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).

Daniëls LA, Krol SD, de Graaf MA, et al.
Impact of cardiovascular counseling and screening in Hodgkin lymphoma survivors.
Int J Radiat Oncol Biol Phys. 2014; 90(1):164-71 [PubMed] Related Publications
PURPOSE: Cardiovascular disease (CVD) is the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. The role of screening for CVD in HL survivors is unclear, but confrontation with risks of CVD may have a negative influence on health-related quality of life (HRQL). As part of a phase 2 screening study using computed tomography angiography (CTA) among HL survivors, an HRQL analysis was done to evaluate the emotional and practical burden and perceived benefits of screening and the effect of CVD-specific counseling on patient satisfaction.
METHODS AND MATERIALS: Patients who participated in the screening study also took part in the HRQL study. The impact of undergoing screening was evaluated with a 9-item questionnaire, and impact on HRQL with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire C30, version 3.0. The effect of counseling of CVD on perceived provision of information was evaluated with EORTC INFO-25. All questionnaires were completed at baseline and after screening.
RESULTS: Baseline questionnaires were received from 48 participants, and 43 completed questionnaires after screening. Mean age was 47 years, and mean time since diagnosis was 21 years. Of the total, 93% of subjects were content with participating, and 80% did not find the emphasis placed on late effects burdensome, although screening did have a small impact on social functioning and global quality of life. Perceived information on disease, medical tests, and treatment increased significantly after screening (P<.01). Differences were clinically relevant. There were no differences in perceived information between patients with and without screen-detected CVD.
CONCLUSIONS: Screening was evaluated favorably, whether CTA showed abnormalities or not. Extensive counseling resulted in substantially increased provision of information and improved information satisfaction. Screening by means of CTA and subsequent cardiac intervention was highly valued, and the benefits were felt to outweigh the emotional and practical burden.

Swerdlow AJ, Cooke R, Bates A, et al.
Risk of premature menopause after treatment for Hodgkin's lymphoma.
J Natl Cancer Inst. 2014; 106(9) [PubMed] Related Publications
BACKGROUND: Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited.
METHODS: Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided.
RESULTS: During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of ≥5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of ≥6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided.
CONCLUSIONS: Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.

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Hutchings M, Kostakoglu L, Zaucha JM, et al.
In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma.
J Clin Oncol. 2014; 32(25):2705-11 [PubMed] Related Publications
PURPOSE: Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2).
PATIENTS AND METHODS: All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years.
RESULTS: A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive.
CONCLUSION: PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment.

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Morales O, Mrizak D, François V, et al.
Epstein-Barr virus infection induces an increase of T regulatory type 1 cells in Hodgkin lymphoma patients.
Br J Haematol. 2014; 166(6):875-90 [PubMed] Related Publications
Epstein-Barr Virus (EBV) is present in the neoplastic cells of around 20-30% of patients with Hodgkin Lymphoma (HL). Although, an immunosuppressive environment is currently described in HL patients, little is known concerning the regulatory mechanism induced by EBV proteins expression in tumour cells. This study aimed to investigate an association between regulatory Type 1 cells (Tr1) and EBV tissue positivity in HL patients. Transcriptomic analysis of both EBV-positive and EBV-negative tumours showed that EBV infection increased gene expression of Tr1-related markers (ITGA2, ITGB2, LAG3) and associated-immunosuppressive cytokines (IL10). This up-regulation was associated with an over-expression of several chemokine markers known to attract T-helper type 2 (Th2) and regulatory T cells thus contributing to immune suppression. This Tr1 cells recruitment in EBV-positive HL was confirmed by immunohistochemical analysis of frozen nodes biopsies and by flow cytometric analysis of peripheral blood mononuclear cells of EBV-positive patients. Additionally, we showed that IL10 production was significantly enhanced in tumours and blood of EBV-positive HL patients. Our results propose a new model in which EBV can recruit Tr1 cells to the nodes' microenvironment, suggesting that the expression of EBV proteins in tumour cells could enable the escape of EBV-infected tumour cells from the virus-specific CTL response.

