[Nodular lymphocyte predominant Hodgkin lymphoma (paragranuloma of Poppema) in children: Case report, review of the literature and treatment]. / Lymphome de Hodgkin nodulaire à prédominance lymphocytaire (paragranulome de Poppema) chez l'enfant : à propos d'un cas, revue de la littérature et traitement.

We present the case of a 12 year old child with a limp. The diagnostic work-up reveals splenomegaly, multifocal bone involvement and abdominal adenopathies. A biopsy of an intra-abdominal lesion shows a lymphoid mass with a nodular architecture composed of poorly defined nodules. We identify large cells with irregular, sometimes poly-lobulated nuclei with a particular immunohistochemical profile. Those "pop-corn" cells are positive for CD20, CD79a, pax-5 and bcl-6 and are negative for CD15, CD30, bcl-2, TdT, CD56 and EMA. There is a diffuse follicular helper T cell population that is located in between the tumour cells. The overall picture is indicative of a nodular lymphocyte predominant Hodgkin lymphoma. Advanced stage of this disease is rare in children and there is currently little data to guide optimal treatment. Because of a stage IV disease, the patient is treated with chemotherapy after which complete metabolic remission is observed. 3.5 years after the initial diagnosis, our patient relapses. He is treated with chemotherapy and an autologous peripheral blood stem cell transplantation. He remains in complete remission since then. This case illustrates the favorable prognosis of the disease even after relapse.

Radiation exposure of the glandular mammary tissue in women patients with mediastinal Hodgkin lymphoma treated with protons.

PURPOSE: Secondary breast cancer is a frequent late adverse event of mediastinal Hodgkin lymphoma radiotherapy. Secondary breast cancers overwhelmingly correspond to ductal carcinoma and develop from the glandular mammary tissue. In addition, during childhood, radiation overexposure of the glandular tissue may lead to a late breast hypotrophy at adult age. The aim of this study was to evaluate the radiation exposure to the glandular tissue in patients treated for mediastinal Hodgkin lymphoma with intensity-modulated proton therapy, in order to evaluate the potential dosimetric usefulness of its delineation for breast sparing. MATERIALS AND METHODS: Sixteen consecutive intermediate-risk mediastinal female patients with Hodgkin lymphoma treated with consolidation radiation with deep inspiration breath hold intensity-modulated proton therapy to the total dose of 30Gy were included. Breasts were delineated according to the European Society for Radiotherapy and Oncology guidelines for treatment optimization ("clinical organ at risk"). The glandular tissue ("glandular organ at risk") was retrospectively contoured on the initial simulation CT scans based on Hounsfield unit (HU) values, using a range between -80HU and 500HU. RESULTS: The mean and maximum doses delivered to the glandular organ at risk were significantly lower than the mean and maximum doses delivered to the clinical organ at risk, but were statistically correlated. Glandular organ at risk volumes were significantly smaller. CONCLUSION: Optimizing the treatment plans on the clinical breast contours will systematically lead to overestimation of the dose received to the glandular tissue and, consequently, to an indistinct and involuntary improved glandular tissue sparing. As such, our findings do not support the consideration of the glandular tissue as an additional organ at risk when planning intensity-modulated proton therapy for mediastinal Hodgkin lymphoma in female patients.

[Strategy of the French Society of Childhood Cancer (SFCE) for pediatric nodular lymphocyte predominant lymphoma]. / Recommandations de la SFCE pour la prise en charge du lymphome de Hodgkin nodulaire à prédominance lymphocytaire de l'enfant et de l'adolescent.

