominant subtype changed from MCHL to NSHL; MCHL fell from 53.3 % to 26.4 % (p < 0.001), and NSHL rose from 24.8 % to 58.2 % (p < 0.001). EBV-positive HL decreased from 66.7 % to 38.2 %. However, in young adult females, EBV positive cases increased, contributing to the peak in this age group. Epidemiology of HL in Korea is rapidly changing into a Western pattern concurrent with the socioeconomic changes. Analysis of the cases stratified by EBV status and sex identified a smaller hidden peak in the young adult age, which confirms the four disease hypothesis proposed by Jarrett. We propose EBV testing as an essential component in epidemiologic study of Hodgkin lymphoma.

Rancea M, Monsef I, von Tresckow B, et al.
High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma.
Cochrane Database Syst Rev. 2013; 6:CD009411 [PubMed] Related Publications
BACKGROUND: Hodgkin lymphoma (HL) is one of the most common malignancies in young adults and has become curable for the majority of patients, even in advanced stage. After first-line therapy, 15% to 20% do not respond to treatment and relapse. For those patients, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is a frequently used therapy option.
OBJECTIVES: To find the best available treatment with HDCT followed by ASCT for patients with relapsed or refractory HL after first-line treatment.
SEARCH METHODS: We searched the Central Register of Controlled Trials (CENTRAL), MEDLINE, and relevant conference proceedings up to January 2013 for randomised controlled trials (RCTs). We also contacted experts for unpublished data.
SELECTION CRITERIA: We included RCTs comparing HDCT followed by ASCT versus conventional chemotherapy without ASCT, or versus additional sequential HDCT (SHDCT) followed by ASCT. We also included RCTs with different HDCT regimens before ASCT in patients with relapsed or primary refractory HL after any first-line therapy.
DATA COLLECTION AND ANALYSIS: Two review authors (MR, NS) independently selected relevant studies, extracted data and assessed trial quality. We used hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS), and we calculated risk ratios (RR) for the other outcomes. We presented all measures with 95% confidence intervals (CI).We assessed the quality of evidence using GRADE methods.
MAIN RESULTS: Our search resulted in 1663 potentially relevant references, of which we included three trials with 14 publications, assessing 398 patients. Overall, we judged the quality of the trials as moderate. The trials were all reported as randomised controlled and open-label. We included two RCTs assessing the effect of HDCT followed by ASCT compared with conventional chemotherapy in a meta-analysis. The number of studies was very low, therefore, the quantification of heterogeneity was not reliable. We included one further RCT (one assessing additional SHDCT followed by ASCT versus HDCT followed by ASCT), which was not compatible with our meta-analysis. For this trial, we performed further analyses.Two trials showed a non-statistically significant trend that HDCT followed by ASCT compared to conventional chemotherapy increases OS (HR 0.67; 95% CI 0.41 to 1.07; P value = 0.10, 157 patients, moderate quality of evidence). However, the increase in PFS was statistically significant for people treated with HDCT followed by ASCT (HR 0.55; 95% CI 0.35 to 0.86; P value = 0.009, 157 patients, moderate quality of evidence). Adverse events were reported in one trial only and did not differ statistically significant between the treatment arms. We were not able to draw conclusions regarding treatment-related mortality (TRM) because of insufficient evidence (RR 0.61; 95% CI 0.16 to 2.22; P value = 0.45, 157 patients, moderate quality of evidence).For the second comparison, SHDCT plus HDCT followed by ASCT versus HDCT followed by ASCT there was no difference between the treatment arms regarding OS (HR 0.93; 95% CI 0.5 to 1.74; P value = 0.816, three-year OS: 80% SHDCT versus 87% HDCT, 241 patients), or PFS (HR 0.87; 95% CI 0.58 to 1.30; P value = 0.505, 241 patients). Seven patients died in the SHDCT arm and one in the HDCT arm due to increased toxicity of the treatment. Adverse events were increased with SHDCT plus HDCT followed by ASCT after two cycles of dexamethasone plus high-dose cytarabine plus cisplatin (DHAP) (88% SHDCT versus 45% HDCT, 223 patients, P value < 0.00001). Overall, more statistically significant World Health Organization (WHO) grade 3/4 infections occurred with SHDCT (48% SHDCT versus 33% HDCT; P value = 0.002, 223 patients).
AUTHORS' CONCLUSIONS: The currently available evidence suggests a PFS benefit for patients with relapsed or refractory HL after first-line therapy, who are treated with HDCT followed by ASCT compared to patients treated with conventional chemotherapy. In addition, data showes a positive trend regarding OS, but more trials are needed to detect a significant effect.Intensifying the HDCT regime before HDCT followed by ASCT did not show a difference as compared to HDCT followed by ASCT, but was associated with increased adverse events.