Related: Cytokines

Girinsky T, Aupérin A, Ribrag V, et al.
Role of FDG-PET in the implementation of involved-node radiation therapy for Hodgkin lymphoma patients.
Int J Radiat Oncol Biol Phys. 2014; 89(5):1047-52 [PubMed] Related Publications
PURPOSE: This study examines the role of (18)F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) in the implementation of involved-node radiation therapy (INRT) in patients treated for clinical stages (CS) I/II supradiaphragmatic Hodgkin lymphoma (HL).
METHODS AND MATERIAL: Patients with untreated CS I/II HL enrolled in the randomized EORTC/LYSA/FIL Intergroup H10 trial and participating in a real-time prospective quality assurance program were prospectively included in this study. Data were electronically obtained from 18 French cancer centers. All patients underwent APET-computed tomography (PET-CT) and a post-chemotherapy planning CT scanning. The pre-chemotherapy gross tumor volume (GTV) and the postchemotherapy clinical target volume (CTV) were first delineated on CT only by the radiation oncologist. The planning PET was then co-registered, and the delineated volumes were jointly analyzed by the radiation oncologist and the nuclear medicine physician. Lymph nodes undetected on CT but FDG-avid were recorded, and the previously determined GTV and CTV were modified according to FDG-PET results.
RESULTS: From March 2007 to February 2010, 135 patients were included in the study. PET-CT identified at least 1 additional FDG-avid lymph node in 95 of 135 patients (70.4%; 95% confidence interval [CI]: 61.9%-77.9%) and 1 additional lymph node area in 55 of 135 patients (40.7%; 95% CI: 32.4%-49.5%). The mean increases in the GTV and CTV were 8.8% and 7.1%, respectively. The systematic addition of PET to CT led to a CTV increase in 60% of the patients.
CONCLUSIONS: Pre-chemotherapy FDG-PET leads to significantly better INRT delineation without necessarily increasing radiation volumes.

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Hartmann S, Eichenauer DA, Plütschow A, et al.
Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma--a matched pair analysis from the German Hodgkin Study Group (GHSG).
Br J Haematol. 2014; 167(2):238-42 [PubMed] Related Publications
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity. We performed a matched-pair analysis to evaluate the prognostic impact of several histopathological features in this distinct Hodgkin lymphoma subtype. Lymph node samples of NLPHL patients were tested for CD15, IgD, phosphorylated STAT6, ICOS and Epstein-Barr virus status of the malignant lymphocyte-predominant cells as well as epithelioid cell clusters and activated T cells in the microenvironment. None of these features was associated with a particular clinical outcome. However, patients presenting with epithelioid cell clusters showed a non-significant trend towards a lower relapse rate, justifying further evaluation of this marker.

Lee JH, Kim Y, Choi JW, Kim YS
Prevalence and prognostic significance of Epstein-Barr virus infection in classical Hodgkin's lymphoma: a meta-analysis.
Arch Med Res. 2014; 45(5):417-31 [PubMed] Related Publications
BACKGROUND AND AIMS: The prevalence and prognostic significance of Epstein-Barr virus (EBV) infection in classical Hodgkin's lymphomas (cHLs) remain elusive. To examine the epidemiological and prognostic differences between EBV-positive and -negative cHLs, we conducted a meta-analysis of 119 published studies including 13,045 cases.
METHODS: We pooled the results of relevant published studies identified using the PubMed and Embase. The effect sizes of outcome parameters were calculated by prevalence, odds ratio (OR), or hazard ratio using a random-effects model.
RESULTS: The pooled prevalence of EBV infection in cHL was 47.9%, which was significantly higher in Africa and Central and South America than other regions. EBV-positive cHL showed higher incidence in children than in adults (69.7 vs. 41.1%). EBV-positive cHL was significantly related to male (OR = 1.8, 95% CI: 1.510-2.038; p <0.001), mixed cellularity subtype (OR = 3.8, 95% CI: 3.243-4.451; p <0.001), and advanced clinical stages (OR = 1.2, 95% CI: 1.072-1.369; p = 0.002). However, the presence of EBV in cHL was not associated with overall or event-free survival.
CONCLUSIONS: The prevalence of EBV differs according to age, sex, region, histologic subtype, and clinical stage of cHL. However, the presence of EBV has little effects on cHL patient's survival.