Nodular Lymphocyte predominant Hodgkin lymphoma (NLPHL) are rare lymphomas in pediatric patients comprising less than 10 % of all Hodgkin lymphoma (HL). They are for the most part diagnosed at stage I or II and indolent with lymphadenopathy often preceding the diagnosis by many months/years. Survival is excellent. Historically, patients were treated according to classical HL protocols. Due to high toxicity and excellent prognosis, management of NLPHL shifted to de-escalation protocol with good results. No treatment beyond surgical resection was proposed for localized unique nodal disease completely resected. The closed European protocol (EuroNet PHL LP1) evaluated the efficacy of low intensity chemotherapy protocol based on CVP courses (cyclophosphamide vinblastine prednisone) for stage IA/IIA not fully resected. Final results are not yet available. Advanced stage NLPHL are rare and there is no clinical trial and no consensus treatment in children. The SFCE lymphoma committee recently established recommendations for staging and treatment of limited and advanced NLPHL in children based on current practices and published results. The goal was to allow homogeneous practice on a national scale. If incomplete resection for patients with stage I/IIA combination of low intensity chemotherapy (CVP) and rituximab is recommended. For intermediary and advanced stage intensification with AVD (adriamycine vinblastine dacarbazine) or CHOP courses (cyclophosphamide doxorubicine vincristine prednisone) combined with rituximab are advocated. In children, there is no indication for first-line local treatment with radiotherapy.

[Human immunodeficiency virus and lymphoma]. / Virus de l'immunodéficience humaine et lymphome.

Lymphomas remain a leading cause of morbidity and mortality for HIV-positive patients. The most common lymphomas include diffuse large B-cell lymphoma, Burkitt lymphoma, primary effusion lymphoma, plasmablastic lymphoma and Hodgkin lymphoma. Appropriate approach is determined by lymphoma stage, performans status, comorbidities, histological subtype, status of the HIV disease and immunosuppression. Treatment outcomes have improved due to chemotherapy modalities and effective antiretroviral therapy. This review summarizes epidemiology, pathogenesis, pathology, and current treatment landscape in HIV associated lymphoma.

Clinical and dosimetric impact of totally implantable venous access devices in radiotherapy of supra diaphragmatic Hodgkin Lymphoma.

PURPOSE: To evaluate attenuation of the totally implantable vascular access device (TIVAD) and assess its clinical and dosimetric impact on radiotherapy (RT) of lymphoma patients. MATERIALS AND METHODS: The first part of the study consisted of an in vitro approach by irradiating the TIVAD with different electron and photon energies. The attenuation data measured were compared with data calculated by our treatment planning system. All patients treated by radiotherapy for Hodgkin's lymphoma with their TIVAD in the target volume were then reviewed to assess the clinical outcome and dosimetric comparison using different plan metrics. All patients were treated by 3D conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy delivered by Helical Tomotherapy (HT). RESULTS: Nineteen patients treated for stage I-III HL were studied. Seven patients were treated exclusively on the side of TIVAD and 12 were treated bilaterally. Median prescription dose was 30Gy. No significant clinical or dosimetric differences were observed between the side of the TIVAD and the contralateral side in patients treated bilaterally. HT resulted in a significantly higher conformity index (P<0.0022) and a significantly lower healthy tissue coverage (P=0.0008) than 3DCRT. The observed attenuation was 79% for 6 MeV, 59% for 9 MeV, and 46% for 12 MeV for electrons and 9% for 4 MV, 8% for 6 MV, 5% for 10 MV and 15 MV and 3% for 20 MV for X photons. CONCLUSION: TIVADs induce significant beam attenuation when using electrons, which can be overcome by using high-energy photons or by creating an exclusion zone in when HT is used.

Hodkgin lymphoma concomitant of tuberculosis, a therapeutic challenge for multidisciplinary management.

Hodgkin lymphoma (HL) is a disease characterized by a high curability rate, and the treatment benefit-risk balance must be carefully addressed to achieve complete disease control with low risk of long-term toxicities. Most patients are treated with a combination of chemotherapy and radiotherapy, after disease staging and response to treatment evaluated by FDG PET/CT. We report the case of a 28-year-old patient concomitantly diagnosed of a Hodgkin lymphoma and active tuberculosis. Initial staging was difficult due to pulmonary and abdominal tuberculosis localization that induced FDG PET/CT hypermetabolism. Anti-tuberculosis treatment was first started, allowing secondary an early accurate Hodgkin lymphoma staging by FDG PET/CT. The patient was then treated by chemotherapy and radiotherapy. Helical TomoTherapy® was used with involved site (IS) irradiation volume was performed to decrease the high doses to organs-at-risk (OAR), especially lungs in this context of tuberculosis.