Naqi N, Ahmad S, Shah I, Khattak J
A multicentre phase-II feasibility study evaluating gemcitabine/vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma.
J Coll Physicians Surg Pak. 2013; 23(6):397-400 [PubMed] Related Publications
OBJECTIVE: To determine the efficacy and toxicity of Gemcitabine, Vinorelbine and Prednisolone (GVP) salvage chemotherapy in relapsed / refractory Hodgkin's Lymphoma (HL).
STUDY DESIGN: A phase-II non-randomized single arm study.
PLACE AND DURATION OF STUDY: This study was conducted at Combined Military Hospital and Medical College Lahore, Mayo Hospital, King Edward Medical University, Lahore, Allied Hospital, Punjab Medical College, Faisalabad and Combined Military Hospital, Rawalpindi, from January 2007 to December 2007.
METHODOLOGY: Fifty adult patients with relapsed/refractory HL, adequate marrow reserve, hepatorenal and pulmonary functions, with radiological measurable disease and Karnofsky performance status of 0 - 2 non-candidates for stem cell transplantation, were enrolled. Four 28 days cycles of GVP (Gemcitabine 1000 mg/m2, Vinorelbine 30 mg/m2 on day 1 and 8 intravenously with oral Prednisolone 100 mg/day on day 1 - 5) were given. Response evaluation done according to Cotswolds meeting recommendations and toxicity was evaluated with NCI-CTC (National Cancer Institute - Common Terminology Criteria for adverse events v 3.0).
RESULTS: Forty patients completing 4 cycles of GVP, 14 refractory/early relapse and 26 late relapsed (one year postprimary treatment with ABVD) were available for evaluation. The overall response (CRu+PR) rate was 77.5% with better response 85% in late relapsed patients. Haematological toxicity was most common and seen in 70% of cases.
CONCLUSION: GVP is well-tolerated regimen with high response rate and needs to be tested in late relapsed HL.

Related: Vinblastine Gemcitabine Vinorelbine

Daniëls LA, Oerlemans S, Krol AD, et al.
Persisting fatigue in Hodgkin lymphoma survivors: a systematic review.
Ann Hematol. 2013; 92(8):1023-32 [PubMed] Related Publications
Hodgkin Lymphoma (HL) survivors are at risk for adverse psychosocial events as a result from cancer diagnosis and treatment. Fatigue is one of the most frequently reported long-term symptoms and is often reported to interfere with daily life. We conducted a systematic review to determine prevalence, severity and predisposing factors of fatigue in HL survivors. A literature search was conducted up to August 2012. Twenty-two articles comparing HL survivors with norm population data met all predefined selection criteria. Prevalence rates, levels of fatigue and clinical relevance of the results were determined. Prevalence of fatigue ranged from 11-76 % in HL survivors compared to 10 % in the general population. Mean fatigue scores were 5-13 % higher compared to the normative population; these findings were clinically relevant in 7 out of 11 studies. Increasing age was associated with higher levels of fatigue in HL survivors. Treatment modality and stage of initial disease were not associated with higher fatigue levels, while comorbidities or other treatment sequelae seemed to impact on the levels of fatigue. HL survivors are at serious risk for developing clinically relevant, long-term fatigue. The impact of patient and treatment characteristics on risk of fatigue is limited. Focus for future research should shift to the role of late-treatment sequelae and psychological distress symptoms.