Greene M, Lai Y, Baella N, et al.
Antibodies to Delta/notch-like epidermal growth factor-related receptor in patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin lymphoma.
JAMA Neurol. 2014; 71(8):1003-8 [PubMed] Article available free on PMC after 01/08/2015 Related Publications
IMPORTANCE: The anti-Tr immune response is associated with paraneoplastic cerebellar degeneration and Hodgkin lymphoma (HL). One case series has reported that the Delta/notch-like epidermal growth factor-related receptor (DNER) is the actual target for anti-Tr antibodies, but this result has not been replicated.
OBJECTIVE: To describe a patient with anti-Tr and confirm that DNER is the autoantigen for a series of patients with anti-Tr.
DESIGN, SETTING, AND PARTICIPANTS: Observational study and analysis of biological samples for antibodies to DNER at the hospital of the University of Pennsylvania. We examined a cerebrospinal fluid sample from 1 patient with anti-Tr and serum and/or cerebrospinal fluid samples from 5 other patients with anti-Tr.
EXPOSURE: Transfection of HEK293T and Hela cells to express DNER coupled to an enhanced green fluorescent protein tag using a plasmid previously used to detect human DNER antibodies.
RESULTS: A man in his 30s with paraneoplastic cerebellar degeneration and anti-Tr underwent treatment with corticosteroids and intravenous immunoglobulin, resulting in clinical improvement before chemotherapy. Despite close oncologic follow-up, a biopsy, positron emission tomography, and computed tomography, he was not diagnosed as having HL until 6 months after symptom onset. The cerebrospinal fluid sample from this patient reacted with cells transfected to express DNER, as did cerebrospinal fluid and/or serum samples from 5 other patients with paraneoplastic cerebellar degeneration, HL, and anti-Tr. Only 4 of the 5 serum samples reacted to permeabilized cells enough to be distinguished from background, but all 5 serum samples convincingly labeled live cells, which had considerably less background. All 6 control serum samples and 1 serum sample from a patient previously diagnosed as having anti-Tr (but without HL or cerebellitis) did not recognize DNER.
CONCLUSIONS AND RELEVANCE: This case demonstrates the importance of testing for the anti-Tr immune response in patients with cerebellar degeneration. The strong association of anti-Tr with HL requires careful surveillance for this tumor. We also confirm that DNER is the target antigen of the anti-Tr immune response. Screening for DNER antibodies against living transfected cells may offer an improved signal-to-noise characteristic compared with immunostaining of fixed, permeabilized cells.

Hoppe BS, Flampouri S, Zaiden R, et al.
Involved-node proton therapy in combined modality therapy for Hodgkin lymphoma: results of a phase 2 study.
Int J Radiat Oncol Biol Phys. 2014; 89(5):1053-9 [PubMed] Related Publications
PURPOSE: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement.
METHODS AND MATERIALS: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis.
RESULTS: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed.
CONCLUSIONS: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy.

Treetipsatit J, Rimzsa L, Grogan T, et al.
Variable expression of B-cell transcription factors in reactive immunoblastic proliferations: a potential mimic of classical Hodgkin lymphoma.
Am J Surg Pathol. 2014; 38(12):1655-63 [PubMed] Related Publications
Reactive immunoblastic proliferations can histologically mimic classical Hodgkin lymphoma (CHL), and show diffuse CD30 expression in large cells. The lack of expression of CD15 in a subset of CHL further complicates their separation from immunoblastic proliferations. Loss of expression of B-cell transcription factors is frequently exploited in making a diagnosis of CHL; however, the staining patterns of B-cell transcription factors in immunoblastic proliferations have not been extensively studied. Thirty-three cases of reactive immunoblastic proliferations were evaluated using a panel of immunohistochemistry for CD30, CD15, CD20, CD3, κ, λ, CD45RB, MUM1, PAX5, OCT2, and BOB.1, as well as Epstein-Barr virus (EBV)/EBV-encoded ribonucleic acid in situ hybridization. A newly developed dual-color chromogenic in situ hybridization technology for detection of κ/λ mRNAs was also used. The majority of immunoblasts expressed CD30 in 14 of 33 (42%) cases; none expressed CD15. Loss or weak expression of at least 1 transcription factor in B immunoblasts, most commonly PAX5, was noted in 24 of 29 (83%) cases. A polytypic light chain expression pattern was detected by immunohistochemistry in 14 of 22 (63.6%) cases and by dual-color chromogenic in situ hybridization in 9 of 10 (90%) cases studied. EBV-encoded ribonucleic acid was detected in 8 of 33 (24.2%) cases, 5 of which were clinically unrelated to infectious mononucleosis. We conclude that B-cell transcription factors can show loss or weak expression in a significant proportion of reactive immunoblastic proliferations, and, therefore, staining for B-cell transcription factors together with CD30 should be interpreted with caution before a diagnosis of CHL is made.