Adolescents and young adults with classical Hodgkin lymphoma in northern Tunisia: insights from an adult single-institutional study.

PURPOSE: The aim of this study was to extensively describe the epidemiological, clinical and therapeutic outcomes of adolescents and young adults (AYA) population with classical Hodgkin Lymphoma (cHL). Then, a comparison between AYAs and adults and between the subgroups of AYAs treated with the same adult protocol was accomplished to further inform on optimal therapy approach of choice for adolescent patients. MATERIAL AND METHODS: In this mono-centric, retrospective study, we reviewed the medical records. We analyzed 112 consecutive North Tunisian patients, including 66 AYAs (15 to 39 years) and 46 adults (≥40years) affected by cHL treated from 2000 to 2015 at Salah Azaiez Institute. Then, we performed a comparative analysis between AYA and 46 adult patients and a subgroup analysis between adolescents and young adults. All patients were treated according to the national protocol for HL, edited by the Tunisian Society of Hematology. The treatment included chemotherapy and involved-field radiotherapy (RT) at a dose of 20 or 30 Grays (Gy) for responders and 36Gy for non-responders. RESULTS: AYA patients presented with adverse features with nodular sclerosis subtype (p=3.88×10-02) and mediastinal mass involvement (p=9.40×10-04). At a median follow-up of 51 and 32 months for AYAs and adults, respectively, no statistical difference in terms of 3 and 5-years overall survival (OS) and event-free survival (EFS) was shown. Using the Kaplan-Meier method, in AYAs, the ABVD regimen has an impact on 3-years EFS (p=4.63×10-02). The 36Gy RT was associated with the best 3-years EFS (p=9.24×10-03). Besides, AYA patients with advanced-stage had the worst 3-years OS (76%) (p=2.41×10-02). Although the adolescents and young adults shared similar clinical presentation, we noted that the adolescent group had the worst 3-years EFS (48%), but the best 3-years OS (91%). We identified 15% of primary refractory patients and a rate of toxicity of 5.3% in AYA. CONCLUSION: The treatment approach used is well tolerated by adult patients. However, the AYA patients and particularly adolescent subgroup had more advanced disease at diagnosis and should be treated more intensively in dedicated units. RT dose<36Gy and ABVD chemotherapy were associated with lower EFS in this population.

Protontherapy versus best photon for mediastinal Hodgkin lymphoma: Dosimetry comparison and treatment using ILROG guidelines.

The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7Gy vs. 8.4Gy) and median dose (0.002Gy vs. 6.9Gy), heart mean dose (2.6Gy vs. 3.7Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4Gy vs. 4.4Gy) and left (1.9Gy vs. 4.6Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant.

PURPOSE: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. MATERIAL AND METHODS: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. RESULTS: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. CONCLUSION: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.

[New therapeutic strategies in non-Hodgkin lymphomas and Hodgkin lymphoma]. / Actualités thérapeutiques dans les lymphomes non hodgkiniens et le lymphome de Hodgkin.

In this review, we report the main advances of the last years in the four most common lymphomas in France, namely Hodgkin lymphoma, large cell diffuse B lymphoma, follicular lymphoma and mantle cell lymphoma. We have identified consensual practices in first line in France and then distinguished the targeting by new molecules. Thus, we wanted to highlight the problems for each of these four lymphomas and understand the tools used to find solutions. Finally, this review makes it possible to understand to what extent the new molecules (targeted therapies, immunotherapy) make it possible to continuously improve the management of patients with lymphomas. The global dynamics seems to reduce the place of conventional chemotherapies in favor of these new molecules. However, because of the increase in therapeutic possibilities, the challenge remains to find the combination associated with the best risk-benefit ratio.

[Autoimmune hemolytic anemia and immune thrombocytopenia associated with Hodgkin disease: Retrospective monocentric study]. / Cytopénies auto-immunes associées au lymphome de Hodgkin : étude rétrospective monocentrique.