Bilgin E, Dizdar Y, Serilmez M, et al.
For which cancer types can neuron-specific enolase be clinically helpful in Turkish patients?
Asian Pac J Cancer Prev. 2013; 14(4):2541-4 [PubMed] Related Publications
BACKGROUND: The aim of the present study was to evaluate the serum neuron-specific enolase (NSE) levels in patients with prostate cancer, Hodgkin lymphoma, lung cancer and peripheral nerve tumors.
MATERIALS AND METHODS: NSE levels were determined by ELISA in the sera of 100 prostate cancer, 47 Hodgkin lymphoma, 35 lung cancer and 35 peripheral nerve tumor patients and also in 132 healthy controls.
RESULTS: The median levels of serum NSE were elevated in patients with lung cancer (p=0.018) and peripheral nerve tumors (p=0.008). NSE levels in prostate cancer and Hodgkin lymphoma patients were higher than the controls but there was no statistically significant difference (p>0.05).
CONCLUSIONS: We conclude that NSE may be applied in routine to gain insight about the clinical statuses of various cancer patients, but more studies are needed to determine the organ specificity.

Related: Lung Cancer Prostate Cancer

Casulo C, Arcila M, Bohn OL, et al.
Tumor associated macrophages in relapsed and refractory Hodgkin lymphoma.
Leuk Res. 2013; 37(9):1178-83 [PubMed] Related Publications
BACKGROUND: Growing evidence demonstrates that an increased number of CD68 positive tumor-associated macrophages (TAM) is associated with decreased survival in patients with newly diagnosed classic Hodgkin lymphoma (HL). However, the impact of TAM in relapsed and refractory disease is unknown.
DESIGN AND METHODS: To investigate whether the presence of elevated CD68 retains its prognostic significance in the relapsed and refractory setting, we analyzed pre-salvage biopsy specimens of 81 patients with relapsed and refractory HL using a tissue microarray. Scoring of CD68 was based on the percentage of CD68 positive TAM compared to the total number of cells in representative areas. The final percent of CD68 positivity for each case was based on the average of cores available for examination.
RESULTS: In a univariate analysis, we found that patients with elevated levels of CD68 positive TAM had inferior overall survival (OS) compared with patients who had lower CD68 levels. For patients undergoing autologous stem cell transplant after salvage treatment, elevated CD68 levels were predictive of both adverse OS and event free survival. However, after adjusting for other variables, increased CD68 positive TAM did not retain prognostic significance in a multivariate model.
CONCLUSIONS: In our dataset of primary refractory and relapsed Hodgkin lymphoma biopsy specimens, TAM infiltration is unable to definitively predict outcome. In order to validate these findings, TAM infiltration of relapsed and refractory specimens should be assessed prospectively and paired to initial Hodgkin lymphoma biopsies at diagnosis.

Navarro A, Muñoz C, Gaya A, et al.
MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin lymphoma patients.
PLoS One. 2013; 8(5):e64716 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
BACKGROUND: In recent years, microRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways.
DESIGN AND METHODS: We analyzed eight miR-SNPs by allelic discrimination in 141 patients with Hodgkin lymphoma and correlated the results with treatment-related toxicity, response, disease-free survival (DFS) and overall survival (OS).
RESULTS: The KRT81 (rs3660) GG genotype was associated with an increased risk of neurological toxicity (P = 0.016), while patients with XPO5 (rs11077) AA or CC genotypes had a higher rate of bleomycin-associated pulmonary toxicity (P = 0.048). Both miR-SNPs emerged as independent factors in the multivariate analysis. The XPO5 AA and CC genotypes were also associated with a lower response rate (P = 0.036). XPO5 (P = 0.039) and TRBP (rs784567) (P = 0.022) genotypes emerged as prognostic markers for DFS, and XPO5 was also associated with OS (P = 0.033). In the multivariate analysis, only XPO5 emerged as an independent prognostic factor for DFS (HR: 2.622; 95%CI 1.039-6.620; P = 0.041). Given the influence of XPO5 and TRBP as individual markers, we then investigated the combined effect of these miR-SNPs. Patients with both the XPO5 AA/CC and TRBP TT/TC genotypes had the shortest DFS (P = 0.008) and OS (P = 0.008).
CONCLUSION: miR-SNPs can add useful prognostic information on treatment-related toxicity and clinical outcome in Hodgkin lymphoma and can be used to identify patients likely to be chemoresistant or to relapse.