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] Article available free on PMC after 01/08/2015 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

Kobe C, Kuhnert G, Kahraman D, et al.
Assessment of tumor size reduction improves outcome prediction of positron emission tomography/computed tomography after chemotherapy in advanced-stage Hodgkin lymphoma.
J Clin Oncol. 2014; 32(17):1776-81 [PubMed] Related Publications
PURPOSE: Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT).
PATIENTS AND METHODS: The analysis set consisted of 739 patients with residues≥2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkin's disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkin's disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression.
RESULTS: In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P=.022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P=.9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%).
CONCLUSION: Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.

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Tanhaei AP, Ziaei A, Mazrouei S, et al.
Livin, a novel marker in lymphoma type distinction.
Ann Diagn Pathol. 2014; 18(3):157-62 [PubMed] Related Publications
Despite advances in immunohistochemical and molecular diagnostics, there are persistent difficulties in differentiating between several subtypes of non-Hodgkin lymphoma (NHL) and classic Hodgkin lymphoma (CHL). Considering high level of livin expression in hematologic malignancies, we aimed to examine the utility of livin expression ratio, as an ancillary biomarker, in distinguishing CHL from NHL in ambiguous cases. We evaluated livin expression in 38 CHL, 23 NHL, and 39 nonneoplastic lymph nodes in paraffin-embedded blocks. Tissue microarray-based semiquantitative immunoflourecent staining was applied for protein expression. Criterion standard of diagnosis was based on selection of only definite cases and not the cases suspected by hemathopathologists. A significant difference was found in the livin/GAPDH mean ratio (M.R) of expression between NHL and CHL cases. A receiver operating characteristic curve analysis confirmed 0.6370 to be the best diagnostic cut-off value for the livin/GAPDH expression M.R in diffuse large B-cell lymphoma (DLBCL) (area under the curve = 0.944); it yielded 92% sensitivity, 94% specificity, likelihood ratios positive 17.5, and likelihood ratios negative 0.07 for diagnosing DLBCL from CHL. Mean ratio of livin/Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression seems to be a valuable index in differentiating DLBCL from CHL. We suggested an optimal cut-off point for livin/GAPDH expression M.R with a high sensitivity and specificity. Thus, in diagnostically difficult cases of DLBCL and CHL, focus on livin as marker may provide useful corroborative information.

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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Crump C, Sundquist J, Sieh W, et al.
Season of birth and risk of Hodgkin and non-Hodgkin lymphoma.
Int J Cancer. 2014; 135(11):2735-9 [PubMed] Article available free on PMC after 01/12/2015 Related Publications
Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973-2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p = 0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04-1.50; p = 0.02] for spring (March-May), 1.22 (95% CI, 1.01-1.48; p = 0.04) for summer (June-August) and 1.11 (95% CI, 0.91-1.35; p = 0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p = 0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL.

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

Xing KH, Connors JM, Lai A, et al.
Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis.
Blood. 2014; 123(23):3567-73 [PubMed] Related Publications
Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71%; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL.

Picardi M, Pugliese N, Cirillo M, et al.
Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures.
Radiology. 2014; 272(1):262-74 [PubMed] Related Publications
PURPOSE: To compare the use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) with the use of a combination of ultrasonography (US) and chest radiography for systematic follow-up of patients with high-risk Hodgkin lymphoma.
MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. In a single center between January 2001 and December 2009, patients with advanced-stage Hodgkin lymphoma who had responded completely to first-line treatment were randomly assigned (1:1) to follow-up with either PET/CT or US/chest radiography. Follow-up included clinical and imaging procedures at 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 84, and 108 months after treatment discontinuation. When clinical and/or imaging results were positive, recurrence was confirmed histologically. The primary endpoint was to compare the sensitivity of the two follow-up imaging approaches. Secondary endpoints were their specificity, positive and negative predictive values, time to recurrence detection, radiation risks, and costs.
RESULTS: A total of 300 patients were randomized into the two arms. The study was closed after a median follow-up time of 60 months, with a relapse rate of 27%. Sensitivity for detection of Hodgkin lymphoma was similar for the two follow-up approaches. All of the relapses (40 of 40) were identified with FDG PET/CT (100%) and 39 of 40 relapses were identified with US/chest radiography (97.5%; P = .0001 for the equivalence test). US/chest radiography showed significantly higher specificity and positive predictive value than did PET/CT (96% [106 of 110] vs 86% [95 of 110], respectively; P = .02; and 91% [39 of 43] vs 73% [40 of 55], respectively; P = .01). Exposure to ionizing radiation was estimated to be 14.5 mSv for one PET/CT examination versus 0.1 mSv for one chest radiographic examination. Estimated cost per relapse diagnosed with routine PET/CT was 10-fold higher compared with that diagnosed with routine US/chest radiography.
CONCLUSION: US and chest radiography are diagnostic tools that enable effective, safe, and low-cost routine surveillance imaging for patients at high risk of Hodgkin lymphoma relapse.