INTRODUCTION: Hodgkin's lymphoma (HL) is less common than non-Hodgkin lymphoma and is rarely associated with autoimmune cytopenia. METHOD: We report a consecutive, monocentric and retrospective series of HL patients diagnosed with concomitant or subsequent autoimmune cytopenia over a period of 8 years. RESULTS: We report 4 out of 84 HL patients (4.8%) diagnosed with autoimmune cytopenia (4 immune thrombocytopenia including 2 Evans' syndromes). They were 4 males (average age 24 years for the 3 youngest, and one over 60 years old). Autoimmune cytopenia revealed lymphoma in 2 patients and occurred after HL treatment in the two other patients (5 and 36 months from the end of chemotherapy) without HL relapse. All cytopenias were resistant to conventional treatments (glucocorticoids, intravenous immune globulin, rituximab) and sensitive to chemotherapy when indicated for HL treatment. CONCLUSION: In our series, the predominance of males, a higher frequency of immune thrombocytopenia than autoimmune hemolytic anemia, the resistance to usual treatments and the efficacy of specific chemotherapy were consistent with the literature. Unexpectedly, patients were young and with nodular sclerosis morphology (vs. mixed cellularity) in 3 of 4 cases.

Multimodality imaging using PET/CT (18F)-fluorodeoxyglucose for radiotherapy field delineation of localized Hodgkin lymphoma.

It is now well demonstrated that (18F)-fluorodeoxyglucose PET/CT is the most accurate imaging method for determining disease extent in Hodgkin lymphoma. Thus, up-front PET/CT is mandatory for involved node radiation therapy design. For a proper use of this new imaging modality for radiotherapy, some adaptations should be made to the PET/CT acquisition as well as to the report. Initial PET/CT should be performed in the radiotherapy treatment position. Nuclear medicine physicians should report to the radiation oncologist the precise location of each involved lymph node, for which the use of a common atlas of upper diaphragmatic nodal stations could be useful. All these new procedures have to be implemented in close collaboration among the different medical specialists providing care to Hodgkin lymphoma patients. We report here the usual procedures of PET/CT acquisition in the radiotherapy environment and propose a more sophisticated description of the different lymph nodes for a more efficient nuclear medicine report to the radiation oncologist.

[Tunisian National Protocol for Adult Hodgkin's Lymphoma Treatment: Results of a therapeutic regimen adapted to the 2-cycle CT response, about 444 patients]. / Protocole national Tunisien prospectif de traitement du Lymphome de Hodgkin de l'adulte : résultats d'un schéma thérapeutique adapté à la réponse par tomodensitométrie à 2 cycles, à propos de 444 patients.

OBJECTIVE: In Tunisia, the management of Adult Hodgkin's Lymphoma (HL) has been standardized since 1999. We propose in this study to report the therapeutic results of the national protocol of adult HL treatment (MDH2008). PATIENTS AND METHODS: Our study is prospective multicenter interesting 444 patients followed for HL between July 2008 and June 2013 and treated according to the MDH2008 protocol. The median age of our patients was 30 years. B symptoms were present in 62.8 % of our patients. According to the Ann Arbor classification, our patients were in stages I, II, III and IV in 3 %, 42 %, 26 % and 29 %, respectively. The MDH2008 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of chemotherapy. RESULTS: Response≥75 % to 2 courses of chemotherapy was achieved in 43 % of patients and the response rate at the end of treatment was 92.1 %. Forty-eight patients (11.4 %) had primary failure. In the multi-variant study, bulky mediastinal mass (IMT≥0.35) was an independent predictive factor of primary failure (P: 0.000). Nineteen toxic deaths (4.35 %) were reported. The relapse rate was 7.8 %. Event free survival, relapse-free survival and overall survival at 5years were 75 %, 89 % and 90 %, respectively. Adaptation of the treatment to the 2 cycles response was effective in unfavorable early stages and advanced stages. CONCLUSION: Compared to MDH2002 (second version of Tunisian prospective protocol), the MDH2008 reduced the primary failure rate, the rate of toxic deaths with escalated BEACOPP and the rate of relapse in Tunisian patients.