Márk Á, Hajdu M, Váradi Z, et al.
Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease--a combined tissue microarray, in vitro and in vivo study.
BMC Cancer. 2013; 13:250 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete.
METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines.
RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents.
CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response.

Related: Apoptosis Signal Transduction

Nathwani BN, Vornanen M, Winkelmann R, et al.
Intranodular clusters of activated cells with T follicular helper phenotype in nodular lymphocyte predominant Hodgkin lymphoma: a pilot study of 32 cases from Finland.
Hum Pathol. 2013; 44(9):1737-46 [PubMed] Related Publications
In nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), little is known about the presence of intranodular clusters of cytologically activated lymphoid cells producing a moth-eaten pattern histologically. This pilot study of 32 NLPHL cases from Finland ascertained (1) the frequency of the intranodular clusters of activated lymphoid cells, (2) the immunophenotype of the activated cells, (3) the size and immunophenotype of the rosetting cells, and (4) the clinical significance of the activated cells. Histologically, intranodular clusters of activated cells produced a moth-eaten pattern in 100% (32 cases; subtle in 62.5%, overt in 37.5%). In immunostains, activated cells in subtle clusters (20 cases) were very difficult to identify. Twelve cases had overt clusters of activated cells, which were positive with CD3, CD4, PD1, CXCL13 (T follicular helper [T(FH)] phenotype), but rarely with Ki-67 and BCL2. Most activated rosetting cells had the same immunophenotype as the nonrosetting cells, except for CXCL13. Clinical presentation for all 32 Finnish patients was distinctive: 97% men, 97% with peripheral lymphadenopathy and 35.5% with stage III/IV disease. Only 22% relapsed; 97% were in remission. There was no significant clinical difference between cases with overt and subtle clusters. Intranodular activated TFH cells in NLPHL appeared to be nonproliferating and not long-living, and they were not associated with any adverse clinical outcome. Although most activated cells were TFH cells, it seemed that they were unable to increase the number of malignant cells. The pathogenetic role of the intranodular activated TFH and the small T cells in NLPHL needs further investigation.

Friedmann AM, Wolfson JA, Hudson MM, et al.
Relapse after treatment of pediatric Hodgkin lymphoma: outcome and role of surveillance after end of therapy.
Pediatr Blood Cancer. 2013; 60(9):1458-63 [PubMed] Related Publications
BACKGROUND: The outcome of treatment for pediatric Hodgkin lymphoma (HL) is excellent using chemotherapy and radiation. However, a minority of patients will relapse after treatment, but additional therapy achieves durable second remission in many cases. The optimal surveillance strategy after modern therapy for HL has not been well defined.
PROCEDURES: We reviewed the outcomes of pediatric patients with HL treated between 1990 and 2006 to determine the primary event that led to the detection of relapse. We determined the probability of relapse detection by routine follow-up procedures, including history, physical examination, laboratory tests, and imaging, and determined the impact of each of these screening methods on the likelihood of survival after relapse.
RESULTS: Relapse occurred in 64 of 402 evaluable patients (15.9%) at a median of 1.7 years from the time of diagnosis. The majority of relapses (60%) were diagnosed at a routine visit, and patient complaint was the most common initial finding that led to a diagnosis of relapse (47% of relapses). An abnormal finding on physical examination was the primary event in another 17% of relapses, and imaging abnormalities led to the diagnosis in the remaining 36%. Laboratory abnormalities were never the primary finding. The method of detection of relapse and timing (whether detected at a routine visit or an extra visit) did not impact survival.
CONCLUSIONS: In pediatric HL, most relapses are identified through history and physical examination. Frequent imaging of asymptomatic patients does not appear to impact survival and is probably not warranted.