Russo F, Corazzelli G, Frigeri F, et al.
A phase II study of dose-dense and dose-intense ABVD (ABVDDD-DI ) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma.
Br J Haematol. 2014; 166(1):118-29 [PubMed] Related Publications
We explored activity and safety of a dose-dense/dose-intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVDDD-DI ) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two-stage Bryant-Day Phase II study to receive six cycles of ABVDDD-DI without consolidation radiotherapy. Cycles were supported with granulocyte colony-stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m2; first four cycles only). Co-primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event-free (EFS) and disease-free survival (DFS). All patients received the four doxorubicin-intensified courses and 96% concluded all six cycles (82.3% within the intended 18 weeks). This translated into a 66.9% increase of received dose-intensity for doxorubicin and 31.8% for the other agents over standard ABVD. The CR rate was 95.1% (78/82) and 87.8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14.6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five-year EFS and DFS was 88.3% and 93.7%, respectively. ABVDDD-DI regimen was well-tolerated and ensured substantial CR and EFS rates without radiotherapy.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Yuan S, Nademanee A, Kaniewski M, et al.
Efficacy of just-in-time plerixafor rescue for Hodgkin's lymphoma patients with poor peripheral blood stem cell mobilization.
Transfusion. 2014; 54(8):2015-21 [PubMed] Related Publications
BACKGROUND: Plerixafor is a Food and Drug Administration-approved agent for improving peripheral blood stem cell (PBSC) mobilization in filgrastim (granulocyte-colony-stimulating factor [G-CSF])-stimulated patients with multiple myeloma and non-Hodgkin's lymphoma. Limited information is available on its use in Hodgkin's lymphoma (HL) patients. We describe our experience with plerixafor as an immediate rescue agent in HL patients with poor PBSC mobilization.
STUDY DESIGN AND METHODS: We retrospectively reviewed the collection data of 27 consecutive HL patients at our center in whom plerixafor was added to rescue a failing PBSC collection after G-CSF and chemotherapy (26) or G-CSF alone (1). Plerixafor was added in 11 patients due to peripheral blood (PB) CD34+ counts that persisted below the threshold (>10 × 10(6) /L) to initiate collection (median, 1.47 × 10(6) ; range 0 × 10(6) -6.28 × 10(6) /L) and in 16 patients due to low collection yields, who had a median yield of 0.33 × 10(6) (0.14 × 10(6) -0.65 × 10(6) ) CD34+ cells/kg on the last collection before plerixafor administration.
RESULTS: After a median of 2 (range, 2-4) collections with plerixafor, the patients collected a median of 1.82 × 10(6) (0.52 × 10(6) -11.14 × 10(6) ) CD34+ cells/kg. The addition of plerixafor enabled 20 patients (74.1%) to reach the 2.0 × 10(6) CD34+ cells/kg minimum required for autologous stem cell transplantation (ASCT) during the same collection cycle. Subsequent remobilization in three patients with plerixafor enabled all three to reach this goal.
CONCLUSION: Plerixafor can be used in HL patients with poor mobilization as a rescue agent and boosts mobilization sufficiently in most patients in the same collection attempt, thus not only permitting ASCT, but also avoiding remobilization and the associated costs, treatment delays, and patient inconvenience.

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.

Bartlett NL, Chen R, Fanale MA, et al.
Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies.
J Hematol Oncol. 2014; 7:24 [PubMed] Article available free on PMC after 01/12/2015 Related Publications
BACKGROUND: Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study ( NCT00947856).
METHODS: Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment.
RESULTS: The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year.Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment.
DISCUSSION: With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials.
CONCLUSIONS: Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL.
TRIAL REGISTRATION: United States registry and results database NCT00947856.