[Hodgkin lymphoma: Current and future therapeutic strategies]. / Le lymphome de Hodgkin : stratégies thérapeutiques actuelles et futures.

Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups. More recently, several groups have tried to develop treatment strategies adapted to the response to chemotherapy, evaluated by interim PET/CT scan. However to date, the combined treatment with chemotherapy followed by radiation therapy remains a standard in most of the above-diaphragmatic localized forms. Immune checkpoint inhibitors, and especially anti-PD1 antibodies, have shown dramatic results in some serious forms of relapsed or refractory HL, with limited toxicity, and may contribute in the future to reduce the toxicities of treatments.

[New therapy outlooks in Hodgkin lymphoma]. / Actualités thérapeutiques dans le lymphome de Hodgkin.

Classical Hodgkin lymphoma (HL) is a curable disease in 80% of advanced and 90% of localized stages. An improvement of the HL curability is still possible with the emergence of first-line therapy with a better balance between efficacy and toxicity and early identification patients with high risk of failure requiring specific treatment. 18FDG PET-CT gained a major role in the baseline staging and response assessment to HL treatment. The prognostic value of early PET-CT allowed to develop PET-CT guided therapies able to optimize the balance between efficacy and toxicity including the modulation of the chemotherapy intensity or the omission of radiotherapy for some localized diseases. New drugs emerged in the treatment of relapse or refractory HL (brentuximab vedotine [BV], immunological checkpoint inhibitor anti-PD1). Although their place in the strategies of salvage therapy is still debated several trials have reported relevant efficacy in some unmet medical need: refractory patients or relapses after auto/allograft. This review addresses the questions of PET-CT-based therapeutic strategies in first-line and the impact of new drugs targeting the micro-environment (anti-PD1) or the Hodgkin Reed Sternberg cells (BV).

[Primary osseous Hodgkin's lymphoma of the sacrum: A diagnostic and therapeutic challenge]. / Lymphome de Hodgkin primitif osseux de la région sacrée : un défi diagnostique et thérapeutique.

Primary osseous Hodgkin's lymphoma is a very rare entity. Cases reported in the literature are limited with often insufficient initial exploration. We report a new case of a 24 years old patient with a diagnosis of primary osseous Hodgkin lymphoma of the lumbosacral region with extension to the soft tissues, without simultaneous lymph node involvement confirmed both by conventional and metabolic imaging. The patient received a combination chemotherapy (two courses BEACOPP® and four courses ABVD) followed by radiotherapy of the lombosacral region at the dose of 40Gy in 20 fractions. Fifteen months after the end of treatment, the patient was in complete remission.

[Autoimmune and inflammatory disorders associated with lymphoid hematological malignancies]. / Manifestations auto-immunes et inflammatoires des hémopathies lymphoïdes.

In this literature review, we reported autoimmune and inflammatory disorders associated with lymphoid hematological malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma and chronic lymphocytic leukemia. The different types of systemic involvement are classified by affected organ. We listed in this review the joint diseases, skin, neurologic, hematologic, renal, and vasculitis. We tried to determine whether there is a correlation between each autoimmune manifestation and a specific type of lymphoma or a particular feature that may support a paraneoplastic origin, if there is an impact on the prognosis of the hematological malignancy, and finally, we identified the different therapeutic strategies used in the literature.

[Lymphomas]. / Lymphome.

Although malignant lymphoma is split in over 60 distinct entities, four of them, diffuse large B cell lymphoma, follicular-, Hodgkin's- and mantle cell lymphoma constitute more than half of all new cases. A recent major revision of the Ann Arbor staging system restricts the suffix "A" and "B" just to Hodgkin's lymphoma. Bone marrow exams are abandonned in Hodgkin's and restricted in DLBCL. PET exams at different time points are crucial. PET guided therapy will lead to a reduction of the use of chemo- and radiation therapy. Many new targeted drugs have been introduced. Their therapeutic index is impressive as is their price tag. The radiation and chemotherapy free treatment of malignant lymphoma is within reach.