Cen J, Shen J, Wang X, et al.
Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients.
Oncol Rep. 2013; 30(1):455-61 [PubMed] Related Publications
The aim of the present study was to investigate the association between lymphoma prognosis and aberrant methylation of inhibitor of DNA binding factor 4 (ID4) and tight junction protein 1 (ZO-1) genes in samples isolated from the bone marrow and paraffin-embedded lymphoma tissues of treatment-naive lymphoma patients. The bone marrow biopsy and paraffin-embedded lymphoma tissue samples from treatment-naive lymphoma patients were obtained, along with corresponding control samples from subjects without lymphoma and from lymph nodes of chronic cholecystitis and reactive lymphadenitis patients. Methylation-specific PCR (MSP) reactions were performed to analyze the methylation status on the promoter regions of ID4 and ZO-1. ID4 and ZO-1 promoter regions in the control group were completely unmethylated, whereas the rates of methylation of ID4 and ZO-1 in paraffin-embedded lymphoma tissues of the lymphoma patients were 80.4 and 84.3%, respectively. The methylation positivity rates of both the ID4 or ZO-1 genes in lymphoma patients were 92.2%, which was significantly higher compared to the rates in the control group (0%). The methylation positivity rates of the ID4 and ZO-1 genes in the bone marrow and paraffin-embedded lymphoma tissues of non-Hodgkin lymphoma patients were significantly higher compared to the rates in the Hodgkin lymphoma patients. The survival rate of lymphoma patients with methylated ID4 was significantly lower compared to that of patients with unmethylated ID4. The methylation of the ID4 and ZO-1 genes may be a specific molecular marker for lymphoma diagnosis. The methylation of the ID4 gene may be an indicator of poor prognosis in lymphoma patients.

Related: Non Hodgkin's Lymphoma

McCarthy PL, Hahn T, Hassebroek A, et al.
Trends in use of and survival after autologous hematopoietic cell transplantation in North America, 1995-2005: significant improvement in survival for lymphoma and myeloma during a period of increasing recipient age.
Biol Blood Marrow Transplant. 2013; 19(7):1116-23 [PubMed] Article available free on PMC after 01/07/2014 Related Publications
Autologous hematopoietic cell transplantation (auto-HCT) is performed to treat relapsed and recurrent malignant disorders and as part of initial therapy for selected malignancies. This study evaluated changes in use, techniques, and survival in a population-based cohort of 68,404 patients who underwent first auto-HCT in a US or Canadian center between 1994 and 2005 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The mean annual number of auto-HCTs performed was highest during 1996-1999 (6948), and decreased subsequently 2000-2003 (4783), owing mainly to fewer auto-HCTs done to treat breast cancer. However, the mean annual number of auto-HCTs increased from 5278 annually in 1994-1995 to 5459 annually in 2004-2005, reflecting increased use for multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Despite an increase in the median recipient age from 44 to 53 years, there has been a significant improvement in overall survival (OS) from 1994 to 2005 in patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma (day +100 OS, from 85% to 96%; 1-year OS, from 68% to 80%; P < .001) and chemotherapy-sensitive multiple myeloma (day +100 OS, from 96% to 98%; 1-year OS, from 83% to 92%; P < .001). This improvement in OS was most pronounced in middle-aged (>40 years) and older (>60 years) individuals.

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

Duan W, Jin X, Xiu Y, et al.
Expression of the novel all-trans retinoic acid-related resistance gene HA117 in pediatric solid tumors.
J Pediatr Hematol Oncol. 2014; 36(1):45-50 [PubMed] Related Publications
This study aimed to detect the protein expression of HA117 in pediatric solid tumors. Immunohistochemistry was performed to detect the expression of HA117 and P-gp in pediatric solid tumors. In Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), nephroblastoma (WT), and neuroblastoma (NB), the positive expression rate of HA117 was 65.4%, 58.3%, 81.3%, and 74.1%, and that of P-gp was 57.7%, 70.8%, 65.6%, and 66.7%, respectively. HA117 expression was closely related to the clinical stage of HL (P=0.004) and to the International Prognostic Index score, mediastinal lesions, and clinical stages of NHL (P=0.01, 0.03, and 0.01). The expression of HA117 in WT was higher than in adjacent normal tissues, but there was no statistical significance (P=0.21). The positive expression of HA117 in NB was markedly higher than that in normal tissues (P=0.002), which closely associated with histologic type and lymph node metastasis (P=0.03 and 0.001). Spearman correlation analysis revealed that HA117 expression was not correlated with P-gp in these 4 tumors. This suggests that HA117 might be an important resistance gene in pediatric solid tumors. The mechanism underlying the resistance to all-trans retinoic acid conferred by HA117 is different from that of P-gp.