Raemaekers JM, André MP, Federico M, et al.
Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial.
J Clin Oncol. 2014; 32(12):1188-94 [PubMed] Related Publications
PURPOSE: Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment.
PATIENTS AND METHODS: Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted.
RESULTS: The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET-negative patients.
CONCLUSION: On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.

Related: Bleomycin Cyclophosphamide Dacarbazine Doxorubicin Etoposide Procarbazine Vinblastine Vincristine

Gentzler RD, Evens AM, Rademaker AW, et al.
F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma.
Br J Haematol. 2014; 165(6):793-800 [PubMed] Related Publications
Total lymphoid irradiation (TLI) followed by high-dose chemotherapy and autologous haematopoietic stem cell transplant (aHSCT) is an effective strategy for patients with relapsed/refractory classical Hodgkin lymphoma (HL). We report outcomes for patients with relapsed/refractory HL who received TLI followed by high-dose chemotherapy and aHSCT. Pre-transplant fludeoxyglucose positron emission tomography (FDG-PET) studies were scored on the 5-point Deauville scale. Of 51 patients treated with TLI and aHSCT, 59% had primary refractory disease and 63% had active disease at aHSCT. The 10-year progression-free survival (PFS) and overall survival (OS) for all patients was 56% and 54%, respectively. Patients with complete response (CR) by PET prior to aHSCT had a 5-year PFS and OS of 85% and 100% compared to 52% and 48% for those without CR (P = 0·09 and P = 0·007, respectively). TLI and aHSCT yields excellent disease control and long-term survival rates for patients with relapsed/refractory HL, including those with high-risk disease features. Achievement of CR with salvage therapy is a powerful predictor of outcome.

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.

Filippi AR, Ciammella P, Piva C, et al.
Involved-site image-guided intensity modulated versus 3D conformal radiation therapy in early stage supradiaphragmatic Hodgkin lymphoma.
Int J Radiat Oncol Biol Phys. 2014; 89(2):370-5 [PubMed] Related Publications
PURPOSE: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints.
METHODS AND MATERIALS: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity.
RESULTS: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043).
CONCLUSIONS: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete response after ABVD-based chemotherapy.

Related: Bleomycin Dacarbazine Doxorubicin Vinblastine

Horst KC, Hancock SL, Ognibene G, et al.
Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma.
Ann Oncol. 2014; 25(4):848-51 [PubMed] Related Publications
BACKGROUND: The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC.
MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs.
RESULTS: One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003).
CONCLUSION(S): BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

Related: Breast Cancer

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.

Sorasio R, Bonferroni M, Grasso M, et al.
Peripheral blood CD34+ percentage at hematological recovery after chemotherapy is a good early predictor of harvest: a single-center experience.
Biol Blood Marrow Transplant. 2014; 20(5):717-23 [PubMed] Related Publications
Several algorithms for early prediction of poor-mobilizing patients after chemotherapy and granulocyte colony-stimulating factor administration have been proposed. They generally define peripheral blood cut-off levels of CD34+ cells at a fixed day after starting chemotherapy, mostly with cyclophosphamide. To define an algorithm for early addition of plerixafor regardless of the chemotherapy regimen used, we retrospectively analyzed 280 chemomobilization attempts in 236 patients treated at our institution between 2002 and 2012. In multivariate analysis, CD34+ absolute count and CD34+ percentage upon total leukocyte count at day 1 (defined as the first day in which leukocytes reached a value > 1 × 10(9)/L) were the only factors able to predict a total harvest ≥ 2 × 10(6) CD34+/kg. In patients with day 1 CD34+ lower than 20/μL, the CD34+ percentage was a more reliable predictor of stem cell harvest in the following days than CD34+ absolute count. Upon definition of the best CD34+ cut-off value for identification of poor-mobilizing patients, an algorithm was set up to guide plerixafor administration. It was prospectively validated in 20 patients in 2013 with encouraging results in terms of low incidences of both mobilization failure and plerixafor use. Large prospective trials that define the most cost-effective strategy for just-in-time rescue plerixafor are warranted.

Related: Cyclophosphamide Cytarabine Non Hodgkin's Lymphoma Acute Lymphocytic Leukemia (ALL)

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