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• W2201879560 abstract "Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct entity from classical Hodgkin lymphoma (cHL), characterized by the presence of the CD20-positive lymphocytic and histiocytic cells (Swerdlow et al, 2008). Biologically, NLPHL shares features with indolent B-cell non-Hodgkin Lymphoma (NHL) and cHL, although cell of origin is a germinal centre B cell and the gene expression signature is closer to cHL or T cell–rich large B-cell lymphoma than other indolent B cell NHL (Brune et al, 2008). Most patients present with limited stage disease, typically involving peripheral sites such as cervical, axillary or inguinal regions. They follow an indolent course that can last more than 10 years but carry a risk of late relapse or transformation into aggressive T cell-rich large B-cell lymphomas (Biasoli et al, 2010). Patients with early-stage disease have a 10-year overall survival of 85–100% with radiation alone or combined with chemotherapy (CT) (Wilder et al, 2002), but little is known concerning the best option for patients with advanced disease or patients not eligible for radiation therapy, given the rarity of the disease. European Society for Medical Oncology guideline (Eichenauer et al, 2014) lists multiple chemotherapy options, such as CVP (cyclophosphamide, vincristine, prednisone), CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) and ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) with or without rituximab, as valid options. Recent publications have also demonstrated a positive benefit of the CD20-targeted monoclonal antibody rituximab for relapsing patients or in frontline treatment (Advani et al, 2014). Since 2002, we have added rituximab to standard ABVD for NLPHL patients considered as ineligible for radiation therapy or with advanced stage disease. We aimed to reduce long-term toxicities by limiting the number of ABVD courses and radiation therapy. Here, we report the results of a retrospective cohort of patients treated in two French institutions between April 2002 and October 2013. Clinical data was collected from 24 patients treated with rituximab ± ABV(D) [R-ABV(D)](Table 1). Half of the patients had early-stage and the other half had advanced-stage disease. Median age at diagnosis was 30 years (range: 21–81). Two patients presented with anaemia, including one with a positive direct Coombs test haemolytic anaemia. Intravenous R-ABV(D) was administered in the outpatient department as follows: rituximab 375 mg/kg, day 1 and doxorubicin 25 mg/m², bleomycin 10 mg/m², vinblastine 6 mg/m² and dacarbazine 375 mg/m² on days 1 and 15 for a total of 3–6 cycles. Median number of treatment cycles was 4 (ranges: 3–4) for patients with early-stage disease versus 6 (ranges: 4–6) for patients with advanced stage disease. Dacarbazine was removed from the regimen in 10 patients (five patients in each group) to reduce immediate digestive intolerance and long-term toxicity related to alkylating agents. Patients with early-stage disease were considered ineligible for radiation therapy because of bulky tumour, infradiaphragmatic, axillary (in young women) or multiple localizations that would have required an extensive radiation field. This treatment was well tolerated and no patient was admitted for febrile neutropenia. Two patients (one in each group) developed a grade II–IV interstitial pneumonitis related to bleomycin and included an elderly patient who was admitted to the intensive care unit for mechanical ventilation. One (human immunodeficiency virus negative) patient developed a Kaposi Sarcoma related to Human herpesvirus 8 one month after first course of rituximab; the lesion resolved with local treatment and rituximab was completely withdrawn. All patients achieved complete responses according to Cheson criteria after four cycles. With a median follow-up of 50 months (2–120), no patient died. Two patients relapsed and two patients experienced a transformation to T cell–rich large B-cell lymphoma at a median of 35 and 20 months, respectively. Five-year lymphoma-free survival estimation was 80% with no difference between patients who had received dacarbazine or not. We observed a better survival in early-stage compared to advanced-stage disease (Fig 1). In the early-stage group, only the oldest patient (aged 81 years) presented a transformation into a large B cell lymphoma. He also had B-symptoms and splenic involvement, which are known poor prognosis factors, at diagnosis (Evens et al, 2013). Two patients (one in each group) were rescued by high dose chemotherapy and autologous stem cell transplantation, the other two are currently under treatment with still measurable disease at the end of follow-up (1 June 2015). Is a treatment similar to those used for cHL or B-cell NHL the better choice for patients with NLPHL? The British Columbia Cancer Agency reported an analysis of 42 patients treated with ABVD or ABVD-like chemotherapy (Xing et al, 2014). The 10-year overall survival and freedom from treatment failure were similar between NHLPL and cHL (75% vs. 73%, P = 0·6). However, the time to progression, which also included development of aggressive lymphomas, was inferior in NLPHL (63 vs. 73% P = 0·04) and was worse for patients with splenic involvement (48 vs. 71%) (Xing et al, 2014). There has been some debate on whether an alkylator-based chemotherapy, such as MOPP (mechlorethamine, vincristine, procarbazine, prednisone), may be superior to ABVD in NLPHL, but there is no definitive evidence to guide clinicians. Alkylator agents are known to increase the rates of subsequent myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) in contrast to ABVD, which has rarely been associated with the development of MDS/AML. Rituximab as single agent has also been evaluated in front-line therapy in advanced stage NLPHL. Although the overall response rate was 100%, the median progression-free survival was only 22 months (range: 8–74 months) suggesting that responses are not as durable as those achieved with chemotherapy or combined modality therapy and is not recommended as monotherapy in front line setting. Immuno-chemotherapy, such as R-CHOP, was investigated at the MD Anderson Cancer Center. Fifteen patients were treated with R-CHOP. No episodes of relapse or transformation were observed at a median follow-up of 42 months (Fanale et al, 2010). Besides theses encouraging results, few data are available about association between ABVD and Rituximab. This combination seems to be very effective and safe in our series of 24 patients, even for the 10 patients not receiving dacarbazine. Four cycles may be sufficient, particularly for patients with a negative positron emission tomography after two cycles. Nevertheless, the risk of pulmonary events leads us to propose either reducing the dose of belomycin or removing this drug from the regimen for elderly patients (Stamatoullas et al, 2015). PB designed the research study, SG performed the research, analysed data and wrote the paper, SH, SA, RB and CT read and corrected the manuscript." @default.
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• W2201879560 date "2015-12-18" @default.
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• W2201879560 title "Rituximab‐<scp>ABV</scp>(D) for patients with Nodular lymphocyte predominant Hodgkin lymphoma ineligible for radiation therapy" @default.
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