Related: Kidney Cancer Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Neuroblastoma Wilms' Tumour Wilms Tumour

Ng AK, Garber JE, Diller LR, et al.
Prospective study of the efficacy of breast magnetic resonance imaging and mammographic screening in survivors of Hodgkin lymphoma.
J Clin Oncol. 2013; 31(18):2282-8 [PubMed] Related Publications
PURPOSE: Current guidelines recommend breast magnetic resonance imaging (MRI) as an adjunct to mammography for breast cancer screening in female cancer survivors treated with chest irradiation at a young age, beginning 8 to 10 years after treatment. Prospective data evaluating its efficacy in female cancer survivors are lacking. This study sought to compare the sensitivity and specificity of breast MRI with those of mammography in women who received chest irradiation for Hodgkin lymphoma (HL).
PATIENTS AND METHODS: We enrolled 148 women treated with chest irradiation for HL at age ≤ 35 years who were > 8 years beyond treatment. Yearly breast MRI and mammogram were performed over a 3-year period. Sensitivity and specificity of the two screening modalities were compared.
RESULTS: With the screening, 63 biopsies were performed in 45 women; 18 (29%) showed a malignancy. All but one of the screen-detected malignancies were preinvasive or subcentimeter node-negative breast cancers. After excluding first-screen MRI and mammogram, mammogram sensitivity was 68% as compared with 67% for MRI (P = 1.0). Sensitivity increased to 94% using both screening modalities. The specificities of mammogram alone, MRI alone, and both were 93%, 94%, and 90%, respectively.
CONCLUSION: In contrast to women with genetic or familial risk, in HL survivors breast MRI was not more sensitive than mammogram for breast cancer detection. However, the two screening modalities complement each other in the detection of early cases of disease. Early diagnosis is particularly important in these patients, given the breast cancer treatment challenges in patients who have received prior cancer therapy.

Related: Breast Cancer Cancer Screening and Early Detection

Allan BJ, Thorson CM, Davis JS, et al.
An analysis of 73 cases of pediatric malignant tumors of the thymus.
J Surg Res. 2013; 184(1):397-403 [PubMed] Related Publications
BACKGROUND: Tumors of the thymus are very rare in the pediatric population. This study examines the current trends and outcomes of children with thymus tumors.
METHODS: The Surveillance, Epidemiology and End Results (SEER) registry was queried for all patients <20 y of age with primary thymic malignancies from 1973 to 2008.
RESULTS: A total of 73 pediatric patients were identified with malignant thymic tumors. The median age at diagnosis was 13 y old. Among the 20 patients that presented with distant disease, 70% died. Conversely, among the 23 patients that presented with locoregional disease, 70% survived. Although the overall mean survival time was 89 ± 116 mo, 45% of patients died over the study period. Patients with Hodgkin lymphomas and germ cell tumors exhibited the highest survival (76% and 60% at 10 y, respectively). Multivariate analysis was used to identify local or regional tumor stage (odds ratio = 4.5, 95% confidence interval = 1.4-14.5) and surgical resection (OR = 3.8, 95% confidence interval = 1.4-10.8) as independent predictors of survival.
CONCLUSIONS: Malignant thymomas and lymphomas are the most common histological variants of pediatric thymus tumors, and patients with Hodgkin lymphomas exhibit the highest survival. Surgery is more commonly performed on malignant thymomas and is an independent prognostic indicator of survival.

Related: Gastrointestinal Carcinoid Tumours Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Germ Cell Tumors Germ Cell Tumours in Children and Young Adults Germ Cell Tumors (Pediatric)

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